Abstracts

Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen that is abundantly expressed during CNS development, where it plays a fundamental role in embryonic vasculogenesis and angiogenesis. In the intact adult brain, VEGF is significantly down regulated and angiogenesis is practically nonexistent; however, VEGF becomes widely expressed in a variety of pathological conditions associated with increases in microvascular permeability, inflammation, and angiogenesis. Subtle up-regulation of VEGF gene expression has recently been reported following a single electroconvulsive seizure. Here we report the dynamics of VEGF protein expression following kainic acid-induced status epilepticus. Several hours of limbic status epilepticus was induced in male Wistar rats by intravenous injection of kainic acid (10 mg/kg). Cohorts of rats were sacrificed at weekly intervals following status induction, along with age matched controls, and processed for paraffin embedding and VEGF immunohistochemistry. Digital images were obtained from 7[mu]m sections at predetermined regions within the hippocampus, amygdala, and piriform cortex. The expression of VEGF within these regions was assayed by quantifying the optical density of VEGF-positive staining using NIH Image software. VEGF was minimally expressed within the regions assayed among control animals regardless of the time of sacrifice. Relative to these controls, VEGF expression was significantly up-regulated in all regions sampled among our status epilepticus animals. This elevation in VEGF expression was well established by two weeks post-status, and remained significantly elevated out to at least four weeks post-status. The expression was concentrated within the principal cell layers, and was closely associated with the neuronal cell bodies. We conclude the trauma associated with status epilepticus is sufficient to induce VEGF expression in a manner analogous to that seen after other forms of neural trauma. This expression could conceivably affect vascular permeability and/or promote angiogenesis within the involved regions, which could, in turn, contribute to epileptogenesis.