Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemic peripheral neuropathy is a frequent, irreversible complication of lower extremity vascular insufficiency. We investigated whether ischemic peripheral neuropathy could be prevented and/or reversed by gene transfer of an endothelial cell mitogen designed to promote therapeutic angiogenesis. Intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor (VEGF) simultaneously with induction of hindlimb ischemia in rabbits abrogated the substantial decrease in motor and sensory nerve parameters, and nerve function recovered promptly. When gene transfer was administered 10 days after induction of ischemia, nerve function was restored earlier and/or recovered faster than in untreated rabbits. These findings are due in part to enhanced hindlimb perfusion. In addition, however, the demonstration of functional VEGF receptor expression by Schwann cells indicates a direct effect of VEGF on neural integrity as well. These findings thus constitute a new paradigm for the treatment of ischemic peripheral neuropathy.
 ...
PMID:Favorable effect of VEGF gene transfer on ischemic peripheral neuropathy. 1074 39

Ischemic neuropathy from sources other than diabetes is less common, but can be encountered in clinical practice. Diagnosis can be challenging, and many patients may be referred to the electrodiagnostic laboratory. Overlapping mononeuritis multiplex is a common presentation, but distal symmetric polyneuropathy and monomelic neuropathy patterns can be seen. Depending on the disease associated with ischemic neuropathy, a mononeuropathy or a sensory-motor, axonal-demyelinating peripheral neuropathy may be seen as well. The treatment of ischemic neuropathy varies depending on the associated disease. Prognosis can be poor in the case of amyloidosis and the primary vasculitides. The literature is limited to cross-sectional case series and rare longitudinal studies likely related to the incidence of the diseases. Further study is needed to fully define the extent of the neurologic consequences of peripheral ischemia and its significance clinically.
 ...
PMID:Ischemic peripheral neuropathy. 1134 13

Ischemic neuropathy is common in subjects with critical limb ischemia, frequently causing chronic neuropathic pain. However, neuropathic pain caused by ischemia is hard to control despite the restoration of an adequate blood flow. Here, we used a rat model of ischemic-reperfusion nerve injury (IRI) to investigate possible effects of hepatocyte growth factor (HGF) against ischemic neuropathy. Hemagglutinating virus of Japan (HVJ) liposomes containing plasmids encoded with HGF was delivered into the peripheral nervous system by retrograde axonal transport following its repeated injections into the tibialis anterior muscle in the right hindlimb. First HGF gene transfer was done immediately after IRI, and repeated at 1, 2 and 3 weeks later. Rats with IRI exhibited pronounced mechanical allodynia and thermal hyperalgesia, decreased blood flow and skin temperature, and lowered thresholds of plantar stimuli in the hind paw. These were all significantly improved by HGF gene transfer, as also were sciatic nerve conduction velocity and muscle action potential amplitudes. Histologically, HGF gene transfer resulted in a significant increase of endoneurial microvessels in sciatic and tibial nerves and promoted nerve regeneration which were confirmed by morphometric analysis. Neovascularization was observed in the contralateral side of peripheral nerves as well. In addition, IRI elevated mRNA levels of P2X3 and P2Y1 receptors, and transient receptor potential vanilloid receptor subtype 1 (TRPV1) in sciatic nerves, dorsal root ganglia and spinal cord, and these elevated levels were inhibited by HGF gene transfer. In conclusion, HGF gene transfer is a potent candidate for treatment of acute ischemic neuropathy caused by reperfusion injury, because of robust angiogenesis and enhanced nerve regeneration.
 ...
PMID:Efficacy of nonviral gene transfer of human hepatocyte growth factor (HGF) against ischemic-reperfusion nerve injury in rats. 3278 Jul 56