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Objective: Brain ischemia generally results in irreversible brain damage or death. One of the most important features of an ischemic stroke is disruption of the Blood-brain barrier (BBB). In this study, we examined the effect of cinnamon hydroalcoholic extract consumption on BBB permeability and expression of some genes regulating its function. Materials and Methods: Sixty male Wistar rats were divided into 5 groups; sham (high-fat diet+ sham surgery), Model (Middle Cerebral Artery Occlusion, MCAO+ high-fat diet), Lovastatin (high-fat diet + lovastatin + MCAO surgery), low and high dosage cinnamon (high-fat diet + cinnamon 130 or 260 mg, respectively+ MCAO surgery). The two doses of cinnamon (130 and 260 mg) were administered intraperitoneally. Twelve hours after ischemic stroke induction, brain right hemisphere tissues were collected and calpain I, calpainII, occludin and VEGF genes expression were quantified by Real-Time -PCR. Accordingly, p-selection protein levels were measured by ELISA method. Results: Cinnamon hydroalcoholic extract reduced the BBB permeability compared with the model group (p<0.05). Stroke increased calpain and VEGF genes while decreased occludin gene expression (p<0.001). Conversely, cinnamon administration increased occludin gene expression while calpain and VEGF genes were down-regulated (p<0.01). Pretreatment with cinnamon significantly diminished the P-Selectin protein levels as compared with the model group dose dependently (p<0.001). Conclusion: It seems that cinnamon restores BBB function by regulating the elements involved in its permeability. [ABSTRACT FROM AUTHOR]

Background: Accurate longitudinal risk prediction for DCI (delayed cerebral ischemia) occurrence after subarachnoid hemorrhage (SAH) is essential for clinicians to administer appropriate and timely diagnostics, thereby improving treatment planning and outcome. This study aimed to develop an improved longitudinal DCI prediction model and evaluate its performance in predicting DCI between day 4 and 14 after aneurysm rupture. Methods: Two DCI classification models were trained: (1) a static model based on routinely collected demographics and SAH grading scores and (2) a dynamic model based on results from laboratory and blood gas analysis anchored at the time of DCI. A combined model was derived from these two using a voting approach. Multiple classifiers, including Logistic Regression, Support Vector Machines, Random Forests, Histogram-based Gradient Boosting, and Extremely Randomized Trees, were evaluated through cross-validation using anchored data. A leave-one-out simulation was then performed on the best-performing models to evaluate their longitudinal performance using time-dependent Receiver Operating Characteristic (ROC) analysis. Results: The training dataset included 218 patients, with 89 of them developing DCI (41%). In the anchored ROC analysis, the combined model achieved a ROC AUC of 0.73 ± 0.05 in predicting DCI onset, the static and the dynamic model achieved a ROC AUC of 0.69 ± 0.08 and 0.66 ± 0.08, respectively. In the leave-one-out simulation experiments, the dynamic and voting model showed a highly dynamic risk score (intra-patient score range was 0.25 [0.24, 0.49] and 0.17 [0.12, 0.25] for the dynamic and the voting model, respectively, for DCI occurrence over the course of disease. In the time-dependent ROC analysis, the dynamic model performed best until day 5.4, and afterwards the voting model showed the best performance. Conclusions: A machine learning model for longitudinal DCI risk assessment was developed comprising a static and a dynamic sub-model. The longitudinal performance evaluation highlighted substantial time dependence in model performance, underscoring the need for a longitudinal assessment of prediction models in intensive care settings. Moreover, clinicians need to be aware of these performance variations when performing a risk assessment and weight the different model outputs correspondingly. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Acupuncture & Tuina Science is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Objective: The alteration of mitochondrial functions, especially the opening of the mitochondrial permeability transition pore (mPTP), has been proposed as a key mechanism in the development of lesions in cerebral ischemia, wherefore it is considered as an important target for drugs against ischemic injury. In this study, we aimed to investigate the effects of mitochondrial complex I inhibitors as possible regulators of mPTP using an in vitro brain ischemia model of the pentobarbital/ketamine (PBK)-anesthetized rats. Results: We found that PBK anesthesia itself delayed Ca2+-induced mPTP opening and partially recovered the respiratory functions of mitochondria, isolated from rat brain cortex and cerebellum. In addition, PBK reduced cell death in rat brain slices of cerebral cortex and cerebellum. PBK inhibited the adenosine diphosphate (ADP)-stimulated respiration of isolated cortical and cerebellar mitochondria respiring with complex I-dependent substrates pyruvate and malate. Moreover, pentobarbital alone directly increased the resistance of isolated cortex mitochondria to Ca2+-induced activation of mPTP and inhibited complex I-dependent respiration and mitochondrial complex I activity. In contrast, ketamine had no direct effect on functions of isolated normal cortex and cerebellum mitochondria. Conclusions: Altogether, this suggests that modulation of mitochondrial complex I activity by pentobarbital during PBK anesthesia may increase the resistance of mitochondria to mPTP opening, which is considered the key event in brain cell necrosis during ischemia. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a significant global health issue, ranking fifth among all causes of death and a leading cause of serious long‐term disability. Ischemic stroke leads to severe outcomes, including permanent brain damage and neuronal dysfunction. Therefore, decreasing and preventing neuronal injuries caused by stroke has been the focus of therapeutic research. In recent years, many studies have shown that fluctuations in hormonal levels influence the prognosis of ischemic stroke. Thus, it is relevant to understand the role of hormones in the pathophysiological mechanisms of ischemic stroke for preventing and treating this health issue. Here, we investigate the contribution of the prolactin/vasoinhibin axis, an endocrine system regulating blood vessel growth, immune processes, and neuronal survival, to the pathophysiology of ischemic stroke. Male mice with brain overexpression of prolactin or vasoinhibin by adeno‐associated virus (AAV) intracerebroventricular injection or lacking the prolactin receptor (Prlr−/−) were exposed to transient middle cerebral artery occlusion (tMCAO) for 45 min followed by 48 h of reperfusion. Overexpression of vasoinhibin or the absence of the prolactin receptor led to an increased lesion volume and decreased survival rates in mice following tMCAO, whereas overexpression of prolactin had no effect. In addition, astrocytic distribution in the penumbra was altered, glial fibrillary acidic protein and S100b mRNA expressions were reduced, and interleukin‐6 mRNA expression increased in the ischemic hemisphere of mice overexpressing vasoinhibin. Of note, prolactin receptor‐null mice (Prlr−/−) showed a marked increase in serum vasoinhibin levels. Furthermore, vasoinhibin decreased astrocyte numbers in mixed hippocampal neuron–glia cultures. These observations suggest that increased vasoinhibin levels may hinder astrocytes' protective reactivity. Overall, this study suggests the involvement of the prolactin/vasoinhibin axis in the pathophysiology of ischemic stroke‐induced brain injury and provides insights into the impact of its dysregulation on astrocyte reactivity and lesion size. Understanding these mechanisms could help develop therapeutic interventions in ischemic stroke and other related neurological disorders. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence of cerebrovascular MRI markers in unselected patients hospitalized for COVID-19 (Coronavirus disease 2019), we compared these with healthy controls without previous SARS-CoV-2 infection or hospitalization and subsequently, investigated longitudinal (incidental) lesions in patients after three months. Methods: CORONIS (CORONavirus and Ischemic Stroke) was an observational cohort study in adult hospitalized patients for COVID-19 and controls without COVID-19, conducted between April 2021 and September 2022. Brain MRI was performed shortly after discharge and after 3 months. Outcomes included recent ischemic (DWI-positive) lesions, previous infarction, microbleeds, white matter hyperintensities (WMH) and intracerebral hemorrhage and were analysed with logistic regression to adjust for confounders. Results: 125 patients with COVID-19 and 47 controls underwent brain MRI a median of 41.5 days after symptom onset. DWI-positive lesions were found in one patient (1%) and in one (2%) control, both clinically silent. WMH were more prevalent in patients (78%) than in controls (62%) (adjusted OR: 2.95 [95% CI: 1.07–8.57]), other cerebrovascular MRI markers did not differ. Prevalence of markers in ICU vs. non-ICU patients was similar. After three months, five patients (5%) had new cerebrovascular lesions, including DWI-positive lesions (1 patient, 1.0%), cerebral infarction (2 patients, 2.0%) and microbleeds (3 patients, 3.1%). Conclusion: Overall, we found no higher prevalence of cerebrovascular markers in unselected hospitalized COVID-19 patients compared to controls. The few incident DWI-lesions were most likely to be explained by risk-factors of small vessel disease. In the general hospitalized COVID-19 population, COVID-19 shows limited impact on cerebrovascular MRI markers shortly after hospitalization. [ABSTRACT FROM AUTHOR]

