Fig. 1

Different effects and therapeutic potential of PEV and BEV on TBI. (a) - (e): PEV mediate the pathophysiological processes that result in secondary damage from TBI, such as inflammation, coagulopathy, brain edema, systemic complications, and neurodegenerative disease. (a) The miRNA and pro-inflammatory cytokines in PEV promote glial and immune cell activation and release of proinflammatory cytokines. (b) The PS/CL and TF in PEV trigger and exacerbate the coagulation cascade. (c) The PS/CL in PEV activate platelets and causes them to release pEVs. (d) The EV-VWF complex disrupts the BBB and EVs enter the peripheral circulation. (e) Misfold proteins in PEV cause neuronal degeneration and apoptosis. (f) - (i): BEV suppress excessive inflammation and participate in tissue repair and regeneration after TBI. (f) The miRNAs and anti-inflammatory cytokines in BEV inhibit glial and immune cell activation and release of pro-inflammatory cytokines. (g) BEV promote the formation of new blood vessels. (h) The miRNA in BEV inhibits hypertrophic glial scar formation. (i) The neurotrophins and miRNA in BEV promote neuronal growth and maturation. Abbreviations: Aβ:amyloid β-peptide;α-syn:α-synuclein; BBB: blood–brain barrier; BEV: biological extracellular vesicles; CL: cardiolipin; EVs: extracellular vesicles; PEV: pathological extracellular vesicles; PS: phosphatidylserine; TDP-43: TAR DNA-binding protein of 43 kDa; TF: tissue factor; VWF: von Willebrand factor. Figure created with BioRender.com