Title : Aging and traumatic brain injuries: involvement of cholinergic transmission in preclinical tests of executive function
Abstract:
Traumatic brain injuries (TBI) impact millions of Americans, with older patients being more likely to have a co-occurring condition, particularly dementia. Galantamine (GAL), a first-line drug used to treat dementia, acts primarily as an acetylcholinesterase inhibitor and has been reported to positively impact cognitive function in older adults. Previously, we demonstrated that a controlled cortical impact (CCI) injury produced significant impairments in executive function in the attentional set-shifting test (AST), a complex cognitive paradigm analogous to the Wisconsin Card Sorting Test, which is used to measure strategy-switching deficits in patients with frontal lobe damage, TBI, and psychiatric disorders. In the current study, we predicted that daily GAL injections would normalize AST performance after a parietal lobe TBI in rats. Isoflurane-anesthetized adult male rats were randomly assigned to either a CCI or sham group. Surgery was administered following a previously established CCI protocol. Following surgery, rats were randomly distributed into three treatment groups: saline or GAL (1 or 2 mg/kg/day), until the test day 4 weeks later. AST results indicated that TBI significantly impairs performance on the first reversal stage, deficits attenuated by both GAL chronic doses (p<0.05). In particular, GAL (2 mg/kg/day) also significantly reduced TBI-induced cortical lesion volumes (p<0.05). In summary, chronic GAL administration provides an efficacious treatment for higher-order cognitive recovery following TBI. Ongoing studies are investigating whether these results are maintained when using aged Sprague-Dawley rats in order to mirror the elderly segment of adults typically treated with GAL in the clinic, as well as assess protein expression of brain cholinergic markers involved in the GAL mechanism of action for restoring executive function after TBI.
Audience take away:
- Clinicians and basic scientists alike will be presented with preclinical findings confirming that a therapy given for dementia is also beneficial as a treatment approach for experimental brain trauma.
- Combining aging processes with brain trauma in the laboratory mimics a large window of the clinical population suffering from brain injury, namely the elderly. The findings in terms of cognitive results and brain mechanisms are clinically relevant to researchers, clinicians, and rehabilitation therapists.
- The data showing that galantamine is effective at restoring cognitive function after brain trauma are of high importance to the clinic, considering that this pharmacotherapy is often prescribed to patients with dementia diagnosis.
