NEUROBEHAVIORAL CONSEQUENCES OF INDUCED SPREADING DEPRESSION FOLLOWING PHOTOTHROMBOTIC MIDDLE CEREBRAL-ARTERY OCCLUSION

In a model of experimental focal cerebral ischemia, we have recently r eported a strong correlation between the magnitude of ischemic depolar izations in the peri-infarct borderzone and the extent of histological injury. In the present study, we assessed the neurobehavioral consequ ences of spontaneously occurring and induced ischemic depolarizations in rats following middle cerebral artery (MCA) occlusion, as well as t he effects of induced spreading depression (SD) in intact animals. Hal othane-anesthetized, artificially ventilated Sprague-Dawley rats under went photothrombotic MCA occlusion coupled with ipsilateral common car otid artery (CCA) occlusion. The electroencephalogram and direct curre nt (DC) potential were recorded in the parietal infarct borderzone-cor responding to the cortical forelimb area-for 3 h following MCA occlusi on. Group 1 rats (n = 9) received MCA/CCA occlusion, and the spontaneo usly occurring negative DC shifts were recorded in the ischemic border zone. In Group 2 animals (n = 9), the (non-ischemic) frontal pole of t he ipsilateral hemisphere was electrically stimulated in order to doub le the frequency of peri-infarct DC shifts occurring over the initial 3 h postocclusion. Group 3 consisted of intact rats (n = 3) in which S D was repeatedly evoked in the frontal pole. Four animals served as sh am-operated controls. A battery of sensorimotor behavioral tests, cons isting of beam balance, postural reflex and elicited forelimb placing, was applied in a blinded fashion. Sham controls and animals of Groups 1 and 2 were tested 24 h after surgery, and Group 3 rats were tested 2, 6 and 24 h after generation of SDs. A cumulative neurobehavioral in dex, ranging from 0 to 144, was calculated by adding the individual te st results. Brains were perfusion-fixed 24 h following surgery for cal culation of volumes of infarction and scattered neuronal injury. Funct ional outcome at 24 h was significantly worse in Group 2 animals (spon taneous plus induced ischemic depolarizations) (neurobehavior index 43 +/- 19, mean +/- S.D.) compared to Group 1 rats, in which only sponta neous depolarizations occurred (neurobehavior index 24 +/- 19, P < 0.0 5). The cumulative neurobehavioral index of Group 1 and 2 animals corr elated positively with the volume of total ischemic injury (r = 0.765, P < 0.001) and with the frequency of ischemic depolarizations (r = 0. 474, P < 0.05). Correlations between severe forelimb placing deficits and severe degrees of histological injury (necrosis or ischemic cell c hange) in the corresponding primary sensorimotor cortical region FR1 w ere significant in these rats. Group 3 rats showed severe neurobehavio ral deficits at 2 and 6 h following SD stimulation (index 57 +/- 1 and 39 +/- 1, respectively) but returned to normal at 24 h (4 +/- 0). The findings indicate that cortical spreading depression is accompanied b y transient neurobehavioral deterioration and that SD in the ischemic hemisphere of animals subjected to MCA occlusion worsened functional o utcome 24 h after surgery.