TY - JOUR
T1 - Effects of hyperglycemia on rat cavernous nerve axons
T2 - A functional and ultrastructural study
AU - Zotova, Elena G.
AU - Schaumburg, Herbert H.
AU - Raine, Cedric S.
AU - Cannella, Barbara
AU - Tar, Moses
AU - Melman, Arnold
AU - Arezzo, Joseph C.
N1 - Funding Information:
The authors would like to thank Shirley Seto, Linda O'Donnell and Mona Litwak for their assistance in preparation of the manuscript. This work was supported by NIH grants R01 NS041194, P01 DK060037, and DK20541.
PY - 2008/10
Y1 - 2008/10
N2 - The present study explored parallel changes in the physiology and structure of myelinated (Aδ) and unmyelinated (C) small diameter axons in the cavernous nerve of rats associated with streptozotocin-induced hyperglycemia. Damage to these axons is thought to play a key role in diabetic autonomic neuropathy and erectile dysfunction, but their pathophysiology has been poorly studied. Velocities in slow conducting fibers were measured by applying multiple unit procedures; histopathology was evaluated with both light and electron microscopy. To our knowledge, these are the initial studies of slow nerve conduction velocities in the distal segments of the cavernous nerve. We report that hyperglycemia is associated with a substantial reduction in the amplitude of the slow conducting response, as well as a slowing of velocities within this very slow range (< 2.5m/s). Even with prolonged hyperglycemia (> 4months), histopathological abnormalities were mild and limited to the distal segments of the cavernous nerve. Structural findings included dystrophic changes in nerve terminals, abnormal accumulations of glycogen granules in unmyelinated and preterminal axons, and necrosis of scattered smooth muscle fibers. The onset of slowing of velocity in the distal cavernous nerve occurred subsequent to slowing in somatic nerves in the same rats. The functional changes in the cavernous nerve anticipated and exceeded the axonal degeneration detected by morphology. The physiologic techniques outlined in these studies are feasible in most electrophysiologic laboratories and could substantially enhance our sensitivity to the onset and progression of small fiber diabetic neuropathy.
AB - The present study explored parallel changes in the physiology and structure of myelinated (Aδ) and unmyelinated (C) small diameter axons in the cavernous nerve of rats associated with streptozotocin-induced hyperglycemia. Damage to these axons is thought to play a key role in diabetic autonomic neuropathy and erectile dysfunction, but their pathophysiology has been poorly studied. Velocities in slow conducting fibers were measured by applying multiple unit procedures; histopathology was evaluated with both light and electron microscopy. To our knowledge, these are the initial studies of slow nerve conduction velocities in the distal segments of the cavernous nerve. We report that hyperglycemia is associated with a substantial reduction in the amplitude of the slow conducting response, as well as a slowing of velocities within this very slow range (< 2.5m/s). Even with prolonged hyperglycemia (> 4months), histopathological abnormalities were mild and limited to the distal segments of the cavernous nerve. Structural findings included dystrophic changes in nerve terminals, abnormal accumulations of glycogen granules in unmyelinated and preterminal axons, and necrosis of scattered smooth muscle fibers. The onset of slowing of velocity in the distal cavernous nerve occurred subsequent to slowing in somatic nerves in the same rats. The functional changes in the cavernous nerve anticipated and exceeded the axonal degeneration detected by morphology. The physiologic techniques outlined in these studies are feasible in most electrophysiologic laboratories and could substantially enhance our sensitivity to the onset and progression of small fiber diabetic neuropathy.
KW - Cavernous nerve
KW - Cavernous smooth muscles
KW - Diabetes
KW - Diabetic autonomic neuropathy
KW - Erectile dysfunction
KW - Major pelvic ganglia
KW - Nerve conduction velocity
KW - Neuroaxonal dystrophy
KW - Parasympathetic
KW - Small fiber neuropathy
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U2 - 10.1016/j.expneurol.2008.07.009
DO - 10.1016/j.expneurol.2008.07.009
M3 - Article
C2 - 18687329
AN - SCOPUS:51349161154
SN - 0014-4886
VL - 213
SP - 439
EP - 447
JO - Experimental Neurology
JF - Experimental Neurology
IS - 2
ER -