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Background: Tranexamic acid (TXA) is increasingly used in the management of haemorrhage during and after delivery and haemorrhage caused by other medical conditions due to its efficacy and safety. However, increasing report of fatal complications from inadvertent intrathecal TXA injection remains a cause of concern. The aim of this case report is to demonstrate clinical presentation and predictors of accidental intrathecal injection of TXA within the structure and processes of care in a health facility. Case Description: A 37‐year‐old woman, multiparous woman presented with a diagnosis of obstructed labour and, therefore, was scheduled for emergency caesarean section. She was assigned the American Society of Anesthesiology II physical status. Spinal anaesthesia was performed at a sitting position through L4‐L5 interspace using a 25‐G spinal needle gauge. The anaesthetist injected 3 mL of an aesthetic agent that was prepared earlier as hyperbaric bupivacaine 0.5%. About 2 min after receiving the injection, the patient reported gluteal discomfort and itching and severe back pain. She subsequently developed progressive altered mentation followed by generalized tonic–clonic seizures. General anaesthesia was conducted with propofol (100 mg), pethidine (50 mg) and suxamethonium (100 mg). Episodes of tonic–clonic seizures continued despite treatment with multiple doses of diazepam (10 mg), propofol (100 mg) and phenytoin infusion (1 gm). Postoperatively, the patient was transferred to the intensive care unit with persistent tachycardia (125–138 beats per minute), hypertension (157/105–175/118 mmHg) and oxygen saturation of 90%–95%. She died due to cardiac arrest after 21 h of stay. Conclusion: Medication error such as accidental intrathecal injection of TXA continues to jeopardise the safety of surgery under spinal anaesthesia. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide. However, existing treatments still face numerous clinical challenges. Building on our prior research showing peripheral nerve-derived stem cell (PNSC) spheroids with Schwann cell-like phenotypes can secrete neurotrophic factors to aid in neural tissue regeneration, we hypothesized that repeated intrathecal injections of PNSC spheroids would improve the delivery of neurotrophic factors, thereby facilitating the restoration of neurological function and brain tissue repair post-TBI. Methods: We generated PNSC spheroids from human peripheral nerve tissue using suspension culture techniques. These spheroids were characterized using flow cytometry, immunofluorescence, and reverse-transcription polymerase chain reaction. The conditioned media were evaluated in SH-SY5Y and RAW264.7 cell lines to assess their effects on neurogenesis and inflammation. To simulate TBI, we established a controlled cortical impact (CCI) model in rats. The animals were administered intrathecal injections of PNSC spheroids on three occasions, with each injection spaced at a 3-day interval. Recovery of sensory and motor function was assessed using the modified neurological severity score (mNSS) and rotarod tests, while histological (hematoxylin and eosin, Luxol fast blue staining) and T2-weighted magnetic resonance imaging analyses, alongside immunofluorescence, were conducted to evaluate the recovery of neural structures and pathophysiology. Results: PNSC spheroids expressed high levels of Schwann cell markers and neurotrophic factors, such as neurotrophin-3 and Ephrin B3. Their conditioned medium was found to promote neurite outgrowth, reduce reactive oxygen species-mediated cell death and inflammation, and influence M1-M2 macrophage polarization. In the CCI rat model, rats receiving repeated triple intrathecal injections of PNSC spheroids showed significant improvements in sensory and motor function, with considerable neural tissue recovery in damaged areas. Notably, this treatment promoted nerve regeneration, axon regrowth, and remyelination. It also reduced glial scar formation and inflammation, while encouraging angiogenesis. Conclusion: Our findings suggest that repeated intrathecal injections of PNSC spheroids can significantly enhance neural recovery after TBI. This effect is mediated by the diverse neurotrophic factors secreted by PNSC spheroids. Thus, the strategy of combining therapeutic cell delivery with multiple intrathecal injections holds promise as a novel clinical treatment for TBI recovery. [ABSTRACT FROM AUTHOR]

Deregulated cyclin‐dependent kinase 5 (Cdk5) activity closely correlates with hyperphosphorylated tau, a common pathology found in neurodegenerative diseases. Previous postmortem studies had revealed increased Cdk5 immunoreactivity in amyotrophic lateral sclerosis (ALS); hence, we investigated the effects of Cdk5 inhibition on ALS model mice and neurons in this study. For the in vitro study, motor neuron cell lines with wild‐type superoxide dismutase 1 (SOD1) or SOD1G93A and primary neuronal cultures from SOD1G93A transgenic (TG) mice or non‐TG mice were compared for the expression of proteins involved in tau pathology, neuroinflammation, apoptosis, and neuritic outgrowth by applying Cdk5‐small interfering RNA or Cdk5‐short hairpin RNA (shRNA). For the in vivo study, SOD1G93A mice and non‐TG mice were intrathecally injected with adeno‐associated virus 9 (AAV9)‐scramble (SCR)‐shRNA or AAV9‐Cdk5‐shRNA at the age of 5 weeks. Weight and motor function were measured three times per week from 60 days of age, longevity was evaluated, and the tissues were collected from 90‐day‐old or 120‐day‐old mice. Neurons with SOD1G93A showed increased phosphorylated tau, attenuated neuritic growth, mislocalization of SOD1, and enhanced neuroinflammation and apoptosis, all of which were reversed by Cdk5 inhibition. Weights did not show significant differences among non‐TG and SOD1G93A mice with or without Cdk5 silencing. SOD1G93A mice treated with AAV9‐Cdk5‐shRNA showed significantly delayed disease onset, delayed rotarod failure, and prolonged survival compared with those treated with AAV9‐SCR‐shRNA. The brain and spinal cord of SOD1G93A mice intrathecally injected with AAV9‐Cdk5‐shRNA exhibited suppressed tau pathology, neuroinflammation, apoptosis, and an increased number of motor neurons compared to those of SOD1G93A mice injected with AAV9‐SCR‐shRNA. Cdk5 inhibition could be an important mechanism in the development of a new therapeutic strategy for ALS. [ABSTRACT FROM AUTHOR]

Over the last decade, it has become evident that cerebrospinal fluid (CSF) plays a pivotal role in brain solute clearance through perivascular pathways and interactions between the brain and meningeal lymphatic vessels. Whereas most of this fundamental knowledge was gained from rodent models, human brain clearance imaging has provided important insights into the human system and highlighted the existence of important interspecies differences. Current gold standard techniques for human brain clearance imaging involve the injection of gadolinium‐based contrast agents and monitoring their distribution and clearance over a period from a few hours up to 2 days. With both intrathecal and intravenous injections being used, which each have their own specific routes of distribution and thus clearance of contrast agent, a clear understanding of the kinetics associated with both approaches, and especially the differences between them, is needed to properly interpret the results. Because it is known that intrathecally injected contrast agent reaches the blood, albeit in small concentrations, and that similarly some of the intravenously injected agent can be detected in CSF, both pathways are connected and will, in theory, reach the same compartments. However, because of clear differences in relative enhancement patterns, both injection approaches will result in varying sensitivities for assessment of different subparts of the brain clearance system. In this opinion review article, the "EU Joint Programme – Neurodegenerative Disease Research (JPND)" consortium on human brain clearance imaging provides an overview of contrast agent pharmacokinetics in vivo following intrathecal and intravenous injections and what typical concentrations and concentration–time curves should be expected. This can be the basis for optimizing and interpreting contrast‐enhanced MRI for brain clearance imaging. Furthermore, this can shed light on how molecules may exchange between blood, brain, and CSF. [ABSTRACT FROM AUTHOR]

Abstract Background Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide. However, existing treatments still face numerous clinical challenges. Building on our prior research showing peripheral nerve-derived stem cell (PNSC) spheroids with Schwann cell-like phenotypes can secrete neurotrophic factors to aid in neural tissue regeneration, we hypothesized that repeated intrathecal injections of PNSC spheroids would improve the delivery of neurotrophic factors, thereby facilitating the restoration of neurological function and brain tissue repair post-TBI. Methods We generated PNSC spheroids from human peripheral nerve tissue using suspension culture techniques. These spheroids were characterized using flow cytometry, immunofluorescence, and reverse-transcription polymerase chain reaction. The conditioned media were evaluated in SH-SY5Y and RAW264.7 cell lines to assess their effects on neurogenesis and inflammation. To simulate TBI, we established a controlled cortical impact (CCI) model in rats. The animals were administered intrathecal injections of PNSC spheroids on three occasions, with each injection spaced at a 3-day interval. Recovery of sensory and motor function was assessed using the modified neurological severity score (mNSS) and rotarod tests, while histological (hematoxylin and eosin, Luxol fast blue staining) and T2-weighted magnetic resonance imaging analyses, alongside immunofluorescence, were conducted to evaluate the recovery of neural structures and pathophysiology. Results PNSC spheroids expressed high levels of Schwann cell markers and neurotrophic factors, such as neurotrophin-3 and Ephrin B3. Their conditioned medium was found to promote neurite outgrowth, reduce reactive oxygen species-mediated cell death and inflammation, and influence M1-M2 macrophage polarization. In the CCI rat model, rats receiving repeated triple intrathecal injections of PNSC spheroids showed significant improvements in sensory and motor function, with considerable neural tissue recovery in damaged areas. Notably, this treatment promoted nerve regeneration, axon regrowth, and remyelination. It also reduced glial scar formation and inflammation, while encouraging angiogenesis. Conclusion Our findings suggest that repeated intrathecal injections of PNSC spheroids can significantly enhance neural recovery after TBI. This effect is mediated by the diverse neurotrophic factors secreted by PNSC spheroids. Thus, the strategy of combining therapeutic cell delivery with multiple intrathecal injections holds promise as a novel clinical treatment for TBI recovery.

