Search

Objective Ischemic stroke is a major cause of death in the global population, with a high disability and mortality rate. Lack of regenerative ability is considered to be the fundamental cause. This study aims to determine the effect of Shh pathway, which mediates regenerative signaling in response to CNS injury, on myelin repair and Olig1 expression in focal ischemic lesions in the rat. Methods A model of middle cerebral artery occlusion (MCAO) was established using the intraluminal suture method where the middle cerebral artery (MCA) was restricted for 120 min. Cyclopamine, a specific inhibitor of Shh, or saline was administered 12 h after MCAO surgery and lasted for 7 days. After MCA occlusion, male Sprague-Dawley rats were randomly allocated to cyclopamine- or saline-treated groups. A group of no-injection animals after MCAO were used as controls. The Shh signaling pathway, myelinogenesis-related factor MBP and Olig1 were testedby immunohistochemistry and RT-PCR assay. Results The levels of Shh and its component Gli1 were elevated from 1 d up to 14 d following ischemia, indicating that the Shh-Gli1 axis was broadly reactivated. Treatment with cyclopamine can partially block the Shh signaling pathway, prevent myelin repair, and decrease the Olig1 expression following ischemic stroke. Conclusion That blockade of Shh signaling concurrently with the creation of a lesion aggravated ischemic myelin damage, probably via its downstream effects on Olig1 transcription. Shh plays a contributory role during regeneration in the CNS, thereby providing promising new therapeutic strategies to assist in recovery from ischemic stroke.

Background: Bilateral striatal necrosis (BSN) is characterized by symmetrical degeneration, predominantly of the caudate and putamen nucleus, in the basal ganglia. It is associated with numerous acquired and hereditary neuro-developmental and motor dysfunction-related pathological conditions. BSN results in high morbidity and mortality among infants and children, and its diagnosis is clinically challenging due to several overlapping disease phenotypes. Therefore, a precise genetic diagnosis is urgently needed for accurate genetic counseling and improved prognostic outcomes as well.Objective: To identify novel missense mutations in the NDUFAF5 gene as a cause of childhood BSN in members of a Chinese family and summarize the clinical characteristics of patients with the NDUFAF5 gene mutations.Methods: This study included a large family living in a remote northwestern area of China. Three siblings developed a neurological disorder characterized by generalized dystonia within the first decade of their lives. Cerebral computed tomography (CT) and magnetic resonance imaging (MRI) showed bilateral lesions of the putamen. Biochemical and genetic approaches were used to identify the cause of BSN.Results: Sequence analysis showed no pathogenic variation in PANK2, SLC25A19, SLC19A3, and NUP62 genes and in the entire mitochondrial genome as well. Whole-exome sequencing revealed compound heterozygous mutations consisting of NDUFAF5:c.425A > C(p.E142A) and c.836T > G (p.M279R). The father, a healthy sister, and a healthy brother of the affected siblings carried the c.836T > G mutation, and the mother carried the c.425A > C mutation. These variants were absent in 100 ethnically matched non-BSN controls. In silico analysis demonstrated that the E142A and M279R mutations in NDUFAF5 protein significantly perturbed the normal conformation of the protein due to alterations in the hydrogen bonding patterns around the evolutionarily conserved catalytic domains, leading to its loss of function in the early stage of mitochondrial complex I assembly.Conclusions: We identified a novel compound heterozygous mutation (c.425A > C and c.836T > G) in the NDUFAF5 gene as the potential cause of autosomal recessive childhood BSN, which extended the pathogenic variation spectrum of the NDUFAF5 gene. This study provides substantial evidence for further improvement of genetic counseling and better clinical management of BSN affected individuals.

