Synaptophysin immunoreactivity in temporal lobe epilepsy-associated hippocampal sclerosis

We have previously devised a semiquantitative grading system for hippocampa l sclerosis (HS) in specimens resected for intractable temporal lobe epilep sy. The grades range from zero to four based on the amount and distribution of neuronal loss and gliosis. In the present study hippocampal sections fr om 25 patients who had temporal lobe epilepsy and had previously been assig ned a grade were examined with synaptophysin immunohistochemistry, and the synaptic content in specific hippocampal fields was correlated with the res ults of the HS grading system. There was evidence of both significant synap tic loss and increased synaptic density in different fields of the hippocam pus with increasing HS. A marked decrement of synaptic immunostaining was p resent in fields CA1 and CA4 that were highly correlated with HS grade. Sec tor CA4 seemed to respond in a more graded or continuous way to the patholo gical insults occurring in temporal lobe epilepsy than did CA1, which appea red to exhibit an all or nothing response. Also, while the width of the out er part of the molecular layer of the dentate (mld) gyrus decreased with in creasing HS grade, the inner part of the mid became wider and showed an inc reased synaptic density so that the overall width of the mid was increased in the high-grade group. We conclude that quantitative measurement of synap tic loss in CA1 and CA4 using synaptophysin immunohistochemistry is a sensi tive method for detecting HS and con-elates well with the empirically deriv ed HS grading scale, with CA4 exhibiting a more graded response than CA1. I n addition, a plasticity response in the inner part of the mid in patients with high-grade HS has been confirmed and quantitated.