Severe hypoglycemia induces brain edema by upregulating aquaporin-4 (AQP4) expression and by degrading tight junctions. Acute severe hypoglycemia induces a proinflammatory environment that may contribute to a disruption in the epithelial barrier by decreasing tight junction protein expression. Interestingly, the altered AQP4 expression has been considered to play a critical role in neuroinflammation during acute brain injury. It has been shown that AQP4 deletion reduces brain inflammation in AQP4-null mice after intracerebral LPS injection. However, the effect of AQP4 deletion regarding protection against hypoglycemia-induced blood-brain barrier (BBB) breakdown is unknown. An acute severe hypoglycemic stress model was established via injection of 4 unit/kg body weight of insulin. Evans blue (EB) staining and water measurement were used to assess BBB permeability. Western blot, reverse transcription polymerase chain reaction, and immunofluorescence were used to detect the expression of related proteins. The production of cytokines was assessed via enzyme-linked immunosorbent assay. Hypoglycemia-induced brain edema and BBB leakage were reduced in AQP4−/− mice. AQP4 deletion upregulated PPAR-γ and inhibited proinflammatory responses. Moreover, knockdown of aquaporin-4 by small interfering RNA in astrocytes co-cultured with endothelial cells effectively reduced transendothelial permeability and degradation of tight junctions. Treatment with PPAR-γ inhibitors showed that upregulation of PPAR-γ was responsible for the protective effect of AQP4 deletion under hypoglycemic conditions. Our data suggest that AQP4 deletion protects BBB integrity by reducing inflammatory responses due to the upregulation of PPAR-γ expression and attenuation of proinflammatory cytokine release. Reduction in AQP4 may be protective in acute severe hypoglycemia.

Thrombus enhancement can be used to predict cardioembolic and cryptogenic strokes and to identify thrombus enhancement–positive thrombi, which have a higher fibrin-to-platelet fraction and a lower ... Background Thrombus enhancement (TE) in large vessel occlusion in patients with acute ischemic stroke can be visualized with thin-slab maximum intensity projection (TS-MIP) image reconstruction of ...

Background: ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) plays a vital role in preventing microvascular thrombosis and inflammation. Reduced ADAMTS13 levels in plasma have been detected in multiple sclerosis (MS) patients. In the present study, we have determined the role of ADAMTS13 in the disease progression of MS using a mouse model of experimental autoimmune encephalomyelitis (EAE). Methods: Female C57BL/6 mice were immunized with MOG_35–55 peptide and then treated with ADAMTS13 or vehicle in preventive and therapeutic settings. Mice were analyzed for clinical deficit, white matter demyelination and inflammatory cell infiltration. To explore the underlying mechanism, VWF expression and blood-spinal cord barriers (BSCB) were determined. Results: Plasma ADAMTS13 activity was suppressed in EAE mice. ADAMTS13-treated EAE mice exhibited an ameliorated disease course, reduced demyelination, and decreased T lymphocyte, neutrophil and monocyte infiltration into the spinal cord. Consistently, ADAMTS13 treatment reduced VWF levels and inhibited BSCB breakdown in the spinal cords of EAE mice. However, leukocytes in the blood and spleen of EAE mice remained unaffected by ADAMTS13 administration. Conclusion: Our results demonstrate that ADAMTS13 treatment ameliorates inflammatory responses, demyelination and disease course in EAE mice. Therefore, our study suggests that ADAMTS13 may represent a potential therapeutic strategy for MS patients.

BACKGROUND: We aim to assess the efficacy of rapid local ischemic postconditioning (RL-IPostC) following successful reperfusion in patients with acute ischemic stroke with anterior circulation large vessel occlusion who underwent endovascular thrombectomy. METHODS: We conducted an ambidirectional cohort study with 78 prospectively enrolled patients with RL-IPostC and endovascular thrombectomy and 129 retrospectively enrolled patients with endovascular thrombectomy. The RL-IPostC procedure involved 5 cycles of 15-s balloon inflation and deflation in the ipsilateral internal carotid artery. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0 to 2. Secondary outcomes included excellent outcomes (modified Rankin Scale score, 0–1) and early therapeutic response. Imaging outcomes involved infarct volume changes and cerebral edema measurements. Outcomes were compared with postpropensity score matching (1:1) and assessed using univariable and multivariable regression models. RESULTS: In the matched cohort of 136 patients (mean age, 71±14 years; 70 men [51%]), RL-IPostC was associated with a higher rate of functional independence (adjusted odds ratio, 2.47 [95% CI, 1.10–5.68]; P =0.030). The RL-IPostC group exhibited significantly reduced infarct volumes at 24 hours (difference, −12.2 [95% CI, −23.9 to −0.53]; P =0.041) and less infarct growth (difference, −12.2 [95% CI, −23.9 to −0.45]; P =0.042). Furthermore, RL-IPostC correlated with lower increases in net water uptake (difference, −0.04 [95% CI, −0.07 to −0.01]; P =0.018), lower decrease cerebrospinal fluid volume (difference, −7.75 [95% CI, −11.7 to −3.84]; P <0.001), and reduced midline shift at 24 hours (difference, −1.39 [95% CI, −2.48 to −0.30]; P =0.013). CONCLUSIONS: RL-IPostC tends to promote functional independence and reduces infarct growth and cerebral edema in patients with acute ischemic stroke post-reperfusion.

Background A study was undertaken to evaluate the impact of high-sensitivity cardiac troponin I (hs-cTnI) elevation and hs-cTnI dynamic changes on 90-day mortality in patients with acute ischemic stroke (AIS) treated with mechanical thrombectomy (MT). Methods Patients with AIS receiving MT were included in the study. Sixty hours after AIS onset, hs-cTnI levels were measured before and after MT to determine elevated and dynamic changes. Patients were stratified into either normal or hs-cTnI elevation groups according to the pre-MT hs-cTnI cut-off value of 0.03 ng/L. hs-cTnI dynamic changes were defined as an increase or decrease of more than 20% pre-MT and post-MT, and at least one hs-cTnI level >0.03 ng/L. Multivariate Cox regression models were used to investigate the association between hs-cTnI elevation, hs-cTnI dynamic changes, and 90-day mortality in patients with AIS after MT. Results A total of 423 patients with AIS after MT were included in our final analysis, of whom only 72 (17%) showed hs-cTnI elevation. Post-MT hs-cTnI retesting was performed in 354 patients, and 90 (25.4%) patients presented with hs-cTnI dynamic changes. 119 patients died within 90 days. After adjusting for potential confounding factors, the Cox regression model showed that patients with hs-cTnI dynamic changes, rather than hs-cTnI elevation, were associated with 90-day mortality (p0.05). Conclusions hs-cTnI dynamic changes, dominated by the rising pattern rather than hs-cTnI elevation, were independent factors associated with 90-day mortality in patients with AIS after MT, especially in elderly subjects.