To investigate the effects and mechanisms of human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSCs EXOs) on inflammatory response and nerve damage after intracerebral hemorrhage (ICH).

(1) A total of 108 healthy male C57BL/6J mice were randomly divided into three groups: Sham group, Model group, and EXO group, with 36 mice in each group. The ICH model was established by stereotactic injection. The EXO group received a tail vein injection of 100 μg hUC-MSCs-EXOs in PBS solution 4 h after ICH surgery. Neurological function was evaluated using the modified neurological severity score (mNSS) on post-operative days 3, 7, and 14. On day 7 post-surgery, pathological morphological changes were observed via HE staining, and brain edema and oxidative stress indicators [malondialdehyde (MDA) content, total superoxide dismutase (SOD) activity] were detected. (2) An in vitro ICH model using BV2 cells was established and divided into three groups: Control group, PBS group, and EXO group. The EXO group was pre-treated with 10 μg/mL hUC-MSCs-EXOs for 2 h, followed by stimulation with 160 μmol/L hemin for 12 h. Subsequently, the relative mRNA expression level of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6], cell viability, apoptosis rate, and relative protein expression level of high mobility group protein B1 (HMGB1), nuclear factor kappa B inhibitory protein alpha (IκBα), nuclear factor kappa B (NF-κB) were detected in each group.

(1) The effect of hUC-MSCs-EXOs on ICH mice: hUC-MSCs-EXOs significantly alleviated the pathological damage and inflammatory cell infiltration in the brain tissue of mice after ICH. Compared with the Model group, the mNSS scores of mice in the EXO group at 3, 7, and 14 d after surgery, as well as the brain tissue water content and MDA content at 7 d after surgery, were significantly reduced, while SOD activity was significantly increased, and the differences were statistically significant (P<0.05). (2) The effect of hUC-MSCs-EXOs on BV2 cells after ICH: Compared with the PBS group, the mRNA relative expression levels of TNF-α, IL-1β, and IL-6, early cell apoptosis levels, and protein levels of HMGB1 and NF-κB in the EXO group were significantly reduced. Cell viability and protein levels of IκBα were significantly increased, and the differences were statistically significant (P<0.05).

hUC-MSCs-EXOs alleviate inflammatory responses and neuronal damage after ICH by inhibiting the HMGB1-NF-κB signaling pathway, providing a new potential strategy for the treatment of ICH.