Selective glial vulnerability following transient global ischemia in rat brain

Selective glial vulnerability following transient global ischemia in rat brain
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DOI:
10.1097/00005072-199803000-00004
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发表时间:
1998-03-01
影响因子:
3.2
通讯作者:
Pulsinelli, WA
Pulsinelli, WA
中科院分区:
医学4区
文献类型:
--
作者:
Petito, CK;Olarte, JP;Pulsinelli, WA

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全脑缺血选择性损伤神经元,但其对神经胶质细胞死亡的影响尚不确定。因此,在10分钟的整体缺血后第1、2、3、5和14天通过灌注固定处死成年雄性大鼠。这种损伤在缺血后 (PI) 第 3 天导致 CA1 海马神经元死亡,但对其他区域的神经元造成轻微或无损害。原位末端标记 (ISEL) 和免疫组织化学鉴定了死亡或垂死神经胶质细胞的 DNA 片段,并区分了神经胶质细胞亚型。对照大脑中存在罕见的 ISEL 阳性少突胶质细胞、星形胶质细胞和小胶质细胞。在 PI 第 1 天,皮层和丘脑中的凋亡小体和 ISEL 阳性神经胶质细胞显着增加 (p < 0.05),但在其他区域和其他 PI 间隔与对照组相似。大多数是少突胶质细胞,但也观察到 ISEL 阳性小胶质细胞和星形胶质细胞。这些结果表明,少突胶质细胞在短暂的整体缺血后迅速死亡,并且比某些大脑区域的神经元更敏感。它们对缺血的选择性脆弱性可能是缺氧或一氧化碳中毒或与白质动脉病相关的迟发性白质损伤的原因。神经胶质细胞凋亡可能有助于在缺血后大脑中发现的凋亡寡核小体的 DNA 梯子。
Global cerebral ischemia selectively damages neurons, but its contribution to glial cell death is uncertain. Accordingly, adult male rats were sacrificed by perfusion fixation at 1, 2, 3, 5, and 14 days following 10 minutes of global ischemia. This insult produces CA1 hippocampal neuronal death at post-ischemic (PI) day 3, but minor or no damage to neurons in other regions. In situ end labeling (ISEL) and immunohistochemistry identified fragmented DNA of dead or dying glia and distinguished glial subtypes. Rare ISEL-positive oligodendroglia, astrocytes, and microglia were present in control brain. Apoptotic bodies and ISEL-positive glia significantly increased at PI day 1 in cortex and thalamus (p < 0.05), but were similar to controls in other regions and at other PI intervals. Most were oligodendroglia, although ISEL-positive microglia and astrocytes were also observed. These results show that oligodendroglia die rapidly after brief global ischemia and are more sensitive than neurons in certain brain regions. Their selective vulnerability to ischemia may be responsible for the delayed white matter damage following anoxia or CO poisoning or that associated with white matter arteriopathies. Glial apoptosis could contribute to the DNA ladders of apoptotic oligonucleosomes that have been found in post-ischemic brain.