Abstract This study aims to collect and analyze adverse event (AE) reports related to Nusinersen from the FAERS database. The study employed a combination of signal quantification techniques, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS), to enhance the accuracy of signal detection and reduce the risk of false positives or negatives. Between the first quarter of 2017 and the third quarter of 2023, the FAERS database collected a total of 11,485,105 drug AE reports, of which 5772 were related to Nusinersen. Through signal mining analysis, 218 preferred term (PT) signals involving 27 system organ classes (SOCs) were identified. The study discovered AEs related to metabolism and nutrition disorders, psychiatric disorders, and cardiac disorders SOCs, which were not mentioned in the product information. Additionally, complications directly related to the intrathecal administration of Nusinersen, such as increased CSF pressure, positive CSF red blood cell count, and AEs related to the method of drug use, such as neuromuscular scoliosis and cerebrospinal fluid reservoir placement, were highlighted. Notably, AEs related to renal function abnormalities, such as abnormal Urine protein/creatinine ratio and protein urine presence, showed higher frequency and signal strength. The findings of this study emphasize the importance of comprehensive safety monitoring in the clinical application of Nusinersen. These results are significant for guiding future clinical practices, improving disease management strategies, and developing safer treatment protocols.

Abstract Background The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety. Methods A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators. Results A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P

Background: Subarachnoid block is the most commonly used anesthetic technique for lower limb surgeries. Fentanyl is very often combined with hyperbaric bupivacaine as an adjuvant. This study was conducted to compare the block characteristics by administrating bupivacaine and fentanyl in a sequential and premixed manner. Aims and Objectives: The primary objective was to compare the effects of hyperbaric bupivacaine and fentanyl administered either as a premixed solution or sequentially on block characteristics-onset of sensory and motor blockade, regression of block and duration of analgesia. The secondary objective was to study the hemodynamic changes and adverse effects. Materials and Methods: A total of 72 patients scheduled to undergo lower limb surgery were allocated to three groups. Patients in Group A received 15 mg of 0.5 % bupivacaine heavy (H), followed by 25 mcg of fentanyl intrathecally using different syringes. Group B received 25 mcg of fentanyl, followed by 15 mg of 0.5% bupivacaine H in a separate syringe. Group C received premixed 0.5 % bupivacaine H 15 mg and fentanyl 25 mcg in single syringe. The block characteristics-onset and regression of sensory and motor blockade, duration of analgesia, and adverse effects were studied. Results: The mean time (minutes) taken for onset of sensory block was 2.40±0.51 in group A, 4.80±0.53 in Group B and 6.70±0.50 in Group C. Mean time (minutes) taken for onset of motor block was 4.35±0.43 in Group A, while it was 5.64±0.65 and 7.32±0.64 in Groups B and C, respectively. Two segment regression and duration of motor blockade were found to be longer in Group A. Conclusion: Sequential intrathecal administration of bupivacaine followed by fentanyl has a faster onset and prolonged duration of block when compared to the premixed group.

Background: The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety. Methods: A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators. Results: A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P < 0.001) and adverse reaction rate was significantly lower in the IDI groups (RR 0.59, 95% CI 0.37-0.92, P = 0.021). Furthermore, CSF leukocytes (WMD - 29.33, 95% CI [- 40.64 to-18.02], P < 0.001) and CSF protein (WMD - 0.79, 95%CI [-0.96 to-0.61], P < 0.001) were significantly lower in the IDI groups. Recovery time indicators were all shorter in the IDI groups, fever (SMD - 2.45, 95% CI [-3.55 to-1.35], P < 0.001), coma (SMD-3.75, 95% CI [-4.33 to-3.17], P < 0.001), and headache (SMD - 3.06, 95% CI [- 4.05 to-2.07], P < 0.001), respectively. Higher-dose IDI was more effective than lower-dose IDI (RR 1.23, 95% CI 1.14-1.33, P < 0.001), with no significant difference in adverse reaction rate between the two (RR 0.82, 95%CI 0.43–1.56, P = 0.544). Conclusion: Adjunct IDI with C anti-TB can enhance therapeutic outcomes and reduce adverse reaction rate in adult TBM patients, with higher-dose IDI showing superior efficacy. These findings highlight the potential of IDI as an adjunctive therapy in TBM management. However, more high-quality RCTs from more regions should be conducted to support our results. Trial registration: Retrospectively registered in PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023388860. [ABSTRACT FROM AUTHOR]

Background: Subarachnoid block is the most commonly used anesthetic technique for lower limb surgeries. Fentanyl is very often combined with hyperbaric bupivacaine as an adjuvant. This study was conducted to compare the block characteristics by administrating bupivacaine and fentanyl in a sequential and premixed manner. Aims and Objectives: The primary objective was to compare the effects of hyperbaric bupivacaine and fentanyl administered either as a premixed solution or sequentially on block characteristics-onset of sensory and motor blockade, regression of block and duration of analgesia. The secondary objective was to study the hemodynamic changes and adverse effects. Materials and Methods: A total of 72 patients scheduled to undergo lower limb surgery were allocated to three groups. Patients in Group A received 15 mg of 0.5 % bupivacaine heavy (H), followed by 25 mcg of fentanyl intrathecally using different syringes. Group B received 25 mcg of fentanyl, followed by 15 mg of 0.5% bupivacaine H in a separate syringe. Group C received premixed 0.5 % bupivacaine H 15 mg and fentanyl 25 mcg in single syringe. The block characteristics-onset and regression of sensory and motor blockade, duration of analgesia, and adverse effects were studied. Results: The mean time (minutes) taken for onset of sensory block was 2.40±0.51 in group A, 4.80±0.53 in Group B and 6.70±0.50 in Group C. Mean time (minutes) taken for onset of motor block was 4.35±0.43 in Group A, while it was 5.64±0.65 and 7.32±0.64 in Groups B and C, respectively. Two segment regression and duration of motor blockade were found to be longer in Group A. Conclusion: Sequential intrathecal administration of bupivacaine followed by fentanyl has a faster onset and prolonged duration of block when compared to the premixed group. [ABSTRACT FROM AUTHOR]

Granulomatosis with polyangiitis (GPA) is a pauci-immune small vessel vasculitis characterised by neutrophil-mediated vasculitis and granuloma. The presence of intracranial parenchymal space-occupying lesions is rarely seen in GPA patients. In this manuscript, we report a case of GPA with granuloma of the fourth ventricle accompanied by obstructive hydrocephalus. Treatment with glucocorticoids (GCs) and multiple immunosuppressants cyclophosphamide (CYC), mycophenolate mofetil (MMF), and rituximab (RTX) showed poor efficacy in this case. After removal of the granuloma by craniotomy, GPA relapsed within 3 months. Under the premise of GC and MMF treatment combined with intrathecal injection of dexamethasone (DXM) and methotrexate (MTX), the intracranial granuloma gradually shrank, and the patient's general condition was alleviated, showing that this is an effective treatment method. Key Points • To date, there are few reports of granulomatous vasculitis combined with granuloma of the fourth ventricle, and our case is the second. • In this case, multiple immunosuppressants and rituximab were ineffective treatments, and the intracranial granuloma was effectively controlled by intrathecal injection of dexamethasone (DXM) and methotrexate (MTX). • Based on this report, it can be suggested that intrathecal injection is effective in treating patients with GPA and central nervous system involvement, but large-scale sample studies are needed. [ABSTRACT FROM AUTHOR]

Background: Cerebral palsy is a severe motor disability in childhood that poses challenges for children, families, and society. Rhesus macaques are the preferred animals for cerebral palsy model, but surgical excision of motor cortex has low success rate and high cost. In this work, we created cerebral palsy rhesus macaque models by intrathecal injection of bilirubin. Methods: The puncture point for injection was identified as the intervertebral disc space two, located below the intersection of the iliac crest line and the posterior median line. Results: The models showed abnormal posture and increased muscle tension. Diffuse deposits of bilirubin were found in the basal ganglia from the magnetic resonance imaging. Pathological slides also revealed the presence of brain lesions, such as vacuole formation, contraction of neuronal nuclei, and deep staining of nuclei in the histopathological sections of the hippocampus and basal ganglia. Conclusion: The model's symptoms closely resemble those observed in humans with spastic cerebral palsy. [ABSTRACT FROM AUTHOR]

