Sialated glycolipids are recognized by platelets as “innate danger signals” of a neuronal damage.

<p>(<b>A</b>) The proposed model of brain lipid rafts recognition by the platelet receptors. Multiple receptors on the platelets and an intact rigid structure of brain lipid rafts are required to form glycosynapses for the coordinated platelet activation and degranulation.The initial recognition of brain lipid rafts involves the interplay of siglecs and adhesion molecules such as Siglec-H, Siglec-15, ALCAM or other molecules, which results in the recruitment of P-selectin on the surface of platelets to the site of glycosynapse formation and eventual platelets degranulation. (<b>B</b>) The schematics of the staged neuronal damage detection process by platelets leading to the recognition of lipid rafts during EAE or neurodegenerative diseases such as MS. In the intact CNS, platelets do not see lipid rafts of astrocytes and neurons due to the impermeable nature of the BBB. The trauma, infection, neurodegeneration or inflammation disrupts the structure of neurovascular units, exposing lipid rafts on the surface of astrocytes and neurons to platelets. The platelets then interact with brain lipid rafts, become activated and secrete proinflammatory cytokines (IL-1) and chemokines (CXCL4/PF4) and serotonin that attract immunocytes to the lesion site and activate them <i>in situ</i>. Thus platelets serve as the first line sensors and responders in the early stages of neuronal damage.