Department of Neurosurgery, The State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
Department of Neurosurgery, The State University of New York Upstate Medical University, Syracuse, NY 13210, USA; VA Health Care Upstate New York, Syracuse VA Medical Center, USA.
Exp Neurol. 2020 Aug;330:113335. doi: 10.1016/j.expneurol.2020.113335. Epub 2020 Apr 30.
Severe traumatic brain injury (TBI) is the major cause of long-term, even life-long disability and cognitive impairments in young adults. The lack of therapeutic approaches to improve recovery in the chronic phase of severe TBI is a big challenge to the medical research field. Using a single severe TBI model in young adult mice, this study examined the restorative efficacy of two hematopoietic growth factors, stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF), on brain repair in the chronic phase of TBI. SCF and G-CSF alone or combination (SCF + G-CSF) treatment was administered at 3 months post-TBI. Functional recovery was evaluated by neurobehavioral tests during the period of 21 weeks after treatment. Neuropathology was examined 22 weeks after treatment. We observed that severe TBI caused persistent impairments in spatial learning/memory and somatosensory-motor function, long-term and widespread neuropathology, including dendritic reduction, decrease and overgrowth of axons, over-generated excitatory synapses, and demyelination in the cortex, hippocampus and striatum. SCF, G-CSF, and SCF + G-CSF treatments ameliorated severe TBI-induced widespread neuropathology. SCF + G-CSF treatment showed superior efficacy in improving long-term functional outcome, enhancing neural plasticity, rebalancing neural structure networks disturbed by severe TBI, and promoting remyelination. These novel findings demonstrate the therapeutic potential of SCF and G-CSF in enhancing recovery in the chronic phase of severe TBI .
严重创伤性脑损伤（TBI）是导致年轻人长期甚至终身残疾和认知障碍的主要原因。缺乏改善严重 TBI 慢性期恢复的治疗方法是医学研究领域的一大挑战。本研究使用年轻成年小鼠的单一严重 TBI 模型，研究了两种造血生长因子，干细胞因子（SCF）和粒细胞集落刺激因子（G-CSF）在 TBI 慢性期对脑修复的恢复作用。在 TBI 后 3 个月给予 SCF 和 G-CSF 单独或联合（SCF+G-CSF）治疗。在治疗后 21 周的时间内通过神经行为测试评估功能恢复。在治疗后 22 周检查神经病理学。我们观察到严重 TBI 导致空间学习/记忆和躯体感觉运动功能持续受损，长期广泛的神经病理学改变，包括树突减少、轴突减少和过度生长、过度产生兴奋性突触和皮质、海马和纹状体脱髓鞘。SCF、G-CSF 和 SCF+G-CSF 治疗改善了严重 TBI 引起的广泛神经病理学改变。SCF+G-CSF 治疗在改善长期功能结局、增强神经可塑性、重新平衡严重 TBI 扰乱的神经结构网络以及促进髓鞘形成方面显示出更好的疗效。这些新发现表明 SCF 和 G-CSF 在增强严重 TBI 慢性期恢复方面具有治疗潜力。
