N-methyl-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke
N-methyl-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke
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DOI：
10.1046/j.0953-816x.2001.01611.x
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发表时间：
2001-07-01
影响因子：
3.4
通讯作者：
Lindvall, O
中科院分区：
文献类型：
--
作者：
Arvidsson, A;Kokaia, Z;Lindvall, O
本文研究了大脑中动脉阻塞（MCAO）所致局灶性脑缺血后成年大鼠齿状回的神经发生。将动物进行30分钟的MCAO，其导致仅限于纹状体的损伤，或2小时的MCAO，其导致纹状体和皮质梗死。与假手术大鼠相比，MCAO大鼠在2小时损伤后5周时，同侧齿状突颗粒细胞层和颗粒下区中5-溴-2 '-脱氧尿苷-5'-单磷酸（BrdU;在缺血后4-6天注射）和神经元特异性抗原（NeuN;有丝分裂后神经元的标记物）双标记的细胞数量显著增加。只有一个温和的和可变的增加BrdU标记的细胞后30分钟的MCAO。增强的神经发生不依赖于海马中的细胞死亡，其幅度与皮质损伤的程度无关。全身给予N-甲基-d-天冬氨酸（NMDA）受体阻断剂马来酸地佐环平（MK-801）完全抑制了MCAO 2 h后神经发生的升高。我们的研究结果表明，中风导致成年大鼠齿状回神经发生增加，通过NMDA受体的突触能机制。这种调节作用可能是介导的几种生长因子的水平的变化，发生在中风后，并可能影响神经发生的各种调节步骤。
Neurogenesis in the adult rat dentate gyrus was studied following focal ischemic insults produced by middle cerebral artery occlusion (MCAO). Animals were subjected to either 30 min of MCAO, which causes damage confined to the striatum, or 2 h of MCAO, which leads to both striatal and cortical infarction. When compared to sham-operated rats, MCAO-rats showed a marked increase of the number of cells double-labelled for 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU; injected during 4-6 days postischemia) and neuronal-specific antigen (NeuN; a marker of postmitotic neurons) in the ipsilateral dentate granule cell layer and subgranular zone at 5 weeks following the 2 h insult. Only a modest and variable increase of BrdU-labelled cells was found after 30 min of MCAO. The enhanced neurogenesis was not dependent on cell death in the hippocampus, and its magnitude was not correlated to the degree of cortical damage. Systemic administration of the N-methyl-d-aspartate (NMDA) receptor blocker dizocilpine maleate (MK-801) completely suppressed the elevated neurogenesis following 2 h of MCAO. Our findings indicate that stroke leads to increased neurogenesis in the adult rat dentate gyrus through glutamatergic mechanisms acting on NMDA receptors. This modulatory effect may be mediated through changes in the levels of several growth factors, which occur after stroke, and could influence various regulatory steps of neurogenesis.