ISCHEMIA-INDUCED CHANGES IN THE EXTRACELLULAR-SPACE DIFFUSION PARAMETERS, K-CALLOSUM(, AND PH IN THE DEVELOPING RAT CORTEX AND CORPUS)

Changes in the ability of substances to diffuse in the intersticial sp ace of the brain are important factors in the pathophysiology of cereb rovascular diseases. Extracellular space (ECS) volume fraction alpha ( alpha = ECS volume/total tissue volume), tortuosity lambda (lambda(2) = free diffusion coefficient/apparent diffusion coefficient), and nons pecific uptake (k') - three diffusion parameters of brain tissue were studied in cortex and subcortical white matter (WM) of the developing rat during anoxia. Changes were compared with the rise in extracellula r potassium concentration ([K+](e)), extracellular pH (pH(e)) shifts, and anoxic depolarization (AD). Diffusion parameters were determined f rom extracellular concentration-time profiles of tetramethylammonium ( TMA(+)) or tetraethylammonium (TEA(+)). TMA(+), TEA(+), K+, and pH cha nges were measured using ion-selective microelectrodes. In the cortex and WM of animals at 4-12 postnatal days (P4-P12), the volume fraction , alpha, is larger than that of animals at greater than or equal to P2 1. Anoxia evoked by cardiac arrest brought about a typical rise in [K](e) to similar to 60-70 mM, AD of 25-30 mV, decrease in alpha, increa se in lambda, and increase in k'. At P4-P6, alpha decreased from simil ar to 0.43 to 0.05 in cortical layer V and from similar to 0.45 to 0.5 in WM. Tortuosity, lambda, increased in the cortex from 1.50 to 2.12 and in WM from similar to 1.48 to 2.08. At P10-P12 and at P21-P23, whe n alpha in normoxic rats is lower than at P4-P6 by similar to 25 and 5 0%, respectively, the final changes in values of alpha and lambda evok ed by anoxia were not significantly different from those in P4-P6. How ever, the younger the animal, the longer the time course of the change s. On P4-P6 final changes in alpha, lambda, and k' in cortex and WM we re reached after 37 +/- 3 min and 54 +/- 2 min; on P10-P12, after 24 /- 2 and 27 +/- 3 min; and on P21-P23 at 151 +/- 1 and 17 +/- 3 min, r espectively (mean +/- SE, n = 6). The time course of the changes was l onger in WM than in gray matter (GM), particularly during the first po stnatal week, i.e., in the period during which WM is largely unmyelina ted. Changes in diffusion parameters occurred in three phases. The fir st slow and second fast changes occurred simultaneously with the rise in [K+](e) and AD. Peaks in [K+](e) and AD were reached simultaneously ; the younger the animal, the longer the time course of the changes. T he third phase outlasted the rise in [K+](e) and AD by 10-15 min and c orrelated with the acid shift in pH(e). Linear regression analysis rev ealed a positive correlation between the normoxic size of the ECS volu me and the time course of the changes. Slower changes in ECS volume fr action and tortuosity in nervous tissue during development can contrib ute to slower impair ment of signal transmission, e.g., due to lower a ccumulation of ions and neuroactive substances released from cells and their better diffusion from the hypoxic area in uncompacted ECS.