FLUID PERCUSSION INJURY CAUSES LOSS OF FOREBRAIN CHOLINE-ACETYLTRANSFERASE AND NERVE GROWTH-FACTOR RECEPTOR IMMUNOREACTIVE CELLS IN THE RAT

Memory dysfunction is a common sequela of human traumatic brain injury (TBI). Cholinergic forebrain neurons are recognized for their role in memory. We tested the hypothesis that forebrain cholinergic neurons are vulnerable to fluid percussion injury (FPI), a model of human TBI. Rodents were subjected to a moderate parasagittal FPI, sham injury, or fimbria/fornix axotomy and then killed 10 days after the procedure. Additional animals underwent FPI or sham injury and were killed 7, 14, and 28 days after the procedure. Neurons in the medial septal nucleus and vertical limb of the nucleus of the diagonal band of Broca were identified and quantitated using choline acetyltransferase (ChAT) and low affinity nerve growth factor receptor (NGF-R) immunohistochemistry. Our results showed a significant decrease in ChAT (17% +/- 5%) and NGF-R (24% +/- 8%) immunoreactive cells in FPI animals killed after 10 days when compared to sham-injured animals. Animals undergoing fimbria/fornix axotomy showed a greater reduction in ChAT (53% +/- 13%) and NGF-R (55% +/- 5%) immunoreactive cells 10 days postaxotomy. The number of ChAT and NGF-R immunoreactive neurons was reduced at all time points. However, statistical significance was present 10 and 14 days postinjury for ChAT immunoreactive neurons and 10 days only for NGF-R immunoreactive neurons. These studies have shown that FPI produces transient loss of ChAT and NGF-R immunoreactive neurons.