Rosell Anna, Ortega-Aznar Arantxa, Alvarez-Sabín José, Fernández-Cadenas Israel, Ribó Marc, Molina Carlos A, Lo Eng H, Montaner Joan
Department of Neurology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
Stroke. 2006 Jun;37(6):1399-406. doi: 10.1161/01.STR.0000223001.06264.af. Epub 2006 May 11.
Abnormal expression of some matrix metalloproteinases (MMP) has shown to play a deleterious role in brain injury in experimental models of cerebral ischemia. We aimed to investigate MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in brain parenchyma in both ischemic and hemorrhagic strokes.
Postmortem fresh brain tissue from 6 ischemic and 8 hemorrhagic stroke patients was obtained within the first 6 hours after death. Finally, 78 brain tissue samples from different areas (infarct, peri-infarct, perihematoma and contralateral hemisphere) were studied. To quantify gelatinase content we performed gelatin zymograms that were confirmed by Western Blot Analysis, immunohistochemistry to localize MMP source, and in situ zymography to detect gelatinase activity.
Among ischemic cases, gelatin zymography showed increased MMP-9 content in infarct core although peri-infarct tissue presented also higher levels than contralateral hemisphere (P<0.0001 and P=0.042, respectively). Within infarct core, MMP-9 was mainly located around blood vessels, associated to neutrophil infiltration and activated microglial cells. In peri-infarct areas the major source of MMP-9 were microglial cells. Tissue around intracranial hemorrhage also displayed higher MMP-9 levels than contralateral hemisphere (P=0.008) in close relationship with glial cells. MMP-2 was constitutively expressed and remained invariable in different brain areas.
Our results demonstrate in situ higher levels of MMP-9 in human brain tissue after ischemic and hemorrhagic stroke, suggesting a contribution of MMP-9 to ischemic brain injury and perihematoma edema.
在脑缺血实验模型中，一些基质金属蛋白酶（MMP）的异常表达已显示出在脑损伤中起有害作用。我们旨在研究缺血性和出血性卒中脑实质中的MMP-2（明胶酶A）和MMP-9（明胶酶B）。
在死亡后的头6小时内获取6例缺血性卒中和8例出血性卒中患者的尸检新鲜脑组织。最后，研究了来自不同区域（梗死灶、梗死周边、血肿周边和对侧半球）的78个脑组织样本。为了定量明胶酶含量，我们进行了明胶酶谱分析，通过蛋白质印迹分析进行确认，采用免疫组织化学定位MMP来源，并通过原位酶谱分析检测明胶酶活性。
在缺血性病例中，明胶酶谱分析显示梗死核心区的MMP-9含量增加，尽管梗死周边组织的水平也高于对侧半球（分别为P<0.0001和P=0.042）。在梗死核心区内，MMP-9主要位于血管周围，与中性粒细胞浸润和活化的小胶质细胞相关。在梗死周边区域，MMP-9的主要来源是小胶质细胞。颅内出血周围的组织也显示出比侧半球更高的MMP-9水平（P=0.008），与神经胶质细胞密切相关。MMP-2呈组成性表达，在不同脑区保持不变。
我们的结果表明，缺血性和出血性卒中后人脑组织中MMP-9的原位水平较高，提示MMP-9对缺血性脑损伤和血肿周围水肿有作用。
