Depolarization time and extracellular glutamate levels aggravate ultraearly brain injury after subarachnoid hemorrhage

Satoshi Murai, Tomohito Hishikawa, Yoshimasa Takeda, Yasuko Okura, Miki Fushimi, Hirokazu Kawase, Yu Takahashi, Naoya Kidani, Jun Haruma, Masafumi Hiramatsu, Kenji Sugiu, Hiroshi Morimatsu, Isao Date

Research output: Contribution to journalArticlepeer-review

Abstract

Early brain injury after aneurysmal subarachnoid hemorrhage (SAH) worsens the neurological outcome. We hypothesize that a longer duration of depolarization and excessive release of glutamate aggravate neurological outcomes after SAH, and that brain hypothermia can accelerate repolarization and inhibit the excessive release of extracellular glutamate and subsequent neuronal damage. So, we investigated the influence of depolarization time and extracellular glutamate levels on the neurological outcome in the ultra-early phase of SAH using a rat injection model as Experiment 1 and then evaluated the efficacy of brain hypothermia targeting ultra-early brain injury as Experiment 2. Dynamic changes in membrane potentials, intracranial pressure, cerebral perfusion pressure, cerebral blood flow, and extracellular glutamate levels were observed within 30 min after SAH. A prolonged duration of depolarization correlated with peak extracellular glutamate levels, and these two factors worsened the neuronal injury. Under brain hypothermia using pharyngeal cooling after SAH, cerebral perfusion pressure in the hypothermia group recovered earlier than that in the normothermia group. Extracellular glutamate levels in the hypothermia group were significantly lower than those in the normothermia group. The early induction of brain hypothermia could facilitate faster recovery of cerebral perfusion pressure, repolarization, and the inhibition of excessive glutamate release, which would prevent ultra-early brain injury following SAH.

Original languageEnglish
Article number10256
JournalScientific reports
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2022

ASJC Scopus subject areas

  • General

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