Fig. 2

The mechanisms of mesenchymal stem cell therapy for ICH. A After ICH occurs, it can cause brain edema through the MAPK signaling pathway. Macrophages can also cause brain tissue edema by secreting cytokines such as TNF-α, IL-1β, and IL-6. In addition to directly inhibiting the above two methods, MSCs can also secrete BDNF to relieve cerebral edema. TNF-α secreted by macrophages can act on MSCs with the help of TNFR-1 and finally increase the level of Prostaglandin E2 (PGE2) through the NF-κB signaling pathway. PGE2 binds to EP2/EP4 on the surface of macrophages to promote IL-10 secretion, thereby inhibiting inflammation. MSCs can directly increase the expression of growth-associated protein-43 (GAP-43) through ERK1/2, thereby exerting neuroprotective effects. B Damaged tissue stimulates inflammatory cells (macrophages, astrocytes) to increase peroxynitrite (ONOO–), a strong oxidant, levels through signal pathways. Increased ONOO– can directly damage tight junction proteins and can also promote the production of Matrix metalloproteinase-9 (MMP-9) and damage tight junction proteins, ultimately leading to the blood–brain barrier BBB damage. TIMP-1 as a MMP inhibitor can inhibit MMP activation, but increasing ONOO– can also inhibit the biological effects of TIMP-1. ONOO– can also inhibit sodium potassium pump and cell metabolism to damage BBB. MSCs can secrete TSG-6, which inhibits the NF-κB signaling pathway through CD44, thereby inhibiting subsequent biological processes to improve damaged BBB