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Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 ôg/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 ôg/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.
RESUMEN
BACKGROUND: Endovascular recanalization (ER) has demonstrated efficacy as a treatment modality for patients presenting with acute ischemic stroke (AIS) caused by large-vessel occlusion (LVO) within a 24-hour timeframe. Nevertheless, the safety and effectiveness of ER in patients with a time of onset exceeding 24 h remain uncertain. OBJECTIVE: To evaluate the safety and efficacy of ER treatment for mild ischemic stroke beyond 24-h from symptom onset. METHODS: A retrospectively maintained database of mild AIS due to LVO from March2018 to September 2022 at a comprehensive stroke center was screened.Patients received ER or standard medical therapies (SMT) for anterior circulation AIS due to LVO > 24-h were selected. RESULTS: We included 47 LVO patients with mild AIS beyond 24-h who suffered neurological deterioration (ND). 34 of these patients underwent ER, the other 13 received SMT. The technical success rate of recanalization was 82.4% (28/34). Patients received ER had significantly lower NIHSS score at discharge and 90-day mRS score (p = 0.028, p = 0.037, respectively) compared to SMT. In addition, they had significantly lower 90-day recurrence of ischemic stroke and lower incidence of moderate-severe stroke (with a NIHSS score at least 5) (p = 0.037, p = 0.033). There were 4 patients (11.7%) had perioperative complications, and no symptomatic intracranial hemorrhage occurred. CONCLUSION: ER treatment for mild AIS due to LVO encountered ND was generally safe and effective, even beyond 24-h, and resulted in a good prognosis and lower 90-day recurrence compared to SMT.
ER for mild anterior stroke might be safe and feasible, even exceeding 24-h;The proposed protocol could be used for individualized treatment decision making;Modelling for heterogeneity of treatment effect.
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Carotid-cavernous fistulas are acquired vascular lesions, representing abnormal connections caused by a direct shunt or dural branches of the internal carotid artery and/or the external carotid artery connected to the cavernous sinus. We present an interesting, rare case of a spontaneous fistula with acute vision loss in an older patient. The patient was diagnosed with a direct carotid-cavernous fistula based on the clinical and radiological findings. We concluded that early diagnosis and etiological treatment could improve the prognosis of this type of carotid-cavernous fistula.
RESUMEN
Background and Objective: The ventral attentional network (VAN) can provide quantitative information on cognitive problems in patients with major depressive disorder (MDD). Nevertheless, little is known about network homogeneity (NH) changes in the VAN of these patients. The aim of this study was to examine the NH values in the VAN by independent component analysis (ICA) and compare the NH values between MDD patients and the normal controls (NCs). Methods: Attentional network test and resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 73 patients, and 70 NCs matched by gender, age, and education years. ICA and NH were employed to evaluate the data. Moreover, the NH values were compared, and Spearman's rank correlation analysis was used to assess the correlations with the executive control reaction time (ECRT). Results: Our results showed that the first-episode, treatment-naive MDD patients had decreased NH in the right precuneus (PCu) and abnormal ECRT compared with NCs. However, no significant correlation was found between the NH values and measured clinical variables. Conclusion: Our results highlight the potential importance of VAN in the pathophysiology of cognitive problems in MDD, thus offering new directions for future research on MDD.