Nitrergic Neurodegeneration in Cerebral Arteries of Streptozotocin-Induced Diabetic Rats

• Published in: Diabetes (New York, N.Y.) Vol. 54; no. 1; pp. 212 - 219
• Main Authors: Cellek, Selim, Anderson, Patrick N., Foxwell, Neale A.
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01.01.2005
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.54.1.212

Nitrergic Neurodegeneration in Cerebral Arteries of Streptozotocin-Induced Diabetic Rats A New Insight into Diabetic Stroke Selim Cellek 1 , Patrick N. Anderson 2 and Neale A. Foxwell 1 1 Wolfson Institute for Biomedical Research, University College London, London, U.K 2 Department of Anatomy and Developmental Biology, University College London, London, U.K Address correspondence and reprint requests to S. Cellek, MD, PhD, Wolfson Institute for Biomedical Research, University College London, Gower St., Cruciform Building, London WC1E 6BT, U.K. E-mail: s.cellek{at}ucl.ac.uk Abstract Although autonomic neuropathy is recognized as an independent risk factor for stroke in diabetes, the mechanism by which autonomic nerves are involved in this pathology is unknown. Parasympathetic (cholinergic) nerves of the autonomic nervous system are known to innervate and to cause relaxation of cerebral arteries by releasing nitric oxide (NO); hence, they are called nitrergic nerves. However, the effect of diabetes on nitrergic nerves is unknown. Here, we show that perivascular nitrergic nerves around the cerebral arteries degenerate in two phases in streptozotocin-induced diabetic rats. In the first phase, perivascular nitrergic nerve fibers remain intact while they lose their neuronal NO synthase content. This phase is reversible with insulin treatment. In the second phase, nitrergic cell bodies in the ganglia are lost via apoptosis in an irreversible manner. Throughout the two phases, irreversible thickening of the smooth muscle layer of cerebral arteries is observed. This is the first demonstration of nitrergic degeneration in diabetic cerebral arteries, which could elucidate the link between diabetic autonomic neuropathy and stroke. AGE, advanced glycation end product FITC, fluorescein isothiocyanate NMDA, N-methyl-d-aspartate nNOS, neuronal nitric oxide synthase STZ, streptozotocin TUNEL, Tdt-mediated dUTP nick-end labeling VAChT, vesicular acetylcholine transporter Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted October 4, 2004. Received July 7, 2004. DIABETES