Mei Wu,1,2,&ast; Jingui Zhao,1,2,&ast; Zhongqiang Liu,1,2 Haiyang Zhang1,2 1Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiyang Zhang, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China, Tel + 86 15756273633, Fax + 86 15756273633, Email icudoc@163.comBackground: Clinically, Carbapenem-resistant Pseudomonas aeruginosa (CRPA) meningitis is extremely difficult to cure and has a high mortality rate. Intrathecal injection of polymyxins B is suggested to be an effective anti-infective means to treat intracranial infection with CRPA. However, due to the potential drug toxicity of polymyxin B in children, this regimen has rarely been reported in pediatrics.Case Description: A 5-year-old male patient diagnosed with Epstein-Barr virus-induced hemophagocytic syndrome (HPS) exhibited persistent fever for over a month despite antibacterial and chemotherapy regimens. During hospitalization, the patient presented with unconsciousness, nystagmus, and myasthenia. Cerebrospinal fluid (CSF) analysis indicated elevated leukocyte counts and protein levels. Sputum and blood cultures, as well as metagenomic next-generation sequencing (mNGS) of CSF, identified CRPA. Intravenous and intrathecal polymyxin B administration resulted in temperature normalization and amelioration of consciousness disturbances and nystagmus. Subsequent CSF analysis yielded normal results, while polymyxin B treatment exhibited no nephrotoxicity or neurotoxicity.Conclusion: Intrathecal injection of polymyxin B in children with meningitis caused by CRPA is an effective treatment without remarkable adverse events.Keywords: polymyxin B, intrathecal injection, carbapenem resistant, Pseudomonas aeruginosa, meningitis

Abstract Background As the first gene therapy for spinal muscular atrophy (SMA), nusinersen is supposed to be administrated via intrathecal injection regularly for a lifetime. However, for SMA patients with severe spinal deformities, bony fusion following posterior spinal instrumentation sets great obstacles for the application of nusinersen. Therefore, efforts have been devoted to the exploration of appropriate approach for nusinersen administration. This study aims to evaluate the safety and reliability of unilateral interlaminar fenestration on the convex side during spinal fusion surgery for intrathecal nusinersen injection in SMA. Results SMA patients receiving posterior spinal fusion and interlaminar fenestration in Peking Union Medical College Hospital from January 2020 to October 2021 were retrospectively analyzed. 13 patients were included. Of the 13 patients, 10 were classified into SMA type II and 3 into SMA type III. Distal fusion to pelvis was undertaken in 11 patients; while L5 was selected as the lowest instrumented vertebra in the other 2 patients. All patients received interlaminar fenestration on the convex side only with an area of about 15 mm × 20 mm. Fenestration at L2–L3 level was performed in 6 patients; while L3–L4 level was selected for windowing in the remaining 7 patients. 9 of the 13 patients received lumbar puncture and intrathecal nusinersen administration during the 1-year follow-up, with an accumulative total of 50 times. All injections were performed successfully under ultrasound guidance, with no one transferred to radiographic assistance. No severe complications occurred after injection. Conclusions In SMA with severe scoliosis planning to receive posterior spinal fusion, unilateral lumbar interlaminar fenestration on the convex side provides a feasible and reliable access for intrathecal nusinersen administration after surgery.

Background: Spinal cord injury (SCI) due to lack of restoration of damaged neuronal cells is associated with sensorimotor impairment. This study was focused on using the human placental mesenchymal stem cells- exosome (HPMSCs- Exosomes) in an animal model of severe SCI under myelogram procedure. Methods and results: Intrathecal injection of exosomes was performed in the acute phase of SCI in female rats. The improved functional recovery of the animals was followed for 6 weeks in control (saline, n = 6) and HPMSCs- EXO (HPMSCs-Exosomes, n = 6) groups. Pathological changes and glial scar size were evaluated. The Immunohistochemistry (IHC) of GFAP and NF200 factors as well as the apoptosis assay was investigated in the tissue samples from the injury site. The results demonstrated that HPMSCs-exosomes can improve motor function by attenuating apoptosis of neurons at the injury site, decreasing GFAP expression and increasing NF200 in the HPMSCs-EXO group. Also, HPMSCs-exosomes by preventing the formation of cavities causes preservation of tissue in SCI rats. Conclusions: These findings demonstrate the effectiveness of HPMSC-Exosomes as a therapeutic method to improve functional recovery, reduce pathological changes associated with injury, and prevent chronicity after SCI. The neuroprotective and anti-apoptotic potential of HPMSCs- Exosomes may be a promising therapeutic approach for SCI. Another result was the importance of intrathecal injection of exosomes in the acute phase, which accelerated the healing process. Furthermore, the myelogram can be a feasible and suitable method to confirm the accuracy of intrathecal injection and examine the subarachnoid space in the laboratory animals. [ABSTRACT FROM AUTHOR]

Background: As the first gene therapy for spinal muscular atrophy (SMA), nusinersen is supposed to be administrated via intrathecal injection regularly for a lifetime. However, for SMA patients with severe spinal deformities, bony fusion following posterior spinal instrumentation sets great obstacles for the application of nusinersen. Therefore, efforts have been devoted to the exploration of appropriate approach for nusinersen administration. This study aims to evaluate the safety and reliability of unilateral interlaminar fenestration on the convex side during spinal fusion surgery for intrathecal nusinersen injection in SMA. Results: SMA patients receiving posterior spinal fusion and interlaminar fenestration in Peking Union Medical College Hospital from January 2020 to October 2021 were retrospectively analyzed. 13 patients were included. Of the 13 patients, 10 were classified into SMA type II and 3 into SMA type III. Distal fusion to pelvis was undertaken in 11 patients; while L5 was selected as the lowest instrumented vertebra in the other 2 patients. All patients received interlaminar fenestration on the convex side only with an area of about 15 mm × 20 mm. Fenestration at L2–L3 level was performed in 6 patients; while L3–L4 level was selected for windowing in the remaining 7 patients. 9 of the 13 patients received lumbar puncture and intrathecal nusinersen administration during the 1-year follow-up, with an accumulative total of 50 times. All injections were performed successfully under ultrasound guidance, with no one transferred to radiographic assistance. No severe complications occurred after injection. Conclusions: In SMA with severe scoliosis planning to receive posterior spinal fusion, unilateral lumbar interlaminar fenestration on the convex side provides a feasible and reliable access for intrathecal nusinersen administration after surgery. [ABSTRACT FROM AUTHOR]

Objective: Spinal cord injury (SCI) is usually caused by compression of spinal cord tissue. The main manifestations are the loss of motor or sensory functions. Because injured individuals are usually relatively young and have no effective treatment measures, there is a heavy economic burden on their families and society. Rice was the most abundant source of GORZ. This compound exhibits both antioxidant and anti-inflammatory properties. γ-Oryzanol has been shown to cross the blood–brain barrier intact and benefit brain function. This study is the first time the effect of γ-Oryzanol on the recovery of motor function after SCI in mice. Therefore, we injected γ-Oryzanol into SCI mice in different ways to observe the effect on motor function recovery of mice. Materials and methods: The mice were randomly divided into 4 groups. In one group, only lamina was opened without damaging the spinal cord tissue (sham group); One group was left untreated after the injured spinal cord tissue (injured group). In the other two groups, mice were given 100 mg/kg of γ-Oryzanol every 2 days through the intraperitoneal or intrathecal for 42 days after injuring the spinal cord. Behavioral tests were performed using the Basso Mouse Scale (BMS) scores and gait analysis. Hematoxylin and Eosin (H&E) and immunofluorescence staining were used to observe changes in the lesion area, demyelination, axonal regeneration, and scar tissue formation. Results: 1. Behavioral experiments showed that the γ-Oryzanol-treated mice showed better exercise capacity than those in the injured group. 2. The pathology and demyelination at the injury site were improved in γ-Oryzanol-treated mice. 3. γ-Oryzanol-treated mice had more M2-type macrophages at the site of injury. At the same time, γ-Oryzanol-treated mice retained more axons associated with motor function and less scarring. Conclusions: Studies have shown that γ-Oryzanol can promote the recovery of motor function in mice after SCI. And the change was even more pronounced in mice treated with intrathecal injection methods. Although more intensive studies are needed, we suggest that γ-Oryzanol has potential clinical value as a recognized inexpensive dietary phytochemical.