Axon regeneration after lesions to the central nervous system (CNS) is largely limited by the presence of growth inhibitory molecules expressed in myelin. Nogo‑A is a principal inhibitor of neurite outgrowth, and blocking the activity of Nogo‑A can induce axonal sprouting and functional recovery. However, there are limited data on the expression of Nogo‑A after CNS lesions, and the mechanism underlying its influences on myelin growth remains unknown. The aim of the present study was to observe the time course of Nogo‑A after cerebral ischemia/reperfusion in rats using immunohistochemistry and western blot techniques, and to test the effect of its inhibitor Nogo extracellular peptide 1‑40 (NEP1‑40) on neural plasticity proteins, growth‑associated binding protein 43 (GAP‑43) and microtubule associated protein 2 (MAP‑2), as a possible mechanism underlying myelin suppression. A classic model of middle cerebral artery occlusion (MCAO) was established in Sprague‑Dawley rats, which were divided into three groups: i) MCAO model group; ii) MCAO + saline group; and iii) MCAO + NEP1‑40 group. Rats of each group were divided into five subgroups by time points as follows: days 1, 3, 7, 14 and 28. Animals that only received sham operation were used as controls. The Nogo‑A immunoreactivity was located primarily in the cytoplasm of oligodendrocytes. The number of Nogo‑A immunoreactive cells significantly increased from day 1 to day 3 after MCAO, nearly returning to the control level at day 7, increased again at day 14 and decreased at day 28. Myelin basic protein (MBP) immunoreactivity in the ipsilateral striatum gradually decreased from day 1 to day 28 after ischemia, indicating myelin loss appeared at early time points and continuously advanced during ischemia. Then, intracerebroventricular infusion of NEP1‑40, which is a Nogo‑66 receptor antagonist peptide, was administered at days 1, 3 and 14 after MCAO. It was observed that GAP‑43 considerably increased from day 1 to day 7 and then decreased to a baseline level at day 28 compared with the control. MAP‑2 expression across days 1‑28 significantly decreased after MCAO. Administration of NEP1‑40 attenuated the reduction of MBP, and upregulated GAP‑43 and MAP‑2 expression at the corresponding time points after MCAO compared with the MCAO + saline group. The present results indicated that NEP1‑40 ameliorated myelin damage and promoted regeneration by upregulating the expression of GAP‑43 and MAP‑2 related to neuronal and axonal plasticity, which may aid with the identification of a novel molecular mechanism of restriction in CNS regeneration mediated by Nogo‑A after ischemia in rats.

Background Benzodiazepines (BZDs) and Z drugs are widely used for patients with chronic insomnia. The long term use of BZDs in older patients can cause cognitive impairment and potentially increase the risk of dementia. However, evidence for an association with Z drugs is limited. This study aimed to investigate the association between the risk of cognitive impairment and exposure to Z drugs in older patients with chronic insomnia.Methods We recorded older patients with chronic insomnia who visited the outpatient department of neurology, Beijing Friendship Hospital, and assessed the global cognitive function (MoCA) and five cognitive domains (CVLT, TMT-B, BNT-30, CDT and DST). Multiple regression analysis was conducted to determine the independent factors of cognition, and evaluate the effect of Z drugs use (zolpidem and zopiclone) on cognition.Results A total of 88 subjects were identified. BZDs use (P=0.03, B=2.67, 95% CI 0.36-4.97) and BZDs exposure density (P=0.01, B=1.22, 95% CI 0.33-2.11) were independent risk factors of cognitive impairment in older patients with chronic insomnia. Neither Z drugs use (P=0.11) nor Z drugs exposure density (P=0.92) correlated with global cognitive function. Moreover, compared with BZDs users, there were positive associations between Z drugs use and memory (P=0.00), attention (P=0.00) and verbal function (P=0.04). Additionlly, education level (P=0.02, OR=0.74, 95% CI 0.57-0.95), duration of insomnia (P=0.04, OR=1.05, 95% CI 1.00-1.11) and severity of insomnia (P=0.03, OR=1.27, 95% CI 1.02-1.57) were also independent factors of global cognitive function.Conclusion We found no evidence that Z drugs use and Z drugs exposure density were associated with cognitive impairment in older patients with chronic insomnia. However, the use of BZDs and BZDs exposure density were associated with an increased risk of cognitive impairment. Thus, BZDs use should be avoided，and Z drugs should be prescribed with extreme caution in the elderly.

