1. *Department of Neurosurgery, Uppsala University Hospital, Uppsala, Sweden
2. ‡Department of Clinical Chemistry, Uppsala University Hospital, Uppsala, Sweden
3. †Department of Institute of Neuropathology, University of Copenhagen, Copenhagen
4. §Department of Pharmaceuticals Division, Novo Nordisk A/S, Måløv, Denmark

Correspondence: L Hillered, Departments of Clinical Chemistry and Neurosurgery, University Hospital, S-75185 Uppsala, Sweden.

Received 28 October 1994; Revised 10 April 1995; Accepted 2 June 1995.

Abstract

Ion-selective microelectrodes were used to study acute effects of N-methyl-D-aspartate (NMDA) and -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 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 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.