Neuroprotective effects of pretreatment with fucoidan and ruthenium red in rats exposed to ischemic stroke injury

BACKGROUND: Ischemic strokes (ISs) lead to multiple neurological disorders, including physical, behavioral, and cognitive impairments. It is associated with high mortality, reduced quality of life if survival occurs, and high healthcare costs. Ruthenium Red (RR) is an inhibitor of the mitochondrial calcium uniporter, and Fucoidan (FCN) is a P-selectin blocker with anti-inflammatory and antioxidant properties. The aim of this study was to investigate the ability of pretreatment with fucoidan and ruthenium red to reduce neural injury as a prophylactic treatment against IS injury. METHODS: Forty-eight male rats were assigned to six groups. The rats in the sham group received no intervention. Global cerebral ischemia and reperfusion were induced in the IS group via the 4-vessel model. A single dose of RR (2.5 mg/kg) or FCN (50 mg/kg) was administered separately and simultaneously in the IS+ pre (RR), IS+ pre (FCN), and IS+ pre (RR+FCN) groups before exposure to IS. The levels of oxidative stress, inflammation, and neuronal death in the hippocampal tissue were assessed. Learning and memory were assessed using the shuttle box and novel object recognition tests. RESULTS: Our study results showed that exposure to stroke significantly decreased superoxide dismutase (SOD) levels while increasing malondialdehyde (MDA), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha. Pretreatment with fucoidan and ruthenium red significantly reduced oxidative stress, tissue inflammation, and neuronal death in the hippocampal CA1 region, especially when both drugs were used simultaneously. Learning and memory impairments following stroke were significantly reduced in the groups that received pretreatment. CONCLUSION: Pretreatment with fucoidan and ruthenium red effectively reduced the incidence of neural complications associated with ischemic stroke. Synergistic neuroprotective effects were observed when the two drugs were used simultaneously.