Search

Background: Most subarachnoid hemorrhage (SAH) patients have no obvious hematoma lesions but exhibit blood–brain barrier dysfunction and vasogenic brain edema. However, there is a few days between blood‒brain barrier dysfunction and vasogenic brain edema. The present study sought to investigate whether this phenomenon is caused by endothelial injury induced by the acute astrocytic barrier, also known as the glial limitans. Methods: Bioinformatics analyses of human endothelial cells and astrocytes under hypoxia were performed based on the GEO database. Wild-type, EGLN3 and PKM2 conditional knock-in mice were used to confirm glial limitan formation after SAH. Then, the effect of endothelial EGLN3-PKM2 signaling on temporal and spatial changes in glial limitans was evaluated in both in vivo and in vitro models of SAH. Results: The data indicate that in the acute phase after SAH, astrocytes can form a temporary protective barrier, the glia limitans, around blood vessels that helps maintain barrier function and improve neurological prognosis. Molecular docking studies have shown that endothelial cells and astrocytes can promote glial limitans-based protection against early brain injury through EGLN3/PKM2 signaling and further activation of the PKC/ERK/MAPK signaling pathway in astrocytes after SAH. Conclusion: Improving the ability to maintain glial limitans may be a new therapeutic strategy for improving the prognosis of SAH patients. [ABSTRACT FROM AUTHOR]

Background: Hematoma expansion is a determinant of poor outcome of intracerebral hemorrhage but occurs frequently, especially in warfarin-associated intracerebral hemorrhage (W-ICH). In the present study, we employ the warfarin-associated intracerebral hemorrhage (W-ICH) rat model, to explore the efficacy and potential mechanism of glibenclamide pretreatment on hematoma expansion after intracerebral hemorrhage, hoping to provide proof of concept that glibenclamide in stroke primary and secondary prevention is also potentially beneficial for intracerebral hemorrhage patients at early stage. Methods: In the present study, we tested whether glibenclamide, a common hypoglycemic drug, could attenuate hematoma expansion in a rat model of W-ICH. Hematoma expansion was evaluated using magnetic resonance imaging; brain injury was evaluated by brain edema and neuronal death; and functional outcome was evaluated by neurological scores. Then blood–brain barrier integrity was assessed using Evans blue extravasation and tight junction-related protein. Results: The data indicated that glibenclamide pretreatment significantly attenuated hematoma expansion at 24 h after W-ICH, thus mitigating brain edema and neuronal death and promoting neurological function recovery, which may benefit from alleviating blood–brain barrier disruption by suppressing matrix metallopeptidase-9. Conclusions: The results indicate that glibenclamide pretreatment in stroke primary and secondary prevention might be a promising therapy for hematoma expansion at the early stage of W-ICH. [ABSTRACT FROM AUTHOR]

• Tolvaptan attenuated brain edema after intracerebral hemorrhage. • Tolvaptan alleviated neurological deficits after intracerebral hemorrhage. • Tolvaptan prevented blood brain barrier destruction after intracerebral hemorrhage. Arginine-vasopressin (AVP) is believed to be positively correlated with the brain edema formation, but the underlying mechanism is still unclear. In this study, we explored the role of the V2 receptors antagonist tolvaptan on brain edema following intracerebral hemorrhage (ICH) with a rat model. Animals were randomly given tolvaptan or vehicle through oral gavage at 12 h, 36 h, and 60 h after ICH surgery. Brain swelling (%), brain water content(BWC), neurological scores, Evans blue fluorescence and blood-brain barrier (BBB) tight junction proteins were measured to evaluate the effect of tolvaptan in ICH. We found that tolvaptan alleviated the brain swelling (%), decreased the BWC growth, and attenuated the neurological deficits after ICH (p < 0.05, vs vehicle). What's more, tolvaptan increased the expression of ZO-1 and occludin (p < 0.05, vs vehicle), which might be attributed to the down-regulated effects of tolvaptan on MMP-9. These results provided evidence supporting the use of tolvaptan for ICH-induced brain edema. Large animal experiments are required to further explore the efficacy and mechanism of tolvaptan in ICH treatment. [ABSTRACT FROM AUTHOR]