Background Recent studies have suggested that cerebral ischemic infarction may contribute to the development of restless legs syndrome (RLS). This study analyzed the clinical and radiological profiles of RLS with onset after acute lacunar infarction. Methods In this retrospective study we enrolled 244 consecutive patients with acute lacunar infarction between January 2012 and June 2014. RLS was identified and evaluated based on the International RLS Rating Scale (IRLS-RS). Individual sleep quality was assessed using the Epworth Sleepiness Scale (ESS). Psychological state was also assessed using the Hamilton Depression Scale (HDS) and the Hamilton Anxiety Scale (HAS). Results The incidence of RLS in patients with lacunar infarction was 5.33%. Our participant group consisted of nine males and four females. Three patients had symptoms in bilateral limbs, and 10 patients had symptoms only contralateral to the cerebral infarction. The infarctions were localized to the pons, centrum semiovale, thalamus, putamen, medulla, and occipital lobe. Contralateral paralysis was found in 13 patients, and contralateral sensory deficit in seven patients. The average IRLS-RS, ESS, HDS, HAS scores were 19.07 ± 8.70, 4.69 ± 5.82, 4.38 ± 4.68, and 3.85 ± 4.76, respectively. Nine patients had diabetes mellitus. After administration of dopaminergic drugs, patients’ RLS significantly improved. Conclusions The incidence of RLS after acute lacunar infarction was 5.33%. Pons, centrum semiovale, and basal ganglia were the common locations of responsible lesions. Compared to idiopathic RLS, symptoms of RLS after acute lacunar infarction appeared more unilateral and more likely involved the arm. Moreover, diabetes mellitus may be a risk factor for RLS in stroke patients.

Objective: Pontine infarction is a common type of stroke in the cerebral deep structures, resulting from occlusion of small penetrating arteries, may manifest as hemi-paralysis, hemi-sensory deficit, ataxia, vertigo, and bulbar dysfunction, but patients presenting with restless legs syndrome (RLS) are extremely rare. Herein, we reported five cases with RLS as a major manifestation of pontine infarction. Methods: Five cases of pontine infarction related RLS were collected from July 2013 to February 2016. The diagnosis of RLS was made according to criteria established by the International RLS Study Group (IRLSSG) in 2003. Neurological functions were assessed according to the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Severity of RLS was based on the International RLS Rating Scale (IRLS-RS). Sleep quality was assessed by Epworth Rating Scale (ERS), and individual emotional and psychological states were assessed by Hamilton Depression Scale (HDS) and Hamilton Anxiety Scale (HAS). Results: The laboratory data at the onset including hemoglobin, serum concentration of homocysteine, blood urea nitrogen (BUN), creatinine, electrolytes, and thyroid hormones were normal. The electroencephalogram (EEG), lower-extremity somatosensory evoked potential (SEP), and nerve conduction velocity (NCV) in four limbs were normal. The average period of follow-up was 34.60 ± 12.76 months. The MRI examination showed acute or subacute pontine infarction lesions, 3 cases in the rostral inner side, 1 case in the rostral lateral and inner side, and 1 case in rostral lateral side. The neurological deficits included weakness in 4 cases, contralateral sensory deficit in 1 case, and ataxia in 2 cases. All 5 patients presented with symptom of RLS at or soon after the onset of infarction and 4 patients experienced uncomfortable sensations in the paralyzed limbs contralateral to the ischemic lesion. Their neurological deficits improved significantly 2 weeks later, but the symptoms of RLS did not resolve. Among them, 3/5 patients were treated with dopaminergic drugs. At the end of the follow-up, RLS symptom eventually resolved in 3 patients but persisted in two. The IRLS-RS, NIHSS and mRS scores were significantly lower at the onset than those at the last follow-up (P = 0.035, 0.024 and 0.049, respectively). However, there was no significant difference in the ERS, HDS and HAS scores (P = 0.477, 0.226 and 0.778, respectively). Conclusion: RLS can be an onset manifestation of pontine infarction, clinicians should be aware of this potential symptom. RLS usually occurs in the paralyzed limbs contralateral to the infarction lesion. The pathogenesis still needs further investigation. Keywords: Restless legs syndrome, Pontine infarction, Clinical features

