Inhibiting Proneurotrophin signaling protects Basal Forebrain Neurons following Traumatic Brain Injury

Traumatic Brain Injury (TBI) can cause degeneration and apoptosis of basal forebrain cholinergic neurons (BFCNs), thereby impairing cognition, particularly spatial memory and learning. Proneurotrophin signaling via p75NTR plays an essential role in this process, as proneurotrophins are highly upregulated at the injured cortex, which is a target of the BFCNs. This study aims to understand whether inhibition of proneurotrophin signaling via p75NTR can preserve and protect the BFCNs. Following a unilateral FPI, mice were categorized into three antibody treatment groups and received treatment via non-invasive intranasal delivery. After perfusion, brain tissue was sectioned, stained immunohistochemically, and analyzed using Fluorescence microscopy to quantify and evaluate cell survival. Results have shown that inhibiting the proneurotrophin activity via the p75NTR can significantly protect the BFCNs on the injury side in comparison to the injured control treatment group. These findings provide an insight into possible future therapeutic interventions that may aid in preserving and protecting neural tissue following TBI.