title: Electrochemical failure of the brain cortex is more deleterious when it is accompanied by low perfusion.
abstract: OBJECTIVE
  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.
authors.affiliation: Center for Stroke Research Berlin, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany. jens.dreier@charite.de
authors.forename: Jens P
authors.initials: JP
authors.lastname: Dreier
authors.forename: Ilya V
authors.initials: IV
authors.lastname: Victorov
authors.forename: Gabor C
authors.initials: GC
authors.lastname: Petzold
authors.forename: Sebastian
authors.initials: S
authors.lastname: Major
authors.forename: Olaf
authors.initials: O
authors.lastname: Windmüller
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernández-Klett
authors.forename: Mahesh
authors.initials: M
authors.lastname: Kandasamy
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
authors.forename: Josef
authors.initials: J
authors.lastname: Priller
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D013181:Cortical Spreading Depression / Q000502:physiology*; D055664:Electrochemical Techniques / Q000379:methods; D051381:Rats