Objective: Nusinersen, an extremely expensive biologic drug (around 100,000 US$ per dose) that needs to be administered intrathecally, is approved for the treatment of 5q-spinal muscular atrophy (SMA). Because of the low muscle tone of the back muscles of pediatric SMA patients, especially type 1 SMA patients, the safe, effective, and fast execution of sheath injection is needed. Therefore, a modified intrathecal injection method was developed accordingly. This paper aims to describe the applicability and safety of this modified method. Methods: The modified intrathecal injection method (MIIM) mainly includes a septal needle-free closed infusion connector between the lumbar puncture needle and the syringe, besides the procedures of routine lumbar puncture. Its applicability and safety were evaluated through clinical observation. Results: A total of 92 children with SMA have successfully received nusinersen treatment at our hospital using the modified method since 2019 without obvious adverse events related to the modified injection method. Based on the clinical feedback of operators, the advantages of the modified method include successfully injecting the total dose of nusinersen with constant injection rate and a more stable fixation of the puncture needle, as well as making the operator more relaxed. However, compared with the routine method, the procedure of the modified method has additional steps. Conclusion: The modified intrathecal injection method is an effective and safe method to inject nusinersen when weighing the pros and cons, and it may also be used for administering intrathecal injections of other expensive medicines or for patients with other strict requirements for intrathecal injection. [ABSTRACT FROM AUTHOR]

Methane has shown protective effects on a variety of diseases. Among these, neurological diseases have attracted much attention. However, there are many different indicators and application methods of methane in the treatment of neurological diseases. In this review, we summarize the indicators related to the protective effects of methane and evaluate the preparation and administration of methane. Thus, we hope to offer available indicators and effective ways to produce and administer methane in future research. [ABSTRACT FROM AUTHOR]

Introduction: Cannabis extracts are being increasingly used to mitigate chronic pain. Current guidelines for their prescription rely on ?9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content as well as the ratio of these major cannabinoids present in the blend. Here we assessed whether these descriptors were representative of product effectiveness to produce a desired outcome such as analgesia. Methods: In this study, we used a rat model of diabetic neuropathy and assessed the reduction in mechanical allodynia following intrathecal injection of pure THC, pure CBD, a 1:1 mix of these compounds and a "balanced" chemotype II cannabis extract. Engagement of endocannabinoid targets by different treatments was investigated using CB1 (AM251) and CB2 (AM630) receptor antagonists as well as a TRPV1 channel blocker (capsazepine). Results: Antinociceptive responses induced by an equivalent amount of THC administered in its pure form, as a THC:CBD mix or as a "balanced" extract were distinct. Furthermore, the 1:1 THC:CBD mix and the balanced extract had not only different response profiles but their relative engagement of CB1, CB2 receptors and TRPV1 channels was distinct. Discussion: These findings indicate that antinociceptive responses and targets engaged by blended cannabinoids are composition-specific, and cannot be simply inferred from THC and CBD contents. This information may have implications in relation to the way medicinal cannabis products are prescribed. [ABSTRACT FROM AUTHOR]

Background/aim: Dorsal root ganglia (DRG) are structures containing primary sensory neurons. Intraganglionic (IG) and intrathecal (IT) applications are the most common methods used for viral vector transfer to DRG. We aim to compare the efficiencies and pathological effects of IT and IG viral vector delivery methods to DRG, through in vivo imaging. Materials and methods: Mice were divided into four groups of six each: IT, IG, IT-vehicle, and IG-vehicle. Adeno-associated virus (AAV) injection was performed for EGFP expression in IT/IG groups. DRGs were made visible through vertebral window surgery and visualized with multiphoton microscopy. After imaging, spinal cords and DRGs were removed and cleared, then imaged with light sheet microscopy. Results: No neuronal death was observed after IT injection, while the death rate was 17% 24 h after IG injection. EGFP expression efficiencies were 90%-95% of neurons in both groups. EGFP expression was only observed in targeted L2 DRG after IG injection, while it was observed in DRGs located between L1-L5 levels after IT injection. Conclusion: IT injection is a more suitable method for labeling DRG neurons in neurodegenerative injury models. However, when the innervation of DRG needs to be specifically studied, IT injection reduces this specificity due to its spread. In these studies, IG injection is the most suitable method for labeling single DRG neurons. [ABSTRACT FROM AUTHOR]

Direct delivery of therapeutics to the central nervous system (CNS) greatly expands opportunities to treat neurological diseases but is technically challenging. This opinion outlines principal technical aspects of direct CNS delivery via intracerebroventricular (ICV) or intrathecal (IT) injection to common nonclinical test species (rodents, dogs, and nonhuman primates) and describes procedure-related clinical and histopathological effects that confound interpretation of test article-related effects. Direct dosing is by ICV injection in mice due to their small body size, while other species are dosed IT in the lumbar cistern. The most frequent procedure-related functional effects are transient absence of lower spinal reflexes after IT injection or death soon after ICV dosing. Common procedure-related microscopic findings in all species include leukocyte infiltrates in CNS meninges or perivascular (Virchow-Robin) spaces; nerve fiber degeneration in the spinal cord white matter (especially dorsal and lateral tracts compressed by dosing needles or indwelling catheters), spinal nerve roots, and sciatic nerve; meningeal fibrosis at or near IT injection sites; hemorrhage; and gliosis. Findings typically are minimal to occasionally mild. Findings tend to be more severe and/or have a higher incidence in the spinal cord segments and spinal nerve roots at or close to the site of administration. [ABSTRACT FROM AUTHOR]

Abstract Background Malfunction of astrocytes is implicated as one of the pathological factors of ALS. Thus, intrathecal injection of healthy astrocytes in ALS can potentially compensate for the diseased astrocytes. AstroRx® is an allogeneic cell-based product, composed of healthy and functional human astrocytes derived from embryonic stem cells. AstroRx® was shown to clear excessive glutamate, reduce oxidative stress, secrete various neuroprotective factors, and act as an immunomodulator. Intrathecal injection of AstroRx® to animal models of ALS slowed disease progression and extended survival. Here we report the result of a first-in-human clinical study evaluating intrathecal injection of AstroRx® in ALS patients. Methods We conducted a phase I/IIa, open-label, dose-escalating clinical trial to evaluate the safety, tolerability, and therapeutic effects of intrathecal injection of AstroRx® in patients with ALS. Five patients were injected intrathecally with a single dose of 100 × 106 AstroRx® cells and 5 patients with 250 × 106 cells (low and high dose, respectively). Safety and efficacy assessments were recorded for 3 months pre-treatment (run-in period) and 12 months post-treatment (follow-up period). Results A single administration of AstroRx® at either low or high doses was safe and well tolerated. No adverse events (AEs) related to AstroRx® itself were reported. Transient AEs related to the Intrathecal (IT) procedure were all mild to moderate. The study demonstrated a clinically meaningful effect that was maintained over the first 3 months after treatment, as measured by the pre-post slope change in ALSFRS-R. In the 100 × 106 AstroRx® arm, the ALSFRS-R rate of deterioration was attenuated from − 0.88/month pre-treatment to − 0.30/month in the first 3 months post-treatment (p = 0.039). In the 250 × 106 AstroRx® arm, the ALSFRS-R slope decreased from − 1.43/month to − 0.78/month (p = 0.0023). The effect was even more profound in a rapid progressor subgroup of 5 patients. No statistically significant change was measured in muscle strength using hand-held dynamometry and slow vital capacity continued to deteriorate during the study. Conclusions Overall, these findings suggest that a single IT administration of AstroRx® to ALS patients at a dose of 100 × 106 or 250 × 106 cells is safe. A signal of beneficial clinical effect was observed for the first 3 months following cell injection. These results support further investigation of repeated intrathecal administrations of AstroRx®, e.g., every 3 months. Trial Registration: NCT03482050.

Introduction: Cannabis extracts are being increasingly used to mitigate chronic pain. Current guidelines for their prescription rely on Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content as well as the ratio of these major cannabinoids present in the blend. Here we assessed whether these descriptors were representative of product effectiveness to produce a desired outcome such as analgesia.Methods: In this study, we used a rat model of diabetic neuropathy and assessed the reduction in mechanical allodynia following intrathecal injection of pure THC, pure CBD, a 1:1 mix of these compounds and a “balanced” chemotype II cannabis extract. Engagement of endocannabinoid targets by different treatments was investigated using CB1 (AM251) and CB2 (AM630) receptor antagonists as well as a TRPV1 channel blocker (capsazepine).Results: Antinociceptive responses induced by an equivalent amount of THC administered in its pure form, as a THC:CBD mix or as a “balanced” extract were distinct. Furthermore, the 1:1 THC:CBD mix and the balanced extract had not only different response profiles but their relative engagement of CB1, CB2 receptors and TRPV1 channels was distinct.Discussion: These findings indicate that antinociceptive responses and targets engaged by blended cannabinoids are composition-specific, and cannot be simply inferred from THC and CBD contents. This information may have implications in relation to the way medicinal cannabis products are prescribed.

