Voltage-gated calcium channel antagonists and traumatic brain injury

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30 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)788-812
Number of pages25
JournalPharmaceuticals
Volume6
Issue number7
DOIs
StatePublished - Jun 26 2013

Fingerprint

Calcium Channel Blockers
Cell Death
Calcium
Research
Astrocytes
Cognition
Cause of Death
Rodentia
Traumatic Brain Injury
Pharmacology
Neurons
Wounds and Injuries
Therapeutics
Pharmaceutical Preparations

Keywords

  • Antagonists
  • Nimodipine
  • Traumatic brain injury
  • Voltage-gated calcium channels
  • Ziconotide

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

Cite this

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AB - 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.

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