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Reversal of experimental diabetic neuropathy by VEGF gene transfer.
J Clin Invest. 2001 May; 107(9):1083-92.JCI

Abstract

The pathogenetic basis for diabetic neuropathy has been enigmatic. Using two different animal models of diabetes, we have investigated the hypothesis that experimental diabetic neuropathy results from destruction of the vasa nervorum and can be reversed by administration of an angiogenic growth factor. Nerve blood flow, as measured by laser Doppler imaging or direct detection of a locally administered fluorescent lectin analogue, was markedly attenuated in rats with streptozotocin-induced diabetes, consistent with a profound reduction in the number of vessels observed. A severe peripheral neuropathy developed in parallel, characterized by significant slowing of motor and sensory nerve conduction velocities, compared with nondiabetic control animals. In contrast, 4 weeks after intramuscular gene transfer of plasmid DNA encoding VEGF-1 or VEGF-2, vascularity and blood flow in the nerves of treated animals were similar to those of nondiabetic control rats; constitutive overexpression of both transgenes resulted in restoration of large and small fiber peripheral nerve function. Similar experiments performed in a rabbit model of alloxan-induced diabetes produced comparable results. These findings support the notion that diabetic neuropathy results from microvascular ischemia involving the vasa nervorum and suggest the feasibility of a novel treatment strategy for patients in whom peripheral neuropathy constitutes a secondary complication of diabetes.

Authors+Show Affiliations

Division of Cardiovascular Research, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11342572

Citation

Schratzberger, P, et al. "Reversal of Experimental Diabetic Neuropathy By VEGF Gene Transfer." The Journal of Clinical Investigation, vol. 107, no. 9, 2001, pp. 1083-92.
Schratzberger P, Walter DH, Rittig K, et al. Reversal of experimental diabetic neuropathy by VEGF gene transfer. J Clin Invest. 2001;107(9):1083-92.
Schratzberger, P., Walter, D. H., Rittig, K., Bahlmann, F. H., Pola, R., Curry, C., Silver, M., Krainin, J. G., Weinberg, D. H., Ropper, A. H., & Isner, J. M. (2001). Reversal of experimental diabetic neuropathy by VEGF gene transfer. The Journal of Clinical Investigation, 107(9), 1083-92.
Schratzberger P, et al. Reversal of Experimental Diabetic Neuropathy By VEGF Gene Transfer. J Clin Invest. 2001;107(9):1083-92. PubMed PMID: 11342572.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversal of experimental diabetic neuropathy by VEGF gene transfer. AU - Schratzberger,P, AU - Walter,D H, AU - Rittig,K, AU - Bahlmann,F H, AU - Pola,R, AU - Curry,C, AU - Silver,M, AU - Krainin,J G, AU - Weinberg,D H, AU - Ropper,A H, AU - Isner,J M, PY - 2001/5/9/pubmed PY - 2001/6/8/medline PY - 2001/5/9/entrez SP - 1083 EP - 92 JF - The Journal of clinical investigation JO - J. Clin. Invest. VL - 107 IS - 9 N2 - The pathogenetic basis for diabetic neuropathy has been enigmatic. Using two different animal models of diabetes, we have investigated the hypothesis that experimental diabetic neuropathy results from destruction of the vasa nervorum and can be reversed by administration of an angiogenic growth factor. Nerve blood flow, as measured by laser Doppler imaging or direct detection of a locally administered fluorescent lectin analogue, was markedly attenuated in rats with streptozotocin-induced diabetes, consistent with a profound reduction in the number of vessels observed. A severe peripheral neuropathy developed in parallel, characterized by significant slowing of motor and sensory nerve conduction velocities, compared with nondiabetic control animals. In contrast, 4 weeks after intramuscular gene transfer of plasmid DNA encoding VEGF-1 or VEGF-2, vascularity and blood flow in the nerves of treated animals were similar to those of nondiabetic control rats; constitutive overexpression of both transgenes resulted in restoration of large and small fiber peripheral nerve function. Similar experiments performed in a rabbit model of alloxan-induced diabetes produced comparable results. These findings support the notion that diabetic neuropathy results from microvascular ischemia involving the vasa nervorum and suggest the feasibility of a novel treatment strategy for patients in whom peripheral neuropathy constitutes a secondary complication of diabetes. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/11342572/Reversal_of_experimental_diabetic_neuropathy_by_VEGF_gene_transfer_ L2 - https://doi.org/10.1172/JCI12188 DB - PRIME DP - Unbound Medicine ER -