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.
|Honmou, O; Young, W (1995) Norepinephrine modulates excitability of neonatal rat optic nerves through calcium-mediated mechanisms. Neuroscience 65:241-51|
|Young, W (1993) The therapeutic window for methylprednisolone treatment of acute spinal cord injury: implications for cell injury mechanisms. Res Publ Assoc Res Nerv Ment Dis 71:191-206|
|Nockels, R; Young, W (1992) Pharmacologic strategies in the treatment of experimental spinal cord injury. J Neurotrauma 9 Suppl 1:S211-7|
|Young, W (1992) Role of calcium in central nervous system injuries. J Neurotrauma 9 Suppl 1:S9-25|
|Iizuka, H; Sakatani, K; Young, W (1990) Neural damage in the rat thalamus after cortical infarcts. Stroke 21:790-4|