Abstracts

RATIONALE: Posttraumatic epilepsy often appears after a latent period, but clinical trials aimed at prevention during this period have been ineffective. In the rat undercut model of posttraumatic epileptogenesis, focal treatment of lesioned neocortex with tetrodotoxin (TTX) during a critical period is antiepileptogenic (Graber KD and Prince DA. Soc Neurosci Abst 25:1352, 1999), but mechanisms by which this occurs are not known. We examined postsynaptic currents to test the hypothesis that TTX treatment prevents pathogenic alterations in the balance of inhibition and excitation in epileptogenic neocortex.
METHODS: Undercuts were made in P28-30 male Sprague-Dawley rats, and thin sheets of Elvax polymer containing TTX or no drug placed subdurally over partial cortical isolations. After TTX washout, spontaneous inhibitory postsynaptic currents (sIPSCs), miniature excitatory postsynaptic currents (mEPSCs) and spontaneous EPSCs (sEPSCs) were recorded in layer V pyramidal neurons of neocortical slices obtained after the latent period, 10-15 days post-lesion.
RESULTS: Mean sIPSC frequency was less in neurons from TTX-treated undercuts (39.4 [plusminus] 6.4, n=6) than in neurons of control undercuts (55.7 [plusminus] 3.7, n = 10, p = 0.03 Student[scquote]s t test). However, mean sIPSC amplitude was significant larger in cells from the TTX treated animals (22.7 [plusminus] 5.8 versus 11.4 [plusminus] 1.2, p = 0.03). Preliminary studies have not shown significant differences in mEPSCs or sEPSCs in these two populations.
CONCLUSIONS: The chronic network effects of TTX treatment remain uncertain, but the dramatic increase in IPSC amplitude raises the possibility that enhanced postsynaptic inhibition may be one mechanism by which TTX treatment and reduction of activity following injury contribute to suppression of epileptogenesis.
Support: NINDS grants [pound]K08 NS02167 and [pound]NS12151.