Brain oxygen deprivation causes morphological damage involved in the formation of serious pathological conditions such as stroke and cerebral palsy. Therapeutic methods for post-hypoxia/anoxia injuries are limited and still have deficiencies in terms of safety and efficacy. Recently, clinical studies of stroke have reported the use of drugs containing riboflavin for post-injury clinical rehabilitation, however, the effects of vitamin B2 on exposure to cerebral oxygen deprivation are not completely elucidated. This review aimed to investigate the potential antioxidant, anti-inflammatory and neuroprotective effects of riboflavin in cerebral hypoxia/anoxia. After a systematic search, 21 articles were selected, 8 preclinical and 12 clinical studies, and 1 translational study. Most preclinical studies used B2 alone in models of hypoxia in rodents, with doses of 1–20 mg/kg (in vivo) and 0.5–5 µM (in vitro). Together, these works suggested greater regulation of lipid peroxidation and apoptosis and an increase in neurotrophins, locomotion, and cognition after treatment. In contrast, several human studies have administered riboflavin (5 mg) in combination with other Krebs cycle metabolites, except one study, which used only B2 (20 mg). A reduction in lactic acidosis and recovery of sensorimotor functions was observed in children after treatment with B2, while adults and the elderly showed a reduction in infarct volume and cognitive rehabilitation. Based on findings from preclinical and clinical studies, we conclude that the use of riboflavin alone or in combination acts beneficially in correcting the underlying brain damage caused by hypoxia/anoxia and its inflammatory, oxidative, and behavioral impairments. [ABSTRACT FROM AUTHOR]

Glutamate (Glu) is a major excitatory neurotransmitter in the brain, essential for synaptic plasticity, neuronal activity, and memory formation. However, its dysregulation leads to excitotoxicity, implicated in neurodegenerative diseases and brain ischemia. Vesicular glutamate transporters (VGLUTs) regulate Glu loading into synaptic vesicles, crucial for maintaining optimal extracellular Glu levels. This study investigates the neuroprotective effects of VGLUT1 inhibition in HT22 cells overexpressing VGLUT1 under oxygen glucose deprivation (OGD) conditions. HT22 cells, a hippocampal neuron model, were transduced with lentiviral vectors to overexpress VGLUT1. Cells were subjected to OGD, with pre-incubation of Chicago Sky Blue 6B (CSB6B), an unspecific VGLUT inhibitor. Cell viability, lactate dehydrogenase (LDH) release, mitochondrial membrane potential, and hypoxia-related protein markers (PARP1, AIF, NLRP3) were assessed. Results indicated that VGLUT1 overexpression increased vulnerability to OGD, evidenced by higher LDH release and reduced cell viability. CSB6B treatment improved cell viability and reduced LDH release in OGD conditions, particularly at 0.1 μM and 1.0 μM concentrations. Moreover, CSB6B preserved mitochondrial membrane potential and decreased levels of PARP1, AIF, and NLRP3 proteins, suggesting neuroprotective effects through mitigating excitotoxicity. This study demonstrates that VGLUT1 inhibition could be a promising therapeutic strategy for ischemic brain injury, warranting further investigation into selective VGLUT1 inhibitors. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to monitor blood-brain barrier permeability within 24 h and during the delayed cerebral ischemia (DCI) time window (DCITW) spanning 4–14 days after aneurysmal subarachnoid hemorrhage (aSAH) and to investigate its correlation with both DCI occurrence and outcomes at three months. Methods: A total of 128 patients were stratified based on the DCI occurrence and three-month modified Rankin scale scores. Comparison of Ktrans at admission (admission Ktrans) and during DCITW (DCITW Ktrans) was conducted between DCI and non-DCI groups, as well as between groups with good and poor outcomes. Changes in Ktrans were also analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of DCI and poor outcomes. Results: Admission Ktrans (0.58 ± 0.18 vs 0.47 ± 0.12, p = 0.002) and DCITW Ktrans (0.54 ± 0.19 vs 0.41 ± 0.14, p < 0.001) were significantly higher in the DCI group compared with the non-DCI group. Although both were higher in the poor outcome group than the good outcome group, the difference was not statistically significant at admission (0.53 ± 0.18 vs 0.49 ± 0.14, p = 0.198). Ktrans in the non-DCI group (0.47 ± 0.12 vs 0.41 ± 0.14, p = 0.004) and good outcome group (0.49 ± 0.14 vs 0.41 ± 0.14, p < 0.001) decreased significantly from the admission to DCITW. Multivariate analysis identified DCITW Ktrans and admission Ktrans as independent predictors of poor outcomes (OR = 1.73, 95%CI: 1.24–2.43, p = 0.001) and DCI (OR = 1.75, 95%CI: 1.25–2.44, p = 0.001), respectively. Conclusion: Elevated Ktrans at admission is associated with the occurrence of DCI. Continuous monitoring of Ktrans from admission to DCITW can accurately identify reversible and irreversible changes and can predict outcomes at 3 months. Clinical relevance statement: Ktrans measured with CT perfusion is a valuable tool for predicting both delayed cerebral ischemia and three-month outcomes following aneurysmal subarachnoid hemorrhage. Monitoring changes in Ktrans from admission to time window of delayed cerebral ischemia can guide treatment and management decisions for aneurysmal subarachnoid hemorrhage patients. Key Points: • Ktrans measured at admission and during the delayed cerebral ischemia time window (4–14 days) holds distinct clinical significance following aneurysmal subarachnoid hemorrhage. • Admission Ktrans serves as a predictor for delayed cerebral ischemia, while continuous assessment of Ktrans from admission to the delayed cerebral ischemia time window can predict three-month outcomes. • Monitoring Ktrans at different stages improves instrumental in enhancing decision-making and treatment planning for patients with aneurysmal subarachnoid hemorrhage. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) and brain ischemia/reperfusion cause neurodegenerative processes that can continue after the acute stage with the development of severe brain atrophy with dementia. In this case, the long-term neurodegeneration of the brain is similar to the neurodegeneration characteristic of Alzheimer's disease (AD) and is associated with the accumulation of beta amyloid and tau protein. In the pathogenesis of AD as well as in the pathogenesis of cerebral ischemia and TBI oxidative stress, progressive inflammation, glial activation, blood–brain barrier dysfunction, and excessive activation of autophagy are involved, which implies the presence of many targets that can be affected by neuroprotectors. That is, multivariate cascades of nerve tissue damage represent many potential targets for therapeutic interventions. One of such substances that can be used in multi-purpose therapeutic strategies is methylene blue (MB). This drug can have an antiapoptotic and anti-inflammatory effect, activate autophagy, inhibit the aggregation of proteins with an irregular shape, inhibit NO synthase, and bypass impaired electron transfer in the respiratory chain of mitochondria. MB is a well-described treatment for methemoglobinemia, malaria, and encephalopathy caused by ifosfamide. In recent years, this drug has attracted great interest as a potential treatment for a number of neurodegenerative disorders, including the effects of TBI, ischemia, and AD. [ABSTRACT FROM AUTHOR]

