Induction of Spreading Depression in the Ischemic Hemisphere following Experimental Middle Cerebral Artery Occlusion: Effect on Infarct Morphology

Abstract

Summary: This study was undertaken to test whether transient depolarizations occurring in periinfarct regions are important in contributing to infarct spread and matu ration. Following middle cerebral artery (MCA) occlusion we stimulated the ischemic penumbra with recurrent waves of spreading depression (SD) and correlated the histopathological changes with the electrophysiological recordings. Halothane-anesthetized, artificially venti lated Sprague-Dawley rats underwent repetitive stimula tion of SD in intact brain (Group 1; n = 8) or photothrom botic MCA occlusion coupled with ipsilateral common carotid artery occlusion (Groups 2 and 3, n = 9 each). The electroencephalogram and direct current (DC) poten tial were recorded for 3 h in the parietal cortex, which represented the periinfarct border zone in ischemic rats. In Group 2, only spontaneously occurring negative DC shifts occurred; in Group 3, the (nonischemic) frontal pole of the ischemic hemisphere was electrically stimu lated to increase the frequency of periinfarct DC shifts. Animals underwent perfusion-fixation 24 h later, and vol umes of complete infarction and scattered neuronal injury ("incomplete infarction") were assessed on stained coro nal sections by quantitative planimetry. Electrical induc tion of SD in Group 1 did not cause morphological injury. During the initial 3 h following MCA occlusion, the num ber of spontaneous periinfarct depolarizations in Group 2 (7.0 ± 1.5 DC shifts) was doubled in Group 3 by frontal

Transient Changes in Cortical Glucose and Lactate Levels Associated with Peri-Infarct Depolarisations, Studied with Rapid-Sampling Microdialysis

“…A downward trend in glucose concentration is maintained at 3 h ( þ : 180 versus 20 mins, t (paired) ¼ 3.075, P ¼ 0.0133), whereas lactate appears more stable. (Takano et al, 1996;Busch et al, 1996;Back et al, 1996), and do so incrementally (because infarct size is proportional to the number of PIDs; Mies et al, 1993).…”

“…These events-periinfarct depolarisations (PIDs)-appear to arise principally at the edge of the core area and spread into the peri-infarct zone (Strong et al, 1996). A role for PIDs as a cause rather than simply as a marker of the progression of infarct growth has been indicated by the positive correlation between number of PID events and infarct size (Gill et al, 1992;Chen et al, 1993;Mies et al, 1993) and, critically, by the demonstration that induction of depolarisations within or adjacent to the penumbra can enlarge the infarct (Back et al, 1996;Busch et al, 1996;Takano et al, 1996).…”

The Utility of EEG, SSEP, and Other Neurophysiologic Tools to Guide Neurocritical Care

“…In rodent models of experimental ischemia, CSD resulted in reduced cerebral blood flow [76] and increased infarct volume [77]. In human studies, cortical spreading depression has been associated with metabolic stress and injury, as measured by elevation in glutamate and lactate/pyruvate ratio, as well as low brain tissue oxygenation [78].…”

Dynamic Changes in Brain Glucose and Lactate in Pericontusional Areas of the Human Cerebral Cortex, Monitored with Rapid Sampling On-Line Microdialysis: Relationship with Depolarisation-Like Events

“…Second, studies of the effects of MCAO in several animal models of stroke have repeatedly yielded evidence of spontaneous events with electrophysiological features similar to those of CSD, but, probably unlike CSD, with proven capacity to augment ischemic damage-PIDs (Back et al, 1996;Busch et al, 1996;Takano et al, 1996). The potential contribution of depolarisation events spreading in the injured cerebral cortex to adverse outcome from acute brain injury in humans is discussed in a review (Strong and Dardis, 2005).…”

“…Subsequently, we applied the method in perilesion cerebral cortex in patients requiring emergency craniotomy for traumatic or spontaneous intracerebral haematoma. Specifically, we reasoned that since peri-infarct depolarisations (PIDs) are a prominent feature of the penumbra in experimental MCAO in non-human primates (Branston et al, 1977;Strong et al, 2000), in the cat (Saito et al, 1995;Strong et al, 1983) and in the rat (Gill et al, 1992;Iijima et al, 1992;Nedergaard and Astrup, 1986) and contribute to its gradual recruitment into the core territory (Back et al, 1996;Busch et al, 1996;Takano et al, 1996), we should first apply rsMD experimentally to characterise the time course of dialysate glucose and lactate in the penumbra, with special reference to PIDs. In this report, we describe our subsequent experience with the application of the same method in 11 patients, with the aim of rapidly and automatically acquiring glucose and lactate time series data for two purposes.…”