Percutaneous endoscopic lumbar discectomy (PELD) is a surgical setting that requires minimal motor impairment. Low-dose spinal ropivacaine induces little motor blockade and could be ideal for maintaining safety of PELD, but its analgesic efficacy is questionable. An adjunct analgesic approach is needed to maximize the benefits of low-dose spinal ropivacaine for PELD. This study aimed to explore the effectiveness and safety of 100 µg intrathecal morphine (ITM) as an adjuvant analgesic method for PELD under low-dose spinal ropivacaine. A double-blind, randomized, placebo-controlled trial. Trial registration: ChiCTR2000039842 (www.chictr.org.cn). Ninety patients scheduled for elective single-level PELD under low-dose spinal ropivacaine. The primary outcome was the overall intraoperative visual analogue scale (VAS) score for pain. Secondary outcomes were intraoperative VAS scores assessed at multiple timepoints; intraoperative rescue analgesic requirement; postoperative VAS scores; disability scale; patients' satisfaction with anesthesia; adverse events; and radiographic outcomes. Patients were randomized to receive low-dose ropivacaine spinal anesthesia with (ITM group, n=45) or without (control group, n=45) 100 µg ITM. The overall intraoperative VAS score in the ITM group was significantly lower than that in the control group (0 [0, 1] vs 2 [1, 3], p<.001). During operation, the VAS scores at cannula insertion, 30 minutes after insertion, 60 minutes after insertion, and 120 minutes after insertion were all significantly lower in the ITM group (all p<.05). Less patients in the ITM group required rescue analgesia during operation compared with those in the control group (14% vs 42%, p=.003). The VAS score for back pain in the ITM group was lower than that in the control group at 1 hour, 12 hours, and 24 hours postoperatively. Besides, the satisfaction score in the ITM group was significantly higher than that in the control group (p=.017). For adverse events, 8/43 of ITM and 1/44 of control participants experienced pruritus (p=.014), with a relative risk (95% confidence interval) of 8.37 (1.09–64.16). The incidence of other adverse events was similar between the two groups. Of note, respiratory depression occurred in one ITM-treated patient. The addition of 100 µg ITM to low-dose ropivacaine appears to be effective in analgesia without compromised motor function for PELD; however, ITM increased the risk of pruritus and clinicians should be vigilant about its potential risk of respiratory depression. [ABSTRACT FROM AUTHOR]

Min Zhou, Richu Liang, Quan Liao, Pingfu Deng, Wentao Fan, Chenzhuo Li The Second affiliated Hospital, Department of Neurosurgery, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of ChinaCorrespondence: Richu Liang, The Second AFfiliated Hospital, Department of Neurosurgery, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China, Email 2015020049@usc.edu.cnBackground: Intracranial infection is a common complication caused by craniotomy. In particular, patients in Intensive Care Units (ICU) are prone to intracranial infection with multiple drug-resistant bacteria. Due to the lack of sensitive antibiotics for the treatment of multiple drug-resistant bacteria, there are few literatures focusing on the treatment of intracranial infection, and patients often fail to receive unified and standardized treatment. Consequently, patients with Carbapenem-resistant bacteria intracranial infection report poor prognosis and high mortality. It is very important to discuss how to treat patients with intracranial infection caused by multidrug resistant bacteria.Case Presentation: We reported a case of intracranial infection of Carbapenem-resistant Klebsiella pneumoniae(CRKp) due to high flap tension, poor wound healing and CSF leakage caused by subcutaneous fluid accumulation after intracerebral hemorrhage craniotomy. Since the patient was exposed to intracranial infection resulted from subcutaneous fluid accumulation, we adopted the method of continuous drainage with subcutaneous tube. When subcutaneous effusion disappeared, the subcutaneous drainage tube was pull out, while patients exhibited high fever again, the waist big pool drainage catheter and continuous drainage were carried out. According to the result of Subcutaneous effusion and CSF culture indicated multiple drug resistant Klebsiella pneumoniae intracranial infection and drug susceptibility, The treatment of gentamicin intrathecal injection, intravenous use amikacin and oral Paediatric Compound Sulfamethoxazole Tablets was adopted, the condition of intracranial infection was eventually controlled, with the consciousness restored. This patient was characterized by intracranial infection with Carbapenem-resistant Klebsiella pneumoniae(CRKp).Conclusions: Subcutaneous effusion is a high-risk factor for poor wound healing and interventions are required to be conducted to promote healing as early as possible to contribute to decreasing the menace of CSF leakage. In this case, Continuous drainage and intrathecal injection of sensitive antibiotics serve as critical process to determine the best strategy for clinical treatment of intracranial infection.Keywords: intracranial infection, carbapenem-resistant Klebsiella pneumoniae, lumbar cistern drainage, intrathecal injection, gentamicin

Nucleic acid-based therapies have demonstrated great potential for the treatment of monogenetic diseases, including neurologic disorders. To date, regulatory approval has been received for a dozen antisense oligonucleotides (ASOs); however, these chemistries cannot readily cross the blood–brain barrier when administered systemically. Therefore, an investigation of their potential effects within the central nervous system (CNS) requires local delivery. Here, we studied the brain distribution and exon-skipping efficacy of two ASO chemistries, PMO and tcDNA, when delivered to the cerebrospinal fluid (CSF) of mice carrying a deletion in exon 52 of the dystrophin gene, a model of Duchenne muscular dystrophy (DMD). Following intracerebroventricular (ICV) delivery (unilateral, bilateral, bolus vs. slow rate, repeated via cannula or very slow via osmotic pumps), ASO levels were quantified across brain regions and exon 51 skipping was evaluated, revealing that tcDNA treatment invariably generates comparable or more skipping relative to that with PMO, even when the PMO was administered at higher doses. We also performed intra-cisterna magna (ICM) delivery as an alternative route for CSF delivery and found a biased distribution of the ASOs towards posterior brain regions, including the cerebellum, hindbrain, and the cervical part of the spinal cord. Finally, we combined both ICV and ICM injection methods to assess the potential of an additive effect of this methodology in inducing efficient exon skipping across different brain regions. Our results provide useful insights into the local delivery and associated efficacy of ASOs in the CNS in mouse models of DMD. These findings pave the way for further ASO-based therapy application to the CNS for neurological disease. [ABSTRACT FROM AUTHOR]

Background: Malfunction of astrocytes is implicated as one of the pathological factors of ALS. Thus, intrathecal injection of healthy astrocytes in ALS can potentially compensate for the diseased astrocytes. AstroRx® is an allogeneic cell-based product, composed of healthy and functional human astrocytes derived from embryonic stem cells. AstroRx® was shown to clear excessive glutamate, reduce oxidative stress, secrete various neuroprotective factors, and act as an immunomodulator. Intrathecal injection of AstroRx® to animal models of ALS slowed disease progression and extended survival. Here we report the result of a first-in-human clinical study evaluating intrathecal injection of AstroRx® in ALS patients. Methods: We conducted a phase I/IIa, open-label, dose-escalating clinical trial to evaluate the safety, tolerability, and therapeutic effects of intrathecal injection of AstroRx® in patients with ALS. Five patients were injected intrathecally with a single dose of 100 × 106 AstroRx® cells and 5 patients with 250 × 106 cells (low and high dose, respectively). Safety and efficacy assessments were recorded for 3 months pre-treatment (run-in period) and 12 months post-treatment (follow-up period). Results: A single administration of AstroRx® at either low or high doses was safe and well tolerated. No adverse events (AEs) related to AstroRx® itself were reported. Transient AEs related to the Intrathecal (IT) procedure were all mild to moderate. The study demonstrated a clinically meaningful effect that was maintained over the first 3 months after treatment, as measured by the pre-post slope change in ALSFRS-R. In the 100 × 106 AstroRx® arm, the ALSFRS-R rate of deterioration was attenuated from − 0.88/month pre-treatment to − 0.30/month in the first 3 months post-treatment (p = 0.039). In the 250 × 106 AstroRx® arm, the ALSFRS-R slope decreased from − 1.43/month to − 0.78/month (p = 0.0023). The effect was even more profound in a rapid progressor subgroup of 5 patients. No statistically significant change was measured in muscle strength using hand-held dynamometry and slow vital capacity continued to deteriorate during the study. Conclusions: Overall, these findings suggest that a single IT administration of AstroRx® to ALS patients at a dose of 100 × 106 or 250 × 106 cells is safe. A signal of beneficial clinical effect was observed for the first 3 months following cell injection. These results support further investigation of repeated intrathecal administrations of AstroRx®, e.g., every 3 months. Trial Registration: NCT03482050. [ABSTRACT FROM AUTHOR]

Objective To investigate the opioid consumption and the healthcare resource utilization in patients with the intrathecal drug delivery system (IDDS) therapy and the comprehensive medical management (CMM) alone. Design A retrospective cohort study with a customized claims database. Setting In a university-based hospital. Subjects Patients with complex regional pain syndrome, post-laminectomy syndrome, and fibromyalgia. Methods Using propensity score matching (1:3), we selected patients with morphine infusion through IDDS (IDDS group) and CMM alone (CMM group). The primary endpoints were comparisons of average morphine equivalents daily dosages (MEDD, mg/day) for 6 and 12 months from an index date. The number of emergency room (ER) visits and hospitalizations and the total medical expenditures were compared as secondary outcomes. Results In total, 82 patients (N = 23 in the IDDS group and N = 59 in the CMM group) were analyzed. Although a 6-month average MEDD did not reach statistical significance, a 12-month average MEDD was significantly decreased in the IDDS group compared to the CMM group (53.2 ± 46.3 vs 123.9 ± 176.4, respectively; P  =   0.008). ER visits were more frequent in the IDDS group than the CMM group at baseline (5.4 vs 0.5, respectively; P  = .002), which was maintained for 12 months (P  <   0.001). Otherwise, the number of hospitalization and the medical expenditures for pain management were not different between the groups for 12 months. Conclusions The combined IDDS therapy had some benefits in reducing opioid consumption for 1-year follow-up compared to the CMM alone in chronic noncancer pain patients. [ABSTRACT FROM AUTHOR]

