Esofago y Estomago

Therapeutic Approaches to Vascular Protection in Ischemic Stroke
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　 Schematic diagram of vascular unit that comprises endothelial cells, astrocytes, and pericytes. MMP 9 is mainly derived from brain endothelial cells and infiltrating neutrophils in the acute phase of a stroke. MMP 9 can degrade the basement membrane, which links the endothelial cells, and maintains theintegrity of the vascular unit.

　

　

　

　

　

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　 Possible mechanism of vascular unit disruption after ischemia and reperfusion with tPA. MMP 9 can disrupt the BBB by degrad ing the basal membrane extracellular matrix proteins, thereby leading to BBB leakage and hemorrhaging. In the acute phase of a stroke, MMP 9 can be activated by pro inflammatory factors (e.g., IL1 , and TNF ) and free radicals. In addition, the tPA that is administered strongly activates MMP 9 through multiple pathways. MMP 9 activation is inhibited by several reagents: NXY 059, edaravone, APC and BB 94 (Table 1). 　 Scientific papers reporting reagents that can attenuate hemorrhagic cerebral infarction in animal models
Drug name Imatinib (PDGFR antagonist) Activated protein C MelatoninBB 94 (MMP9 inhibitor) Minocycline NXY 059 Edaravone Supposed mechanisms Suppressing PDGFR activation Animal model Mouse hemorrhagic cerebral infarction model Mouse hemorrhagic cerebral infarction model Rat hemorrhagic cerebral infarction model Rat hemorrhagic cerebral infarction model Rat hemorrhagic cerebral infarction model Rabbit hemorrhagic cerebral infarction model Rat hemorrhagic cerebralinfarction model References Su et al. 28 Cheng et al. Hung et al. Sumii et al. Murata et al. Lapchck et al. Yamashita et al. 22 29 30 31 32 23

Suppressing the tPA PAR1 MMP9 pathway Suppressing MMP9 activity Suppressing MMP9 activity Suppressing MMP9 activity Scavenging free radicals Scavenging free radicals

　

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