scholarly journals Current Knowledge of Microglia in Traumatic Spinal Cord Injury

2022 ◽  
Vol 12 ◽  
Author(s):  
Lintao Xu ◽  
Jingyu Wang ◽  
Yueming Ding ◽  
Linlin Wang ◽  
Yong-Jian Zhu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Proinflammatory Cytokines ◽  
Immune Cells ◽  
Microglial Activation ◽  
Neuronal Injury ◽  
Traumatic Spinal Cord Injury ◽  
Activated Microglia ◽  
Cord Injury ◽  
Anti Inflammatory

Microglia are the resident immune cells in the central nervous system (CNS). After traumatic spinal cord injury (SCI), microglia undergo activation, proliferation, and changes in gene and protein expression and morphology, with detrimental and beneficial effects. Activated microglia cause secondary neuronal injury via the production of proinflammatory cytokines, reactive oxygen species, and proteases. However, activated microglia also promote neuronal repair through the secretion of anti-inflammatory growth factors and cytokines. Proinflammatory cytokines increase endothelial permeability, promote A1 astrocyte activation and axonal demyelination, and reduce neural stem/progenitor cells (NSPCs), leading to the exacerbation of neuronal injury. In contrast, anti-inflammatory factors facilitate angiogenesis, reduce reactive astrocytes, and promote axonal remyelination and the propagation of NSPCs, contributing to tissue repair and locomotor recovery. Due to its limited regenerative capacity, the CNS requires beneficial microglia for continuous protection against injury. Understanding and regulating microglial activation status are beneficial to reducing detrimental effects and promoting repair behaviors and to obtain more information on efficient therapies for traumatic SCI. This review discusses microglial activation and the differences between microglia and similar immune cells, microglial interactions with other cells in the spinal cord, and the progress in the development of therapies targeting microglia in SCI.

scholarly journals Beyond the lesion site: minocycline augments inflammation and anxiety-like behavior following SCI in rats through action on the gut microbiota

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Emma K. A. Schmidt ◽  
Pamela J. F. Raposo ◽  
Abel Torres-Espin ◽  
Keith K. Fenrich ◽  
Karim Fouad
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Gut Microbiota ◽  
Microglial Activation ◽  
Motor Recovery ◽  
Long Term Effects ◽  
Cord Injury ◽  
Anti Inflammatory

Abstract Background Minocycline is a clinically available synthetic tetracycline derivative with anti-inflammatory and antibiotic properties. The majority of studies show that minocycline can reduce tissue damage and improve functional recovery following central nervous system injuries, mainly attributed to the drug’s direct anti-inflammatory, anti-oxidative, and neuroprotective properties. Surprisingly the consequences of minocycline’s antibiotic (i.e., antibacterial) effects on the gut microbiota and systemic immune response after spinal cord injury have largely been ignored despite their links to changes in mental health and immune suppression. Methods Here, we sought to determine minocycline’s effect on spinal cord injury-induced changes in the microbiota-immune axis using a cervical contusion injury in female Lewis rats. We investigated a group that received minocycline following spinal cord injury (immediately after injury for 7 days), an untreated spinal cord injury group, an untreated uninjured group, and an uninjured group that received minocycline. Plasma levels of cytokines/chemokines and fecal microbiota composition (using 16s rRNA sequencing) were monitored for 4 weeks following spinal cord injury as measures of the microbiota-immune axis. Additionally, motor recovery and anxiety-like behavior were assessed throughout the study, and microglial activation was analyzed immediately rostral to, caudal to, and at the lesion epicenter. Results We found that minocycline had a profound acute effect on the microbiota diversity and composition, which was paralleled by the subsequent normalization of spinal cord injury-induced suppression of cytokines/chemokines. Importantly, gut dysbiosis following spinal cord injury has been linked to the development of anxiety-like behavior, which was also decreased by minocycline. Furthermore, although minocycline attenuated spinal cord injury-induced microglial activation, it did not affect the lesion size or promote measurable motor recovery. Conclusion We show that minocycline’s microbiota effects precede its long-term effects on systemic cytokines and chemokines following spinal cord injury. These results provide an exciting new target of minocycline as a therapeutic for central nervous system diseases and injuries.

scholarly journals Schwann Cell Transplantation Subdues the Pro-Inflammatory Innate Immune Cell Response after Spinal Cord Injury

2018 ◽  
Vol 19 (9) ◽  
pp. 2550 ◽  
Author(s):  
Damien Pearse ◽  
Johana Bastidas ◽  
Sarah Izabel ◽  
Mousumi Ghosh
Keyword(s):  
Spinal Cord ◽  
Flow Cytometry ◽  
Spinal Cord Injury ◽  
Immune Cells ◽  
Innate Immune ◽  
Injured Spinal Cord ◽  
Multicolor Flow Cytometry ◽  
Cord Injury ◽  
Anti Inflammatory ◽  
Cluster Of Differentiation

