scholarly journals Sirtuins: Potential Therapeutic Targets for Defense against Oxidative Stress in Spinal Cord Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jialiang Lin ◽  
Zhencheng Xiong ◽  
Jionghui Gu ◽  
Zhuoran Sun ◽  
Jiang Shuai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Pathological Process ◽  
Secondary Injury ◽  
Beneficial Effects ◽  
Cord Injury ◽  
Primary Injury ◽  
Antioxidant Mechanisms ◽  
Antioxidant Effects

Spinal cord injury (SCI) is one of the most incapacitating neurological disorders. It involves complex pathological processes that include a primary injury and a secondary injury phase, or a delayed stage, which follows the primary injury and contributes to the aggravation of the SCI pathology. Oxidative stress, a key pathophysiological event after SCI, contributes to a cascade of inflammation, excitotoxicity, neuronal and glial apoptosis, and other processes during the secondary injury phase. In recent years, increasing evidence has demonstrated that sirtuins are protective toward the pathological process of SCI through a variety of antioxidant mechanisms. Notably, strategies that modulate the expression of sirtuins exert beneficial effects in cellular and animal models of SCI. Given the significance and novelty of sirtuins, we summarize the oxidative stress processes that occur in SCI and discuss the antioxidant effects of sirtuins in SCI. We also highlight the potential of targeting sirtuins for the treatment of SCI.

scholarly journals Hematogenous Macrophages: A New Therapeutic Target for Spinal Cord Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuanzhe Ding ◽  
Di Zhang ◽  
Sheng Wang ◽  
Xiaolei Zhang ◽  
Jingquan Yang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Therapeutic Target ◽  
Pathological Process ◽  
Secondary Injury ◽  
Cord Injury ◽  
Peripheral Monocyte ◽  
Primary Injury ◽  
M1 Type

Spinal cord injury (SCI) is a devastating disease leading to loss of sensory and motor functions, whose pathological process includes mechanical primary injury and secondary injury. Macrophages play an important role in SCI pathology. According to its origin, it can be divided into resident microglia and peripheral monocyte-derived macrophages (hematogenous Mφ). And it can also be divided into M1-type macrophages and M2-type macrophages on the basis of its functional characteristics. Hematogenous macrophages may contribute to the SCI process through infiltrating, scar forming, phagocytizing debris, and inducing inflammatory response. Although some of the activities of hematogenous macrophages are shown to be beneficial, the role of hematogenous macrophages in SCI remains controversial. In this review, following a brief introduction of hematogenous macrophages, we mainly focus on the function and the controversial role of hematogenous macrophages in SCI, and we propose that hematogenous macrophages may be a new therapeutic target for SCI.

scholarly journals Revascularization After Traumatic Spinal Cord Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Chun Yao ◽  
Xuemin Cao ◽  
Bin Yu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Blood Vessel ◽  
Vascular System ◽  
Mechanical Damage ◽  
Pathological Process ◽  
Secondary Injury ◽  
Traumatic Spinal Cord Injury ◽  
Physical Stimulation ◽  
Cord Injury

Traumatic spinal cord injury (SCI) is a complex pathological process. The initial mechanical damage is followed by a progressive secondary injury cascade. The injury ruptures the local microvasculature and disturbs blood-spinal cord barriers, exacerbating inflammation and tissue damage. Although endogenous angiogenesis is triggered, the new vessels are insufficient and often fail to function normally. Numerous blood vessel interventions, such as proangiogenic factor administration, gene modulation, cell transplantation, biomaterial implantation, and physical stimulation, have been applied as SCI treatments. Here, we briefly describe alterations and effects of the vascular system on local microenvironments after SCI. Therapies targeted at revascularization for SCI are also summarized.

Therapeutic targets and nanomaterial-based therapies for mitigation of secondary injury after spinal cord injury

Nanomedicine ◽  
2021 ◽  
Vol 16 (22) ◽  
pp. 2013-2028
Author(s):  
Jun Gao ◽  
Minkyung Khang ◽  
Zhen Liao ◽  
Megan Detloff ◽  
Jeoung Soo Lee
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Therapeutic Targets ◽  
Neurological Dysfunction ◽  
Secondary Injury ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier ◽  
And Oxidative Stress

Spinal cord injury (SCI) and the resulting neurological trauma commonly result in complete or incomplete neurological dysfunction and there are few effective treatments for primary SCI. However, the following secondary SCI, including the changes of microvasculature, inflammatory response and oxidative stress around the injury site, may provide promising therapeutic targets. The advances of nanomaterials hold promise for delivering therapeutics to alleviate secondary SCI and promote functional recovery. In this review, we highlight recent achievements of nanomaterial-based therapy, specifically targeting blood–spinal cord barrier disruption, mitigation of the inflammatory response and lightening of oxidative stress after spinal cord injury.

scholarly journals Tauroursodeoxycholic Acid Alleviates Secondary Injury in Spinal Cord Injury Mice Through Reducing Oxidative Stress, Apoptosis, and Inflammatory Response

2021 ◽  
Author(s):  
Yonghui Hou ◽  
Jiyao Luan ◽  
Tiancheng Deng ◽  
Taida Huang ◽  
Xing Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Cortical Neurons ◽  
Axon Regeneration ◽  
Secondary Injury ◽  
Primary Cortical Neurons ◽  
Cord Injury

