Repeated Low Intensity Blast Exposure Is Associated with Damaged Endothelial Glycocalyx and Downstream Behavioral Deficits.
Repeated Low Intensity Blast Exposure Is Associated with Damaged Endothelial Glycocalyx and Downstream Behavioral Deficits.
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DOI：
10.3389/fnbeh.2017.00104
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发表时间：
2017
影响因子：
3
通讯作者：
Ahlers ST
中科院分区：
文献类型：
--
作者：
Hall AA;Mendoza MI;Zhou H;Shaughness M;Maudlin-Jeronimo E;McCarron RM;Ahlers ST
目前对轻度创伤性脑损伤（mTBI）的临床研究集中在通过先进的基于MRI的成像技术鉴定的白色物质变化。然而，在被诊断患有mTBI的个体的脑中血管周围tau积聚表明脉管系统在病理学中起关键作用。本研究使用大鼠模型来检查内皮糖萼（负责感知管腔剪切力的血管系统层）是否因暴露于重复低强度冲击波而受损，以及该层是否与观察到的行为缺陷相关。所使用的爆炸暴露包括12，40 kPa爆炸暴露，爆炸之间至少间隔24 h。我们发现，反复的爆炸暴露减少了不同脑区的糖萼长度和密度，表明损伤。这种冲击波暴露模式与评估学习和记忆的Morris水迷宫（MWM）中的轻度性能下降相关。给予透明质酸酶，一种结合并降解透明质酸（糖萼的主要结构成分）的酶，在冲击波暴露前减少了观察到的行为缺陷，并诱导糖萼层增厚。总之，这些发现表明，反复爆炸后的内皮糖萼降解与行为减退有关，这可以通过透明质酸酶治疗来预防。
Current clinical research into mild traumatic brain injury (mTBI) has focused on white matter changes as identified by advanced MRI based imaging techniques. However, perivascular tau accumulation in the brains of individuals diagnosed with mTBI suggests that the vasculature plays a key role in the pathology. This study used a rat model to examine whether the endothelial glycocalyx, a layer of the vasculature responsible for sensing luminal shear forces, is damaged by exposure to repeated low intensity blast, and whether this layer is associated with observed behavioral deficits. The blast exposure used consisted of 12, 40 kPa blast exposures conducted with a minimum of 24 h between blasts. We found that repeated blast exposure reduced glycocalyx length and density in various brain regions indicating damage. This blast exposure paradigm was associated with a mild performance decrement in the Morris water maze (MWM) which assesses learning and memory. Administration of hyaluronidase, an enzyme that binds to and degrades hyaluronan (a major structural component of the glycocalyx) prior to blast exposure reduced the observed behavioral deficits and induced a thickening of the glycocalyx layer. Taken together these findings demonstrate that the endothelial glycocalyx degradation following repeated blast is associated with behavioral decrements which can be prevented by treatment with hyaluronidase.