Relative preservation of GABAA receptor β‐subunit immunoreactivity in the hippocampus in mesial temporal sclerosis

The pattern of cell loss and changes in the expression of inhibitory and excitatory receptors in the subzones of the hippocampus in patients with pharmacoresistant (drug-refractory) complex partial seizures was studied. Neuronal densities were measured in the mid-hippocampus in temporal lobectomy (n = 10) and total hemispherectomy (n = 2) specimens from 12 patients with mesial temporal sclerosis (MTS), in temporal lobectomy (n = 6) and hemispherectomy (n = 5) samples from 11 epileptic patients without MTS, and in six autopsy brains from patients without neurological disease. No differences in hippocampal cell densities were found between the autopsy and the non-MTS group. The MTS group, compared with the non-MTS or the autopsy group, showed a 95% decrease in neuronal density in CA1, a 70% decrease in cornu ammonis (CA)2, an 85% decrease in CA3, and an 80% decrease in CA4. The proportion of neurons staining positively with a polyclonal antibody for the α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) glutamate receptor subunits GluR2 and GluR3 was increased to 32% in the CA1 region in the MTS group, compared with 21% in the non-MTS hippocampi. This difference was, however, just at the level of statistical significance (P = 0.054). Elsewhere in the hippocampus no significant change was observed. By contrast, the proportion of cells staining positively with a monoclonal antibody to the β-subunit of the GABAA benzodiazepine (BZ) receptor was markedly increased in the MTS hippocampi, from 13% in non-MTS CA1 to 50% in MTS CA1 region; and from 26% in non-MTS CA3 to 63% in MTS CA3. Although previous studies (in vivo and ex vivo) have emphasized a loss of BZ receptors in temporal lobe epilepsy, this study shows that the expression of the GABAA receptor immunopositive population appears to be increased relative to the neuronal density.