Astrocyte heme oxygenase-1 reduces mortality and improves outcome after collagenase-induced intracerebral hemorrhage

作者：Chen-Roetling, Jing; Kamalapathy, Pramod; Cao, Yang; Song, Wei; Schipper, Hyman M.; Regan, Raymond F.^*

来源：Neurobiology of Disease, 2017, 102: 140-146.

DOI：10.1016/j.nbd.2017.03.008

• Glia
• Intracerebral hemorrhage
• Nrf2
• Stroke
• Subarachnoid hemorrhage

Pharmacotherapies that increase CNS expression of heme oxygenase-1 (HO-1) and other antioxidant proteins have improved outcome in experimental models of spontaneous intracerebral hemorrhage (ICH). In order to more specifically investigate the relationship between HO-1 and ICH outcome, mice expressing human HO-1 driven by the glial fibrillary acidic protein (GFAP) promoter (GFAP"HMOX1 mice) were tested in a model of in situ parenchymal hemorrhage. Injection of collagenase into the striata of wild-type (WT) mice resulted in a 26.3% mortality rate, with deaths equally distributed between males and females. Mortality was reduced to 4.48% in GFAP"HMOX1 mice. Cell viability in the injected striata of surviving WT mice was reduced by about half at one week and was significantly increased in transgenics; this benefit persisted over a 22 day observation period. Cell counts guided by design-based stereology indicated loss of similar to 40% of neurons in WT hemorrhagic striata at one week, which was decreased by half in transgenics; no significant differences in microglia or astrocyte numbers were observed. Blood-brain barrier disruption and short-term neurological deficits were also mitigated in GFAP" HMOX1 mice, but long-term outcome did not differ from that of WT survivors. These results suggest that astrocyte HO-1 overexpression provides robust neuroprotection after acute intracerebral hemorrhage. Further investigation of drug or genetic therapies that selectively increase astrocyte HO-1 is warranted.

• 出版日期2017-6