A new model for diffuse brain injury by rotational acceleration: II. Effects on extracellular glutamate, intracranial pressure, and neuronal apoptosis

The aim of this study is to monitor excitatory amino acids (EAAs) in the ex tracellular fluids of the brain and to characterize regional neuronal damag e in a new experimental model for brain injury, in which rabbits were expos ed to 180-260 krad/s(2) rotational head acceleration, This loading causes e xtensive subarachnoid hemorrhage, focal tissue bleeding, reactive astrocyto sis, and axonal damage. Animals were monitored for intracranial pressure (I CP) and for amino acids in the extracellular fluids, Immunohistochemistry w as used to study expression of the gene c-Jun and apoptosis with the termin al deoxynucleotidyl transferase nick-end labeling (TUNEL) technique. Extrac ellular glutamate, glycine, and taurine increased significantly in the hipp ocampus within a few hours and remained high after 24 h. Neuronal nuclei in the granule layers of the hippocampus and cerebellum were positive for c-J un after 24 h. Little immunoreactivity was detected in the cerebral cortex. c-Jun-positive neuronal perikarya and processes were found in granule and pyramidal CA4 layers of the hippocampus and among the Purkinje cells of the cerebellum. Also some microglial cells stained positively for c-Jun. TUNEL reactivity was most intense at 10 days after trauma and was extensive in n eurons of the cerebral cortex, hippocampus, and cerebellum. The initial res ponse of the brain after rotational head injury involves brain edema after 24 h and an excitotoxic neuronal microenvironment in the first hour, which leads to extensive delayed neuronal cell death by apoptosis necrosis in the cerebral cortex, hippocampus and cerebellum.