Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: implications for chemical-induced peripheral sensory neuropathies.
Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG), which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.
Jimenez-Andrade
Juan M
JM
Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA. jmjimene@email.arizona.edu
Herrera
Monica B
MB
Ghilardi
Joseph R
JR
Vardanyan
Marina
M
Melemedjian
Ohannes K
OK
Mantyh
Patrick W
PW
D000818:Animals; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000098:blood supply* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010525:Peripheral Nerves / Q000098:blood supply* / Q000648:ultrastructure; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology
D019408:Platelet Endothelial Cell Adhesion Molecule-1