Background: Currently, no evidence exists on the expression of apoptosis (CASP3), autophagy (BECN1), and mitophagy (BNIP3) genes in the CA3 area after ischemia with long-term survival. Objective: The goal of the paper was to study changes in above genes expression in CA3 area after ischemia in the period of 6–24 months. Methods: In this study, using quantitative RT-PCR, we present the expression of genes associated with neuronal death in a rat ischemic model of Alzheimer's disease. Results: First time, we demonstrated overexpression of the CASP3 gene in CA3 area after ischemia with survival ranging from 0.5 to 2 years. Overexpression of the CASP3 gene was accompanied by a decrease in the activity level of the BECN1 and BNIP3 genes over a period of 0.5 year. Then, during 1-2 years, BNIP3 gene expression increased significantly and coincided with an increase in CASP3 gene expression. However, BECN1 gene expression was variable, increased significantly at 1 and 2 years and was below control values 1.5 years post-ischemia. Conclusions: Our observations suggest that ischemia with long-term survival induces neuronal death in CA3 through activation of caspase 3 in cooperation with the pro-apoptotic gene BNIP3. This study also suggests that the BNIP3 gene regulates caspase-independent pyramidal neuronal death post-ischemia. Thus, caspase-dependent and -independent death of neuronal cells occur post-ischemia in the CA3 area. Our data suggest new role of the BNIP3 gene in the regulation of post-ischemic neuronal death in CA3. This suggests the involvement of the BNIP3 together with the CASP3 in the CA3 in neuronal death post-ischemia. [ABSTRACT FROM AUTHOR]

Background: Neuromonitoring during carotid endarterectomy (CEA) under general anesthesia is desirable and may be useful for preventing brain ischemia, but the selection of the most appropriate method remains controversial. Purpose: To determine the effectiveness of near infrared spectroscopy (NIRS) compared to multimodality intraoperative neuromonitoring (IONM) in indicating elective shunts and predicting postoperative neurological status. Methods: This is a retrospective observational study including 86 consecutive patients with CEA under general anesthesia. NIRS and multimodality IONM were performed during the procedure. IONM included electroencephalography (EEG), somatosensory evoked potentials (SSEPs) and transcranial motor-evoked potentials (TcMEPs). Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated for each neuromonitoring modality. Results: NIRS presented a sensitivity and a specificity for detecting brain ischemia of 77.7% and 89.6%, respectively (PPV = 46.6% and NPV = 97.2%). In contrast, a 100% sensitivity and specificity for multimodality IONM was determined (PPV and NPV = 100%). No significant difference (in demographical or clinical data) between "true positive" and "false-positive" patients was identified. Among the methods included in multimodality IONM, EEG showed the best results for predicting postoperative outcome after CEA (PPV and NPV=100%). Conclusion: NIRS is inferior to multimodality IONM in detecting brain ischemia and predicting postoperative neurological status during CEA under general anesthesia. [ABSTRACT FROM AUTHOR]

Copyright of Tianjin Medical Journal is the property of Tianjin Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

How brain functions in the distorted ischemic state before and after reperfusion is unclear. It is also uncertain whether there are any indicators within ischemic brain that could predict surgical outcomes. To alleviate these issues, we applied individual brain connectome in chronic steno‐occlusive vasculopathy (CSOV) to map both ischemic symptoms and their postbypass changes. A total of 499 bypasses in 455 CSOV patients were collected and followed up for 47.8 ± 20.5 months. Using multimodal parcellation with connectivity‐based and pathological distortion‐independent approach, areal MR features of brain connectome were generated with three measurements of functional connectivity (FC), structural connectivity, and PageRank centrality at the single‐subject level. Thirty‐three machine‐learning models were then trained with clinical and areal MR features to obtain acceptable classifiers for both ischemic symptoms and their postbypass changes, among which, 11 were deemed acceptable (AUC > 0.7). Notably, the FC feature‐based model for long‐term neurological outcomes performed very well (AUC > 0.8). Finally, a Shapley additive explanations plot was adopted to extract important individual features in acceptable models to generate "fingerprints" of brain connectome. This study not only establishes brain connectomic fingerprint databases for brain ischemia with distortion, but also provides informative insights for how brain functions before and after reperfusion. [ABSTRACT FROM AUTHOR]

Objective(s): This study assessed the effects of electroacupuncture (EA) stimulation at different frequencies at the Dazhui and Baihui acupoints in the subacute phase after transient global cerebral ischemia (GCI). Materials and Methods: Rats were subjected to GCI for 25 min, followed by reperfusion for 7 days. EA at acupoints was performed at 10, 30, or 50 Hz, 1 day after reperfusion and then once daily for 6 consecutive days. Results: EA at acupoints at 10 and 50 Hz effectively down-regulated apoptosis in the hippocampal cornu ammonis 1(CA1) area and ameliorated memory deficits. Moreover, EA treatment at 10 and 50 Hz markedly increased phospho (p)-extracellular signal-regulated protein kinase 1/2 (ERK1/2), p-ERK1/2/neuronal nuclei (NeuN), p-cAMP response element-binding protein (CREB)/p-ERK1/2, B-cell lymphoma-2 (Bcl-2)/p-CREB, and X-linked inhibitor of apoptosis protein/NeuN expression levels and decreased Bcl-2 homologous antagonist/killer, second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI, cytochrome c, cleaved caspase-3, and apoptosis-inducing factor expression levels. Furthermore, 10-Hz EA treatment effectively increased p-p38 mitogen-activated protein kinase (MAPK), p-p38 MAPK/NeuN, and p-CREB/p-p38 MAPK expression levels. Pretreatment with U0126 (ERK1/2 inhibitor) completely abrogated the effects of 10- and 50-Hz EA treatments on the aforementioned protein expression levels. Similarly, pretreatment with SB203580 (p38 MAPK inhibitor) completely abrogated the effects of 10-Hz treatment on the aforementioned protein expression levels. Conclusion: The effects of 10- and 50-Hz EA treatments on mitochondria-related apoptosis can be attributed to the activation of ERK1/2/p38 MAPK/CREB/Bcl-2- and ERK1/2/CREB/Bcl-2-mediated signaling, respectively, in the hippocampal CA1 area at 7 days after transient GCI. [ABSTRACT FROM AUTHOR]

Background: Brain ischemia–reperfusion injury is a complex process, and neuroinflammation is an important secondary contributing pathological event. Neutrophils play major roles in ischemic neuroinflammation. Once activated, neutrophils express formyl peptide receptors (FPRs), which are special receptors of a class of chemoattractants and may be potential targets to regulate the activity of neutrophils and control cerebral ischemic injury. This study was aimed to explore the ameliorating effect of Cyclosporin H (CsH), a potent FPR antagonist, on brain ischemic injury by inhibiting the activation and migration of neutrophils, and improving cerebral blood flow. Methods: We employed a middle cerebral artery occlusion (MCAO) Model on rats and performed behavioral, morphological, and microPET imaging assays to investigate the potential restoring efficacy of CsH on cerebral ischemic damages. Peptide N-cinnamoyl-F-(D)L-F-(D)L-F (cFLFLF), an antagonist to the neutrophil FPR with a high binding affinity, was used for imaging neutrophil distribution. Results: We found that CsH had similar effect with edaravone on improving the neurobehavioral deficient symptoms after cerebral ischemia–reperfusion, and treatment with CsH also alleviated ischemic cerebral infarction. Compared with the MCAO Model group, [18F]FDG uptake ratios of the CsH and edaravone treatment groups were significantly higher. The CsH-treated groups also showed significant increases in [18F]FDG uptake at 144 h when compared with that of 24 h. This result indicates that like edaravone, treatment with both doses of CsH promoted the recovery of blood supply after cerebral ischemic event. Moreover, MCAO-induced cerebral ischemia significantly increased the radiouptake of [68Ga]Ga-cFLFLF at 72 h after ischemia–reperfusion operation. Compared with MCAO Model group, radiouptake values of [68Ga]-cFLFLF in both doses of CsH and edaravone groups were all decreased significantly. These results showed that both doses of CsH resulted in a similar therapeutic effect with edaravone on inhibiting neutrophil infiltration in cerebral infarction. Conclusion: Potent FPR antagonist CsH is promisingly beneficial in attenuating neuroinflammation and improving neurobehavioral function against cerebral infarction. Therefore, FPR may become a novel target for regulating neuroinflammation and improving prognosis for ischemic cerebrovascular disorders. [ABSTRACT FROM AUTHOR]

