Memantine inhibits cortical spreading depolarization and improves neurovascular function following repetitive traumatic brain injury

Mark A. MacLean, Jamil H. Muradov, Ryan Greene, Gerben Van Hameren, David B. Clarke, Jens P. Dreier, David O. Okonkwo, Alon Friedman

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Cortical spreading depolarization (CSD) is a promising target for neuroprotective therapy in traumatic brain injury (TBI). We explored the effect of NMDA receptor antagonism on electrically triggered CSDs in healthy and brain-injured animals. Rats received either one moderate or four daily repetitive mild closed head impacts (rmTBI). Ninety-three animals underwent craniectomy with electrocorticographic (ECoG) and local blood flow monitoring. In brain-injured animals, ketamine or memantine inhibited CSDs in 44 to 88% and 50 to 67% of cases, respectively. Near-DC/AC-ECoG amplitude was reduced by 44 to 75% and 52 to 67%, and duration by 39 to 87% and 61 to 78%, respectively. Daily memantine significantly reduced spreading depression and oligemia following CSD. Animals (N = 31) were randomized to either memantine (10 mg/kg) or saline with daily neurobehavioral testing. Memantine-treated animals had higher neurological scores. We demonstrate that memantine improved neurovascular function following CSD in sham and brain-injured animals. Memantine also prevented neurological decline in a blinded, preclinical randomized rmTBI trial.

Original languageEnglish
Article numbereadj2417
JournalScience advances
Volume9
Issue number50
DOIs
StatePublished - 1 Dec 2023

ASJC Scopus subject areas

  • General

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