Abstract
Development of novel pharmacotherapies for the treatment of traumatic injury to the nervous system has been ongoing for over 40 years. Despite many promising compounds discovered using animal models, no treatments have successfully translated into the clinic. The central dogma in this field is that brain trauma initiates a complex chain of biochemical events leading to secondary brain damage and sustained neurological deficits. The delayed secondary brain injury is likely to result from multiple insults including oxidative stress, mitochondrial dysfunction, breakdown of the blood brain barrier, dysregulated release of glutamate, pro-inflammatory cytokines, and other mediators. However, therapies targeting these systems have generally met with failure in clinical trials. The purpose of this review is to summarize the models used for preclinical neurotrauma research, provide a brief overview of previous failed clinical trials in head and spinal cord injury, and finally, to review involvement of the cholinergic system and discuss implications for future research. Possibilities and pitfalls of targeting the cholinergic system for neuroprotection and/or enhancement of functional recovery are also discussed.
Keywords: Acetylcholine, traumatic brain injury, nicotinic receptor, Excitotoxicity, Muscarinic and Alpha 7.
Current Pharmaceutical Design
Title:Targeting the Cholinergic System for Neuroprotection and/or Enhancement of Functional Recovery Following Neurotrauma
Volume: 22 Issue: 14
Author(s): Kathleen B.G. Huber, Victor V. Uteshev and James R. Pauly
Affiliation:
Keywords: Acetylcholine, traumatic brain injury, nicotinic receptor, Excitotoxicity, Muscarinic and Alpha 7.
Abstract: Development of novel pharmacotherapies for the treatment of traumatic injury to the nervous system has been ongoing for over 40 years. Despite many promising compounds discovered using animal models, no treatments have successfully translated into the clinic. The central dogma in this field is that brain trauma initiates a complex chain of biochemical events leading to secondary brain damage and sustained neurological deficits. The delayed secondary brain injury is likely to result from multiple insults including oxidative stress, mitochondrial dysfunction, breakdown of the blood brain barrier, dysregulated release of glutamate, pro-inflammatory cytokines, and other mediators. However, therapies targeting these systems have generally met with failure in clinical trials. The purpose of this review is to summarize the models used for preclinical neurotrauma research, provide a brief overview of previous failed clinical trials in head and spinal cord injury, and finally, to review involvement of the cholinergic system and discuss implications for future research. Possibilities and pitfalls of targeting the cholinergic system for neuroprotection and/or enhancement of functional recovery are also discussed.
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Cite this article as:
Huber B.G. Kathleen, Uteshev V. Victor and Pauly R. James, Targeting the Cholinergic System for Neuroprotection and/or Enhancement of Functional Recovery Following Neurotrauma, Current Pharmaceutical Design 2016; 22 (14) . https://dx.doi.org/10.2174/1381612822666160127113631
DOI https://dx.doi.org/10.2174/1381612822666160127113631 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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