Jiang Wen, Xiao Lan, Wang Jin-Cun, Huang Yuan-Gui, Zhang Xia
Neuropsychiatry Research Unit, A114 Medical Research Building, University of Saskatchewan, 103 Wiggins Road, Saskatoon, Canada S7N5E4.
Neurosci Lett. 2004 Sep 9;367(3):344-8. doi: 10.1016/j.neulet.2004.06.031.
Epileptic seizures have been shown to increase the proliferation of granule cell precursors in the adult brain, but the underlying mechanisms remain largely unknown. This study examined the effect of nitric oxide (NO) on the proliferation of granule cell precursors in adult rats after pentylenetrazol (PTZ)-induced generalized clonic seizures. Using systemic bromodeoxyuridine (BrdU) to label dividing cells, we found that injection of the neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (50 mg/kg i.p.) 10 min before PTZ significantly reduced the number of BrdU labeled cells in the dentate gyrus 3, 7, and 14 days after seizures (P < 0.05). Administration of the inducible NOS (iNOS) inhibitor aminoguanidine (100 mg/kg i.p.) also significantly inhibited the proliferation rate of neural precursor cells in the dentate gyrus at various time points after PTZ-induced seizures. Our findings suggest that epileptic seizures lead to increased cell proliferation in the adult rat dentate gyrus through NO-dependent mechanisms. Both the NO originating from nNOS and iNOS may be involved in brain repair after seizures.
癫痫发作已被证明会增加成年大脑中颗粒细胞前体的增殖，但潜在机制在很大程度上仍不清楚。本研究考察了一氧化氮（NO）对戊四氮（PTZ）诱导的成年大鼠全身性阵挛性癫痫发作后颗粒细胞前体增殖的影响。使用全身注射溴脱氧尿苷（BrdU）标记分裂细胞，我们发现，在PTZ注射前10分钟腹腔注射神经元型一氧化氮合酶（nNOS）抑制剂7-硝基吲唑（50mg/kg），在癫痫发作后3、7和14天，显著减少了齿状回中BrdU标记细胞的数量（P<0.05）。给予诱导型一氧化氮合酶（iNOS）抑制剂氨基胍（100mg/kg腹腔注射）也显著抑制了PTZ诱导癫痫发作后不同时间点齿状回中神经前体细胞的增殖率。我们的研究结果表明，癫痫发作通过NO依赖机制导致成年大鼠齿状回中细胞增殖增加。源自nNOS和iNOS的NO都可能参与癫痫发作后的脑修复。
