Nitrergic neurodegeneration in cerebral arteries of streptozotocin-induced diabetic rats: a new insight into diabetic stroke.
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.
Cellek
Selim
S
Wolfson Institute for Biomedical Research, University College London, Gower St., Cruciform Building, London WC1E 6BT, UK. s.cellek@ucl.ac.uk
Anderson
Patrick N
PN
Foxwell
Neale A
NA
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D004195:Disease Models, Animal; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000503:physiopathology*; D050494:Vesicular Acetylcholine Transport Proteins
D001786:Blood Glucose; D007328:Insulin; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat