http://stroke.ahajournals.org/content/early/2013/01/03/STROKEAHA.112.660589.short
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.
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