Electrophysiological and behavioral studies have demonstrated that
muscimol administered through the cranial meninges can prevent focal neocortical
seizures. It was proposed that transmeningeal
muscimol delivery can be used for the treatment of intractable focal neocortical
epilepsy. However, it has not been proved that
muscimol administered via the transmeningeal route can penetrate into the neocortex. The purpose of the present study was to solve this problem by using combined autoradiography-histology methods. Four rats were implanted with epidural cups over the parietal cortices. A 50 μL mixture of [³H]
muscimol and unlabeled
muscimol with a final concentration of 1.0mM was delivered through each cup on the dura mater. After a 1-hour exposure, the
muscimol solution was removed and replaced with
formalin to trap the transmeningeally diffused molecules. Then the whole brain was fixed transcardially, sectioned, with the sections subjected to autoradiography and
thionine counterstaining. Results showed that (1) [³H]
muscimol diffused through the meninges into the cortical tissue underlying the epidural cup in all rats. (2) [³H]
muscimol-related autoradiography grains were distributed in all six neocortical layers. (3) [³H]
muscimol-related autoradiography grains were localized to the cortical area underneath the epidural delivery site and were absent in the cerebral cortical white matter and other brain structures. This study provided evidence that
muscimol can be delivered via the transmeningeal route into the neocortical tissue in a spatially controlled manner. The finding further supports the rationale of using transmeningeal
muscimol for the treatment of intractable focal neocortical
epilepsy.