Abstract DP349: Optogenetic Neuronal Stimulation Modulates Cholesterol Dynamics in Post-Stroke Recovery

Background: Post-stroke brain stimulation is a promising neurorestorative strategy, yet the underlying molecular mechanisms driving recovery remain unclear. Our prior work demonstrated that post-stroke optogenetic stimulation of the ipsilesional motor cortex (iM1) enhances functional recovery, and our RNA sequencing suggested cholesterol metabolism as a key pathway modulated by stimulation. Here, we examined the temporal dynamics of 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), a key cholesterol enzyme, after stroke and assessed how optogenetic iM1 stimulation influences this expression. Methods: Male C57BL/6 mice (6-7 weeks) underwent stereotaxic surgery to express Channelrhodopsin in iM1 excitatory neurons and optical fiber implantation. After 5-6 weeks, mice received transient middle cerebral artery occlusion (30 min). Optogenetic stimulations were delivered from post-stroke days (PD) 5–14. Motor performance was assessed using the rotating beam test at pre-stroke baseline, PD4, 7 and 14. Brains were collected from stroke (PD1, 7&15) and sham control mice (n=4-5/group), and processed for immunohistochemistry using antibodies against HMGCS1, NeuN and CD68. Results: iM1 stimulation enhanced recovery at PD14, improving beam performance in both travel distance and speed (p