CCR5 Blockade Promotes M2 Macrophage Activation and Improves Locomotor Recovery After Spinal Cord Injury in Mice

Li, Fengtao; Cheng, Bin; Cheng, Jian; Wang, Dong; Li, Haopeng; He, Xijing

doi:10.1007/s10753-014-0014-z

Cited by 29 publications

(23 citation statements)

References 36 publications

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“…The detrimental effect of CCL3 and its pathway has been demonstrated in other disease models. CCL3 −/− mice show reduced lesion sizes and plaque formation in atherosclerosis [45] and blockade of CCR5, using neutralizing antibodies, promotes locomotor recovery after SCI [46]. However, it is important to note that CCR5 is the receptor for various chemokines besides CCL3.…”

Section: Discussionmentioning

confidence: 99%

CCL3 contributes to secondary damage after spinal cord injury

Pelisch

Almanza

Stehlik

et al. 2020

Preprint

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Background: Secondary damage after spinal cord injury (SCI) is characterized by a cascade of events including hemorrhage, apoptosis, oxidative stress and inflammation which increase the lesion size which can influence the functional impairment. Thus, identifying specific mechanisms attributed to secondary injury is critical in minimizing tissue damage and improving neurological outcome. In this work, we are investigating the role of CCL3 (Macrophage inflammatory protein 1- α, MIP-1α), a chemokine involved in the recruitment of inflammatory cells, which plays an important role in inflammatory conditions of the central and peripheral nervous system. Methods: A mouse model of lower thoracic (T11) spinal cord contusion injury was used. We assessed expression levels of CCL3 and its receptors on the mRNA and protein level and analyzed changes in locomotor recovery and the inflammatory response in the injured spinal cord of wild-type and CCL3-/- mice.Results: The expression of CCL3 and its receptors is increased after thoracic contusion SCI in mice. We then examined the role of CCL3 after SCI and its direct influence on the inflammatory response, locomotor recovery and lesion size using CCL3 −/− mice. CCL3 −/− mice showed mild but significant improvement of locomotor recovery and a smaller lesion size compared to wild-type controls. In addition, neutrophil numbers as well as the pro-inflammatory cytokines and chemokines, known to play a deleterious role after SCI, were markedly reduced in the absence of CCL3 .Conclusion: We have identified CCL3 as a potential target to modulate the inflammatory response and secondary damage after SCI. Collectively, this study shows that the absence of CCL3 can contribute to reduced tissue damage and better functional recovery during secondary injury after SCI.

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Section: Discussionmentioning

confidence: 99%

CCL3 contributes to secondary damage after spinal cord injury

Pelisch

Almanza

Stehlik

et al. 2020

Preprint

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“…CXCR2 encodes the IL‐8 receptor, which is required for PMN chemotaxis 35 . CCR5 expressed on monocytes/macrophages is crucial in regulating macrophage activation 36 . CD11b is an adhesion molecule abundant in PMNs and macrophages.…”

Section: Discussionmentioning

confidence: 99%

Glutamine Administration After Sublethal Lower Limb Ischemia Reduces Inflammatory Reaction and Offers Organ Protection in Ischemia/Reperfusion Injury

Shih

Pai

et al. 2015

J Parenter Enteral Nutr

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“…; Li et al . ). The mice were evaluated by two researchers blinded to this experiment at the same time and same place for 8 weeks after injury.…”

Section: Methodsmentioning

confidence: 97%

Deficiency of TREK‐1 potassium channel exacerbates secondary injury following spinal cord injury in mice

Fang

Huang

Wan

et al. 2017

Journal of Neurochemistry

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Spinal cord injury (SCI) involves complex pathological process which can be complicated by secondary injury. TREK-1 is a member of the two-pore domain potassium (K2P) channel family, which can be modulated by a number of physiological and pathological stimuli. Recent studies suggest that TREK-1 plays an active role in depression, pain and neuroprotection. However, its role in the pathological process after SCI remains unclear. In this study, we tested the expression and function of TREK-1 in spinal cord of mice after traumatic SCI. TREK-1 was widely expressed in mice spinal cord, including astrocytes and neurons. Deficiency of TREK-1 significantly exacerbated focal inflammatory responses as indicated by the increased accumulation of microglia/macrophage as well as pro-inflammatory factor interleukin-1 beta (IL-1β) and tumor necrosis factor alpha expression. Meanwhile, TREK-1 knockout mice showed enhanced reactive astrogliosis, chondroitin sulphate proteoglycans (CSPGs) production and decreased glutamate transporter-1 expression compared to the wide-type mice after SCI. Furthermore, TREK-1 deficiency promoted neurons and oligodendrocytes apoptosis, aggravated demyelination, cavity formation and retarded motor recovery. In summary, our findings provide the first in vivo evidence suggesting that TREK-1 may thereby constitute a promising therapeutic target to treat acute SCI.

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CCR5 Blockade Promotes M2 Macrophage Activation and Improves Locomotor Recovery After Spinal Cord Injury in Mice

Cited by 29 publications

References 36 publications

CCL3 contributes to secondary damage after spinal cord injury

CCL3 contributes to secondary damage after spinal cord injury

Glutamine Administration After Sublethal Lower Limb Ischemia Reduces Inflammatory Reaction and Offers Organ Protection in Ischemia/Reperfusion Injury

Deficiency of TREK‐1 potassium channel exacerbates secondary injury following spinal cord injury in mice

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