Objective: To compare effect of intrathecal meperidine, tramadol, magnesium sulfate, and dexmedetomidine on the prevention of postspinal anesthesia shivering and adverse events in hip fracture repair patients. Methods: In a randomized, double-blind trial, 132 patients with American Society of Anesthesiology (ASA) I and II spinal anesthesia who needed hip fracture surgery were enrolled. Patients were stratified into 4 intervention groups based on a randomized block pattern: meperidine, tramadol, magnesium sulfate, and dexmedetomidine. Hemodynamic parameters including blood pressure, heart rate, and oxygen saturation, as well as the severity of shivering, core body temperature, Ramsay sedation score, adverse events, meperidine consumption were recorded and compared. Results: There was no statistically significant difference in the normal hemodynamic parameters, temperature, duration of surgery, meperidine consumption, and adverse events such as dizziness, hypotension, nausea, and bradycardia among groups (P>0.05). Compared to other groups, severity of shivering was the lower in the dexmedetomidine group 6 and 8 h after surgery. The Ramsay sedation scores were higher in the dexmedetomidine and meperidine groups 4 h after surgery (P=0.020). Conclusion: Dexmedetomidine acts better than the other three adjuvants in reducing complications such as shivering. Overall, these four adjuvants are helpful to prevent postoperative shivering and could be put forward as promising local anesthetics in spinal anesthesia, based on anesthesiologists' discretion and patients' general conditions. Clinical registration: The study was approved by the Research and Ethics Committee at the Valiasr Hospital (Arak, Iran) with the clinical trial code of IRCT20141209020258N153. [ABSTRACT FROM AUTHOR]

Nowadays it is observed that the number of stem-cell based experimental therapies in neurodegenerative disorders is massively increasing. Most of the clinical trials registered to date have been based on autologous mesenchymal stem/stromal cells (MSC) obtained from somatic tissues. In the conducted clinical trials neither serious side effects, nor statistically significant improvement were observed. The lack of statistical significance could result from a relatively small number of patients involved in clinical trials or highly incoherent study protocols. However, most clinical groups describe a trend towards improvement in MSC-treated patients. Hence, the question arises which factors associated with MSC-based therapy may be the key and result in better therapeutic response. In the presented paper, we summarize, in our opinion, the most important factors that could increase the effectiveness of this therapy.

Chronic compressive myelopathy (CCM) is a major cause of spinal cord disorders in the elderly, in which the spinal cord is compressed by bony or soft tissue structures. Although computed tomography myelography (CTM) has been clinically used for the diagnosis of CCM, a method of CTM in rodents remains to be developed. A 50 μl Hamilton syringe attached to a disposable needle was percutaneously inserted into the subarachnoid space (cisterna magna) between the occipital bone and C1 lamina in an anesthetized adult mouse, followed by the injection of contrast medium and CT imaging. CTM clearly visualized the shape of the spinal cord of intact mice and tiptoe-walking Yoshimura (Twy) mice without any health issues. Unlike histology, the current method functions in live mice, directly depicts the compressed spinal cord, and provides clinically related image information. Furthermore, the intrathecal administration of contrast medium through the percutaneous route makes CTM less invasive and takes less time than a conventional intrathecal injection method. The CTM method used in the present study enables clear visualization of the shape of the dural sac and spinal cord and is useful when conducting experiments on CCM and other spinal diseases in rodents. • A novel method of cervical myelography in mice was developed. • Contrast medium is intrathecally injected through a percutaneous administration. • CT myelography clearly depicts spinal cord in chronic compressive myelopathy mice. [ABSTRACT FROM AUTHOR]

Objective: To compare effect of intrathecal meperidine, tramadol, magnesium sulfate, and dexmedetomidine on the prevention of postspinal anesthesia shivering and adverse events in hip fracture repair patients. Methods: In a randomized, double-blind trial, 132 patients with American Society of Anesthesiology (ASA) I and II spinal anesthesia who needed hip fracture surgery were enrolled. Patients were stratified into 4 intervention groups based on a randomized block pattern: meperidine, tramadol, magnesium sulfate, and dexmedetomidine. Hemodynamic parameters including blood pressure, heart rate, and oxygen saturation, as well as the severity of shivering, core body temperature, Ramsay sedation score, adverse events, meperidine consumption were recorded and compared. Results: There was no statistically significant difference in the normal hemodynamic parameters, temperature, duration of surgery, meperidine consumption, and adverse events such as dizziness, hypotension, nausea, and bradycardia among groups (P>0.05). Compared to other groups, severity of shivering was the lower in the dexmedetomidine group 6 and 8 h after surgery. The Ramsay sedation scores were higher in the dexmedetomidine and meperidine groups 4 h after surgery (P=0.020). Conclusion: Dexmedetomidine acts better than the other three adjuvants in reducing complications such as shivering. Overall, these four adjuvants are helpful to prevent postoperative shivering and could be put forward as promising local anesthetics in spinal anesthesia, based on anesthesiologists’ discretion and patients’ general conditions. Clinical registration: The study was approved by the Research and Ethics Committee at the Valiasr Hospital (Arak, Iran) with the clinical trial code of IRCT20141209020258N153.

Background and Aims: Avoidance of general anaesthesia for short-duration surgeries is a prerequisite, especially for children. Spinal anaesthesia is established as an appropriate anaesthetic procedure for this target. Midazolam has been proven to be safe for children as premedication. This study aimed to evaluate the effects of adding midazolam to intrathecal bupivacaine on intraoperative quality, duration of spinal anaesthesia and postoperative (PO) analgesia for children undergoing lower abdominal surgeries. Methods: A prospective, comparative interventional study included 120 paediatric patients who were randomly divided into two groups that received intrathecal bupivacaine plus normal saline (B/S) or intrathecal bupivacaine plus midazolam (B/M). The efficacy of PO analgesia was assessed using the observational pain–discomfort scale (OPS). Duration of PO analgesia was measured, and recovery of motor block was assessed every 30 min till the Bromage scale reached 0. The level of PO sedation was assessed using the modified Wilson Sedation Score (WSS). Results were analysed using the one-way analysis of variance (ANOVA) test, Mann–Whitney test and Chi-square test. Results: Onset of sensory and motor blocks was significantly faster, and the frequency of patients having Bromage score of 3 within ≤10 min was significantly higher in group B/M than group B/S. Durations till sensory and motor recovery were significantly longer, the number of requests for PO analgesia was significantly lower and the mean of WSS was significantly higher at 30 and 120 min in group B/M than group B/S. Conclusion: Intrathecal bupivacaine–midazolam combination significantly prolonged the duration of spinal anaesthesia and provided prolonged PO analgesia.

Haoming Chen,&ast; Jianmang Yu,&ast; Lihua Hang,&ast; Shuai Li, Weikang Lu, Zhenkai Xu Department of Anesthesiology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, 215300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihua HangDepartment of Anesthesiology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Suzhou, Jiangsu Province, Peoples Republic of ChinaTel +86-18013273169Email zjhanglihua@foxmail.comIntroduction: Bone cancer pain (BCP) seriously affects the quality of life of patients with advanced cancer, but effective treatment methods are lacking. This study mainly investigates the role of EZH2 in a well-established BCP model induced by Walker 256 breast cancer cells in rats.Methods: Female Sprague–Dawley rats of the same age weighing approximately 160 g were selected for the experiment. The BCP model was established by injecting inactivated Walker 256 breast cancer cells into the tibia. von Frey filaments were used to measure the paw withdrawal threshold, and bone destruction in the rat was observed using x-ray. The spinal EZH2 and H3K27Tm levels were measured using Western blotting and RT–qPCR analysis. Intrathecal injection of an EZH2 inhibitor was performed to examine the role of EZH2 in trigeminal BCP.Results: Experimental results showed that injecting Walker 256 breast cancer cells into the tibia induced bone cancer pain. Spinal EZH2 and H3K27Tm levels were significantly increased over time in BCP rats. An intrathecal injection of 3-deazaneplanocin A (DZNep), a selective EZH2 inhibitor, downregulated the expression of EZH2 and attenuate the BCP-induced mechanical allodynia state.Conclusion: Intrathecal injection of DZNep relieve bone cancer pain in rats. EZH2 expressed in spinal cord tissue may be involved in the process of bone cancer pain in rats.Keywords: enhancer of zeste homologue 2, bone cancer pain, histone methyltransferase, 3 deazaneplanocin A, intrathecal injection

Summary: Background: Animal experiments have demonstrated the dependency of cerebrospinal fluid clearance function on age and sleep, which partially underlay the cognitive decline in the elderly. However, human evidence is lacking, which could be mainly attributed to the limited methods of cerebrospinal fluid clearance function assessment. Method: Serial T1-weighted and T2-fluid attenuated inversion recovery imaging were performed in 92 patients before and at multiple time points including 4.5 h, 15 h and 39 h after intrathecal injection of contrast agent to visualize the putative meningeal lymphatic pathway, peri-olfactory nerve pathway, and peri-optic nerve pathway. We defined the clearance function as the percentage change in signal unit ratio of critical locations in these pathways from baseline to 39 h after intrathecal injection, and further analysed their relationships with age, sleep, and cognitive function. Findings: Cerebrospinal fluid clearance through the putative meningeal lymphatic and perineural pathways were clearly visualized. The clearance function of putative meningeal lymphatic and perineural pathways were impaired with ageing (all P