We investigated the association between serum levels of high-sensitivity C-reactive protein (hs-CRP) and stroke recurrence events in a cohort of patients with acute ischemic stroke (IS). We prospectively studied 286 patients with acute IS who were admitted within 24 h after the onset of symptoms. Serum levels of hs-CRP, and National Institutes of Health stroke scale (NIHSS) were measured at admission. The primary endpoint was stroke recurrence 1 year after stroke onset. We used logistic regression models to assess the relationship between hs-CRP levels and the risk of recurrent stroke. In multivariable models, hs-CRP levels were associated with an increased risk of an NIHSS greater than 6 [odds ratio=1.17; 95% confidence interval (CI)=1.05-1.48; P=0.021]. Among the participants, stroke recurrence was found in 48 (16.8%) cases. In multivariate analyses, the third and fourth quartiles of hs-CRP were significantly associated with stroke recurrence during the observation period compared with the first quartile group (P

Liquiritin is one of flavone compounds derived from licorice, a common flavoring and sweetening agent in food products. This study investigated the effects and mechanisms of liquiritin in interleukin (IL)-1β-stimulated SW982 human synovial cells, which is a useful tool to study the inflammatory response of rheumatoid arthritis (RA). The SW982 cells were pretreated with various concentrations (0, 10 and 40 μM) of liquiritin, followed by IL-1β (10 ng/mL) stimulation. Liquiritin significantly inhibited protein and mRNA levels of inflammatory cytokines IL-6 and IL-8 in IL-1β-stimulated SW982 cells. Liquiritin suppressed IL-1β-induced phosphorylation of p38, c-jun N-terminal kinase (JNK), and adenosine monophosphate-activated protein kinase (AMPK), inhibited p-c-Jun activation and decreased p65 protein translocation into the nucleus induced by IL-1β. These results indicate that liquiritin exerts an anti-inflammatory effect via modulating JNK, p38, activator protein-1 (AP-1), AMPK and nuclear factor-κB (NF-κB) pathways in IL-1β-induced human synovial cells.

The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is important for remyelination in the central nervous system. Nevertheless, this process is often limited and incomplete in ischemic injury. Oligodendrocyte transcription factor 1 (Olig1) is important for the maturation of OPCs and the repair of demyelinated lesions. However, how Olig1 modulates the development of OPCs or the remyelination associated with ischemic injury remains unclear. The present study aimed to examine alterations in OPCs, and the expression of myelin and Olig1, at different time-points after focal cerebral ischemia using immunohistochemistry and western blot techniques to elucidate the role of Olig1 in the maturation of OPCs and remyelination. The present results showed that the expression of Olig1 significantly decreased at 1 day after middle cerebral artery occlusion (MCAO) and returned to normal levels from day 3 to 28. Additionally, Olig1 was found to translocate into the nucleus following ischemia in the brain. The number of OPCs in the ischemic striatum significantly declined at days 1 and 3 following MCAO, and increased at days 7, 14 and 28 compared with the control. The expression of myelin basic protein, a marker of mature oligodendrocytes and myelin, gradually decreased from day 1 to 7 after ischemia and recovered at day 14 and 28; however, the levels were lower than those in the control group. The present results indicated that the restored normal level of Olig1 following ischemia may play an important role in the maturation of OPCs through its translocation into the nucleus, where it may promote the growth and development of myelin under pathological conditions. However, this endogenous recovery mechanism fails to fully repair the demyelinated lesion. The data of the present study may help clinicians understand the expression pattern of Olig1 and its potential role in endogenous remyelination after ischemia, which may have implications for the treatment of diseases that lead to demyelination.

Objective To identify risk factors for preoperative respiratory complications associated with tracheobronchial foreign body aspiration (TFBA) by retrospectively analysing paediatric cases presenting with or without complications. Methods Paediatric patients who presented with TFBA and were admitted to hospital were enrolled in the study. Patients were divided into two groups based on occurrence of preoperative respiratory complications as confirmed by computed tomography. Age, sex, TFBA symptoms, type of foreign body, retention timeand location of the foreign body were documented and compared between the groups. Results In total, 223 children were included: group A ( n = 161) included those with respiratory complications; group B ( n = 62) included those without respiratory complications. Univariate and multivariate analyses found that type of foreign body, and symptoms differed significantly between the two groups. Conclusion Respiratory complications of TFBA in children were correlated with the type of foreign body and symptoms.

