Research Reports - Donepezil rescues spatial learning and memory deficits following traumatic brain injury
PLoS One. 2015 Feb 25;10(2)
Yu TS(1), Kim A(1), Kernie SG(1)
Traumatic brain injury (TBI) is ubiquitous and effective treatments for it remain
supportive largely due to uncertainty over how endogenous repair occurs.
Recently, we demonstrated that hippocampal injury-induced neurogenesis is one
mechanism underlying endogenous repair following TBI. Donepezil is associated
with increased hippocampal neurogenesis and has long been known to improve
certain aspects of cognition following many types of brain injury through unknown
mechanisms. By coupling donepezil therapy with temporally regulated ablation of
injury-induced neurogenesis using nestin-HSV transgenic mice, we investigated
whether the pro-cognitive effects of donepezil following injury might occur
through increasing neurogenesis. We demonstrate that donepezil itself enhances
neurogenesis and improves cognitive function following TBI, even when
injury-induced neurogenesis was inhibited. This suggests that the therapeutic
effects of donepezil in TBI occur separately from its effects on neurogenesis.