IONIC BASIS OF ISCHEMIC CEREBRAL EDEMA

Large tissue net ionic shifts are associated with cerebral edema after middle cerebral artery occlusion (MCAo). The net ionic shifts correlate highly with water concentration changes with regression slopes of 150-160 mu moles/ml, close to plasma ionic concentrations, suggesting that ionic shifts caused edema since participation of other osmotic agents would reduce the slope. The causes of the net ionic shift are not known. We will test the hypotheses that (a) net ionic shifts result from differences in extracellular Na and K gradients driving Na entry and K loss and (b) glial K uptake causes different in the Na and K gradients. Extracellular Na and K will be measured with ion-selective microelectrodes after MCAo and compared with tissue ionic and water shifts. Albumen and IgG passage across the blood brain barrier, regional blood flow, blood pressure, and plasma ionic levels will be monitored. Ionic shifts will be investigated in rat cortical freeze lesions. Freezing disrupts glial cells, prevent K uptake, and thereby should reduce net ionic shift and edema. The effects of systemic furosemide, mannitol, and/or methylprednisolone on extracellular and tissue ionic shifts will be studied in the rat MCAo and cortical freeze models. Neurophysiological and morphological changes will be correlated with ionic shifts. These studies will clarify ionic mechanisms in edema, relate tissue ionic shifts to tissue damage, and establish rational bases for treating ionic edema in stroke.