Table 1.

Temporal expression profile of matrix metalloproteinases in experimental intracerebral hemorrhage

Authors, year	Study model	Species	Main findings
Power et al., 2003 [36]	Collagenase-induced ICH	Rat	ICH increased brain mRNA levels of MMP-2, MMP-3, MMP-7, and MMP-9 in proximity of the hematoma. MMP-12 (macrophage metalloelastase) was the most highly induced MMP (> 80-fold). MMP-12 was localized in activated monocytoid cells surrounding the ICH
Wang and Tsirka, 2005 [37]	Collagenase-induced ICH	C57BL/6 mouse	MMP-9 was activated and upregulated after ICH, and its activity was mostly colocalized with neurons and endothelial cells of blood vessel matrix. MMP-9 played a deleterious role in acute brain injury within the first 3 days after ICH
Tejima et al., 2007 [39]	Autologous and homologous blood-induced ICH	WT and MMP-9 KO mouse	MMP-9 was elevated in WT hemorrhagic brain tissue but absent from KO hemorrhagic brain tissue. Edematous water content was elevated when WT blood was injected into WT brain. Exposure to hemoglobin rapidly upregulated MMP-9 in primary mouse astrocyte cultures within 1 to 24 h
Xue et al., 2006 [41]	Autologous blood-induced ICH	Mouse	Brain damage, neuronal death, microglia/macrophage activation, and neutrophil accumulation occurred by 24 h of injury. These neuropathological features were reduced in MMP-9 null mice compared with WT controls. Thrombin and MMP-9 interact to promote the acute neurotoxicity following ICH
Wu et al., 2010 [43]	Autologous blood intracerebral injection	Rat	mRNA and/or protein expression of MMP-9 was upregulated between 2 h and 5 days after ICH and reached a maximal level at day 2. Brain water content after ICH presented a similar trend
Grossetete and Rosenberg, 2008 [44]	Collagenase-induced ICH	Mouse	MMP-3 mRNA increased in ICH; similar MMP-2 and MMP-9 mRNA expression levels were found in ICH and saline-injected mice. Protein levels of pro and cleaved MMP-3 were increased in ICH, and MMP-9 activity was elevated at 72 h after ICH
Kawakita et al., 2006 [45]	Thrombin intracerebral injection	Rat	MMP-9 activity was detected in basal ganglia and cortex at 12 h, expressed maximally at 24 h, and remained high 72 h after thrombin injection. MMP-9 mRNA cortical expression was clearly evident at 12 and 24 h and diminished 72 h after thrombin injection. Brain water contents in basal ganglia and overlying cortex rapidly increased at 12 h, maximized at 24 h, and slightly decreased at 72 h
Mun-Bryce et al., 2004 [56]	Collagenase-induced ICH	Swine	MMP-9 levels increased by 24 h in the white matter of ipsilateral SI and SII cortex, and in contralateral SI gray matter. A further increase in MMP-9 level occurred in ipsilateral SI and SII gray matter, and in contralateral SI white matter by 48 h. By 7 days, significant levels of MMP-9 were detected only in ipsilateral SI white and gray matter tissues. A rise in MMP-9 was found in CA1 of ipsilateral and contralateral hemispheres during 1–2 days. The raise in MMP-2 levels was delayed until 7 days post-ICH in ipsilateral SII gray matter

ICH = intracerebral hemorrhage; KO = knockout; MMP = matrix metalloproteinase; SI = primary somatosensory; SII = secondary somatosensory; WT = wild type