Department of Neurology, Seoul National University Hospital, Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea.
Biochem Biophys Res Commun. 2010 Dec 3;403(1):66-72. doi: 10.1016/j.bbrc.2010.10.116. Epub 2010 Oct 30.
Our data have shown that nitrite therapy can rescue the ischemic brain when injected <3h after cerebral ischemic-reperfusion (I/R) injury and its effects can be prolonged to 4.5h in combination with memantine. We investigated whether or not long-term nitrite therapy is beneficial in ischemic brains. Sodium nitrite (1-100 μg/kg ip) or saline were administered to rats subjected to focal I/R injury for 7 days beginning 24h after I/R. Behavioral tests for 5 weeks revealed better functional recovery in the high-dose nitrite group than the control group. Other nitrite groups with relatively low doses showed no functional benefits. Hemispheric atrophy was attenuated by approximately 30% in the high-dose nitrite group. High-dose nitrite therapy also reduced inflammatory cytokine levels and caspase activity in the subacute period, and increased BrdU(+)MAP2(+) and BrdU(+)laminin(+) cells, and vascular density in the 5-week ischemic brain. Long-term nitrite therapy, when initiated 24h after I/R, corrected the subacute hostile environment, induced tissue and vascular regeneration, and improved functional recovery. Early and subsequent long term nitrite therapy may be effective in the management for ischemic stroke patients.
我们的数据表明，亚硝酸盐治疗可以在脑缺血再灌注（I/R）损伤后 <3 小时内挽救缺血性大脑，并且与美金刚联合使用可以将其效果延长至 4.5 小时。我们研究了长期亚硝酸盐治疗是否对缺血性大脑有益。在 I/R 后 24 小时开始，对经历局灶性 I/R 损伤的大鼠给予亚硝酸钠（1-100 μg/kg ip）或生理盐水，持续 7 天。5 周的行为测试显示，高剂量亚硝酸盐组的功能恢复明显优于对照组。其他剂量相对较低的亚硝酸盐组没有表现出功能益处。高剂量亚硝酸盐组的半球萎缩减少了约 30%。高剂量亚硝酸盐治疗还在亚急性期降低了炎性细胞因子水平和半胱天冬酶活性，并增加了 BrdU(+)MAP2(+)和 BrdU(+)层粘连蛋白(+)细胞以及 5 周缺血性大脑中的血管密度。在 I/R 后 24 小时开始的长期亚硝酸盐治疗纠正了亚急性期的恶劣环境，诱导了组织和血管再生，并改善了功能恢复。早期和随后的长期亚硝酸盐治疗可能对缺血性脑卒中患者的治疗有效。
