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粒细胞集落刺激因子对创伤性脑损伤啮齿动物模型认知功能恢复的促进作用

Enhancement in cognitive function recovery by granulocyte-colony stimulating factor in a rodent model of traumatic brain injury.

作者信息

Sikoglu Elif M, Heffernan Meghan E, Tam Kelly, Sicard Kenneth M, Bratane Bernt T, Quan Meina, Fisher Marc, King Jean A

机构信息

Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.

Department of Neurology, University of Massachusetts Memorial Medical Center, 119 Belmont St, Worcester, MA 01605, USA.

出版信息

Behav Brain Res. 2014 Feb 1;259:354-6. doi: 10.1016/j.bbr.2013.11.008. Epub 2013 Nov 14.

Abstract

Traumatic brain injury (TBI) is characterized by neuronal damage and commonly, secondary cell death, leading to functional and neurological dysfunction. Despite the recent focus of TBI research on developing therapies, affective therapeutic strategies targeting neuronal death associated with TBI remain underexplored. This study explored the efficacy of granulocyte-colony stimulating factor (G-CSF) as an intervention for improving cognitive deficits commonly associated with TBI. Although G-CSF has been studied with histological techniques, to date, its effects on functional outcome remain unknown. To this end, we used a closed head injury (CHI) model in Wistar rats that were randomly assigned to one of four groups (untreated TBI, G-CSF treated TBI, G-CSF treated Control, Control). The treatment groups were administered subcutaneous injections of G-CSF 30 min (120 μg/kg) and 12 h (60 μg/kg) post-trauma. The Morris Water Maze test was used to measure any treatment-associated changes in cognitive deficits observed in TBI animals at days 2-6 post-injury. Our findings demonstrate a significant improvement in cognitive performance in the G-CSF treated TBI animals within a week of injury, compared to untreated TBI, indicative of immediate and beneficial effect of G-CSF on cognitive performance post CHI. Our model suggests that early G-CSF exposure may be a promising therapeutic approach in recovery of cognitive deficits due to TBI.

摘要

创伤性脑损伤(TBI)的特征是神经元损伤,通常还伴有继发性细胞死亡,从而导致功能和神经功能障碍。尽管最近TBI研究的重点是开发治疗方法,但针对与TBI相关的神经元死亡的有效治疗策略仍未得到充分探索。本研究探讨了粒细胞集落刺激因子(G-CSF)作为改善通常与TBI相关的认知缺陷的干预措施的疗效。尽管已经用组织学技术对G-CSF进行了研究,但迄今为止,其对功能结局的影响仍不清楚。为此,我们在Wistar大鼠中使用了闭合性颅脑损伤(CHI)模型,将其随机分为四组之一(未治疗的TBI、G-CSF治疗的TBI、G-CSF治疗的对照组、对照组)。治疗组在创伤后30分钟(120μg/kg)和12小时(60μg/kg)皮下注射G-CSF。在损伤后第2-6天,使用莫里斯水迷宫试验来测量TBI动物中观察到的与治疗相关的认知缺陷变化。我们的研究结果表明,与未治疗的TBI相比,在损伤后一周内,G-CSF治疗的TBI动物的认知表现有显著改善,这表明G-CSF对CHI后的认知表现具有即时和有益的影响。我们的模型表明,早期接触G-CSF可能是治疗TBI所致认知缺陷恢复的一种有前途的治疗方法。

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