Neuroprotective Bioactive Compounds from Marine Algae and Their By-Products Against Cerebral Ischemia–Reperfusion Injury: A Comprehensive Review

Cerebral ischemia–reperfusion (I/R) injury is a leading cause of death and long-term disability worldwide, characterized by a complex interplay of pathophysiological mechanisms and currently limited therapeutic options. This critical unmet need underscores the importance of exploring novel multi-targeted neuroprotective agents. Marine algae represent a rich and underexplored source of structurally diverse bioactive compounds with promising therapeutic potential against cerebral I/R injury. This comprehensive review systematically summarizes the preclinical evidence on the neuroprotective effects and underlying mechanisms of key bioactive compounds found in marine algae, including polysaccharides (e.g., fucoidan, laminarin, porphyran), carotenoids (e.g., astaxanthin, fucoxanthin, lutein, zeaxanthin), polyphenols (e.g., dieckol, phlorotannins), and sterols (e.g., β-sitosterol). These compounds consistently demonstrate significant efficacy across various in vitro and in vivo models, primarily through multifaceted actions encompassing anti-excitotoxic, antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as the modulation of crucial signaling pathways and preservation of blood–brain barrier integrity. While the existing preclinical evidence is highly promising, successful clinical translation necessitates further rigorous research to overcome challenges related to precise molecular understanding, translational relevance, pharmacokinetics, and safety. Beyond their pharmacological significance, the sustainable utilization of marine by-products as renewable sources of bioactive agents further highlights their dual value, offering not only novel therapeutic avenues for cerebral I/R injury but also contributing to marine resource valorization.