SS-31 Protects Aged Rat Brains from Glycocalyx Degradation and Cognitive Decline

Aging is often accompanied by neuroinflammation and progressive cognitive impairment, significantly impacting quality of life. The endothelial glycocalyx, a protective layer on blood vessel walls, is crucial for vascular health and brain function. However, its degradation is increasingly linked to age-related neurological issues. This study aimed to understand how endothelial glycocalyx degradation contributes to neuroinflammation and cognitive decline in aged rats, and whether the peptide SS-31 can offer protection.

The study revealed that aged rats treated with SS-31 exhibited significant improvements in cognitive performance compared to controls. In the Morris Water Maze, SS-31 treated rats showed a 28% reduction in escape latency (p<0.01) and spent 35% more time in the target quadrant (p<0.001). Furthermore, SS-31 markedly attenuated neuroinflammation, with brain levels of pro-inflammatory cytokines like IL-6 and TNF-α reduced by 43% and 38% respectively (p<0.01 for both). The most striking finding was the preservation of the endothelial glycocalyx, as SS-31 treatment led to a 2.5-fold increase in heparan sulfate content and a 1.8-fold increase in syndecan-1 expression in brain microvessels compared to untreated aged controls (p<0.001). This indicates a direct protective effect on vascular integrity.