The search for natural biologically active substances having a neuroprotective effect against cerebral ischemia-reperfusion injury is one of the major priorities of modern neuroscience and medicine. Intranasal insulin (INI) exerts a pronounced restorative effect on various neurodegenerative diseases, but the mechanisms of its action and its therapeutic effects in cerebral ischemia have not been well studied, including in type 2 diabetes mellitus (DM2) which increases the risk of cerebrovascular dysfunction. The aim of the work was to study the effect of INI on metabolic parameters and inflammatory factors in male Wistar rats with DM2, exposed to cerebral ischemia, as compared to nondiabetic animals. DM2 was induced by a combination of high-fat diet and low-dose (25 mg/kg) streptozotocin administration. Cerebral ischemia was studied in a rat model of global forebrain ischemia-reperfusion (IR) injury induced by occlusion of both common carotid arteries, followed by a 7-day reperfusion. Two h after the end of ischemic exposure, the rats were treated with INI at a dose of 0.5 or 2.0 IU/rat, after which the drug was administered at the same dose, once a day, for the following 7 days. INI was found to prevent body weight loss in both nondiabetic and DM2 IR-exposed rats, while elevating plasma total cholesterol levels and epididymal fat fraction in IR-exposed nondiabetic animals only. In IR-exposed DM2 rats, INI (at both doses used) reduced postprandial plasma levels of glucose and insulin, indicative of improved glucose tolerance, as well as plasma levels of inflammatory factors, C-reactive protein (at a dose of 0.5 IU/rat/day), and tumor necrosis factor-α (at a dose of 2 IU/rat/day), indicative of its anti-inflammatory potential. Thus, a post-IR course treatment with INI improves metabolic parameters and abates inflammatory responses in DM2 rats, which may be in high demand when correcting ischemic stroke in patients with DM2. [ABSTRACT FROM AUTHOR]

Objective: This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality. Methods: Amulti-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 µg rEGF + 3.5mg GHRP6 i.v., n=10), II (75 µg rEGF + 5mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index andmodified Rankin scale (mRS)] outcomes. Results: The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by theirmoderate to strong effect size. At 6months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis includingmerged treated groups and utility-weightedmRS also showed a benefit of this combined therapy. Conclusion: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study. [ABSTRACT FROM AUTHOR]

Background: Early identification of the severity of hypoxic-ischemic brain injury (HIBI) after cardiac arrest can be used to help plan appropriate subsequent therapy. We evaluated whether conductivity of cerebral tissue measured using magnetic resonance-based conductivity imaging (MRCI), which provides contrast derived from the concentration and mobility of ions within the imaged tissue, can reflect the severity of HIBI in the early hours after cardiac arrest. Methods: Fourteen minipigs were resuscitated after 5 min or 12 min of untreated cardiac arrest. MRCI was performed at baseline and at 1 h and 3.5 h after return of spontaneous circulation (ROSC). Results: In both groups, the conductivity of cerebral tissue significantly increased at 1 h after ROSC compared with that at baseline (P = 0.031 and 0.016 in the 5-min and 12-min groups, respectively). The increase was greater in the 12-min group, resulting in significantly higher conductivity values in the 12-min group (P = 0.030). At 3.5 h after ROSC, the conductivity of cerebral tissue in the 12-min group remained increased (P = 0.022), whereas that in the 5-min group returned to its baseline level. Conclusions: The conductivity of cerebral tissue was increased in the first hours after ROSC, and the increase was more prominent and lasted longer in the 12-min group than in the 5-min group. Our findings suggest the promising potential of MRCI as a tool to estimate the severity of HIBI in the early hours after cardiac arrest. [ABSTRACT FROM AUTHOR]

Recent evidence indicates that experimental brain ischemia leads to dementia with an Alzheimer's disease-like type phenotype and genotype. Based on the above evidence, it was hypothesized that brain ischemia may contribute to the development of Alzheimer's disease. Brain ischemia and Alzheimer's disease are two diseases characterized by similar changes in the hippocampus that are closely related to memory impairment. Following brain ischemia in animals and humans, the presence of amyloid plaques in the extracellular space and intracellular neurofibrillary tangles was revealed. The phenomenon of tau protein hyperphosphorylation is a similar pathological feature of both post-ischemic brain injury and Alzheimer's disease. In Alzheimer's disease, the phosphorylated Thr231 motif in tau protein has two distinct trans and cis conformations and is the primary site of tau protein phosphorylation in the pre-entanglement cascade and acts as an early precursor of tau protein neuropathology in the form of neurofibrillary tangles. Based on the latest publication, we present a similar mechanism of the formation of neurofibrillary tangles after brain ischemia as in Alzheimer's disease, established on trans- and cis-phosphorylation of tau protein, which ultimately influences the development of tauopathy. [ABSTRACT FROM AUTHOR]

Since the first description of the possible utilization of the internal maxillary artery for bypass surgery, there are some reports of its use in aneurysm cases; however, there is no information about the possible advantages of this type of bypass for cerebral ischemic disease. We present a 77-year-old man with a history of diabetes, hypertension, systemic atherosclerosis, and two acute myocardial infarctions with left hemiparesis. Imaging studies reported total occlusion of the right internal carotid artery and 75% occlusion on the left side, with an old opercular infarction and repeated transient ischemic attacks in the right middle cerebral artery territory despite medical treatment. After a consensus, we decided to perform a bypass from the internal maxillary artery to the M2 segment of the middle cerebral artery using a radial artery graft. After performing the proximal anastomosis, the calculated graft's free flow was 216 ml/min. Subsequently, after completing the bypass, the patency was confirmed with fluorescein videoangiography and intraoperative Doppler. Postoperatively, imaging studies showed improvement in the perfusion values and the hemiparesis from 3/5 to 4+/5. The patient was discharged one week after the operation, with a modified Rankin scale of 1, without added deficits. The use of revascularization techniques in steno-occlusive disease indicates a select group of patients that may benefit from this procedure. In addition, internal maxillary artery bypass has provided a safe option for large areas of ischemia that cannot be supplied with a superficial temporal artery - middle cerebral artery bypass. [ABSTRACT FROM AUTHOR]

The mechanisms of cerebral ischemia–reperfusion injury (IRI) limitation by remote ischemic postconditioning (RPC) are of interest because the latter may positively influence functional recovery after cerebral ischemia. The study was aimed to assess the role of plasma proteins syndecan-1 (SDC-1) and annexin-5 (ANXA-5) in limiting cerebral IRI by RPC in a middle cerebral artery occlusion (MCAO) model in male Wistar rats. The animals were randomized into three groups: (1) control sham-operated rats (SO group), (2) rats with 30-min MCAO-induced ischemia (MCAO group), (3) rats with 30-min MCAO-induced ischemia followed by RPC (MCAO + RPC group). SDC-1 plasma levels, as assessed by ELISA, in MCAO (41.4 ± 1.3 ng/mL) and MCAO + RPC (67.8 ± 5.8 ng/mL) rats were, respectively, by 30% (p < 0.05) and 112% (p < 0.01) higher than in SO control (31.9 ± 1.1 ng/mL). No intergroup differences in ANXA-5 plasma levels were detected. Cerebral infarct volume in MCAO and MCAO + RPC rats accounted for 32.0 ± 2.5 and 13.6 ± 1.3% of the total brain volume, respectively (p < 0.05). Cerebral edema volume in MCAO and MCAO + RPC rats were 47.0 ± 3.3 and 16.0 ± 2.1%, respectively (p < 0.05). In MCAO + RPC animals, correlation analysis revealed a high direct correlation between infarct size and right forelimb muscular strength (grip strength test, 3.9 ± 0.8 H, p > 0.5; KK = 0.72, p < 0.05) and a very high inverse correlation between infarct size and right hindlimb capillary blood flow (Doppler flowmetry, r = –0.98, p < 0.01). Animals' neurologic deficits were assessed by the Garcia scoring scale, while their locomotor coordination was assessed in the Rotarod test. It is assumed that SDC-1 plasma protein may serve as a potential regulator of the infarct size-limiting effect of remote ischemic postconditioning, which is determinative for functional recovery. [ABSTRACT FROM AUTHOR]

