[Abstract Title]. - Society for Neuroscience

1 Mario Negri Inst. for Pharmacol. Res., Milano, Italy; 2 Inst. de la Santé et de la Recherche
Medicale U661, Montpellier, France; 3 Dept Neurophysiol., Inst. Neurologico, 20133 Milan, Italy
Abstract: Rationale: Brain inflammation, angiogenesis and increased blood-brain barrier (BBB)
permeability occur in adult rodent and human epileptogenic brain tissue. No information is
available on whether inflammation is responsible for neovascularization and BBB damage;
moreover, the contribution of these factors to epileptogenesis is largely unexplored.
Aim: This study addresses the role of these events in epileptogenesis using a developmental
approach since the propensity to develop spontaneous seizures, therefore the induction of
epileptogenesis, is age-dependent and increases with brain maturation.
Method:Immunohistochemical analysis of inflammation, angiogenesis and BBB permeability
was done in postnatal day (PN)9 and PN21 rats, at 4 h, 1 week and 4 months after pilocarpineinduced
status epilepticus. Brain inflammation was evaluated by reactive gliosis and
interleukin(IL)-1β immunohistochemistry. Microvessels were identified using an anti-laminin
antibody or by intraluminal signal of intracardial FITC-albumin, and their density was
quantified. BBB integrity was evaluated by extravascular IgG immunostaining or by detection of
parenchymal extravasation of FITC-albumin.
Results: Status epilepticus in PN9 rats did not induce either inflammation or angiogenesis or
changes in BBB permeability and these rats did not develop spontaneous seizures in adulthood.
Differently, status epilepticus in PN21 rats induced chronic inflammation, angiogenesis and BBB
leakage in the hippocampus in about 70% of rats. Inflammation invariably preceded the onset of
angiogenesis and BBB damage. In the remaining 30% of rats, only transient inflammation was
observed. Epilepsy developed in about 70% of PN21 rats exposed to SE and these epileptic rats
showed the three phenomena in their hippocampi. About 30% of PN21 rats exposed to SE did
not develop epilepsy; these rats did not show angiogenesis and BBB damage in any of the
forebrain areas analyzed.
Conclusion: Our data show that angiogenesis and BBB permeability are concomitantly altered
by status epilepticus in an age-dependent manner; moreover, these phenomena are spatiotemporally
correlated with the extent of inflammation in various forebrain areas. This evidence
suggests the occurrence and persistence of these phenomena in the hippocampus only if
epileptogenesis is induced, thus highlighting the possibility that they are implicated in the
mechanisms predisposing to the occurrence of spontaneous seizures.
Disclosures: T. Ravizza, None; M. De Curtis , None; B. Gagliardi, None; J. Marcon,
None; F. Noe', None; A. Vezzani, None; M. Morin, None; M. Lerner-Natoli, None.
Poster
250. Epilepsy: Networks
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 250.5/V17