Electrochemical failure of the brain cortex is more deleterious when it is accompanied by low perfusion

Jens P Dreier, Ilya V Victorov, Gabor C Petzold, Sebastian Major, Olaf Windmüller, Francisco Fernández-Klett, Mahesh Kandasamy, Ulrich Dirnagl, Josef Priller

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND AND PURPOSE: Clinical and experimental evidence suggests that spreading depolarization facilitates neuronal injury when its duration exceeds a certain time point, termed commitment point. We here investigated whether this commitment point is shifted to an earlier period, when spreading depolarization is accompanied by a perfusion deficit.

METHODS: Electrophysiological and cerebral blood flow changes were studied in a rat cranial window model followed by histological and immunohistochemical analyses of cortical damage.

RESULTS: In group 1, brain topical application of artificial cerebrospinal fluid (ACSF) with high K(+) concentration ([K(+)](ACSF)) for 1 hour allowed us to induce a depolarizing event of fixed duration with cerebral blood flow fluctuations around the baseline (short-lasting initial hypoperfusions followed by hyperemia). In group 2, coapplication of the NO-scavenger hemoglobin ([Hb](ACSF)) with high [K(+)](ACSF) caused a depolarizing event of similar duration, to which a severe perfusion deficit was coupled (=spreading ischemia). In group 3, intravenous coadministration of the L-type calcium channel antagonist nimodipine with brain topical application of high [K(+)](ACSF)/[Hb](ACSF) caused spreading ischemia to revert to spreading hyperemia. Whereas scattered neuronal injury occurred in the superficial cortical layers in the window areas of groups 1 and 3, necrosis of all layers with partial loss of the tissue texture and microglial activation were observed in group 2.

CONCLUSIONS: The results suggest that electrochemical failure of the cortex is more deleterious when it is accompanied by low perfusion. Thus, the commitment point of the cortex is not a universal value but depends on additional factors, such as the level of perfusion.

Original languageEnglish
Pages (from-to)490-6
Number of pages7
JournalStroke
Volume44
Issue number2
DOIs
Publication statusPublished - 18 Jan 2013

Keywords

  • Animals
  • Cerebral Cortex
  • Cerebrovascular Circulation
  • Cortical Spreading Depression
  • Electrochemical Techniques
  • Rats
  • Journal Article
  • Research Support, Non-U.S. Gov't

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