Title:Traumatic Brain Injury: Central and Peripheral Role of α7 Nicotinic Acetylcholine Receptors
Volume: 13
Issue: 5
Author(s): Matthew L. Kelso, Julie H. Oestreich
Affiliation:
Keywords:
cytokine, excitotoxicity, inflammation, leukocyte, macrophage, neurodegeneration, platelet, traumatic brain injury, Nicotinic Acetylcholine Receptors, biomarker
Abstract: Traumatic brain injury (TBI) is a significant public health concern worldwide for which there is no cure. Once trauma has occurred, multiple biochemical pathways are set into motion that leads to a chronic, neurodegenerative condition. Two of the most widely studied pathological pathways are excitotoxicity and inflammation, processes that are influenced by α7 nicotinic acetylcholine receptors (nAChR). Previous studies have found a bilateral decrease in α7 nAChR expression in regions of the cortex and hippocampus that occurs in relation to injury severity. Subsequent studies showed that this decrease was evident in some parts of the hippocampus as early as 1 hour post-injury and remained decreased through 21 days. Other ligand-gated ion channels, such as non-α7 nAChRs and n-methyl-D-aspartate (NMDA) receptors did not show a similar widespread and consistent pattern of change following TBI, nor did the G-protein coupled muscarinic acetylcholine receptors, suggesting that the α7 nAChR could be a key mediator in the pathophysiology of traumatic brain injury.
In addition to its expression in the brain, the α7 nAChR has been found outside of the central nervous system (CNS) on many different cell types, including peripheral blood leukocytes, where they have a role in the cholinergic antiinflammatory pathway, and have recently been identified on platelets where they may have a role in activation. How these receptors are regulated in response to injury has not been investigated, but could potentially serve as a marker of neurodegeneration as has been done in Alzheimer's disease and schizophrenia. In this review, we will detail the role of α7 nAChR following TBI as well as explore the evidence of this receptor subtype in regards to blood component (leukocytes and platelets) involvement and the potential influence TBI has on peripheral expression and function.