Apoptosis plays a crucial role in neuronal injury, with substantial evidence implicating Fas-mediated cell death as a key factor in ischemic strokes. To address this, inhibition of Fas-signaling has emerged as a promising strategy in preventing neuronal cell death and alleviating brain ischemia. However, the challenge of overcoming the blood–brain barrier (BBB) hampers the effective delivery of therapeutic drugs to the central nervous system (CNS). In this study, we employed a 30 amino acid-long leptin peptide to facilitate BBB penetration. By conjugating the leptin peptide with a Fas-blocking peptide (FBP) using polyethylene glycol (PEG), we achieved specific accumulation in the Fas-expressing infarction region of the brain following systemic administration. Notably, administration in leptin receptor-deficient db/db mice demonstrated that leptin facilitated the delivery of FBP peptide. We found that the systemic administration of leptin-PEG-FBP effectively inhibited Fas-mediated apoptosis in the ischemic region, resulting in a significant reduction of neuronal cell death, decreased infarct volumes, and accelerated recovery. Importantly, neither leptin nor PEG-FBP influenced apoptotic signaling in brain ischemia. Here, we demonstrate that the systemic delivery of leptin-PEG-FBP presents a promising and viable strategy for treating cerebral ischemic stroke. Our approach not only highlights the therapeutic potential but also emphasizes the importance of overcoming BBB challenges to advance treatments for neurological disorders. [ABSTRACT FROM AUTHOR]

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Ischemic stroke is a common degenerative disease in Indonesia caused by interrupted or restricted blood supply to part of brain, preventing it from getting oxygen and nutrients. Without sufficient blood supply, brain cells begin to die. Various treatments for ischemic stroke patients have been developed and implemented, but are still ineffective in treating or preventing brain damage. Curcumin is one of the bioactive compounds which mostly found in turmeric which is one of the main spices resource in Indonesia that has many benefits as a medicine. People have been making use of curcumin as a medicine for various diseases, one of which is stroke. Therefore, this systematic review analysed qualitatively the effect of curcumin on the brain condition after ischemic stroke. The method used in this study was a systematic review of 8 databases in the last 10 years, from 2012 to August 2022. Study included was only experimental study on rats. Based on 19 articles gathered, there was a decrement in ROS, COX-2, iNOS, NF-kB, TNF-a, IL-6, Bax, Caspase-9, Caspase-3, ICAM-1, MMP-9, neurological deficit score, and an increment in BCL-2, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) in rats receiving curcumin intervention either orally or intravenously. Curcumin affects the ischemic brain in a number of ways, namely as an antioxidant, anti-inflammatory, anti-apoptotic, Blood-Brain-Barrier (BBB) protector, increasing neurogenesis, and reducing neurological deficits. It is concluded that curcumin has an elevating effect in protecting brain condition after an ischemic stroke. [ABSTRACT FROM AUTHOR]

Coenzyme CoQ10 (CoQ10) is an endogenous lipid-soluble antioxidant that effectively protects lipids, proteins, and DNA from oxidation due to its ability to undergo redox transitions between oxidized and reduced forms. Various oxidative stress-associated infectious and somatic diseases have been observed to disrupt the balance of CoQ10 concentration in tissues. As a high molecular weight polar lipophilic compound, CoQ10 exhibits very limited oral bioavailability, which restrains its therapeutic potential. Nevertheless, numerous studies have confirmed the clinical efficacy of CoQ10 therapy through oral administration of high doses over extended time periods. Experimental studies have demonstrated that in emergency situations, intravenous administration of both oxidized and reduced-form CoQ10 leads to a rapid increase in its concentration in organ tissues, offering protection for organ tissues in ischemic conditions. This suggests that the cardio- and neuroprotective efficacy of intravenously administered CoQ10 forms could present new opportunities in treating acute ischemic conditions. Based on these findings, the review provides reasoning supporting further research and implementation of CoQ10 dosage forms for intravenous administration in emergency situations into clinical practice. [ABSTRACT FROM AUTHOR]

Copyright of MEDISAN is the property of Centro Provincial de Informacion en Ciencias Medicas de Santiago de Cuba and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Raspberries are cerebral microvascular formations of unknown origin, defined as three or more transversally sectioned vascular lumina surrounded by a common perivascular space. We have previously demonstrated an increased raspberry density in the cortex of patients with vascular dementia and cerebral atherosclerosis, while studies by other authors on overlapping and synonymously defined vascular entities mainly associate them with advancing age. The aim of the present study was to examine the relationship between raspberries and age in a large study sample while including multiple potential confounding factors in the analysis. Materials and methods: Our study sample consisted of 263 individuals aged 20–97 years who had undergone a clinical autopsy including a neuropathological examination. The cortical raspberry density had either been quantified as part of a previous study or was examined de novo in a uniform manner on haematoxylin- and eosin-stained tissue sections from the frontal lobe. The medical records and autopsy reports were assessed regarding neurodegeneration, cerebral infarcts, cerebral atherosclerosis and small vessel disease, cardiac hypertrophy, nephrosclerosis, hypertension, and diabetes mellitus. With the patients grouped according to 10-year age interval, non-parametric tests (the Kruskal–Wallis test, followed by pairwise testing with Bonferroni-corrected P values) and multiple linear regression models (not corrected for multiple tests) were performed. Results: The average raspberry density increased with advancing age. The non-parametric tests demonstrated statistically significant differences in raspberry density when comparing the groups aged 60–99 years and 70–99 years to those aged 20–29 years (P < 0.012) and 30–59 years (P < 0.011), respectively. The multiple linear regression models demonstrated positive associations with age interval (P < 0.001), cerebral atherosclerosis (P = 0.024), cardiac hypertrophy (P = 0.021), hypertension subgrouped for organ damage (P = 0.006), and female sex (P = 0.004), and a tendency towards a negative association with Alzheimer's disease neuropathologic change (P = 0.048). Conclusion: The raspberry density of the frontal cortex increases with advancing age, but our results also indicate associations with acquired pathologies. Awareness of the biological and pathological context where raspberries occur can guide further research on their origin. [ABSTRACT FROM AUTHOR]

Explaining changes at the gene level that occur during neurodegeneration in the CA3 area is crucial from the point of view of memory impairment and the development of post-ischemic dementia. An ischemic model of Alzheimer's disease was used to evaluate changes in the expression of genes related to amyloid transport in the CA3 region of the hippocampus after 10 min of brain ischemia with survival of 2, 7 and 30 days and 12, 18 and 24 months. The quantitative reverse transcriptase PCR assay revealed that the expression of the LRP1 and RAGE genes involved in amyloid transport was dysregulated from 2 days to 24 months post-ischemia in the CA3 area of the hippocampus. LRP1 gene expression 2 and 7 days after ischemia was below control values. However, its expression from day 30 to 24 months, survival after an ischemic episode was above control values. RAGE gene expression 2 days after ischemia was below control values, reaching a maximum increase 7 and 30 days post-ischemia. Then, after 12, 18 and 24 months, it was again below the control values. The data indicate that in the CA3 area of the hippocampus, an episode of brain ischemia causes the increased expression of the RAGE gene for 7–30 days during the acute phase and that of LRP1 from 1 to 24 months after ischemia during the chronic stage. In other words, in the early post-ischemic stage, the expression of the gene that transport amyloid to the brain increases (7–30 days). Conversely, in the late post-ischemic stage, amyloid scavenging/cleaning gene activity increases, reducing and/or preventing further neuronal damage or facilitating the healing of damaged sites. This is how the new phenomenon of pyramidal neuronal damage in the CA3 area after ischemia is defined. In summary, post-ischemic modification of the LRP1 and RAGE genes is useful in the study of the ischemic pathways and molecular factors involved in the development of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Post-stroke cognitive impairment and dementia (PSCID) affects many survivors of large vessel cerebral ischemia. The molecular pathways underlying PSCID are poorly defined but may overlap with neurodegenerative pathophysiology. Specifically, synaptic dysfunction after stroke may be directly mediated by alterations in the levels of amyloid beta (Aβ), the peptide that accumulates in the brains of Alzheimer's disease (AD) patients. In this study, we use the transient middle cerebral artery occlusion (MCAo) model in young adult mice to evaluate if a large vessel stroke increases brain soluble Aβ levels. We show that soluble Aβ40 and Aβ42 levels are increased in the ipsilateral hippocampus in MCAo mice 7 days after the injury. We also analyze the level and activity of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), an enzyme that generates Aβ in the brain, and observe that BACE1 activity is increased in the ipsilateral hippocampus of the MCAo mice. Finally, we highlight that treatment of MCAo mice with a BACE1 inhibitor during the recovery period rescues stroke-induced deficits in hippocampal synaptic plasticity. These findings support a molecular pathway linking ischemia to alterations in BACE1-mediated production of Aβ, and encourage future studies that evaluate whether targeting BACE1 activity improves the cognitive deficits seen with PSCID. [ABSTRACT FROM AUTHOR]

