Fluid percussion brain injury exacerbates glutamate-induced focal damage in the rat

The role of glutamate-mediated neuronal damage in neurotrauma remains contr oversial. The cerebral levels measured in patients by microdialysis are suf ficient to kill neurons in culture, but not in the intact brain of the norm al rat. A synergistic effect between excitatory amino acid-mediated damage and other posttrauma mechanisms must therefore be proposed, if glutamate is indeed a significant cause of posttraumatic brain damage. The presence of such a synergistic mechanism was therefore investigated by combining in viv o glutamate perfusion and fluid percussion injury (FPI). Twenty-four adult male Sprague Dawley rats were randomly assigned to three groups: (1) vehicl e (n = 9): mock cerebrospinal fluid (CSF) perfusion plus FPI; (2) glutamate + FPI (n = 9): 0.1 M glutamate intracortical perfusion plus FPI; and (3) g lutamate without FPI (n = 6), After preparation for central FPI, at a moder ate level of injury (2 +/- 0.5 atm), glutamate or mock CSF perfusion was pe rformed via a CMA/12 microdialysis probe (3 mm), Animals were then perfusio n fixed, under deep anesthesia, after 3-h survival, for volumetric histopat hology, The glutamate perfusion + FPI group (2.42 +/- 1.63 mm(3)) produced a significantly bigger lesion than mock CSF perfusion + FPI (0.063 +/- 0.41 mm(3)) and glutamate perfusion alone (1.00 +/- 0.47 mm(3)). Traumatic brai n injury thus seems to enhance glutamate-mediated brain damage, and this ma y be due to qualitative changes induced in ion channels and receptors, such as the N-methyl-D-aspartate channel, after shear injury.