Table 2.

Matrix metalloproteinases and clinical outcome in patients with acute intracerebral hemorrhage

Study, year	Study population	Main findings
Abilleira et al., 2003 [65]	57 patients	Blood concentrations of MMP-9 within 24 h from ICH onset were raised. In patients with deep ICH, this increase was associated with perihematoma edema and acute neurological worsening
Alvarez-Sabín et al., 2004 [66]	21 patients	Highest levels of MMP-2 and TIMP-2 were found at baseline, for MMP-9 and TIMP-1 at 24 h, and for MMP-3 at 24–48 h. Baseline MMP-9 correlated positively and TIMP-1 correlated negatively to perihematoma edema. MMP-3 was related to mortality. MMP-9 and MMP-3 correlated to 3-month residual scar volume
Wu et al., 2008 [67]	60 patients; 30 healthy age-matched controls (blood); 10 age–sex-matched controls undergoing lumbar anesthesia (CSF)	Plasma and CSF levels of MMP-9 were increased at day 1, peaked at day 4, and remained at a high level until day 7. MMP-9 was not detected in normal CSF. MMP-9 level was positively correlated with hematoma volume and NIHSS score, and negatively correlated with GCS score
Petrovska-Cvetkovska et al., 2014 [68]	62 patients	There was a significant rise in serum MMP-9 levels from day 1 to 7 after ICH, with peak values at day 3. There was a positive, significant correlation between serum MMP-9 concentration and NIHSS score
Castellazzi et al., 2010 [69]	28 patients	Serum MMP-9 concentrations increased from 24 to 48 h and reached the peak at day 7. Serum MMP-2 levels progressively declined at 48 h and 7 days. Perihematoma edema increased at 48 h and day 7: it was positively correlated with MMP-9 and MMP-2 at 24 h and with MMP-9 at 48 h, and was inversely correlated with MMP-2 at day 7
Silva Y et al., 2005 [76]	183 patients	Plasma concentrations of MMP-9 were significantly higher in patients with early hematoma expansion
Yang et al., 2016 [77]	186 patients	Increasing plasma MMP-9 level was an independent risk factor for hematoma expansion
Li et al., 2013 [78]	59 patients	Increased MMP-3 levels on admission were independently associated with perihematoma edema volume at day 3. Levels of MMP-3 ≥ 12.4 ng/mL and MMP-9 ≥ 192.4 ng/mL independently predicted poor 3-month outcome
Howe et al., 2018 [79]	79 patients	MMP-10 within 2 days from ICH was associated with hematoma expansion and MMP-3 at day 1 was associated with early neurological deterioration. Perihematoma edema and delayed neurological deterioration were associated with MMP-8 at day 6–8 and MMP-1 at day 3–5, respectively. MMP-1, MMP-8, and MMP-10 also correlated with discharge status and 3-month mRS
Howe et al., 2019 [80]	55 patients	In male patients, MMP-1, MMP-2, MMP-3, and MMP-9 levels increased from baseline until 10 days post stroke. In female patients, MMP-8 was the only isoform to significantly change over time and reached a peak at 3–5 days post-injury. MMP-1, MMP-2, MMP-3, and MMP-9 were associated with initial and peak perihematoma edema in females. Serum levels of MMP-3 in males and MMP-10 in females were independent predictors of 90-day functional outcome

CSF = cerebrospinal fluid; GCS = Glasgow Coma Scale; ICH = intracerebral hemorrhage, MMP = matrix metalloproteinase; mRS = modified Ranking scale; NIHSS = National Institute Health Stroke Scale; TIMP = tissue inhibitor of matrix metalloproteinase