Temporal Profile of Changes in Brain Tissue Extracellular Space and Extracellular Ion (Na +,K + ) Concentrations after Cerebral Ischemia and the Effects of Mild Cerebral Hypothermia

Abstract

Cerebral ischemic cellular swelling occurs primarily in astrocytes. This water influx into the intracellular space is believed to result from osmotic water movement after disruption of membrane ionic homeostasis. However, cellular swelling occurs earlier than expected after ischemia and new ionic and water channels have been discovered. This study examined the temporal profile of the water and ionic movement across the cell membrane after global ischemia by measuring the changes in extracellular space (ECS), extracellular K⁺ and Na⁺ ion concentrations ([K⁺]_e and [Na⁺]_e) using a high resolution tissue impedance probe and ion selective micropipettes in the rat cortex. The effect of mild cerebral hypothermia (31.5 ± 2.6°C brain temperature) on these parameters was also examined. The ECS started to decrease at 34 ± 8 sec after global ischemia and reached half the maximum change at 61 ± 17 sec. [K⁺]_e started to increase initially at 33 ± 11 sec (phase 1) and then increased rapidly at 62 ± 25 sec (phase 2), and [Na⁺]_e started to decrease at 88 ± 27 sec after ischemia. With mild hypothermia, the ECS started to decrease at 75 ± 35 sec after ischemia and reached half the maximum change at 123 ± 44 sec, [K⁺]_e started to increase initially at 80 ± 24 sec(phase 1) and then increased rapidly at 120 ± 32 sec (phase 2), and [Na⁺]_e started to decrease at 172 ± 70 sec. The present study shows that ischemic cellular swelling(decreased ECS) occurs concomitantly with the phase 1 increase of [K⁺]_e but precedes the disruption of ionic membrane homeostasis (phase 2). Mild hypothermia prolongs the onset of these phenomena but does not affect the magnitude of the changes in ECS and ion concentrations.