Imaging anoxic depolarization during ischemia-like conditions in the mouse hemi-brain slice
Imaging anoxic depolarization during ischemia-like conditions in the mouse hemi-brain slice
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DOI：
10.1152/jn.2001.85.1.414
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发表时间：
2001-01-01
影响因子：
2.5
通讯作者：
Andrew, RD
中科院分区：
文献类型：
--
作者：
Joshi, I;Andrew, RD
局灶性缺血引起缺血核心神经元和胶质细胞膜电位的突然丧失，称为缺氧去极化（AD）。在部分血流代谢受损的区域，梗死周围去极化（PIDs）进一步消耗能量储备，促进急性和延迟性神经元损伤。在完整的动物中，对AD和PIDs及其急性有害作用进行可视化和量化是困难的。在本研究中，我们对本征光信号进行成像，以测量AD发生期间小鼠冠状半脑切片的透光率变化。AD是由氧/葡萄糖剥夺（OGD）或瓦巴因暴露诱导的。测试了使用谷氨酸受体拮抗剂或降低温度的潜在神经保护策略。8分钟OGD （n = 18片）或4分钟100mum瓦巴因（n = 14片）诱导新皮层II/III层的光透射率（LT）增加灶性增加，该光透射率（LT）集中扩大，形成穿过新皮层并独立穿过纹状体的波前。与细胞外电位负电压移相一致。无论LT锋面（表示细胞肿胀）扩展到哪里，LT（表示树突状串珠）都会随之减少。此外，诱发场电位永久性丧失，表明神经元损伤。谷氨酸受体拮抗剂不能阻断阿尔茨海默病的发生和传播，也不能阻断阿尔茨海默病后不可逆损伤的程度。将温度降低到25-30度，可以通过抑制AD的发生来保护组织免受OGD损伤。本研究表明，全脑缺血样条件引起的缺氧去极化是一个扩散性过程，在皮层和皮层下灰质的多个部位局部启动。O-2/葡萄糖剥夺和AD的联合能量需求极大地加剧了神经元的损伤。谷氨酸受体拮抗剂既不能阻断缺血核心的AD，也不能阻断核心附近的复发性PID。
Focal ischemia evokes a sudden loss of membrane potential in neurons and glia of the ischemic core termed the anoxic depolarization (AD). In metabolically compromised regions with partial blood flow, peri-infarct depolarizations (PIDs) further drain energy reserves, promoting acute and delayed neuronal damage. Visualizing and quantifying the AD and PIDs and their acute deleterious effects are difficult in the intact animal. In the present study, we imaged intrinsic optical signals to measure changes in light transmittance in the mouse coronal hemi-brain slice during AD generation. The AD was induced by oxygen/glucose deprivation (OGD) or by ouabain exposure. Potential neuroprotective strategies using glutamate receptor antagonists or reduced temperature were tested. Eight minutes of OGD (n = 18 slices) or 4 min of 100 muM ouabain (n = 14) induced a focal increase of increased light transmittance (LT) in neocortical layers II/III that expanded concentrically to form a wave front coursing through neocortex and independently through striatum. The front was coincident with a negative voltage shift in extracellular potential. Wherever the LT front (denoting cell swelling) propagated, a decrease in LT (denoting dendritic beading) followed in its wake. In addition the evoked field potential was permanently lost, indicating neuronal damage. Glutamate receptor antagonists did not block the onset and propagation of AD or the extent of irreversible damage post-AD. Lowering temperature to 25-30 degreesC protected the tissue from OGD damage by inhibiting AD onset. This study shows that anoxic depolarization evoked by global ischemia-like conditions is a spreading process that is focally initiated at multiple sites in cortical and subcortical gray. The combined energy demands of O-2/ glucose deprivation and the AD greatly exacerbate neuronal damage. Glutamate receptor antagonists neither block the AD in the ischemic core nor, we propose, block recurrent PID arising close to the core.