Time Course of Changes in the Neurovascular Unit after Hypoxic-Ischemic Injury in Neonatal Rats.

Time Course of Changes in the Neurovascular Unit after Hypoxic-Ischemic Injury in Neonatal Rats.
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新生大鼠缺氧 - 缺血性损伤后神经血管单元的变化时间。

DOI:
10.3390/ijms23084180
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发表时间:
2022-04-10
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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新生儿暴露于缺氧缺血(HI)损伤可使其易患严重的神经系统后遗症。HI相关脑损伤的机制尚未完全阐明。神经血管单位(NVU)是保护大脑免受有害分子流入的结构的复合物。HI后NVU的变化很重要,因为它们可以揭示脑微血管中的内源性神经保护通路。此外,新生儿暴露于HI后NVU变化的时间过程仍有待确定。在这项研究中,我们研究了严重HI对新生大鼠NVU变化的时间过程的影响。从出生后第7天暴露于右颈动脉结扎和2小时缺氧的大鼠收集脑,暴露于假处理(Sham)或HI后恢复6或48小时。通过定量免疫组织化学检查大脑右侧HI和左侧缺氧侧的大脑皮质、白色物质和海马的微血管中的血管密度(层粘连蛋白)、周细胞血管覆盖率(PDGFRβ)、星形胶质细胞血管覆盖率(GFAP)和claudin-5表达。新生大鼠HI相关脑损伤与HI后48 h皮质和海马中血管密度增加以及神经血管重塑相关,包括HI后6 h皮质中周细胞覆盖的丧失和海马中claudin-5的增加。星形胶质细胞覆盖率不受HI损伤的影响。暴露于HI后,NVU不同成分的反应的时间过程不同。也有不同的区域响应的元素的NVU在HI和缺氧单独。
Exposure to hypoxic-ischemic (HI) insults in newborns can predispose them to severe neurological sequela. The mechanisms underlying HI-related brain injury have not been completely elucidated. The neurovascular unit (NVU) is a composite of structures that protect the brain from the influx of detrimental molecules. Changes in the NVU after HI are important because they could reveal endogenous neuroprotective pathways in the cerebral microvasculature. Furthermore, the time course of changes in the NVU after exposure to HI in the newborn remains to be determined. In this study, we examined the effects of severe HI on the time course of changes in the NVU in neonatal rats. Brains were collected from rats exposed to right carotid artery ligation and 2 h of hypoxia on postnatal day 7 with recovery for 6 or 48 h after exposure to sham treatment (Sham) or HI. The right HI and left hypoxic alone sides of the brains were examined by quantitative immunohistochemistry for vascular density (laminin), pericyte vascular coverage (PDGFRβ), astrocyte vascular coverage (GFAP), and claudin-5 expression in the microvasculature of the cerebral cortex, white matter, and hippocampus. HI-related brain injury in neonatal rats was associated with increases in vascular density in the cortex and hippocampus 48 h after HI as well as neurovascular remodeling, including loss of pericyte coverage in the cortex and increases in claudin-5 in the hippocampus 6 h after HI. Astrocyte coverage was not affected by HI injury. The time course of the responses in the different components of the NVU varied after exposure to HI. There were also differential regional responses in the elements of the NVU in response to HI and hypoxia alone.
DOI: 10.3390/ijms22041585
发表时间: 2021-02-04
影响因子: 5.6
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