Calcium Movements in Traumatic Brain Injury: The Role of Glutamate Receptor-Operated Ion Channels

Abstract

Ion-selective microelectrodes were used to study acute effects of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptor blockade on posttraumatic calcium disturbances. An autoradiographic technique with ⁴⁵Ca²⁺ was used to study calcium disturbances at 8, 24, and 72 h. Compression contusion trauma of the cerebral cortex was produced by a 21-g weight dropped from a height of 35 cm onto a piston that compressed the brain 2 mm. Pre- and posttrauma interstitial [Ca²⁺] ([Ca²⁺]_e) concentrations were measured in the perimeter, 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 divided into controls and groups pretreated with dizocilipine maleate (MK-801) or with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[F]quinoxaline (NBQX). In all groups, [Ca²⁺]_e decreased from pretrauma-values of approximately 1 m M to posttraumatic values of 0.1 m M in both the CR and the SSZ. This was followed by a slow restitution toward pretraumatic levels during the 2-h observation period. There was no significant difference in recovery pattern between controls and pretreated animals. Accumulation of ⁴⁵Ca²⁺ 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 ⁴⁵Ca²⁺. Posttraumatic treatment with MK-801 or NBQX had no obvious effect on neuronal injury in the SSZ. We conclude that (a) acute [Ca²⁺]_e disturbances in compression contusion brain trauma are not affected by blockade of NMDA or AMPA receptors, (b) ⁴⁵Ca²⁺ accumulation in the SSZ reflects mainly protein accumulation due to 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.