TY - JOUR
T1 - Targeting the cholinergic system for neuroprotection and/or enhancement of functional recovery following neurotrauma
AU - Huber, Kathleen B.G.
AU - Uteshev, Victor V.
AU - Pauly, James R.
N1 - Publisher Copyright:
© 2016 Bentham Science Publishers.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - Acetylcholine
KW - Excitotoxicity
KW - Muscarinic and Alpha 7
KW - Nicotinic receptor
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=84969255668&partnerID=8YFLogxK
U2 - 10.2174/1381612822666160127113631
DO - 10.2174/1381612822666160127113631
M3 - Article
C2 - 26818862
AN - SCOPUS:84969255668
SN - 1381-6128
VL - 22
SP - 2072
EP - 2082
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
IS - 14
ER -