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BACKGROUND To analyze the correlation between thrombospondin-2 (TSP2), matrix metalloproteinase (MMP)-9, and perihematomal edema, as well as the short-term prognosis of patients with hypertensive intracerebral hemorrhage. METHODS The clinical data of 114 patients with hypertensive intracerebral hemorrhage admitted to our hospital from January 2018 to February 2020 were collected and divided into groups according to the levels of TSP2 and MMP-9. We compared edema indexes in patients with different levels of TSP2 and MMP-9, and analyzed the correlation between TSP2, MMP-9 and relative edema volume index (REI), edema change index (AEI). We also assessed the TSP2 and MMP-9 levels in patients with different prognoses, and analyzed the predictive value of TSP2 and MMP-9 for poor prognosis of patients. RESULTS (I) There was no difference in the REI and AEI values between the low and high TSP2 groups at admission and 24 h after admission (P>0.05), while the REI and AEI values of the high TSP2 group at 5 and 15 d after admission were significantly lower than those of the low TSP2 group (P<0.05); (II) the REI and AEI values of patients with different MMP-9 levels were not different between admission and 24 h after admission (P>0.05), while the REI and AEI values of the high MMP-9 group were significantly higher than those of the low MMP-9 group at 5 and 15 d after admission (P<0.05); (III) Pearson correlation analysis showed that MMP-9 was positively correlated with REI and AEI, while TSP2 was negatively correlated (P<0.05); (IV) among 114 patients, 39 had poor prognosis, 75 had good prognosis The MMP-9 levels of patients with a poor prognosis were significantly higher than those of patients with a good prognosis, and the TSP2 level was the opposite (P<0.05); (V) receiver operating characteristic (ROC) curve showed that the sensitivity, specificity and the area under the curve (AUC) of the TSP2 + MMP-9 combination in the diagnosis of hypertensive cerebral hemorrhage were significantly higher than when TSP2 and MMP-9 were tested separately (P<0.05). CONCLUSIONS In patients with hypertensive intracerebral hemorrhage, TSP2 is negatively correlated with edema around the hematoma, while MMP-9 is positively correlated.