Ciliary Neurotrophic Factor Improves Nerve Conduction and Ameliorates Regeneration Deficits in Diabetic Rats

Ciliary Neurotrophic Factor Improves Nerve Conduction and Ameliorates Regeneration Deficits in Diabetic Rats Andrew P. Mizisin , Yvonne Vu , Michelle Shuff and Nigel A. Calcutt From the Department of Pathology, University of California, San Diego, La Jolla, California Address correspondence and reprint requests to Andrew P. Mizisin, PhD, Department of Pathology, 0612, School of Medicine, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0612. E-mail: amizisin{at}ucsd.edu Abstract Ciliary neurotrophic factor (CNTF) protein and bioactivity are reduced in the peripheral nerve of hyperglycemic rats with a cause related to metabolism of hexose sugars by aldose reductase. Here the efficacy of CNTF treatment against disorders of nerve function in hyperglycemic rats was investigated. CNTF treatment from the onset of 8 weeks of galactose feeding prevented nerve conduction slowing in a dose-dependent manner. Streptozotocin-induced diabetic rats were maintained for 4 weeks before CNTF treatment was initiated. Four weeks of CNTF treatment significantly improved nerve conduction compared with untreated diabetic rats and also normalized the recovery of toe spread after sciatic nerve crush. One week of CNTF treatment significantly improved the distance of sensory nerve regeneration achieved after nerve crush injury compared with untreated diabetic rats. CNTF was without effects on any parameter in nondiabetic rats. Eight weeks of diabetes did not impair macrophage recruitment 1 and 7 days after nerve crush; neither did intraneural injections of CNTF and CNTFRα enhance recruitment in diabetic or control rats. These observations point to the potential utility of CNTF in treating nerve dysfunction in experimental diabetes. CNTF, ciliary neurotrophic factor MNCV, motor nerve conduction velocity NCV, nerve conduction velocity SNCV, sensory nerve conduction velocity STZ, streptozotocin Footnotes Accepted March 29, 2004. Received October 10, 2003. DIABETES