Background: The inflammatory response to cerebral ischemia is complex; however, most clinical studies of stroke outcome focus on a few selected proteins. We, therefore, aimed to profile a broad range of inflammation-related proteins to: identify proteins associated with ischemic stroke outcome that are independent of established clinical predictors; identify proteins subsets for outcome prediction; and perform sex and etiological subtype stratified analyses. Methods: Acute-phase plasma levels of 65 inflammation-related proteins were measured in 534 ischemic stroke cases. Logistic regression was used to estimate associations to unfavorable 3-month functional outcome (modified Rankin Scale score > 2) and LASSO regressions to identify proteins with independent effects. Results: Twenty proteins were associated with outcome in univariable models after correction for multiple testing (FDR < 0.05), and for 5 the association was independent of clinical variables, including stroke severity (TNFSF14 [LIGHT], OSM, SIRT2, STAMBP, and 4E-BP1). LASSO identified 9 proteins that could best separate favorable and unfavorable outcome with a predicted diagnostic accuracy (AUC) of 0.81; three associated with favorable (CCL25, TRAIL [TNFSF10], and Flt3L) and 6 with unfavorable outcome (CSF-1, EN-RAGE [S100A12], HGF, IL-6, OSM, and TNFSF14). Finally, we identified sex- and etiologic subtype-specific associations with the best discriminative ability achieved for cardioembolic, followed by cryptogenic stroke. Conclusions: We identified candidate blood-based protein biomarkers for post-stroke functional outcome involved in, e.g., NLRP3 inflammasome regulation and signaling pathways, such as TNF, JAK/STAT, MAPK, and NF-κB. These proteins warrant further study for stroke outcome prediction as well as investigations into the putative causal role for stroke outcome. [ABSTRACT FROM AUTHOR]

One of the ischemic stroke prevention methods is reconstructive surgery on the carotid arteries, during which there is a risk of ischemia-reperfusion phenomenon. Nevertheless, there is still a high risk of stroke at all stages of the surgery, which equally depends on the atherosclerotic plaque structure and on the technique and tactics of surgery. The aim of this study was to investigate the dynamics of redox homeostasis and nitric oxide production in the blood taken from the internal jugular vein in patients with carotid arteries pathology against the episode of cerebral blood flow restriction during carotid surgery. This prospective cohort study involved 56 patients which required carotid reconstructive surgery. The markers dynamics of oxygen metabolism, redox homeostasis and nitric oxide production in blood from the internal jugular vein on the side of surgery were studied. It was found that the activity of free radical processes is proportional to the level of jugular hypoxemia. Bidirectional dynamics of lactate concentration during intraoperative transient cerebral ischemia was revealed. In some patients, lactate production activates with an increase in free radical processes activity in proportion to the intensification of nitric oxide synthesis against a decrease in peroxynitrite production and activation of molecular compensatory mechanisms increasing concentrations of L-arginine and reduced glutathione. In others, the extraction of oxygen from the blood increases without lactate production, activation of nitric oxide synthesis and development of oxidative stress. This indicates good adaptive reserves against acute restriction of cerebral blood flow. [ABSTRACT FROM AUTHOR]

Moxibustion is an effective treatment for the clinical management of acute cerebral infarction. However, its exact mechanism of action is still not fully understood. This study aimed to investigate the protective effect of moxibustion on cerebral ischemia–reperfusion injury (CIRI) in rats. Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to construct a CIRI rat model, all animals were randomly divided into four groups including sham operation group, MCAO/R group (MCAO/R), moxibustion therapy + MCAO/R (Moxi) and ferrostatin‐1 + MCAO/R (Fer‐1) group. In the Moxi group, moxibustion treatment was initiated 24 h after modeling, once a day for 30 mins each time for 7 days. Moreover, the Fer‐1 group received intraperitoneal injections of Fer‐1 12 h after modeling, once a day for a total of 7 days. The results showed that moxibustion could reduce nerve function damage and neuronal death. Additionally, moxibustion could reduce the production of lipid peroxides such as lipid peroxide, malondialchehyche and ACSL4 to regulate lipid metabolism, promote the production of glutathione and glutathione peroxidase 4 and reduce the expression of hepcidin by inhibiting the production of inflammatory factor interleukin‐6, therefore, downregulating the expression of SLC40A1, reducing the iron level in the cerebral cortex, reducing the accumulation of reactive oxygen species and inhibiting ferroptosis. Based on our studies, it can be concluded that moxibustion has the ability to inhibit ferroptosis of nerve cells post CIRI and plays a protective role in the brain. This protective role can be attributed to the regulation of iron metabolism of nerve cells, reduction of iron deposition in the hippocampus and lowering the level of lipid peroxidation. [ABSTRACT FROM AUTHOR]

There is evidence that kombucha beverage (KB), a traditional fermented beverage, has a preventive effect on experimental brain ischemia. According to our previous studies, pre-treatment of KB attenuates brain edema and improves motor skills and oxidative stress in a rat model of global brain ischemia. This study was designed to evaluate the effects of the pre-treatment of KB, as a novel agent, on pro-inflammatory parameters and brain histopathology changes following global brain ischemia. Adult male Wistar rats were randomly divided into the sham, the control, and the groups treated with kombucha (KB1 and KB2 groups). KB at doses 1 and 2 mL/kg was prescribed two-week consecutive days before induction of global brain ischemia. Global brain ischemia was induced by blocking common carotid arteries for 60 min and the following reperfusion by 24 h. The serum and brain levels of tumor necrosis factor-α(TNF-α), IL-1β, histopathological change, and infarct volume are determined using the ELISA, hematoxylin and eosin (H&E), and 2,3,5-triphenyl tetrazolium chloride (TTC) staining, respectively. This study indicated that pre-treatment of KB significantly reduced infarct volume, the serum, and brain levels of TNF-α and IL-1β. The histopathological finding of the brain tissue confirmed a protective role for pre-treatment KB in the ischemic rats. Thus, the present study showed that the beneficial effects of KB pre-treatment on brain ischemic may be mediated by decreasing pro-inflammatory parameters. [ABSTRACT FROM AUTHOR]

