HIPPOCAMPAL CA3 LESION PREVENTS POSTCONCUSSIVE METABOLIC DYSFUNCTION IN CA1

Immediately following fluid-percussion (F-P) brain injury, the hippocampus exhibits a marked increase in its local CMR(glc) (LCMR(glc); mumol/100 g/min) as determined using [C-14]2-deoxy-D-glucose autoradiography This injury-induced increase in metabolism is followed in 6 h by a subsequent decrease in LCMR(glc). These two postinjury metabolic states may be the result of ionic disruptions following trauma via stimulation of glutamategated ion channels. To determine if endogenous glutamate innervation to the CA, region of the hippocampus can provide an anatomical basis for this proposed mechanism, it was removed by kainic-acid-induced destruction of CA3, and the effect on CA, metabolism following concussive injury was studied. Five days before a lateral F-P injury (3.5-4.5 atm), kainic acid (0.5 mug) or vehicle was stereotaxically injected into the left ventricle of 65 rats. Histological inspection indicated that kainic acid produced severe cell loss primarily in the CA1 region of the hippocampus ipsilateral to the injection. The metabolic results indicated that immediately following injury, animals with an intact hippocampus exhibited an increase in LCMR(glc) to 84.6 +/- 5 within the CA1 region, representing a 81.5% increase over controls. However, in the CA3-lesioned animals, CA1 showed no evidence of an injury-induced hypermetabolism, with LCMR(glc) remaining at control levels (51.4 +/- 3.9). At 6 h postinjury, the intact hippocampus exhibited a reduction of LCMR(glc) to rates of 40.7 +/- 4.7 within the CA1 region, representing a 17.9% reduction compared with controls. In contrast, CA3-lesioned animals exhibited less of an injury-induced decrease in LCMR(glc) within the CA1 region, exhibiting a mean rate of 43.4 +/- 4.5, representing only a 12.5% reduction compared with controls. These results indicate that the removal of the CA3 projection to CA1 protects the CA1 cells from the metabolic dysfunction typically seen following injury. This supports our previous work indicating the important role glutamate plays in the ionic flux and subsequent metabolic changes that follow traumatic brain injury.