CALCIUM MOVEMENTS IN TRAUMATIC BRAIN INJURY - THE ROLE OF GLUTAMATE RECEPTOR-OPERATED ION CHANNELS

Ion-selective microelectrodes were used to study acute effects of N-me thyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptor blockade on posttraumatic calcium disturbances. An au toradiographic technique with Ca-45(2+) was used to study calcium dist urbances at 8, 24, and 72 h. Compression contusion trauma of the cereb ral cortex was produced by a 21-g weight dropped from a height of 35 c m onto a piston that compressed the brain 2 mm. Pre- and posttrauma in terstitial [Ca2+] ([Ca2+](e)) concentrations were measured in the peri meter, i.e., the shear stress zone (SSZ) and in the central region (CR ) of the trauma site. For the [Ca2+](e) studies the animals were divid ed into controls and groups pretreated with dizocilipine maleate (MK-8 01) or with -dihydroxy-6-nitro-7-sulfamoyl-benzo[F]quinoxaline (NBQX). In all groups, [Ca2+](e) decreased from pretrauma values of approxima tely 1 mM to posttraumatic values of 0.1 mM in both the CR and the SSZ . This was followed by a slow restitution toward pretraumatic levels d uring the 2-h observation period. There was no significant difference in recovery pattern between controls and pretreated animals. Accumulat ion of Ca-45(2+) and serum proteins was seen in the entire SSZ, while neuronal necrosis was confined to a narrow band within the SSZ. The CR was unaffected apart from occasional eosinophilic neurons and showed no accumulation of Ca-45(2+). Posttraumatic treatment with MK-801 or N BQX had no obvious effect on neuronal injury in the SSZ. We conclude t hat (a) acute [Ca2+](e) disturbances in compression contusion brain tr auma are not affected by blockade of NMDA or AMPA receptors, (b) C-45( 2+) accumulation in the SSZ reflects mainly protein accumulation due t o blood-brain barrier breakdown rather than cell death, and (c) acute cellular Ca2+ overload per se does not seem to be a major determinant of cell death after cerebral trauma in our model.