Elevation of MMP-9 Levels Promotes Epileptogenesis After Traumatic Brain Injury

• DOI: 10.1007/s12035-018-1061-5
• Publication Date: 2018-04-17T05:29:35Z
• Authors: Barbara Pijet; Marzena Stefaniuk; Agnieszka Kostrze...; Photini-Effie Tsi...; Athina Tzinia; Leszek Kaczmarek
• Keywords: Pentylenetetrazol; Knockout mouse

Posttraumatic epilepsy (PTE) is a recurrent seizure disorder that often develops secondary to traumatic brain injury (TBI) caused by an external mechanical force. Recent evidence shows the extracellular matrix plays major role in remodeling of neuronal connections after injury. One proteases presumably responsible for this process metalloproteinase-9 (MMP-9). The levels MMP-9 are elevated rodent tissue and human blood samples TBI. However, no studies have described influence on development PTE. present study used controlled cortical impact (CCI) as mouse model We examined detailed kinetics 1 month TBI observed two peaks (30 min 6 h injury). tested hypothesis high predispose individuals PTE, inhibition would protect against transgenic animals with either knockout or overexpression. overexpression increased number mice exhibited TBI-induced spontaneous seizures, decreased appearance seizures. also evaluated changes responsiveness single dose chemoconvulsant pentylenetetrazol. MMP-9-overexpressing significantly shorter latency between pentylenetetrazol administration first epileptiform spike. opposite response profile. Finally, we found occurrence PTE was correlated size lesion Overall, our data emphasize contribution structural physiological alterations circuitry may lead