Introduction: Internal carotid artery occlusion (ICAO) causes high annual rates of mortality and morbidity. It has been established that atherosclerosis is the normal cause of ICAO. As the pathogenesis of atherosclerosis may involve blood lipids, inflammatory factors and other biomarkers, the aim of this study was to assess the changes in these biomarkers and investigate the relationship between these biomarkers and the development of ICAO in stroke patients. Material and methods: A total of 89 ischaemic stroke inpatients with ICAO (ICAO group) and 89 without ICAO (control group) were studied, retrospectively. The serum was collected from each patient on the 3 rd day of admission, to measure the lipid parameters and biomarkers, e.g. high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and lactic acid (LA). Histories were taken including age, gender, smoking history, and disease history. Additional analysis was carried out to compare between the genders and evaluate the association between certain biomarkers and ICAO. Results: Among the 89 ICAO cases in this study, the serum levels of hs-CRP, ESR and LA were significantly higher than those in the control group (p ≤ 0.001). No significant differences were found in the mean levels of total cholesterol, triacylglycerol, HDL cholesterol or glucose, or the known risk factors. Gender also had no influence on these biomarkers. Logistic regression analysis indicated that hs-CRP, ESR and LA were significantly associated with ICAO (p ≤ 0.05). Conclusions: These results suggest that hs-CRP, ESR and LA are associated with ICAO in ischaemic stroke patients, but gender has no effect. Therefore, Hs-CRP, ESR and LA may be useful in the early detection of patients with ICAO.

Objective A retrospective case–control study to identify stroke-associated risk factors and quantify serum C-reactive protein in patients with ischaemic stroke, with or without intracranial and/or extracranial artery occlusion (IEAO). Methods Patients with ischaemic stroke and internal carotid artery occlusion (ICAO), middle cerebral artery occlusion (MCAO), ICAO + MCAO, or no IEAO (control patients) were retrospectively recruited. Data regarding stroke-associated risk factors were retrieved from medical records. High sensitivity (hs)-CRP was quantified within 3 days of hospital admission. Results Patients with ICAO ( n = 89), MCAO ( n = 74) and ICAO + MCAO ( n = 29) had significantly higher serum hs-CRP concentrations, and were significantly more likely to have coronary heart disease, a history of stroke, and more than three stroke-associated risk factors than control patients ( n = 84). Conclusions Coronary heart disease and a history of stroke are risk factors for ischaemic stroke with IEAO. Hs-CRP may be used as a marker for IEAO.

Objectives Patients who present with Guillain-Barre syndrome (GBS) and acute transverse myelitis (ATM), either simultaneously or consecutively, are defined as having GBS/ATM overlap syndrome. As this syndrome has been underinvestigated, we performed a literature review to evaluate case reports of GBS/ATM overlap syndrome to facilitate its early diagnosis. Patients and methods We searched four scientific literature databases (PUBMED, EMBASE, ELSEVIER and WEB OF SCIENCE) for cases that presented as GBS/ATM overlap syndrome. Eighteen articles that described 23 cases were included, and the clinical and prognostic data were analyzed. Results Initially, only five (29.4%) patients were diagnosed with GBS/ATM overlap syndrome. Patients with GBS/ATM overlap syndrome presented as four clinical features. First, some of the patients displayed abnormal pyramidal signs, including 29.4% of patients who had positive pyramidal signs or a negative plantar reflex and 17.6% of patients who had signs of areflexia or hyporeflexia combined with positive pyramidal signs. Second, patients suffered pain and respiratory failure at a high rate (43.5% with pain at the onset of the disease, 43.5% with ventilator support, and 47.8% shown with respiratory failure). Third, patients had a partial clinical recovery of immunomodulators, 56.5% of patients had a favorable outcome, 46.2% of patients who received intravenous immunoglobulin (IVIG) combined steroids responded well to the treatment. Four, acute axonal polyneuropathy seemed to be associated with poor outcomes (odds ratio = 3.00, 95% CI = 1.35–6.68, P = 0.01). Abnormalities in spinal cord magnetic resonance imaging (MRI) were detected in all patients, and the most frequently involved segments were the cervical cord (69.6%) and the thoracic cord (69.6%). In addition to spinal cord lesions, in three patients lesions in the medulla and cerebral hemisphere were also observed. The most common prescriptions included a high dose of methylprednisolone at 1 g/day for 3–5 days that was followed by a 6-week course of oral prednisone and IVIG at 0.4 g/kg/day for 5 days. Conclusion While it is difficult to make an early diagnosis of GBS/ATM overlap syndrome, electrophysiology is helpful in the diagnosis of GBS and spinal cord MRIs are key to identifying ATM. Brain MRIs are also recommended to detect subclinical lesions. The combined use of IVIG and steroids was the most frequent treatment. However, less than half of the patients responded positively to treatment. Acute axonal neuropathy may be a risk factor for a poor prognosis.

