Fluid percussion brain injury exacerbates glutamate-induced focal damage in the rat.
The role of glutamate-mediated neuronal damage in neurotrauma remains controversial. The cerebral levels measured in patients by microdialysis are sufficient to kill neurons in culture, but not in the intact brain of the normal 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 vivo glutamate perfusion and fluid percussion injury (FPI). Twenty-four adult male Sprague Dawley rats were randomly assigned to three groups: (1) vehicle (n = 9): mock cerebrospinal fluid (CSF) perfusion plus FPI; (2) glutamate + FPI (n = 9): 0.1 M glutamate intracortical perfusion plus FPI; and (3) glutamate without FPI (n = 6). After preparation for central FPI, at a moderate level of injury (2 +/- 0.5 atm), glutamate or mock CSF perfusion was performed via a CMA/12 microdialysis probe (3 mm). Animals were then perfusion fixed, under deep anesthesia, after 3-h survival, for volumetric histopathology. The glutamate perfusion + FPI group (2.42 +/- 1.63 mm3) produced a significantly bigger lesion than mock CSF perfusion + FPI (0.063 +/- 0.41 mm3) and glutamate perfusion alone (1.00 +/- 0.47 mm3). Traumatic brain injury thus seems to enhance glutamate-mediated brain damage, and this may be due to qualitative changes induced in ion channels and receptors, such as the N-methyl-D-aspartate channel, after shear injury.
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Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0631, USA.
Gordon
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J
Bullock
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R
D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018698:Glutamic Acid / Q000633:toxicity*; D007091:Image Processing, Computer-Assisted; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D016612:Paraffin Embedding; D051381:Rats; D017207:Rats, Sprague-Dawley; D016707:Tissue Fixation
D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid