Research Group of Experimental Neuropathology, Laboratory of Experimental Neuroscience. University of South Santa Catarina, Postgraduate Program in Health Sciences, Palhoça, SC, Brazil.
Curr Neurovasc Res. 2017;14(1):60-64. doi: 10.2174/1567202613666161201204549.
Congenital Muscular Dystrophy type 1D (CMD1D) is characterized by an abnormal glycosylation of α-DG (α-dystroglycan) and is associated to the central nervous system (CNS) abnormalities such as cognitive impairment. The purpose of the research was to evaluate the blood-brain barrier permeability (BBB) permeability and matrix metalloproteinases (MMP) -2 and -9 in adult Largemyd-/- mice in order to understand the physiopathology of brain involvement during the CMD1D process. To this aim, we used adult homozygous Largemyd-/- (mutation in Large), heterozygous Largemyd+/- as well as wild-type (C57BL/6) mice. The animals were submitted to the evaluation of BBB permeability and MMP-2 and MMP-9 in striatum, hippocampus and cerebral cortex. There was an increase in BBB permeability in the hippocampus and striatum associated with an increase in the protein levels of MMP-2 in the cerebral cortex and striatum and MMP-9 in the hippocampus in adult Largemyd-/- mice. Our results suggest that the pathophysiologic processes can be associated to the action of MMPs and BBB disruption and that the BBB breakdown is relevant to the perpetuation of brain inflammation and can be related to brain dysfunction observed in CMD1D patients.
先天性肌肉营养不良症 1D 型（CMD1D）的特征是α-DG（α-肌营养不良蛋白）的异常糖基化，与中枢神经系统（CNS）异常有关，如认知障碍。研究的目的是评估成年 Large 缺失型/- （Large 基因发生突变）小鼠的血脑屏障通透性（BBB）和基质金属蛋白酶（MMP）-2 和 -9，以了解 CMD1D 过程中大脑受累的病理生理学。为此，我们使用了成年纯合子 Large 缺失型/-（Large 基因突变）、杂合子 Large+/（Large 基因杂合突变）以及野生型（C57BL/6）小鼠。这些动物接受了 BBB 通透性和 MMP-2 和 MMP-9 在纹状体、海马体和大脑皮层中的评估。在成年 Large 缺失型/-小鼠中，海马体和纹状体的 BBB 通透性增加，与大脑皮层和纹状体中 MMP-2 蛋白水平升高以及海马体中 MMP-9 蛋白水平升高有关。我们的结果表明，病理生理过程可能与 MMPs 和 BBB 破坏的作用有关，并且 BBB 破坏与大脑炎症的持续存在有关，并可能与 CMD1D 患者观察到的大脑功能障碍有关。
