Kallmünzer Bernd, Tauchi Miyuki, Schlachetzki Johannes C, Machold Kristin, Schmidt Ariana, Winkler Jürgen, Schwab Stefan, Kollmar Rainer
Department of Neurology, University Medical Center Erlangen, Germany.
Int J Stroke. 2014 Aug;9(6):783-8. doi: 10.1111/ijs.12217. Epub 2013 Dec 19.
Hematopoietic growth factors have been suggested to induce neuroprotective and regenerative effects in various animal models of cerebral injury. However, the pathways involved remain widely unexplored.
This study aimed to investigate effects of local and systemic administration of granulocyte colony-stimulating factor on brain damage, functional recovery, and cerebral neurogenesis in an intracerebral haemorrhage whole blood injection model in rats.
Eight-week-old male Wistar rats (n = 100) underwent induction of striatal intracerebral haemorrhage by autologous whole blood injection or sham procedure and were randomly assigned to either (a) systemic treatment with granulocyte colony-stimulating factor (60 μg/kg) for five-days; (b) single intracerebral injection of granulocyte colony-stimulating factor (60 μg/kg) into the cavity; or (c) application of vehicle for five-days. Bromodeoxyuridine-labelling and immunohistochemistry were used to analyze proliferation and survival of newly born cells in the sub-ventricular zone and the hippocampal dentate gyrus. Moreover, functional deficits and lesion volume were assessed until day 42 after intracerebral haemorrhage.
Differences in lesion size or hemispheric atrophy between granulocyte colony-stimulating factor-treated and control groups did not reach statistical significance. Neither systemic, nor local granulocyte colony-stimulating factor administration induced neurogenesis within the dentate gyrus or the sub-ventricular zone. The survival of newborn cells in these regions was prevented by intracerebral granulocyte colony-stimulating factor application. A subtle benefit in functional recovery at day 14 after intracerebral haemorrhage induction was observed after granulocyte colony-stimulating factor treatment.
There was a lack of neuroprotective or neuroregenerative effects of granulocyte colony-stimulating factor in the present rodent model of intracerebral haemorrhage. Conflicting results from functional outcome assessment require further research.
造血生长因子已被证明可在各种脑损伤动物模型中诱导神经保护和再生作用。然而，其中涉及的途径仍未得到广泛探索。
本研究旨在探讨在大鼠脑出血全血注射模型中，局部和全身给予粒细胞集落刺激因子对脑损伤、功能恢复和脑内神经发生的影响。
8周龄雄性Wistar大鼠（n = 100）通过自体全血注射或假手术诱导纹状体脑出血，并随机分为以下三组：（a）全身给予粒细胞集落刺激因子（60μg/kg），持续5天；（b）向脑腔内单次注射粒细胞集落刺激因子（60μg/kg）；或（c）给予载体5天。使用溴脱氧尿苷标记和免疫组织化学分析脑室下区和海马齿状回新生细胞的增殖和存活情况。此外，在脑出血后第42天之前评估功能缺陷和损伤体积。
粒细胞集落刺激因子治疗组和对照组之间的损伤大小或半球萎缩差异未达到统计学意义。全身或局部给予粒细胞集落刺激因子均未诱导齿状回或脑室下区内的神经发生。脑内应用粒细胞集落刺激因子可阻止这些区域新生细胞的存活。粒细胞集落刺激因子治疗后，在脑出血诱导后第14天观察到功能恢复有轻微改善。
在目前的啮齿动物脑出血模型中，粒细胞集落刺激因子缺乏神经保护或神经再生作用。功能结局评估的矛盾结果需要进一步研究。