This study explored the expression of connexin 43 (Cx43) in the testes of prepubertal Sprague-Dawley (SD) rats following in utero flutamide (Flu) exposure. Connexins constitute the major protein type in gap junctions. Connexin 43, the most prominent connexin family member expressed by testes, is localized at the base of seminiferous tubules in humans and rodents, and may be involved in fertility. Flutamide was injected subcutaneously into pregnant SD rats on gestational days 12-21 (25 mg/kg/day). Immunohistochemistry, Western blotting, and real-time PCR was used to investigate the distribution and the expression of Cx43 protein and mRNA in the testis on postnatal day 20 (PD20). Following Flu-exposure, Cx43 was observed between Sertoli cells in the seminiferous tubules. On PD20, no Cx43 protein was expressed by the spermatogonial cell layer of the seminiferous tubules in the controls, but was observed in the Flu-exposed group. Western blotting showed that Cx43 was expressed at significantly lower levels in Flu-exposed testes than controls on PD20 (p 0.001). On PD20, levels of Cx43 mRNA in undescended Flu-exposed testes were significantly lower than in controls (p 0.05) and descended Flu-exposed testes (p 0.01). After Flu-exposure in the rat embryonic period, Cx43 mRNA and protein expression were downregulated, and its distribution in the seminiferous tubules was abnormal.

Background/PurposeIt has been shown that the abnormality in immune cells in chronic fatigue syndrome (CFS) patients is closely associated with the participation of TGF-β. In order to study the relationship between TGF-β1 and CFS, we investigated the mRNA levels of TGF-β1 in peripheral blood mononuclear cells (PBMCs) in patients with CFS.MethodsFluorescent quantitative real time reverse-transcription polymerase chain reaction (FQ-RT-PCR) was performed to test TGF-β1 mRNA expression in PBMCs in 63 cases of CFS, 50 cases of disease controls, and 50 cases of healthy controls.ResultsThe mean value of TGF-β1 mRNA expression in CFS patients was ΔΔCt=1.17±0.58, which was significantly higher than the disease controls (ΔΔCt=0.07±1.08, df=111, p 0.05).ConclusionThe expression of TGF-β1 in PBMCs is significantly elevated in patients with CFS. It might be correlated to the pathogenesis of the disease.

We simulate the rock’s movement and defoemation process in the coal mining, and research the overlying strata movement and deformation under the conditions of shortwall and longwall mining. The conclusion of the experiment indicates: with the method of double deck mining, the rock’s damage level in caving layer is more serious, the final subsidence curve presents a tooth geometry. The subsidence curve of fissure and flexure zone is simily with the longwall mining condition.

Miller Fisher's syndrome (MFS) commonly presents in the fourth and fifth decades and are rare in people over 70 years. An 85-year-old female with no significant medical history presented with upper extremity anesthesia, ptosis, and unsteady gait. The patient had a history of hypertension and diabetes mellitus. Physical examination showed bilateral total external ophthalmoplegia, areflexia, and cerebellar ataxia. Radiological and laboratory studies were unremarkable. Lumbar puncture showed albuminocytological dissociation. The combined history, physical examination, and lumbar puncture results established a presumptive diagnosis of MFS. Intravenous immunoglobulin was given for 5 days. The patient gradually improved 10 days after the onset of symptoms. Ophthalmoplegia had fully recovered after 6 months. To the best of our knowledge, this case represented the oldest patient with MFS.