Cholinergic and opioid mediation of traumatic brain injury

There is considerable evidence for the involvement of cholinergic and opioid systems in the pathophysiological responses associated with traumatic brain injury (TBI). To some extent, interest in this area has been eclipsed by a strong focus on, and rapid progress in, studies of the role of excitatory amino acids in TBI. We present evidence that both cholinergic and opioid systems are important modulators of the pathophysiological response to TBI, potentially equally as important as excitatory amino acids. There is a relatively large body of experimental data documenting the involvement of these systems in TBI that has yielded important principles with general significance for laboratory studies of the neuropharmacology of TBI. In fact, the first demonstration of excitotoxic mechanisms of TBI involved studies of the role of acetylcholine in experimental TBI. There also are clinical data suggesting that modulation of opioid and cholinergic systems could benefit patients.