Calcium antagonists fail to protect mammalian spinal neurons after physical injury.
Most investigations of calcium antagonists as treatments for experimental spinal cord injury (SCI) have not demonstrated significant reduction of tissue damage or improvement in neurologic outcome. Many of these studies were prompted by reports that these agents increase blood flow to ischemic tissues. However, in vitro studies of renal and neuronal tissues subjected to an anoxic stress have shown that the calcium antagonists can confer direct protection on stressed parenchymal cells. We have used a tissue culture model of nerve cell injury to investigate whether calcium antagonists increase the probability of survival of spinal cord neurons after a defined physical trauma. Preliminary toxicity studies determined the maximum nontoxic dosages of verapamil (80 microM), nifedipine (10 microM), and chlorpromazine (10 microM) for neurons in our cultures. Preselected neurons (100-200 per study) were subjected to amputation of one primary dendrite at a distance of 100 microns from the perikaryon. Erythrosine B tests of viability conducted 24 h after lesioning failed to demonstrate that neurons injured in the presence of any one of these agents had an increased probability of survival compared to operated control neurons. Viability evaluations conducted 2 h after injury with phase contrast microscopy showed no evidence of slowed deterioration. Correction for other lesion physical parameters (lesion diameter and the extent of proximal segment retraction) also failed to reveal any increased protection by these agents. We conclude that calcium antagonists alone will not be useful for treatment of the primary injury of SCI.
Shi
R Y
RY
Department of Biological Sciences, University of North Texas, Denton.
Lucas
J H
JH
Wolf
A
A
Gross
G W
GW
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology* / Q000627:therapeutic use; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D014700:Verapamil; D009543:Nifedipine; D002746:Chlorpromazine