Poor blood flow in the lower limbs is a significant health problem that leads to neurological symptoms such as chronic pain, sensory impairment, reflex loss and muscle wasting and weakness. These result from pathological alterations in peripheral nerves, including loss of myelin and axonal degeneration. Despite advances in surgical and percuteaneous revascularization techniques, the prognosis remains poor. In the current issue of Nat. Med. (6, 405–413) Jeffrey Isner and colleagues have investigated whether neurological symptoms can be prevented/reversed by intramuscular transfer of a gene encoding an endothelial cell mitogen used to promote therapetic angiogenesis. Using a well-established animal model of hindlimb ischemia, the authors transferred naked DNA encoding vascular endothelial factor (VEGF) 10 days after the induction of ischemia and studied neuronal activity. Sure enough, nerve function was restored earlier and/or recovered faster in treated animals. These findings were in part due to enhanced limb perfusion, but also indicated a direct effect of VEGF on neural integrity. Indeed, their results suggest that VEGF may act directly on Schwann cells during nerve recovery by protecting them against hypoxia-induced apoptosis arising from the peripheral ischemia.

Untreated
Treated