INDUCTION OF SPREADING DEPRESSION IN THE ISCHEMIC HEMISPHERE FOLLOWING EXPERIMENTAL MIDDLE CEREBRAL-ARTERY OCCLUSION - EFFECT ON INFARCT MORPHOLOGY

This study was undertaken to test whether transient depolarizations oc curring in periinfarct regions are important in contributing to infarc t spread and maturation. Following middle cerebral artery (MCA) occlus ion we stimulated the ischemic penumbra with recurrent waves of spread ing depression (SD) and correlated the histopathological changes with the electrophysiological recordings. Halothane-anesthetized, artificia lly ventilated Sprague-Dawley rats underwent repetitive stimulation of SD in intact brain (Group 1 ; n = 8) or photothrombotic MCA occlusion coupled with ipsilateral common carotid artery occlusion (Groups 2 an d 3, n = 9 each), The electroencephalogram and direct current (DC) pot ential were recorded for 3 h in the parietal cortex, which represented the periinfarct border zone in ischemic rats. In Group 2, only sponta neously occurring negative DC shifts occurred; in Group 3, the (nonisc hemic) frontal pole of the ischemic hemisphere was electrically stimul ated to increase the frequency of periinfarct DC shifts. Animals under went perfusion-fixation 24 h later, and volumes of complete infarction and scattered neuronal injury (''incomplete infarction'') were assess ed on stained coronal sections by quantitative planimetry. Electrical induction of SD in Group 1 did not cause morphological injury. During the initial 3 h following MCA occlusion, the number of spontaneous per iinfarct depolarizations in Group 2 (7.0 +/- 1.5 DC shifts) was double d in Group 3 by frontal current application(l3.4 +/- 2.7 DC shifts; p < 0.001). The duration as well as the integrated negative amplitude of DC shifts over time were significantly greater in Group 3 than in Gro up 2 rats (duration, 5.7 +/- 3.8 vs, 4.1 +/- 2.5 min; p < 0.05). Histo pathological examination disclosed well-defined areas of pannecrosis s urrounded by a cortical rim exhibiting selectively damaged acidophilic neurons and astrocytic swelling in otherwise normal-appearing brain. Induction of SD in the ischemic hemisphere led to a significant increa se in the volume of incomplete infarction (19.0 +/- 6.1 mm(3) in Group 3 vs. 10.3 +/- 5.1 mm(3) in Group 2; p < 0.01) and of total ischemic injury (100.7 +/- 41.0 mm(3) in Group 3 vs. 66.5 +/- 24.7 mm(3) in Gro up 2; p < 0.05). The integrated magnitude of DC negativity per experim ent correlated significantly with the volume of total ischemic injury (r = 0.780, p < 0.0001). Thus, induction of SD in the ischemic hemisph ere accentuated the development of scattered neuronal injury and incre ased the volume of total ischemic injury. This observation may be expl ained by the fact that, with limited perfusion reserve, periinfarct de polarizations are associated with episodic energy failure in the acute ischemic penumbra.