The use of spreading depression waves for acute and long-term monitoring of the penumbra zone of focal ischemic damage in rats.

Abstract

Slow potential recording was used for longterm monitoring of the penumbra zone surrounding an ischemic region produced by middle cerebral artery (MCA) occlusion in adult hooded rats (n = 32). Four capillary electrodes were chronically implanted at 2-mm intervals from AP -3, L 2 (El) to AP 0, L 5 (E4). Spontaneous or evoked slow potential waves of spreading depression (SD) were recorded during and 4 h after a 1-h MCA occlusion and at 2-to 3-day intervals afterward for 3 weeks. Duration of the initial focal ischemic depolarization was maximal at E4 and decreased with distance from the focus. SD waves in the penumbra zone were high at El and E2, low and prolonged at E3, and almost absent at E4. Amplitude of elicited SD waves was further reduced 3 days later and slowly increased in the following week. Cortical areas displaying marked reduction of SD waves in the first days after MCA occlusion either remained low or showed substantial (60%) recovery, the probability ofwhich decreased with the duration of the initial focal ischemic depolarization and increased with the distance from the focus. It is concluded that the outcome of ischemia monitored by long-term SD recovery in the perifocal region can be partly predicted from the acute signs ofMCA occlusion.Research into Leao spreading depression (SD) (1), a selfpropagating neurohumoral reaction mediated by release of potassium ions and excitotoxic amino acids from depolarized areas of cerebral cortex, has always been tightly related to studies of electrophysiological manifestations of brain anoxia or ischemia (2, 3). The anoxic depolarization (AD) (4)

A3 adenosine receptor antagonists delay irreversible synaptic failure caused by oxygen and glucose deprivation in the rat CA1 hippocampus in vitro

“…In particular, the propagation of the AD to the hypoxic/hypoglycemic region (penumbral area) surrounding the ischaemic core may extend the damage. Consistently, it has been demonstrated that one major factor contributing to neuronal death in the penumbra is the propagation of spreading depression waves ( Koroleva & Bures, 1996 ). Because the penumbra constitutes potentially salvageable tissue, the molecular responses of the perifocal neurons to focal ischaemia and AD are of interest ( Obeidat et al ., 2000 ).…”

Distinct phases of cryogenic tissue damage in the cerebral cortex of wild‐type and c‐fos deficient mice

“…In addition, NMDA antagonists can reduce the size of the penumbra in models of both ischaemia [ 45] and traumatic brain injury [ 37]. Therefore, c‐fos expression may be a marker for the perilesional depolarization or spreading depression observed in the penumbra of ischaemic lesions, which is thought to enhance cell death by energy depletion [ 30, 35, 60]…”

Spreading Depression, Spreading Depolarizations, and the Cerebral Vasculature

“…Similarly, SD recovery in isolated retinal preparation is independent of O 2 availability, albeit with substantially elevated glucose levels (501). Moreover, pharmacological interventions that diminish the hyperemic response to SD also prolong the DC shift (155,353), and the durations of peri-infarct SDs are prolonged in hypoperfused penumbra despite relatively mild ischemia (202,229). These data suggest that tissue perfusion per se may be critical for the restoration of ionic homeostasis.…”