Adelaide Centre for Neuroscience Research, School of Medical Sciences, The University of Adelaide, SA 5000, Australia.
Neuroscience. 2012 Jul 12;214:78-83. doi: 10.1016/j.neuroscience.2012.04.028. Epub 2012 Apr 21.
Inhibition of substance P (SP) activity through the use of NK1 receptor antagonists has been shown to be a promising neuroprotective therapy following traumatic brain injury (TBI). Conversely, recent research has implicated SP in the stimulation of neurogenesis, suggesting that the neuropeptide has the potential to promote recovery following TBI. This study characterised the effects of SP and the NK1 antagonist, n-acetyl tryptophan (NAT), on cell proliferation following diffuse TBI. Adult male Sprague-Dawley rats were injured using the impact acceleration model of TBI and randomly assigned to one of five treatment groups: sham, vehicle control, NAT alone, SP alone or SP with NAT. Cellular proliferation was assessed with immunostaining for bromodeoxyuridine (BrdU) and cell-specific markers. Infusion of SP (±NAT) promoted cellular proliferation in the subventricular zone and dentate gyrus following TBI. This increase was largely associated with microglial proliferation and did not correspond with functional improvements. These results suggest that NAT treatment results in neuroprotection following TBI, mediated in part via inhibition of microglia.
通过使用 NK1 受体拮抗剂抑制 P 物质 (SP) 的活性已被证明是创伤性脑损伤 (TBI) 后有前途的神经保护治疗方法。相反，最近的研究表明 SP 参与了神经发生的刺激，这表明该神经肽有可能促进 TBI 后的恢复。本研究描述了 SP 和 NK1 拮抗剂 N-乙酰色氨酸 (NAT) 在弥漫性 TBI 后对细胞增殖的影响。成年雄性 Sprague-Dawley 大鼠使用 TBI 的冲击加速模型受伤，并随机分为五组治疗：假手术、载体对照、NAT 单独、SP 单独或 SP 与 NAT。通过溴脱氧尿苷 (BrdU) 和细胞特异性标志物的免疫染色评估细胞增殖。SP（±NAT）的输注促进了 TBI 后室下区和齿状回的细胞增殖。这种增加主要与小胶质细胞增殖有关，与功能改善不对应。这些结果表明，NAT 治疗可通过抑制小胶质细胞介导，对 TBI 后产生神经保护作用。
