Hippocampal CA 3 Lesion Prevents Postconcussive Metabolic Dysfunction in CA 1

Immediately following fluid-percussion (F-P) brain injury, the hippocampus exhibits a marked increase in its local CMR_glc (LCMR_glc; μmol/100 g/min) as determined using [¹⁴C]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 CA₁ 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 CA₁ metabolism following concussive injury was studied. Five days before a lateral F-P injury (3.5–4.5 atm), kainic acid (0.5 μg) 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 CA₃ 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.