The Inflammatory Response after Moderate Contusion Spinal Cord Injury: A Time Study

Lund, Minna Christiansen; Ellman, Ditte Gry; Nissen, Maiken; Nielsen, Pernille Sveistrup; Nielsen, Pernille Vinther; Jørgensen, Charlotte Adam; Andersen, Ditte Caroline; Gao, Han; Brambilla, Roberta; Degn, Matilda; Clausen, Bettina Hjelm; Lambertsen, Kate Lykke

doi:10.3390/biology11060939

Cited by 13 publications

(27 citation statements)

References 85 publications

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“…The locomotion is affected by the SCI in mice. This result was similar to those of previous SCI studies, which included either a SCI induced by the occlusion of the aorta, for a brief amount of time, or a SCI induced by contusions in mice [24,25].…”

Section: Discussionsupporting

confidence: 89%

Endoplasmic Reticulum Stress Causing Apoptosis in a Mouse Model of an Ischemic Spinal Cord Injury

Soni

Hwang

Mahesh

et al. 2023

IJMS

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A spinal cord injury (SCI) is the devastating trauma associated with functional deterioration due to apoptosis. Most laboratory SCI models are generated by a direct impact on an animal’s spinal cord; however, our model does not involve the direct impact on the spinal cord. Instead, we use a clamp compression to create an ischemia in the descending aortas of mice. Following the success of inducing an ischemic SCI (ISCI), we hypothesized that this model may show apoptosis via an endoplasmic reticulum (ER) stress pathway. This apoptosis by the ER stress pathway is enhanced by the inducible nitric oxide synthase (iNOS). The ER is used for the protein folding in the cell. When the protein folding capacity is overloaded, the condition is termed the ER stress and is characterized by the accumulation of misfolded proteins inside the ER lumen. The unfolded protein response (UPR) signaling pathways that deal with the ER stress response then become activated. This UPR activates the three signal pathways that are regulated by the inositol-requiring enzyme 1α (IRE1α), the activating transcription factor 6 (ATF6), and the protein kinase RNA-like ER kinase (PERK). IRE1α and PERK are associated with the expression of the apoptotic proteins. Apoptosis caused by an ISCI is assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. An ISCI also reduces synaptophysin and the neuronal nuclear protein (NeuN) in the spinal cord. In conclusion, an ISCI increases the ER stress proteins, resulting in apoptosis in neuronal cells in the spinal cord.

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Section: Discussionsupporting

confidence: 89%

Endoplasmic Reticulum Stress Causing Apoptosis in a Mouse Model of an Ischemic Spinal Cord Injury

Soni

Hwang

Mahesh

et al. 2023

IJMS

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“…Diminishing the robust neuroinflammatory response and the detrimental immune signaling could reduce tissue damage and accelerate functional recovery following SCI [30]. In line with these findings, HMGB2 knockdown inhibited SCI-induced microglial activation.…”

Section: Discussionsupporting

confidence: 60%

“…A recent study indicated that suppressing microglia-mediated neuroinflammation was a potential therapeutic strategy for neuropathic pain in the spinal cord of mice [ 29 ]. Diminishing the robust neuroinflammatory response and the detrimental immune signaling could reduce tissue damage and accelerate functional recovery following SCI [ 30 ]. In line with these findings, HMGB2 knockdown inhibited SCI-induced microglial activation.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of High mobility group box 2 relieves spinal cord injury by inhibiting microglia-mediated neuroinflammation

Yang

Chen

et al. 2023

Exp. Anim.

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Spinal cord injury (SCI), characterized by sensory disturbance and motor deficits, is associated with excessive inflammatory cytokine production of microglial cells.Previous studies have demonstrated High mobility group box 2 (HMGB2) as a microglial pro-inflammatory factor in stroke. This present study aims to evaluate the function of HMGB2 in a SCI rat model induced by striking the spinal cord at T9 to T12 using a rod. Our results showed that the levels of HMGB2 were significantly increased in the spinal cord tissues of SCI rats. Besides, HMGB2 downregulation was achieved by receiving an injection of lentivirus encoding HMGB2 shRNA in the spinal cord. Knockdown of HMGB2 suppressed SCI-induced microglial activation and neuroinflammation, as well as alleviated neuronal loss. In addition, we confirmed that HMGB2 silencing lessened lipopolysaccharide (LPS)-induced neuroinflammation in BV-2 cells. Furthermore, our findings demonstrated that HMGB2 knockdown suppressed the canonical nuclear factor of kB (NF-κB) signaling pathway both in vivo and in vitro. Collectively, this study manifested strong anti-inflammatory roles of HMGB2 knockdown on microglia-mediated neuroinflammation and suggested that HMGB2 might serve as a potential target for SCI therapy.

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“…The initial traumatic event, or primary injury, is followed by several biological events termed the secondary injury. There are, however, three pathological stages that define the secondary injury in SCI: the acute phase (48 h), subacute phase (2–14 days), and chronic phase (more than 6 months) 4 – 7 .…”

Section: Sci Pathophysiologymentioning

confidence: 99%

Cell Transplantation for Repair of the Spinal Cord and Prospects for Generating Region-Specific Exogenic Neuronal Cells

Roman,

Huntemer-Silveira,

Waldron

et al. 2024

Cell Transplant

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Spinal cord injury (SCI) is associated with currently irreversible consequences in several functional components of the central nervous system. Despite the severity of injury, there remains no approved treatment to restore function. However, with a growing number of preclinical studies and clinical trials, cell transplantation has gained significant potential as a treatment for SCI. Researchers have identified several cell types as potential candidates for transplantation. To optimize successful functional outcomes after transplantation, one key factor concerns generating neuronal cells with regional and subtype specificity, thus calling on the developmental transcriptome patterning of spinal cord cells. A potential source of spinal cord cells for transplantation is the generation of exogenic neuronal progenitor cells via the emerging technologies of gene editing and blastocyst complementation. This review highlights the use of cell transplantation to treat SCI in the context of relevant developmental gene expression patterns useful for producing regionally specific exogenic spinal cells via in vitro differentiation and blastocyst complementation.

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The Inflammatory Response after Moderate Contusion Spinal Cord Injury: A Time Study

Cited by 13 publications

References 85 publications

Endoplasmic Reticulum Stress Causing Apoptosis in a Mouse Model of an Ischemic Spinal Cord Injury

Endoplasmic Reticulum Stress Causing Apoptosis in a Mouse Model of an Ischemic Spinal Cord Injury

Downregulation of High mobility group box 2 relieves spinal cord injury by inhibiting microglia-mediated neuroinflammation

Cell Transplantation for Repair of the Spinal Cord and Prospects for Generating Region-Specific Exogenic Neuronal Cells

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