The neuron-astrocyte-microglia triad in a rat model of chronic cerebral hypoperfusion: protective effect of dipyridamole.
The neuron-astrocyte-microglia triad in a rat model of chronic cerebral hypoperfusion: protective effect of dipyridamole.
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DOI：
10.3389/fnagi.2014.00322
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发表时间：
2014
影响因子：
4.8
通讯作者：
Giovannini MG
中科院分区：
文献类型：
--
作者：
Lana D;Melani A;Pugliese AM;Cipriani S;Nosi D;Pedata F;Giovannini MG
随着脑缺血的持续，衰老过程中的慢性脑低灌流可能会导致进行性的神经变性。神经元和神经胶质细胞之间相互作用的正常功能是大脑功能组织的基础。本研究旨在研究双血管阻断(2VO)所致慢性脑低灌流模型(n=15)的病理生理机制，特别是神经元与星形胶质细胞-小胶质细胞相互作用的紊乱，形成“三联体”。对2VO后早期给予潘生丁(4 mg/kg/d，前7天静脉注射)的保护作用进行验证(n=15)。以假手术大鼠(n=15)为对照。2VO后90d行神经元(Neun)、星形胶质细胞(GFAP)和小胶质细胞(IBA1)免疫荧光三重染色。我们发现CA1Str的“异位”神经元、神经元碎片和凋亡神经元的数量显著增加。Radiatum和Str.2VO大鼠的锥体细胞。在CA1应力中辐射2VO大鼠，星形胶质细胞的数量(cell/mm2)没有增加。在某些情况下，几个星形细胞包围了异位神经元，并在它们周围形成了一个“微疤痕”。星形胶质细胞分支可渗入异位神经元胞体，并与激活的小胶质细胞形成“三联体”。在三和弦中，CA1Str的数量明显更多。与假手术组相比，星形胶质细胞和小胶质细胞协同吞噬异位神经元。这些事件可能是许多神经退化过程的共同机制。它们出现的频率可能取决于神经退行性变的负担和严重程度，也可能是神经退行性变的原因。潘生丁显著逆转了上述所有事件。长期给予潘生丁的保护作用可能与其在2VO后早期的血管扩张、抗氧化和抗炎作用有关。
Chronic cerebral hypoperfusion during aging may cause progressive neurodegeneration as ischemic conditions persist. Proper functioning of the interplay between neurons and glia is fundamental for the functional organization of the brain. The aim of our research was to study the pathophysiological mechanisms, and particularly the derangement of the interplay between neurons and astrocytes-microglia with the formation of “triads,” in a model of chronic cerebral hypoperfusion induced by the two-vessel occlusion (2VO) in adult Wistar rats (n = 15). The protective effect of dipyridamole given during the early phases after 2VO (4 mg/kg/day i.v., the first 7 days after 2VO) was verified (n = 15). Sham-operated rats (n = 15) were used as controls. Immunofluorescent triple staining of neurons (NeuN), astrocytes (GFAP), and microglia (IBA1) was performed 90 days after 2VO. We found significantly higher amount of “ectopic” neurons, neuronal debris and apoptotic neurons in CA1 Str. Radiatum and Str. Pyramidale of 2VO rats. In CA1 Str. Radiatum of 2VO rats the amount of astrocytes (cells/mm2) did not increase. In some instances several astrocytes surrounded ectopic neurons and formed a “micro scar” around them. Astrocyte branches could infiltrate the cell body of ectopic neurons, and, together with activated microglia cells formed the “triads.” In the triad, significantly more numerous in CA1 Str. Radiatum of 2VO than in sham rats, astrocytes and microglia cooperated in the phagocytosis of ectopic neurons. These events might be common mechanisms underlying many neurodegenerative processes. The frequency to which they appear might depend upon, or might be the cause of, the burden and severity of neurodegeneration. Dypiridamole significantly reverted all the above described events. The protective effect of chronic administration of dipyridamole might be a consequence of its vasodilatory, antioxidant and anti-inflammatory role during the early phases after 2VO.
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影响因子：
2.1
作者：
Al-Bahrani, Ali;Taha, Safa;Bakhiet, Moiz
通讯作者：
Bakhiet, Moiz
影响因子：
3.7
作者：
Cerbai F;Lana D;Nosi D;Petkova-Kirova P;Zecchi S;Brothers HM;Wenk GL;Giovannini MG
通讯作者：
Giovannini MG
影响因子：
2.9
作者：
Farkas, E;Instit贸ris, A;Bari, F
通讯作者：
Bari, F
影响因子：
5.3
作者：
Bushong, EA;Martone, ME;Ellisman, MH
通讯作者：
Ellisman, MH
DOI：
10.1111/j.1749-6632.2002.tb04800.x
发表时间：
2002-01-01
期刊：
ALZHEIMER'S DISEASE: VASCULAR ETIOLOGY AND PATHOLOGY
影响因子：
--
作者：
Farkas, E;DeWilde, MC;Luiten, PGM
通讯作者：
Luiten, PGM