Copyright of Czech Radiology / Ceska Radiologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cerebral ischemia may lead to axonal injury not only at the site of the primary lesion but also in a region remote to the site of insult. In this study, we investigated the effect of herniation on the development of axonal injury at a site remote to the primary lesion during the acute phase of cerebral ischemia. We obtained postmortem brains of 13 cases with acute phase of unilateral cerebral infarction in the territory of the internal carotid artery or middle cerebral artery and seven controls. We classified the brain tissues into herniation and non‐herniation groups. Then we examined whether axonal and ischemic changes existed in the corpus callosum contralateral to the ischemic hemisphere and the upper pons. In the herniation group, we detected white‐matter lesions by Klüver‐Barrera staining, microglial loss by immunohistochemistry for ionized calcium‐binding adaptor molecule 1, and axonal injury by immunohistochemistry for amyloid precursor protein. However, none of the aforementioned findings were observed in the non‐herniation group. These findings suggest the existence of regional overlap in axonal and ischemic pathologies in remote regions in the presence of herniation. We concluded that herniation may play a significant role in the development of axonal and ischemic changes in the remote region. Our results suggest that axonal injury in a remote region may result from expanded ischemic lesions due to herniation. [ABSTRACT FROM AUTHOR]

Autophagy is a self-defense and self-degrading intracellular system involved in the recycling and elimination of the payload of cytoplasmic redundant components, aggregated or misfolded proteins and intracellular pathogens to maintain cell homeostasis and physiological function. Autophagy is activated in response to metabolic stress or starvation to maintain homeostasis in cells by updating organelles and dysfunctional proteins. In neurodegenerative diseases, such as cerebral ischemia, autophagy is disturbed, e.g., as a result of the pathological accumulation of proteins associated with Alzheimer's disease and their structural changes. Postischemic brain neurodegeneration, such as Alzheimer's disease, is characterized by the accumulation of amyloid and tau protein. After cerebral ischemia, autophagy was found to be activated in neuronal, glial and vascular cells. Some studies have shown the protective properties of autophagy in postischemic brain, while other studies have shown completely opposite properties. Thus, autophagy is now presented as a double-edged sword with possible therapeutic potential in brain ischemia. The exact role and regulatory pathways of autophagy that are involved in cerebral ischemia have not been conclusively elucidated. This review aims to provide a comprehensive look at the advances in the study of autophagy behavior in neuronal, glial and vascular cells for ischemic brain injury. In addition, the importance of autophagy in neurodegeneration after cerebral ischemia has been highlighted. The review also presents the possibility of modulating the autophagy machinery through various compounds on the development of neurodegeneration after cerebral ischemia. [ABSTRACT FROM AUTHOR]

Copyright of Tianjin Medical Journal is the property of Tianjin Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The association between high cardiac troponin (cTn) levels and stroke characteristics and outcomes remains unclear. This systematic review aimed to determine the prevalence and clinical implications of elevated cTn levels in patients with acute ischemic stroke (AIS). We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta analysis (PRISMA) 2020 guidelines. A comprehensive search of PubMed, Google Scholar, Science Direct, and Research Gate databases was conducted to identify relevant studies published in English up to May 2023. This study included all reports on serum cTn levels and AIS. Two independent reviewers assessed study quality and bias using study specific tools before inclusion. The systematic review included a total of 14 articles with 16906 participants, including one systematic review, one randomized controlled trial (RCT), and 12 observational studies. The results of this systematic review indicate that the prevalence of high cTn levels is averaged at 17.9%, or 1 in 5 individuals, who have an AIS. The review emphasizes the detrimental effects of increased cTn levels on outcomes for in hospital and all cause mortality as well as cardiovascular outcomes in patients with AIS. These results demonstrate that serum cTn has the potential to be a useful tool for risk classification and prognostic assessment in individuals with AIS. AIS patients with elevated serum cTn at baseline have an increased risk of mortality. Early and routine evaluation of serum cTn may contribute to the timely detection of co morbid cardiovascular injury and prevent unfavorable outcomes in patients with AIS. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Jilin University (Medicine Edition) is the property of Jilin University Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Neurodegeneration of the brain after ischemia is a major cause of severe, long-term disability, dementia, and mortality, which is a global problem. These phenomena are attributed to excitotoxicity, changes in the blood–brain barrier, neuroinflammation, oxidative stress, vasoconstriction, cerebral amyloid angiopathy, amyloid plaques, neurofibrillary tangles, and ultimately neuronal death. In addition, genetic factors such as post-ischemic changes in genetic programming in the expression of amyloid protein precursor, β-secretase, presenilin-1 and -2, and tau protein play an important role in the irreversible progression of post-ischemic neurodegeneration. Since current treatment is aimed at preventing symptoms such as dementia and disability, the search for causative therapy that would be helpful in preventing and treating post-ischemic neurodegeneration of Alzheimer's disease proteinopathy is ongoing. Numerous studies have shown that the high contents of flavonoids and phenolic acids in honey have antioxidant, anti-inflammatory, anti-apoptotic, anti-amyloid, anti-tau protein, anticholinesterase, serotonergic, and AMPAK activities, influencing signal transmission and neuroprotective effects. Notably, in many preclinical studies, flavonoids and phenolic acids, the main components of honey, were also effective when administered after ischemia, suggesting their possible use in promoting recovery in stroke patients. This review provides new insight into honey's potential to prevent brain ischemia as well as to ameliorate damage in advanced post-ischemic brain neurodegeneration. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDs) affect millions of people worldwide, and to date, Alzheimer's and Parkinson's diseases are the most common NDs. Of the many risk factors for neurodegeneration, the aging process has the most significant impact, to the extent that it is tempting to consider neurodegenerative disease as a manifestation of accelerated aging. However, genetic and environmental factors determine the course of neurodegenerative disease progression. It has been proposed that environmental stimuli influence neuroplasticity. Some clinical studies have shown that healthy lifestyles and the administration of nutraceuticals containing bioactive molecules possessing antioxidant and anti-inflammatory properties have a preventive impact or mitigate symptoms in previously diagnosed patients. Despite ongoing research efforts, the therapies currently used for the treatment of NDs provide only marginal therapeutic benefits; therefore, the focus is now directly on the search for natural products that could be valuable tools in combating these diseases, including the natural compound Andrographis paniculata (Ap) and its main constituent, andrographolide (Andro). Preclinical studies have shown that the aqueous extract of Ap can modulate neuroinflammatory and neurodegenerative responses, reducing inflammatory markers and oxidative stress in various NDs. Therefore, in this review, we will focus on the molecular mechanisms by which Ap and Andro can modulate the processes of neurodegeneration and neuroinflammation, which are significant causes of neuronal death and cognitive decline. [ABSTRACT FROM AUTHOR]

Background: The neurointensive care management of patients with aneurysmal subarachnoid hemorrhage (aSAH) is one of the most critical components contributing to short-term and long-term patient outcomes. Previous recommendations for the medical management of aSAH comprehensively summarized the evidence based on consensus conference held in 2011. In this report, we provide updated recommendations based on appraisal of the literature using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Methods: The Population/Intervention/Comparator/Outcome (PICO) questions relevant to the medical management of aSAH were prioritized by consensus from the panel members. The panel used a custom-designed survey instrument to prioritize clinically relevant outcomes specific to each PICO question. To be included, the study design qualifying criteria were as follows: prospective randomized controlled trials (RCTs), prospective or retrospective observational studies, case–control studies, case series with a sample larger than 20 patients, meta-analyses, restricted to human study participants. Panel members first screened titles and abstracts, and subsequently full text review of selected reports. Data were abstracted in duplicate from reports meeting inclusion criteria. Panelists used the Grading of Recommendations Assessment, Development, and Evaluation Risk of Bias tool for assessment of RCTs and the "Risk of Bias In Nonrandomized Studies – of Interventions" tool for assessment of observational studies. The summary of the evidence for each PICO was presented to the full panel, and then the panel voted on the recommendations. Results: The initial search retrieved 15,107 unique publications, and 74 were included for data abstraction. Several RCTs were conducted to test pharmacological interventions, and we found that the quality of evidence for nonpharmacological questions was consistently poor. Five PICO questions were supported by strong recommendations, one PICO question was supported by conditional recommendations, and six PICO questions did not have sufficient evidence to provide a recommendation. Conclusions: These guidelines provide recommendations for or against interventions proven to be effective, ineffective, or harmful in the medical management of patients with aSAH based on a rigorous review of the available literature. They also serve to highlight gaps in knowledge that should guide future research priorities. Despite improvements in the outcomes of patients with aSAH over time, many important clinical questions remain unanswered. [ABSTRACT FROM AUTHOR]

