Induction of VEGF and VEGF receptors in the spinal cord after mechanical spinal injury and prostaglandin administration

Vascular endothelial growth factor (VEGF) is an angiogenetic factor that pr omotes endothelial cell proliferation during development and after injury t o various types of tissue, including the central nervous system (CNS). Usin g immunohistochemical and in situ hybridization methods we have here demons trated that VEGF and its receptors Flk-1, Flt-1 and Neuropilin-1 mRNAs and proteins are induced after incisions in the rat spinal cord. The inducible enzyme for prostaglandin synthesis cyclooxygenase-2 (COX-2) is known to be upregulated after spinal injury, cerebral ischemia and to stimulate angioge nesis. To test the hypothesis that prostaglandins may be involved in the VE GF response after lesion we investigated whether intraspinal microinjection s of prostaglandin F2 alpha (PGF2 alpha) alters VEGF expression in the spin al cord. Such treatment was followed by a strong upregulation of VEGF mRNA and protein in the injection area. Finally, by use of an in vitro model wit h cell cultures of meningeal fibroblast and astrocyte origin, resembling th e lesion area cellular content after spinal cord injury but devoid of infla mmatory cells, we showed that VEGF is expressed in this in vitro model cell system after treatment with PGF2 alpha and prostaglandin E2 (PGE2). These data suggest that cells within a lesion area in the spinal cord are capable of expressing VEGF and its receptors in response to mechanical injury and that prostaglandins may induce VEGF expression in such cells, even in the a bsence of inflammatory cells.