Objective: To investigate the effects of intrathecal injection of nalbuphine on the behavioral ability and the expression of transient receptor potential V1 (TRPV1) in the dorsal root ganglion of diabetic neuralgia model rats. Methods: The diabetic neuralgia model rats (n=48) were randomly divided into three groups - model group, nalbuphine group 1 and nalbuphine group 2, with 16 rats in each groups. The nalbuphine group 1 and the nalbuphine group 2 were given intrathecal injection of 0.5 μg/10 μL and 1.0 μg/10 μL of nalbuphine respectively, and the model group were given an equal dose of 0.9 % sodium chloride solution, once a day, On the 7th and 14th days of treatment, the fasting blood glucose (FBG) level was measured and recorded with a blood glucose meter, and the mechanical pain threshold was detected; On the 14th and 28th days of treatment, the serum levels of IL-6 and TNF-α were detected by enzyme-linked immunosorbent assay, and the relative expression of TRPV1 protein in the dorsal root ganglia was detected by western blotting. Results: The fasting blood glucose levels of the model group, nalbuphine group 1 and nalbuphine group 2 were all higher than 20.00 mmol/L on the 7th and 14th days of treatment, and the differences between the groups were not statistically significant(P>0.05). The mechanical pain threshold of nalbuphine group 1 and nalbuphine group 2 on the 7th and 14 th days of treatment were higher than that of the model group (P<0.05), and were also higher than that before treatment (P<0.05). The difference between the nalbuphine 2 group and the nalbuphine 1 group was statistically significant(P<0.05). The levels of serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the nalbuphine 1 group and the nalbuphine 2 group on the 14 th and 28 th days of treatment were significantly lower than those in the model group (P<0. 05), the nalbuphine 2 group were significantly lower than the nalbuphine 1 group (P<0.05). The relative expression levels of TRPV1 in the dorsal root ganglia of the nalbuphine group 1 and nalbuphine group 2 on the 14 th and 28 th days of treatment were significantly lower than those in the model group (P<0.05), and the nalbuphine group 2 were significantly lower than the nalbuphine group 1(P<0.05). Conclusion: The application of intrathecal injection of nalbuphine in diabetic neuralgia model rats can improve behavioral ability, inhibit the expression of TRPV1 in the dorsal root ganglion, and also inhibit the release of serum IL-6 and TNF-α, thereby exerting analgesic treatment. utility. [ABSTRACT FROM AUTHOR]

Background: Multiple brain tuberculomas (MBT), characterized by disseminated tuberculous granulomas in the brain, is a rare disease like tuberculosis encountered after in vitro fertilization, embryo transfer (IVF-ET), and abortion. This study aimed to investigate the clinical characteristics, diagnostic methods, and therapeutic strategies of MBT after IVF-ET and abortion. Methods: A retrospective analysis was performed on the data of two patients who suffered from MBT after IVF-ET and abortion. Results: Both patients manifested headache and vomiting, which are the common symptoms of intracranial hypertension, accompanied by tuberculous meningitis. Besides, case 1 was affected by fever and epilepsy. In terms of imaging characteristics, T2-weighted imaging (T2WI) displayed multiple intracranial punctate or patchy high-intensity signals, some of which were presented as "target sign" or enhanced-like disseminated nodules, similar to miliary tuberculosis. Regular anti-tuberculosis therapy with isoniazid, rifampicin, pyrazinamide, and ethambutol was administered but failed to achieve a significant effect in the initial stage. The symptoms were gradually relieved, and the brain lesions in MRI were significantly alleviated after combining with intrathecal injections of isoniazid, dexamethasone, and chymotrypsin. Conclusions: In vitro fertilization, embryo transfer (IVF-ET)may be a risk factor for MBT, the common manifestations of which are intracranial hypertension. In addition to multiple nodular enhancement on brain MRI, the "target sign" on T2WI is likely to be another typical feature of MBT. Provided that there is no obvious effect of regular anti-tuberculosis therapy (ATT), intrathecal injections of isoniazid, dexamethasone, and chymotrypsin are considered to produce a favorable prognosis, but further studies are still needed to confirmthe efficacy. [ABSTRACT FROM AUTHOR]

Deregulated cyclin-dependent kinase 5 (Cdk5) activity closely correlates with hyperphosphorylated tau, a common pathology found in neurodegenerative diseases. Previous postmortem studies had revealed increased Cdk5 immunoreactivity in amyotrophic lateral sclerosis (ALS); hence, we investigated the effects of Cdk5 inhibition on ALS model mice and neurons in this study. For the in vitro study, motor neuron cell lines with wild-type superoxide dismutase 1 (SOD1) or SOD1 G93A and primary neuronal cultures from SOD1 G93A transgenic (TG) mice or non-TG mice were compared for the expression of proteins involved in tau pathology, neuroinflammation, apoptosis, and neuritic outgrowth by applying Cdk5-small interfering RNA or Cdk5-short hairpin RNA (shRNA). For the in vivo study, SOD1 G93A mice and non-TG mice were intrathecally injected with adeno-associated virus 9 (AAV9)-scramble (SCR)-shRNA or AAV9-Cdk5-shRNA at the age of 5 weeks. Weight and motor function were measured three times per week from 60 days of age, longevity was evaluated, and the tissues were collected from 90-day-old or 120-day-old mice. Neurons with SOD1 G93A showed increased phosphorylated tau, attenuated neuritic growth, mislocalization of SOD1, and enhanced neuroinflammation and apoptosis, all of which were reversed by Cdk5 inhibition. Weights did not show significant differences among non-TG and SOD1 G93A mice with or without Cdk5 silencing. SOD1 G93A mice treated with AAV9-Cdk5-shRNA showed significantly delayed disease onset, delayed rotarod failure, and prolonged survival compared with those treated with AAV9-SCR-shRNA. The brain and spinal cord of SOD1 G93A mice intrathecally injected with AAV9-Cdk5-shRNA exhibited suppressed tau pathology, neuroinflammation, apoptosis, and an increased number of motor neurons compared to those of SOD1 G93A mice injected with AAV9-SCR-shRNA. Cdk5 inhibition could be an important mechanism in the development of a new therapeutic strategy for ALS., (© 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Systemic administration of adeno-associated virus (AAV) vectors for spinal cord gene therapy has challenges including toxicity at high doses and pre-existing immunity that reduces efficacy. Intrathecal (IT) delivery of AAV vectors into cerebral spinal fluid can avoid many issues, although distribution of the vector throughout the spinal cord is limited, and vector entry to the periphery sometimes initiates hepatotoxicity. Here we performed biopanning in non-human primates (NHPs) with an IT injected AAV9 peptide display library. We identified top candidates by sequencing inserts of AAV DNA isolated from whole tissue, nuclei, or nuclei from transgene-expressing cells. These barcoded candidates were pooled with AAV9 and compared for biodistribution and transgene expression in spinal cord and liver of IT injected NHPs. Most candidates displayed increased retention in spinal cord compared with AAV9. Greater spread from the lumbar to the thoracic and cervical regions was observed for several capsids. Furthermore, several capsids displayed decreased biodistribution to the liver compared with AAV9, providing a high on-target/low off-target biodistribution. Finally, we tested top candidates in human spinal cord organoids and found them to outperform AAV9 in efficiency of transgene expression in neurons and astrocytes. These capsids have potential to serve as leading-edge delivery vehicles for spinal cord-directed gene therapies., Competing Interests: Declaration of interests C.A.M. has financial interests in Chameleon Biosciences, Skylark Bio, and Sphere Gene Therapeutics, companies developing adeno-associated virus (AAV) vector technologies for gene therapy applications. C.A.M. performs paid consulting work for all three companies. C.A.M. received sponsored research funding from SwanBio Therapeutics for the research described here. C.A.M. received royalty payments from licensing agreements between SwanBio Therapeutics and the Massachusetts General Hospital. C.A.M.’s interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict-of-interest policies. C.A.M. and K.S.H. have a filed patent application surrounding the iTransduce library. K.S.H. performed paid consulting work for SwanBio Therapeutics., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Intrathecal administration of nalbuphine causes lower incidences of respiratory depression, nausea or vomiting, pruritus when compared to other opioids. Previous studies have compared various doses of nalbuphine including higher doses as an adjuvant to local anaesthetic. Aim and Objectives: To compare different doses of nalbuphine and to find out the most optimum amount. Material and Methods: One hundred twenty patients were assigned to Group A or B, each comprising of sixty patients after randomization. Group A, B patients received 0.4, 0.6 mg of nalbuphine respectively as an adjunct to 0.5% hyperbaric bupivacaine 3 ml. Primary outcomes were sensory, motor block duration, post-operative pain relief while secondary outcomes were assessment of haemodynamic parameters. Undesirable effects namely pruritus, shivering, nausea, vomiting were noted if any. Results: The onset of sensory, motor blocks didn't differ significantly (p=0.801, 0.616). However, the span of sensory, motor block, and analgesia after surgery were significantly more in group B (p=0.0005). Group A required more rescue analgesics (p=0.0005). The pulse rate was significantly lesser in group B, although it was clinically insignificant. The mean arterial pressures didn't differ significantly (P>0.05). Conclusion: Nalbuphine 0.6 mg significantly prolonged the span of sensory, motor blocks, and analgesia after surgery with stable haemodynamics and negligible incidence of nausea, vomiting. We believe that 0.6 mg is the optimum amount of nalbuphine as a supplement in spinal anaesthesia.