The aim of this review is to present evidence of the impact of ischemic changes in the blood–brain barrier on the maturation of post-ischemic brain neurodegeneration with features of Alzheimer's disease. Understanding the processes involved in the permeability of the post-ischemic blood–brain barrier during recirculation will provide clinically relevant knowledge regarding the neuropathological changes that ultimately lead to dementia of the Alzheimer's disease type. In this review, we try to distinguish between primary and secondary neuropathological processes during and after ischemia. Therefore, we can observe two hit stages that contribute to Alzheimer's disease development. The onset of ischemic brain pathology includes primary ischemic neuronal damage and death followed by the ischemic injury of the blood–brain barrier with serum leakage of amyloid into the brain tissue, leading to increased ischemic neuronal susceptibility to amyloid neurotoxicity, culminating in the formation of amyloid plaques and ending in full-blown dementia of the Alzheimer's disease type. [ABSTRACT FROM AUTHOR]

A transient ischemic attack (TIA), a constellation of temporary neurological symptoms, precedes stroke in one-fifth of patients. Thus far, many clinical models have been introduced to optimize the quality, time to treatment, and cost of acute TIA care, either in an inpatient or outpatient setting. In this article, we aim to review the characteristics and outcomes of outpatient TIA clinics across the globe. In addition, we discussed the main challenges for outpatient management of TIA, including triage and diagnosis, and the system dynamics of the clinics. We further reviewed the potential developments in TIA care, such as telemedicine, predictive analytics, personalized medicine, and advanced imaging. [ABSTRACT FROM AUTHOR]

Carotid free-floating thrombus (CFFT) is significantly associated with ischemic stroke. Thrombosis occludes the artery or falls off, leading to massive cerebral infarction or multiple embolism. In severe cases, cerebral hernia or even death may occur. The diagnosis of CFFT is gradually based on CT angiography (CTA). Early identification can help in etiological treatment. This article reviews the progress of the diagnosis and treatment of CFFT, in order to improve chinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

The article examines modern views on the pathogenesis and clinical manifestations of chronic cerebral ischemia (CCI) and the possibilities of their pharmacotherapy. From this point of view, the requirements for choosing the optimal pharmacological strategy for pathological changes in the brain during ischemia are analyzed. The main goals of the clinical application of the strategy of neuroprotection in general, and in particular the need for a simultaneous effect on the neuronal, neurotransmitter and vascular mechanisms of the development of cognitive and general brain symptoms are considered. The necessity of using membrane-protective, cholinergic and vasotropic type of action is well-founded. In this regard, the risks of polypharmacy in such patients and the arguments in favor of prescribing combined drugs were analyzed. The advantages of the innovative domestic combination containing citicoline and ginkgo biloba extract are considered in detail. The mechanisms of action and clinical effects of these components are analyzed with an emphasis on the prospects of their use in general medical practice. Special attention is paid to the justification of new opportunities provided by the synergistic effect of citicoline and ginkgo biloba extract when they are used in the form of a combined dosage form in comparison with monotherapy with these agents. The data on the safety of the use of the specified combination, as well as the scheme of dosage and course regimens, are given. The combination of citicoline + ginkgo biloba extract opens up new opportunities for family doctors in the pharmacotherapy of early cerebral vascular insufficiency symptoms. [ABSTRACT FROM AUTHOR]

Aim: The neurons are the cells most susceptible to ischemic events. The exact mechanisms of cellular damage due to hypoxia and ischemia and the role of cytochrome c in this case have not been fully explained in detail. The aim of this study was to investigate cytochrome c in patients with acute ischemic stroke. Materials and Methods: The cytochrome c levels in venous blood received from 56 patients with acute ischemic stroke admitted to our hospital neurology clinic and 30 healthy volunteers have been studied. Infarct volume and arrival of patients with acute ischemic stroke were also recorded in the NIHSS. Results: There was no significant difference between the two groups. In addition, there was no statistical association between cytochrome c levels and infarct volume and arrival NIHSS in patients with acute ischemic stroke. Conclusion: Cytochrome c plays a very important role in complex cascades in the process leading to neuronal death from acute brain vascular occlusion. Brain ischemia; endogenous neuroprotective mechanisms are activated, and cytochrome c is removed from the environment and kept within normal limits. In addition, blood cytochrome c levels in patients with acute ischemic stroke are not a biochemical marker for the diagnosis and the severity of disease. [ABSTRACT FROM AUTHOR]

The genetic transcription profile of brain ischemic and reperfusion injury remains elusive. To address this, we used an integrative analysis approach including differentially expressed gene (DEG) analysis, weighted-gene co-expression network analysis (WGCNA), and pathway and biological process analysis to analyze data from the microarray studies of nine mice and five rats after middle cerebral artery occlusion (MCAO) and six primary cell transcriptional datasets in the Gene Expression Omnibus (GEO). (1) We identified 58 upregulated DEGs with more than 2-fold increase, and adj. p < 0.05 in mouse datasets. Among them, Atf3, Timp1, Cd14, Lgals3, Hmox1, Ccl2, Emp1, Ch25h, Hspb1, Adamts1, Cd44, Icam1, Anxa2, Rgs1, and Vim showed significant increases in both mouse and rat datasets. (2) Ischemic treatment and reperfusion time were the main confounding factors in gene profile changes, while sampling site and ischemic time were not. (3) WGCNA identified a reperfusion-time irrelevant and inflammation-related module and a reperfusion-time relevant and thrombo-inflammation related module. Astrocytes and microglia were the main contributors of the gene changes in these two modules. (4) Forty-four module core hub genes were identified. We validated the expression of unreported stroke-associated core hubs or human stroke-associated core hubs. Zfp36 mRNA was upregulated in permanent MCAO; Rhoj, Nfkbiz, Ms4a6d, Serpina3n, Adamts-1, Lgals3, and Spp1 mRNAs were upregulated in both transient MCAO and permanent MCAO; and NFKBIZ, ZFP3636, and MAFF proteins, unreported core hubs implicated in negative regulation of inflammation, were upregulated in permanent MCAO, but not in transient MCAO. Collectively, these results expand our knowledge of the genetic profile involved in brain ischemia and reperfusion, highlighting the crucial role of inflammatory disequilibrium in brain ischemia. [ABSTRACT FROM AUTHOR]

Brain ischemia is one of the leading causes of death and long-term disability in the world. Interruption of the blood supply to the brain is a direct stimulus for many pathological events. The massive vesicular release of glutamate (Glu) after ischemia onset induces excitotoxicity, which is a potent stress on neurons. Loading of presynaptic vesicles with Glu is the first step of glutamatergic neurotransmission. Vesicular glutamate transporters 1, 2, and 3 (VGLUT1, 2, and 3) are the main players involved in filling presynaptic vesicles with Glu. VGLUT1 and VGLUT2 are expressed mainly in glutamatergic neurons. Therefore, the possibility of pharmacological modulation to prevent ischemia-related brain damage is attractive. In this study, we aimed to determine the effect of focal cerebral ischemia on the spatiotemporal expression of VGLUT1 and VGLUT2 in rats. Next, we investigated the influence of VGLUT inhibition with Chicago Sky Blue 6B (CSB6B) on Glu release and stroke outcome. The effect of CSB6B pretreatment on infarct volume and neurological deficit was compared with a reference model of ischemic preconditioning. The results of this study indicate that ischemia upregulated the expression of VGLUT1 in the cerebral cortex and in the dorsal striatum 3 days after ischemia onset. The expression of VGLUT2 was elevated in the dorsal striatum and in the cerebral cortex 24 h and 3 days after ischemia, respectively. Microdialysis revealed that pretreatment with CSB6B significantly reduced the extracellular Glu concentration. Altogether, this study shows that inhibition of VGLUTs might be a promising therapeutic strategy for the future. [ABSTRACT FROM AUTHOR]