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Voltage-Gated Calcium Channel Antagonists and Traumatic Brain Injury
Department of Neurological Surgery, One Shields Avenue, University of California, Davis, CA 95616, USA
NSF Center for Biophotonics Science and Technology, Suite 2700 Stockton Blvd, Suite 1400, Sacramento, CA, 95817, USA
* Author to whom correspondence should be addressed.
Received: 29 March 2013; in revised form: 6 June 2013 / Accepted: 6 June 2013 / Published: 26 June 2013
Abstract: Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Despite more than 30 years of research, no pharmacological agents have been identified that improve neurological function following TBI. However, several lines of research described in this review provide support for further development of voltage gated calcium channel (VGCC) antagonists as potential therapeutic agents. Following TBI, neurons and astrocytes experience a rapid and sometimes enduring increase in intracellular calcium ([Ca2+]i). These fluxes in [Ca2+]i drive not only apoptotic and necrotic cell death, but also can lead to long-term cell dysfunction in surviving cells. In a limited number of in vitro experiments, both L-type and N-type VGCC antagonists successfully reduced calcium loads as well as neuronal and astrocytic cell death following mechanical injury. In rodent models of TBI, administration of VGCC antagonists reduced cell death and improved cognitive function. It is clear that there is a critical need to find effective therapeutics and rational drug delivery strategies for the management and treatment of TBI, and we believe that further investigation of VGCC antagonists should be pursued before ruling out the possibility of successful translation to the clinic.
Keywords: voltage-gated calcium channels; antagonists; ziconotide; nimodipine; traumatic brain injury
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MDPI and ACS Style
Gurkoff, G.; Shahlaie, K.; Lyeth, B.; Berman, R. Voltage-Gated Calcium Channel Antagonists and Traumatic Brain Injury. Pharmaceuticals 2013, 6, 788-812.
Gurkoff G, Shahlaie K, Lyeth B, Berman R. Voltage-Gated Calcium Channel Antagonists and Traumatic Brain Injury. Pharmaceuticals. 2013; 6(7):788-812.
Gurkoff, Gene; Shahlaie, Kiarash; Lyeth, Bruce; Berman, Robert. 2013. "Voltage-Gated Calcium Channel Antagonists and Traumatic Brain Injury." Pharmaceuticals 6, no. 7: 788-812.