Time-dependent alterations of cholinergic markers after experimental traumatic brain injury.

Traumatic brain injury (TBI) is one of the leading causes of death and disability. Cognitive deficits are believed to be connected with impairments of the cholinergic system. The present study was conducted to evaluate the cholinergic system in a model of focal brain injury with special attention to the time course of posttraumatic events in critical brain regions. Three groups of male Sprague-Dawley rats (post-TBI survival time: 2 h, 24 h and 72 h) were subjected to sham-operation (control) or controlled cortical impact injury. Receptor densities were determined on frozen ipsilateral sagittal brain sections with [(3)H]epibatidine (nicotinic acetylcholine receptors) and [(3)H]QNB (muscarinic acetylcholine receptors). The density of the vesicular acetylcholine transporter (vAChT) was evaluated with (-)[(3)H]vesamicol. Compared to control, vAChT was lowered (up to 50%) at each time point after trauma, with reductions in olfactory tubercle, basal forebrain, motor cortex, putamen, thalamic and hypothalamic areas and the gigantocellular reticular nucleus. Time-dependent reductions of about 20% of nAChR-density in the thalamus, hypothalamus, olfactory tubercle, gigantocellular reticular nucleus and motor cortex were observed post-TBI at 24 and 72 h. The same brain regions showed reductions of mAChR at 24 and 72 h after trauma with additional decreases in the corpus callosum, basal forebrain and anterior olfactory nucleus. In conclusion, cholinergic markers showed significant time-dependent impairments after TBI. Considering the role of the cholinergic system for cognitive processes in the brain, it seems likely that these impairments contribute to clinically relevant cognitive deficits.