[Abstract Title]. - Society for Neuroscience

Title: Modulating inflammatory pathway and epileptogenesis in mouse neocortex
Authors: H. KOCH 1 , S. MARLER 1 , *M. TURNER 2 , J.-M. RAMIREZ 1 ;
1 Organismal Biol. & Anat., 2 Neurosurg., Univ. Chicago, Chicago, IL
Abstract: Traumatic brain injury is a common cause of epileptogenesis. The underlying
mechanisms are poorly understood. Thus, it is also unknown how epileptogenesis can be
prevented. Here we investigated the possible involvement of the COX-2 dependent inflammatory
pathway in the progression from injury to seizure activity. The short term effects of PGE-2 were
studied by directly applying low concentration of PGE-2 to both cultured and acute neocortical
slices. The long-term consequences of manipulating the COX-2 pathway were explored in
organotypic cultures that were incubated for 48 hours in PGE-2. In acute slices (n=6) PGE-2
decreased the amplitude of evoked excitatory postsynaptic potentials (EPSP) by 32.59 ± 17.01 %
compared to controls The specific PGE-2 receptor (EP-3) agonist sulprostone mimicked the
effect of PGE-2 and reduced in acute slices (n=5) the amplitude of EPSPs by 29.52 ± 10.07 % .
PGE-2 reversibly suppressed spontaneous network activity in acute and spontaneously occurring
upstates (amplitude: 13.95 ± 4.46 mV) in slices cultured in normal media. Chronic treatment
with PGE-2 for 48 hours dramatically altered the network behavior of organotypic slice cultures.
In PGE-2 treated slices, upstates triggered paroxysmal depolarization shifts (PDSs) that were
characterized by significantly larger depolarization amplitudes (36.65 ± 9.11 mV;n=11). The
triggering of high amplitude PDSs suggests a possible mechanism for epileptogenesis.
Specifically we propose that prolonged PGE-2 exposure resulting in prolonged activity
deprivation evokes a homeostatic response that increases synaptic transmission and induces
high-amplitude paroxysmal depolarization shifts at the network level.
Disclosures: H. Koch, None; S. Marler, None; M. Turner , None; J. Ramirez, None.
Poster
250. Epilepsy: Networks
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 250.3/V15
Topic: C.06.h. In vivo mechanisms
Support: MEST-CT-2005-019217
Academy of Finland
Title: Pilocarpine-induced status epilepticus triggers angiogenesis in adult rat hippocampus