Abstracts

Several clinical and experimental reports have suggested that irradiation of epileptic foci at subnecrotic doses can reduce the incidence of spontaneously recurring seizures. We hypothesized that these effects may be mediated, in part, by a selective depletion of parvalbumin-positive GABAergic interneurons within the hippocampus. Networks of these perisomatic inhibitory neurons, which are connected via both chemical and electrical synapses, are critically involved in the emergence of large-scale synchrony among principal neurons within the hippocampus, and might therefore contribute to the initiation or elaboration of limbic seizures within this structure.
Male Wistar rats were kindled by daily (afterdischarge threshold) electrical stimulation of the left amygdala, until a minimum of 10 stage 5 seizures were observed. The left amygdala was irradiated via dorsoventral exposure to a beam-collimated 18MV x-ray source, with a 2.5 mm radius (90% isodose), at isocenter doses of either 18 or 25 Gy. Kindled control animals received sham irradiation. Animals were transcardially perfused 160 days after irradiation with fixative containing 4% paraformaldehyde and 0.08% gluteraldehyde, postfixed overnight, paraffin embedded, microtome sectioned (7[micro]m), and processed for parvalbumin immunohistochemistry. Parvalbumin and total cell counts were performed bilaterally using the method of Mouritzen Dam in all hippocampal subfields. Volume calculations for each of these subfields were performed using Scion (NIH) Image software.
There were no effects of irradiation at either 18 or 25 Gy on seizure threshold or seizure duration during the entire post-irradiation interval prior to perfusion. Similarly, there were no significant differences in parvalbumin-positive neuronal densities associated with exposure to ionizing radiation at either 18 or 25 Gy. Parvalbumin-positive neuronal density was significantly increased (p [lt] 0.003) in the pyramidal layer of CA1 in the hemisphere in which kindling was initiated, relative to the contralateral hemisphere. No consistently significant differences in total (principal) cell density within the hippocampus were observed among our groups as a function of either kindling or irradiation.
We conclude that parvalbumin-positive neuronal density within the hippocampus is not affected by irradiation at the doses employed in these investigations. Further investigations are required to determine whether analogous radiation exposures might affect chemical and/or electrical synaptic function among these neurons. The apparent increase in parvalbumin-positive neuronal density within the hippocampus as a function of kindling also warrants further investigation. This may reflect kindling-induced increases in parvalbumin expression with CA1.