Abstracts

In adult patients with intractable temporal lobe epilepsy (TLE), we previously described inflammatory processes and neurogenesis; unexpectedly, we observed the presence of immature micro-vessels. The present study was designed to demonstrate: i) a pathological vascularization associated with TLE, ii) angiogenic processes active in chronic focus, iii) an impact of vascular remodeling on epileptogenicity., Hippocampi were collected from 40 patients after surgery for intractable TLE with various etiologies and from 5 non epileptic (NE) patients ( autopsies or hippocampectomy for parahippocampal tumor). By immunohistochemistry or immunoblot, we evaluated: microvessel density, expression of markers of immature endothelial cells, of angiogenic factors and their receptors. We also checked impairments of blood brain barrier (BBB).
In parallel, we studied the kinetics of these processes in the rat model of lithium-pilocarpine-induced limbic epilepsy., We observed division markers in vascular cells in neurogenic areas of epileptic hippocampi. The microvessel density was significantly higher in TLE patients than in NE patients. More, there was no quantitative differences between TLE with hippocampal sclerosis and TLE with other etiologies. Most of these microvessels were positive for markers of immature endothelial cells. The angiogenic factor VEGF was expressed mainly by neurons and often by astrocytes, and its receptor Flk-1 was localized on thin vascular sprouts. In all cases of TLE, we observed impairments of BBB, allowing IgG leakage and blood cell extravasation. In rats, the degree of vascularization increased progressively from 1 week after status epilepticus. VEGF was rapidly and strongly overexpressed after seizures, whereas the other markers appeared during the silent period. The BBB was early damaged. In the chronic stage, these phenomena were still obvious, as for human TLE., For the first time, we demonstrate a neo-vascularization of the TLE focus, independently of etiology. We suggest that the pathological angiogenic processes are related to the persistent inflammation and are maintained by recurrent seizures. The consequences of this vascular remodeling may concern hemodynamics, inflammation, neurotoxicity, BBB permeability and drug refractoriness.[figure1], (Supported by French Fondation for Research on Epilepsy.)