Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation.
Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation.
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DOI：
10.1186/s40478-021-01269-5
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发表时间：
2021-10-15
影响因子：
7.1
通讯作者：
Elder GA
中科院分区：
文献类型：
--
作者：
Gama Sosa MA;De Gasperi R;Pryor D;Perez Garcia GS;Perez GM;Abutarboush R;Kawoos U;Hogg S;Ache B;Janssen WG;Sowa A;Tetreault T;Cook DG;Tappan SJ;Gandy S;Hof PR;Ahlers ST;Elder GA
爆炸引起的创伤性脑损伤导致的脑血管损伤主要是爆炸波引起的神经血管单元内机械破坏的结果。在爆炸引起的创伤性脑损伤的啮齿动物模型中，慢性血管退行性过程与年龄依赖性创伤后应激障碍样表型的发展有关。为了研究爆炸引起的慢性血管退行性变化的演变，对 Long-Evans 大鼠进行爆炸暴露（3 × 74.5 kPa），并在暴露后不同时间通过 X 射线微计算机断层扫描、免疫组织化学和电子显微镜对它们的大脑进行分析。在微型计算机断层扫描中，早在爆炸后 48 小时就观察到局部脑血管衰减或闭塞，并且在爆炸后 6 周时就可以看到脑血管紊乱，在爆炸后 13 个月时更加严重。迟发性病理学进展的特征是由于小动脉血管周围星形胶质细胞的变性和损失，内皮细胞和平滑肌细胞成分从神经毡上脱离。这种病理学的发展与血管重塑和神经炎症有关，因为在受影响的脉管系统中观察到基质金属蛋白酶（MMP-2 和 MMP-9）水平增加、IV 型胶原蛋白丢失和小胶质细胞活化。爆炸引起的神经血管单元内的慢性改变会影响脑血液循环、类淋巴液流和壁内动脉周围引流，所有这些都可能有助于爆炸引起的行为表型的发展。我们的结果还确定星形细胞变性是开发治疗爆炸引起的脑损伤的疗法的潜在目标。
Cerebral vascular injury as a consequence of blast-induced traumatic brain injury is primarily the result of blast wave-induced mechanical disruptions within the neurovascular unit. In rodent models of blast-induced traumatic brain injury, chronic vascular degenerative processes are associated with the development of an age-dependent post-traumatic stress disorder-like phenotype. To investigate the evolution of blast-induced chronic vascular degenerative changes, Long-Evans rats were blast-exposed (3 × 74.5 kPa) and their brains analyzed at different times post-exposure by X-ray microcomputed tomography, immunohistochemistry and electron microscopy. On microcomputed tomography scans, regional cerebral vascular attenuation or occlusion was observed as early as 48 h post-blast, and cerebral vascular disorganization was visible at 6 weeks and more accentuated at 13 months post-blast. Progression of the late-onset pathology was characterized by detachment of the endothelial and smooth muscle cellular elements from the neuropil due to degeneration and loss of arteriolar perivascular astrocytes. Development of this pathology was associated with vascular remodeling and neuroinflammation as increased levels of matrix metalloproteinases (MMP-2 and MMP-9), collagen type IV loss, and microglial activation were observed in the affected vasculature. Blast-induced chronic alterations within the neurovascular unit should affect cerebral blood circulation, glymphatic flow and intramural periarterial drainage, all of which may contribute to development of the blast-induced behavioral phenotype. Our results also identify astrocytic degeneration as a potential target for the development of therapies to treat blast-induced brain injury.
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影响因子：
3.4
作者：
Ahlers ST;Vasserman-Stokes E;Shaughness MC;Hall AA;Shear DA;Chavko M;McCarron RM;Stone JR
通讯作者：
Stone JR
影响因子：
4.8
作者：
Aldea, Roxana;Weller, Roy O.;Richardson, Giles
通讯作者：
Richardson, Giles
影响因子：
5.7
作者：
Dorr, A.;Sled, J. G.;Kabani, N.
通讯作者：
Kabani, N.
影响因子：
5
作者：
Carare, R. O.;Bernardes-Silva, M.;Weller, R. O.
通讯作者：
Weller, R. O.
影响因子：
4.2
作者：
Ackermans NL;Varghese M;Wicinski B;Torres J;De Gasperi R;Pryor D;Elder GA;Gama Sosa MA;Reidenberg JS;Williams TM;Hof PR
通讯作者：
Hof PR