Background: Chronic cerebral hypoperfusion disrupts hippocampal circuits that support learning and memory. Whether near infrared photobiomodulation at 810 nanometers can remodel disease related proteomic programs in this region remains unclear. Methods: We analyzed hippocampal proteomes from three groups: sham, bilateral common carotid artery occlusion, and occlusion plus 810 nanometer photobiomodulation. Protein level changes were ranked and tested with gene set enrichment using Benjamini Hochberg control of false discovery. We summarized leading edge proteins and organized pathway signals into thematic modules. To enhance generalizability, we prespecified an external benchmarking plan that harmonizes our pipeline with public rodent hippocampal hypoperfusion or ischemia datasets from GEO or ArrayExpress, followed by pathway level concordance tests and rank based meta analysis. Results: Hypoperfusion showed coherent enrichment patterns consistent with mitochondrial translation and inner membrane remodeling together with amino acid metabolism, alongside reductions in endosomal lysosomal trafficking and multivesicular body organization, indicating bioenergetic stress with vesicular transport dysfunction. With 810 nanometer photobiomodulation, enrichment patterns shifted toward postsynaptic structure, junctional and actin organization, and neurodevelopmental modules, with concurrent modulation of transporter heavy and respiratory chain programs, indicating partial rescue of hypoperfusion signatures. Leading edge protein sets converged on tractable postsynaptic density candidates for targeted validation. These directions were reproducible across complementary enrichment resources in our pipeline. Conclusions: Hippocampal proteomics indicate that 810 nanometer photobiomodulation reprograms pathway level signatures engaged by chronic hypoperfusion, supporting a mechanism of network stabilization through postsynaptic and cytoskeletal remodeling with tuning of mitochondrial and vesicular systems. The planned public data validation will provide cross cohort confirmation and figure ready visualizations, motivating prospective studies that pair photobiomodulation with cognitive and electrophysiological endpoints in models of vascular cognitive impairment.
Zhang et al. (Thu,) studied this question.