In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 6 ( 2021-6-3), p. e0252584-
Abstract:
Intracerebral hemorrhage (ICH) is a devastating insult with few effective treatments. Edema and raised intracranial pressure contribute to poor outcome after ICH. Glibenclamide blocks the sulfonylurea 1 transient receptor potential melastatin 4 (Sur1-Trpm4) channel implicated in edema formation. While glibenclamide has been found to improve outcome and reduce mortality in animal models of severe ischemic stroke, in ICH the effects are less clear. In our previous study, we found no benefit after a moderate-sized bleed, while others have reported benefit. Here we tested the hypothesis that glibenclamide may only be effective in severe ICH, where edema is an important contributor to outcome. Glibenclamide (10 μg/kg loading dose, 200 ng/h continuous infusion) was administered 2 hours post-ICH induced by collagenase injection into the striatum of adult rats. A survival period of 24 hours was maintained for experiments 1–3, and 72 hours for experiment 4. Glibenclamide did not affect hematoma volume (~81 μL) or other safety endpoints (e.g., glucose levels), suggesting the drug is safe. However, glibenclamide did not lessen striatal edema (~83% brain water content), ionic dyshomeostasis (Na + , K + ), or functional impairment (e.g., neurological deficits (median = 10 out of 14), etc.) at 24 hours. It also did not affect edema at 72 h (~86% brain water content), or overall mortality rates (25% and 29.4% overall in vehicle vs. glibenclamide-treated severe strokes). Furthermore, glibenclamide appears to worsen cytotoxic edema in the peri-hematoma region (cell bodies were 46% larger at 24 h, p = 0.0017), but no effect on cell volume or density was noted elsewhere. Overall, these findings refute our hypothesis, as glibenclamide produced no favorable effects following severe ICH.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0252584
DOI:
10.1371/journal.pone.0252584.g001
DOI:
10.1371/journal.pone.0252584.g002
DOI:
10.1371/journal.pone.0252584.g003
DOI:
10.1371/journal.pone.0252584.g004
DOI:
10.1371/journal.pone.0252584.g005
DOI:
10.1371/journal.pone.0252584.g006
DOI:
10.1371/journal.pone.0252584.g007
DOI:
10.1371/journal.pone.0252584.g008
DOI:
10.1371/journal.pone.0252584.g009
DOI:
10.1371/journal.pone.0252584.g010
DOI:
10.1371/journal.pone.0252584.s001
DOI:
10.1371/journal.pone.0252584.s002
DOI:
10.1371/journal.pone.0252584.r001
DOI:
10.1371/journal.pone.0252584.r002
DOI:
10.1371/journal.pone.0252584.r003
DOI:
10.1371/journal.pone.0252584.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