Abstract Background Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid derivative, which has been demonstrated to have neuroprotective effects in different neurological disease models. However, the effect and underlying mechanism of TUDCA on spinal cord injury (SCI) have not been fully elucidated. This study is aim to investigate the protective effects of TUDCA in SCI mouse model and the related mechanism involved.Methods The primary cortical neurons were isolated from E16.5 C57BL/6 mouse embryos. To evaluate the effect of TUDCA on oxidative stress in vitro, the cortical neurons were treated with H2O2 with or without TUDCA added. Mice were randomly divided into sham, SCI and TUDCA groups. SCI model was induced using a pneumatic impact device at T9-T10 level of vertebra. TUDCA (200 mg/kg) or equal volume of saline was intragastrically administrated daily post injury for 14 days. ResultsWe found that TUDCA reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) release and restored superoxide dismutase (SOD) activity to protect primary cortical neurons from oxidative stress in vitro. In vivo, TUDCA treatment significantly reduced tissue injury, oxidative stress, inflammatory response, and apoptosis; promoted axon regeneration and remyelination in the lesion site of spinal cord of SCI mice. The functional recovery test revealed that TUDCA treatment significantly ameliorated recovery of limb function.ConclusionsTUDCA treatment can alleviate secondary injury and promote functional recovery through reducing oxidative stress, inflammatory response and apoptosis induced by primary injury, and promote axon regeneration and remyelination, which could be used as a potential therapy for human SCI recovery.

Modulation of the secondary injury process after spinal cord injury in Bach1-deficient mice by heme oxygenase–1

2008 ◽  
Vol 9 (6) ◽  
pp. 611-620 ◽  
Author(s):  
Kiyotaka Yamada ◽  
Nobuhiro Tanaka ◽  
Kazuyoshi Nakanishi ◽  
Naosuke Kamei ◽  
Masakazu Ishikawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Heme Oxygenase ◽  
Blue Staining ◽  
Heme Oxygenase 1 ◽  
Secondary Injury ◽  
Wild Type ◽  
Early Stages ◽  
Cord Injury

Object Oxidative stress contributes to secondary injury after spinal cord injury (SCI). The expression of heme oxygenase-1 (HO-1), which protects cells from various insults including oxidative stress, is upregulated in injured spinal cords. Mice deficient in Bach1 (Bach1−/−), a transcriptional repressor of the HO-1 and beta-globin genes, express high levels of HO-1 mRNA and protein in various organs. The authors hypothesized that HO-1 modulates the secondary injury process after SCI in Bach1−/− mice. Methods Male C57BL/6 (wild-type) and homozygous Bach1−/− C57BL/6 mice were subjected to moderate SCI, and differences in hindlimb motor function, and electrophysiological, molecular biological, and histopathological changes were assessed for 2 weeks. Results Functional recovery was greater, and motor evoked potentials were significantly larger in Bach1−/− mice than in wild-type mice throughout the observation period. The expression of HO-1 mRNA in the spinal cord was significantly increased in both mice until 3 days after injury, and it was significantly higher in Bach1−/− mice than in wild-type mice at every assessment point. Histological examination using Luxol fast blue staining at 1 day after injury showed that the injured areas were smaller in Bach1−/− mice than in wild-type mice. The HO-1 immunoreactivity was not detected in uninjured spinal cord, but 3 days postinjury the number of HO-1–immunoreactive cells was obviously higher in the injured area in both mice, particularly in Bach1−/− mice. The HO-1 was primarily induced in microglia/macrophage in both mice. Conclusions These results suggest that HO-1 modulates the secondary injury process, and high HO-1 expression may preserve spinal cord function in the early stages after SCI in Bach1−/− mice. Treatment that induces HO-1 expression at these early stages may preserve the functional outcome after SCI.

scholarly journals A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2245
Author(s):  
Jue-Zong Yeh ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Yi-Wen Wang ◽  
Gang-Yi Fan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Neural Plasticity ◽  
Collagen Scaffold ◽  
Glial Scar ◽  
Beneficial Effects ◽  
Cord Injury

In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

Subacute posttraumatic ascending myelopathy in a 15-year-old boy

2014 ◽  
Vol 21 (3) ◽  
pp. 454-457 ◽  
Author(s):  
Timothy J. Kovanda ◽  
Eric M. Horn
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rare Event ◽  
Fracture Dislocation ◽  
Secondary Injury ◽  
Spinal Cord Trauma ◽  
Rare Occurrence ◽  
Time Period ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Secondary injury following initial spinal cord trauma is uncommon and frequently attributed to mismanagement of an unprotected cord in the acute time period after injury. Subacute posttraumatic ascending myelopathy (SPAM) is a rare occurrence in the days to weeks following an initial spinal cord injury that is unrelated to manipulation of an unprotected cord and involves 4 or more vertebral levels above the original injury. The authors present a case of SPAM occurring in a 15-year-old boy who sustained a T3–4 fracture-dislocation resulting in a complete spinal cord injury, and they highlight the imaging findings and optimum treatment for this rare event.

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