The transplantation of Schwann cells (SCs) has been shown to provide tissue preservation and support axon growth and remyelination as well as improve functional recovery across a diverse range of experimental spinal cord injury (SCI) paradigms. The autologous use of SCs has progressed to Phase 1 SCI clinical trials in humans where their use has been shown to be both feasible and safe. The contribution of immune modulation to the protective and reparative actions of SCs within the injured spinal cord remains largely unknown. In the current investigation, the ability of SC transplants to alter the innate immune response after contusive SCI in the rat was examined. SCs were intraspinally transplanted into the lesion site at 1 week following a thoracic (T8) contusive SCI. Multicolor flow cytometry and immunohistochemical analysis of specific phenotypic markers of pro- and anti-inflammatory microglia and macrophages as well as cytokines at 1 week after SC transplantation was employed. The introduction of SCs significantly attenuated the numbers of cluster of differentiation molecule 11B (CD11b)+, cluster of differentiation molecule 68 (CD68)+, and ionized calcium-binding adapter molecule 1 (Iba1)+ immune cells within the lesion implant site, particularly those immunoreactive for the pro-inflammatory marker, inducible nitric oxide synthase (iNOS). Whereas numbers of anti-inflammatory CD68+ Arginase-1 (Arg1+) iNOS− cells were not altered by SC transplantation, CD68+ cells of an intermediate, Arg1+ iNOS+ phenotype were increased by the introduction of SCs into the injured spinal cord. The morphology of Iba1+ immune cells was also markedly altered in the SC implant, being elongated and in alignment with SCs and in-growing axons versus their amoeboid form after SCI alone. Examination of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and anti-inflammatory cytokines, interleukin-4 (IL-4) and interleukin-10 (IL-10), by multicolor flow cytometry analysis showed that their production in CD11b+ cells was unaltered by SC transplantation at 1 week post-transplantation. The ability of SCs to subdue the pro-inflammatory iNOS+ microglia and macrophage phenotype after intraspinal transplantation may provide an important contribution to the neuroprotective effects of SCs within the sub-acute SCI setting.

scholarly journals The Role of Interleukins after Spinal Cord Injury

2021 ◽  
Author(s):  
Daniel J. Hellenbrand ◽  
Rylie M. Roddick ◽  
Sophia M. Mauney ◽  
Ryan T. Elder ◽  
Carolyn N. Morehouse ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Cord Injury ◽  
Anti Inflammatory

In skin wound healing the injured tissue goes through a normal progression, inflammation subsides and remodeling occurs. However after spinal cord injury inflammation persists and there is less progression into a regenerative/rebuilding phase. This inflammatory process after spinal cord injury is orchestrated by many cell types and numerous cytokines. Although there are several positive effects of inflammation after spinal cord injury, such as the removal of debris, the substantial upregulation of immune cells has been shown to contribute to neural degeneration. Several chemokines and cytokines including many interleukins are involved in guiding these immune cells to the lesion. While there are many inflammatory cytokines acting on these immune cells after SCI, there are also several anti-inflammatory interleukins that have shown beneficial effects in reducing inflammation. After SCI in a rat model, interleukin-10 and interleukin-19 have been shown to downregulate the synthesis of pro-inflammatory species including interleukin-1β and tumor necrosis factor-α, which resulted in a significant improvement in rat hind limb function. Also, interleukin-4 and interleukin-13 are related anti-inflammatory cytokines that regulate many aspects of inflammation and have also been shown to induce alternative macrophage activation. The differing and complex roles interleukins play, highlight their importance on the inflammation that persists after spinal cord injury. Here we review both the positive effects and negative effects that interleukins have during the multifaceted inflammation process following spinal cord injury.

Neurological Recovery in Traumatic Spinal Cord Injury Patient with Delayed Surgical Intervention

2018 ◽  
Vol 1 (2) ◽  
pp. 34
Author(s):  
Mochamad Targib Alatas
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Surgical Intervention ◽  
Case Series ◽  
Spinal Cord Injury Patient ◽  
Traumatic Spinal Cord Injury ◽  
Best Interest ◽  
Score Improvement ◽  
Cord Injury ◽  
Injury Patient

Early surgical treatment for traumatic spinal cord injury (SCI) patients has been proven to yield better improvement on neurological state, and widely practiced among surgeons in this field. However, it is not always affordable in every clinical setting. It is undeniable that surgery for chronic SCI has more challenges as the malunion of vertebral bones might have initiated, thus requires more complex operating techniques. In this case series, we report 7 patients with traumatic SCI whose surgical intervention is delayed due to several reasons. Initial motoric scores vary from 0 to 3, all have their interval periods supervised between outpatient clinic visits. On follow up they demonstrate significant neurological development defined by at least 2 grades motoric score improvement. Physical rehabilitation also began before surgery was conducted. These results should encourage surgeons to keep striving for the patient’s best interest, even when the injury has taken place weeks or even months before surgery is feasible because clinical improvement for these patients is not impossible. 

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