As. Obeidat et Rd. Andrew, SPREADING DEPRESSION DETERMINES ACUTE CELLULAR-DAMAGE IN THE HIPPOCAMPAL SLICE DURING OXYGEN GLUCOSE DEPRIVATION/, European journal of neuroscience, 10(11), 1998, pp. 3451-3461
During ischaemia neurons depolarize and release the neurotransmitter L
-glutamate, which accumulates extracellularly and binds to postsynapti
c receptors. This initiates a sequence of events thought to culminate
in immediate and delayed neuronal death. However, there is growing evi
dence that during ischaemia the development of spreading depression (S
D) can be an important determinant of the degree and extent of ischaem
ic damage. in contrast, SD without metabolic compromise (as occurs in
migraine aura) causes no discernible damage to brain tissue. SD is a p
rofound depolarization of neurons and glia that propagates like a wave
across brain tissue. Brain cell swelling, an early event of both the
excitotoxic process and of SD, can be assessed by imaging associated i
ntrinsic optical signals (IOSs). We demonstrate here that IOS imaging
clearly demarcates the ignition site and migration of SD across the su
bmerged hippocampal slice of the rat. If SD is induced by elevating [K
+](o), the tissue fully recovers, but in slices that are metabolically
compromised at 37.5 degrees C by oxygen/glucose deprivation (OGD) or
by ouabain exposure, cellular damage develops only where SD has propag
ated. Specifically, the evoked CA1 field potential is permanently lost
, the cell bodies of involved neurons swell and their dendritic region
s increase in opacity. In contrast to OGD, bath application of L-gluta
mate (6-10 mM) at 37.5 degrees C evokes a non-propagating LT increase
in CA1 that reverses without obvious cellular damage. Moreover, applic
ation of 2-20 mM glutamate or various glutamate agonists fail to evoke
SD in the submerged hippocampal slice. We propose that SD and OGD tog
ether (but not alone) constitute a 'one-two punch', causing acute neur
onal death in the slice that is not replicated by elevated glutamate.
These findings support the proposal that SD generation during stroke p
romotes and extends acute ischaemic damage.