Early mobilization in spinal cord injury promotes changes in microglial dynamics and recovery of motor function.

脊髓损伤早期动员促进小胶质细胞动力学变化和运动功能恢复。

• 发表时间: Jun 2022
• 来源期刊: IBRO Neurosci Rep
• DOI: 10.1016/j.ibneur.2022.04.002
• PMID: 35586775
• 文章类型: Journal Article
• 作者列表: Asano K,Nakamura T,Funakoshi K

关键词: BBB score, The Basso, Beattie, Bresnahan locomotor rating scale score; CNS, central nervous system; CSPGs, chondroitin sulfate proteoglycans; DAPI, 4′,6-diamidino-2-phenylindole; EM, early mobilization; Early mobilization; GAP43, growth associated protein 43; GFAP, glial fibrillary acidic protein; IL1β, interleukin-1β; MMPs, matrix metalloproteinases; Matrix metalloproteinases; Microglia; Motor function; NEM, non-early mobilization; Neuroinflammation; PBS, phosphate-buffered saline; PBST, PBS containing 0.05% Tween 20; PFA, paraformaldehyde; SCI, spinal cord injury; Spinal cord injury; TNF-α, tumor necrosis factor-α; iNOS, inducible nitric oxide synthase; tomato lectin, Lycopersicon Esculentum lectin

Abstract

In the acute phase of spinal cord injury, the initial injury triggers secondary damage due to neuroinflammation, leading to the formation of cavities and glial scars that impair nerve regeneration. Following injuries to the central nervous system, early mobilization promotes the recovery of physical function. Therefore, in the present study, we investigated the effects of early mobilization on motor function recovery and neuroinflammation in rats. Early mobilization of rats with complete spinal cord transection resulted in good recovery of hindlimb motor function after 3 weeks. At 1 week after spinal cord injury, the early-mobilized rats expressed fewer inflammatory M1 microglia/macrophages and more anti-inflammatory M2 microglia. In addition, significantly more matrix metalloproteinase 2 (MMP2)-positive cells were observed at the lesion site 1 week after injury in the early-mobilized rats. Multiple labeling studies suggested that many MMP2-positive cells were M2 microglia. MMP9-positive cells that highly co-expressed GFAP were also observed more frequently in the early-mobilized rats. The density of growth-associated protein-positive structures in the lesion center was significantly higher in the early-mobilized rats at 3 weeks after spinal cord injury. The present results suggest that early mobilization after spinal cord injury reduced the production of M1 microglia/macrophages while increasing the production of M2 microglia at the lesion site. Early mobilization might also activate the expression of MMP2 in M2 microglia and MMP9 in astrocytes. These cellular dynamics might suppress neuroinflammation at the lesion site, thereby inhibiting the progression of tissue destruction and promoting nerve regeneration to recover motor function.

摘要

在脊髓损伤的急性期，最初的损伤会引发神经炎症引起的继发性损伤，导致损害神经再生的空洞和神经胶质疤痕的形成。中枢神经系统受伤后，早期动员促进身体功能的恢复。因此,在本研究中，我们研究了早期动员对大鼠运动功能恢复和神经炎症的影响。完全脊髓横断的大鼠早期动员3周后后肢运动功能恢复良好。脊髓损伤后1周，早期动员的大鼠表达较少的炎性M1小胶质细胞/巨噬细胞和较多的抗炎M2小胶质细胞。此外,在早期动员的大鼠损伤后1周，在病变部位观察到明显更多的基质金属蛋白酶2（MMP2）阳性细胞。多重标记研究表明，许多MMP2阳性细胞是M2小胶质细胞。在早期动员的大鼠中也更频繁地观察到高度共表达GFAP的MMP9阳性细胞。脊髓损伤后3周，早期动员的大鼠病变中心的生长相关蛋白阳性结构的密度显着升高。目前的结果表明，脊髓损伤后的早期动员减少了M1小胶质细胞/巨噬细胞的产生，同时增加了病变部位M2小胶质细胞的产生。早期动员还可能激活M2小胶质细胞中MMP2和星形胶质细胞中MMP9的表达。这些细胞动力学可能会抑制病变部位的神经炎症，从而抑制组织破坏的进展并促进神经再生以恢复运动功能。