Introduction/Aims: Previous papers on ultrasound (US)‐guided delivery of nusinersen in patients with spinal muscle atrophy (SMA) described good results with translaminar approach. However, this approach is not possible in patients with spinal fusion and no visible interlaminar space on pre‐procedural computed tomography (CT). US‐guided transforaminal nusinersen delivery is a potential option that warrants investigation. Methods: Twenty adult SMA patients with challenging access were treated in our institution under cone beam CT (CBCT) guidance. The patients were already in the maintenance phase of the dosing protocol and were prospectively evaluated for US‐guided transforaminal approach. After they completed one injection via US‐guided transforaminal approach, success and safety of the approach were analyzed. Patients shared their experience on US‐guided in comparison to CBCT‐guided injections. Results: US‐guided transforaminal puncture was possible in 14 (70.0%) patients, although 2 of them required needle repositioning under fluoroscopy due to inadvertent access of a prominent vein. US‐guided transforaminal approach was therefore successful in 60% of patients. Mild adverse events were recorded in four patients. The survey on patients' experience showed that seven reported no difference in the two approaches, six preferred the US‐guided procedure, and one preferred the CBCT‐guided procedure. Discussion: US‐guided transforaminal lumbar approach is an effective and safe method of intrathecal nusinersen delivery in adult SMA patients with challenging spinal access and could be considered the first option in appropriately selected adult SMA patients requiring transforaminal nusinersen delivery. [ABSTRACT FROM AUTHOR]

Cogan's syndrome (CS) is a rare autoimmune disease in which approximately 10%–13% of people with the condition develop neurological symptoms. While glucocorticoids are the standard of care for patients with CS, disease‐modifying anti‐rheumatic drugs (DMARDs) and biologics agents are more widely used to treat the systemic and vestibular auditory manifestations of CS. Herein, we report a rare case of CS with central nervous system damage who failed to respond to systemic use of glucocorticoids and DMARDs. However, his symptoms were successfully improved by intrathecal injection of methotrexate (MTX) and dexamethasone. To our knowledge, the use of intrathecal injections of MTX and dexamethasone to treat CS has not been reported in any literature. Therefore, the present case may provide a new idea for clinicians to treat central nervous system symptoms in patients with CS. [ABSTRACT FROM AUTHOR]

NMDAR antibody encephalitis is the most common autoimmune encephalitis characterized by a myriad of neuropsychiatric symptoms. It predominantly affects females and is associated with ovarian teratoma (58%). Nineteen percent do not respond to treatment and are left with serious neurological deficits. A subset of NMDAR encephalitis with antibody positivity in CSF alone without ovarian teratoma is often found to be refractory to treatment. We name them Pure CSF positive, non-teratomatous type anti-NMDAR encephalitis. We report two such cases who responded to intrathecal rituximab, to highlight a novel treatment as a rescue therapy to prevent long-term disability and improve clinical outcomes.

Nucleic acid-based therapies have demonstrated great potential for the treatment of monogenetic diseases, including neurologic disorders. To date, regulatory approval has been received for a dozen antisense oligonucleotides (ASOs); however, these chemistries cannot readily cross the blood–brain barrier when administered systemically. Therefore, an investigation of their potential effects within the central nervous system (CNS) requires local delivery. Here, we studied the brain distribution and exon-skipping efficacy of two ASO chemistries, PMO and tcDNA, when delivered to the cerebrospinal fluid (CSF) of mice carrying a deletion in exon 52 of the dystrophin gene, a model of Duchenne muscular dystrophy (DMD). Following intracerebroventricular (ICV) delivery (unilateral, bilateral, bolus vs. slow rate, repeated via cannula or very slow via osmotic pumps), ASO levels were quantified across brain regions and exon 51 skipping was evaluated, revealing that tcDNA treatment invariably generates comparable or more skipping relative to that with PMO, even when the PMO was administered at higher doses. We also performed intra-cisterna magna (ICM) delivery as an alternative route for CSF delivery and found a biased distribution of the ASOs towards posterior brain regions, including the cerebellum, hindbrain, and the cervical part of the spinal cord. Finally, we combined both ICV and ICM injection methods to assess the potential of an additive effect of this methodology in inducing efficient exon skipping across different brain regions. Our results provide useful insights into the local delivery and associated efficacy of ASOs in the CNS in mouse models of DMD. These findings pave the way for further ASO-based therapy application to the CNS for neurological disease.

Background and Aims: Avoidance of general anaesthesia for short-duration surgeries is a prerequisite, especially for children. Spinal anaesthesia is established as an appropriate anaesthetic procedure for this target. Midazolam has been proven to be safe for children as premedication. This study aimed to evaluate the effects of adding midazolam to intrathecal bupivacaine on intraoperative quality, duration of spinal anaesthesia and postoperative (PO) analgesia for children undergoing lower abdominal surgeries. Methods: A prospective, comparative interventional study included 120 paediatric patients who were randomly divided into two groups that received intrathecal bupivacaine plus normal saline (B/S) or intrathecal bupivacaine plus midazolam (B/M). The efficacy of PO analgesia was assessed using the observational pain–discomfort scale (OPS). Duration of PO analgesia was measured, and recovery of motor block was assessed every 30 min till the Bromage scale reached 0. The level of PO sedation was assessed using the modified Wilson Sedation Score (WSS). Results were analysed using the one-way analysis of variance (ANOVA) test, Mann–Whitney test and Chi-square test. Results: Onset of sensory and motor blocks was significantly faster, and the frequency of patients having Bromage score of 3 within ≤10 min was significantly higher in group B/M than group B/S. Durations till sensory and motor recovery were significantly longer, the number of requests for PO analgesia was significantly lower and the mean of WSS was significantly higher at 30 and 120 min in group B/M than group B/S. Conclusion: Intrathecal bupivacaine–midazolam combination significantly prolonged the duration of spinal anaesthesia and provided prolonged PO analgesia. [ABSTRACT FROM AUTHOR]

Cryptococcal meningitis is a fungal infectious disease with a poor prognosis and high mortality. Amphotericin B (AMB) is the first choice for the treatment of cryptococcal meninges. The blood-brain barrier (BBB) is the major barrier for the effective delivery of drugs to the brain. In this study, AMB was incorporated in a thermosensitive gel for intrathecal injection. We first synthesized AMB-loaded thermogel, investigated its in vitro cumulative release, and in vivo neurotoxicity, and therapeutic effect. The thermosensitive gel was comprised of 25 wt% poly (lactic acid-co-glycolic acid)-poly (ethylene glycol)-poly (lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock polymer aqueous solution. The AMB loaded in the thermosensitive gel (AMB in gel) had low viscosity at low temperature and resulted in the formation of a non-flowing gel at 37 °C (physiological temperature). AMB loading in gel sustained its release for 36 days and the in vitro cumulative release rate was satisfactory. Compared with the AMB solution, intrathecal administration of AMB in gel could reduce the neurovirulence of AMB and get a better treatment effect. The findings of the current study show that the injectable PLGA–PEG–PLGA thermogel is a biocompatible carrier for the delivery of drugs into the intrathecal.

Recent studies have shown that the use of mesenchymal stem/stromal cells (MSCs) may be a promising strategy for treating spinal cord injury (SCI). This study aimed to explore the effectiveness of human umbilical cord-derived MSCs (hUC-MSCs) with different administration routes and dosages on SCI rats. Following T10-spinal cord contusion in Sprague-Dawley rats (N = 60), three different dosages of hUC-MSCs were intrathecally injected into rats (SCI-ITH) after 24 h. Intravenous injection of hUC-MSCs (SCI-i.v.) and methylprednisolone reagent (SCI-PC) were used as positive controls (N = 10/group). A SCI control group without treatment and a sham operation group were injected with Multiple Electrolyte Injection solution. The locomotor function was assessed by Basso Beattie Bresnahan (BBB) rating score, magnetic resonance imaging (MRI), histopathology, and immunofluorescence. ELISA was conducted to further analyze the nerve injury and inflammation in the rat SCI model. Following SCI, BBB scores were significantly lower in the SCI groups compared with the sham operation group, but all the treated groups showed the recovery of hind-limb motor function, and rats receiving the high-dose intrathecal injection of hUC-MSCs (SCI-ITH-H) showed improved outcomes compared with rats in hUC-MSCs i.v. and positive control groups. Magnetic resonance imaging revealed significant edema and spinal cord lesion in the SCI groups, and significant recovery was observed in the medium and high-dose hUC-MSCs ITH groups. Histopathological staining showed that the necrotic area in spinal cord tissue was significantly reduced in the hUC-MSCs ITH-H group, and the immunofluorescence staining confirmed the neuroprotection effect of hUC-MSCs infused on SCI rats. The increase of inflammatory cytokines was repressed in hUC-MSCs ITH-H group. Our results confirmed that hUC-MSC administered via intrathecal injection has dose-dependent neuroprotection effect in SCI rats. [ABSTRACT FROM AUTHOR]