Harris Alex K, Ergul Adviye, Kozak Anna, Machado Livia S, Johnson Maribeth H, Fagan Susan C
Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, Georgia, USA.
BMC Neurosci. 2005 Aug 3;6:49. doi: 10.1186/1471-2202-6-49.
While gelatinase (MMP-2 and -9) activity is increased after focal ischemia/reperfusion injury in the brain, the relative contribution of neutrophils to the MMP activity and to the development of hemorrhagic transformation remains unknown.
Anti-PMN treatment caused successful depletion of neutrophils in treated animals. There was no difference in either infarct volume or hemorrhage between control and PMN depleted animals. While there were significant increases in gelatinase (MMP-2 and MMP-9) expression and activity and edema formation associated with ischemia, neutrophil depletion failed to cause any change.
The main finding of this study is that, in the absence of circulating neutrophils, MMP-2 and MMP-9 expression and activity are still up-regulated following focal cerebral ischemia. Additionally, neutrophil depletion had no influence on indicators of ischemic brain damage including edema, hemorrhage, and infarct size. These findings indicate that, at least acutely, neutrophils are not a significant contributor of gelatinase activity associated with acute neurovascular damage after stroke.
虽然在脑局灶性缺血/再灌注损伤后明胶酶(基质金属蛋白酶-2和-9)活性增加,但中性粒细胞对基质金属蛋白酶活性及出血性转化发展的相对贡献仍不清楚。
抗中性粒细胞治疗成功使治疗动物体内的中性粒细胞减少。对照动物和中性粒细胞减少的动物在梗死体积或出血方面均无差异。虽然与缺血相关的明胶酶(基质金属蛋白酶-2和基质金属蛋白酶-9)表达、活性及水肿形成有显著增加,但中性粒细胞减少并未引起任何变化。
本研究的主要发现是,在没有循环中性粒细胞的情况下,局灶性脑缺血后基质金属蛋白酶-2和基质金属蛋白酶-9的表达及活性仍上调。此外,中性粒细胞减少对缺血性脑损伤指标(包括水肿、出血和梗死大小)没有影响。这些发现表明,至少在急性期,中性粒细胞不是与中风后急性神经血管损伤相关的明胶酶活性的重要贡献者。