Spinal cord regeneration induced by a voltage-gated calcium channel agonist.
Regeneration in the central nervous system (CNS) is prohibitive. This is likely due to an interplay of cellular (gene expression, growth factors) and environmental (inhibition by CNS myelin) factors. Calcium supports various intracellular functions, and multiple in vitro studies have shown a role of calcium in axonal growth. In this study, we examine the role of a calcium agonist, S(-)-Bay K 8644, in promoting or impeding CNS growth in vivo, in an effort to understand further the relationship between the voltage-gated L type calcium channel and regeneration. Using a well-established rat spinal cord model of regeneration, we have injected various doses of S(-)-Bay K 8644 (30-240 M) around the injured spinal cord. Our results demonstrate that S(-)-Bay K 8644 enhances regeneration in a dose-dependent fashion. In addition, at very specific concentrations, the same agonist has no effect on or even inhibits regeneration. We conclude that spinal regeneration is highly dependent on intracellular calcium concentration. Furthermore, depending on the dose used, the effect of calcium agonist supplementation on spinal regeneration can be supportive or inhibitory.
Unlu
Agahan
A
Department of Neurological Surgery, University of Wisconsin Medical School, Clinical Science Center, Madison, USA.
Hariharan
Nithya
N
Iskandar
Bermans J
BJ
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D016380:Brain Tissue Transplantation; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D003714:Denervation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D012183:Retrograde Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D012584:Sciatic Nerve / Q000637:transplantation; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013266:Stilbamidines; D016896:Treatment Outcome
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D002120:Calcium Channel Agonists; D015220:Calcium Channels; D005456:Fluorescent Dyes; D013266:Stilbamidines; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium