Dizocilpine but not ketamine reduces the volume of ischaemic damage after acute subdural haematoma in the rat

Abstract

Background and objective Increased glutamate concentration in the cerebrospinal fluid has been reported in severely head–injured patients, suggesting that an excessive release of glutamate may be involved in the process of neuronal damage. Ischaemic damage after subdural haematoma has been reported to be reduced by glutamate (N-methyl-D-aspartate: NMDA) receptor antagonists such as dizocilpine and CGS 19755; even though these drugs were given 20–30 min after insult. Excessive release of excitatory amino acids may produce the neural damage after subdural haematoma and NMDA receptor antagonists may become valuable therapeutic drugs. This study compared the effects of ketamine and dizocilpine, on intracranial pressure and histopathological changes after acute subdural haematoma produced by an injection of autologous blood (150 μL) in rats.

Methods The control (n =9), ketamine (n =9) and dizocilpine (n =9) groups, respectively, received saline, ketamine (total dose: 210 mgkg⁻¹) or dizocilpine (total dose: 1.0 mgkg⁻¹) from 0.5 to 8 h after acute subdural haematoma. A silicone group (n =9) had the same volume of silicone injected subdurally.

Results The volume of ischaemic damage in the silicone group (1.3±1.2mm³) was significantly smaller than in the control group (11.9±3.8mm³). Ketamine and dizocilpine did not increase intracranial pressure. Dizocilpine significantly decreased the volume of ischaemic damage (6.1±3.8mm³). Ketamine failed to significantly decrease damage (7.8±5.0mm³).

Conclusions These results suggest that the factors elicited by the clotted blood contribute to the ischaemic damage after subdural haematoma, and that the glutamate receptor antagonist dizocilpine reduces the damage, while ketamine shows only a trend reduction of the damage.