title: Gabapentin decreases epileptiform discharges in a chronic model of neocortical trauma.
abstract: Gabapentin (GBP) is an anticonvulsant that acts at the α2δ-1 submit of the L-type calcium channel. It is recently reported that GBP is a potent inhibitor of thrombospondin (TSP)-induced excitatory synapse formation in vitro and in vivo. Here we studied effects of chronic GBP administration on epileptogenesis in the partial cortical isolation ("undercut") model of posttraumatic epilepsy, in which abnormal axonal sprouting and aberrant synaptogenesis contribute to occurrence of epileptiform discharges. Results showed that 1) the incidence of evoked epileptiform discharges in undercut cortical slices studied 1 day or ~2 weeks after the last GBP dose, was significantly reduced by GBP treatments, beginning on the day of injury; 2) the expression of GFAP and TSP1 protein, as well as the number of FJC stained cells was decreased in GBP treated undercut animals; 3) in vivo GBP treatment of rats with undercuts for 3 or 7 days decreased the density of vGlut1-PSD95 close appositions (presumed synapses) in comparison to saline treated controls with similar lesions;4) the electrophysiological data are compatible with the above anatomical changes, showing decreases in mEPSC and sEPSC frequency in the GBP treated animals. These results indicate that chronic administration of GBP after cortical injury is antiepileptogenic in the undercut model of post-traumatic epilepsy, perhaps by both neuroprotective actions and decreases in excitatory synapse formation. The findings may suggest the potential use of GBP as an antiepileptogenic agent following traumatic brain injury.
authors: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: Huifang
authors: H
authors: Li
authors: Kevin D
authors: KD
authors: Graber
authors: Sha
authors: S
authors: Jin
authors: Whitney
authors: W
authors: McDonald
authors: Ben A
authors: BA
authors: Barres
authors: David A
authors: DA
authors: Prince
mesh_terms: D000588:Amines / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015153:Blotting, Western; D001930:Brain Injuries / Q000150:complications*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D004834:Epilepsy, Post-Traumatic / Q000517:prevention & control*; D000077206:Gabapentin; D007150:Immunohistochemistry; D008297:Male; D019579:Neocortex / Q000187:drug effects* / Q000293:injuries; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin