Cell Death in Spinal Cord Injury (SCI) Requires de Novo Protein Synthesis

2006 ◽  
Vol 939 (1) ◽  
pp. 436-449 ◽  
Author(s):  
SWAPAN K. RAY ◽  
DENISE D. MATZELLE ◽  
GLORIA G. WILFORD ◽  
EDWARD L. HOGAN ◽  
NAREN L. BANIK
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Protein Synthesis ◽  
De Novo ◽  
Cord Injury ◽  
De Novo Protein Synthesis

Induction of Autophagy and Autophagic Cell Death in Damaged Neural Tissue After Acute Spinal Cord Injury in Mice

Spine ◽  
2011 ◽  
Vol 36 (22) ◽  
pp. E1427-E1434 ◽  
Author(s):  
Haruo Kanno ◽  
Hiroshi Ozawa ◽  
Akira Sekiguchi ◽  
Seiji Yamaya ◽  
Eiji Itoi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Neural Tissue ◽  
Acute Spinal Cord Injury ◽  
Autophagic Cell Death ◽  
Cord Injury

scholarly journals VDAC1 is essential for neurite maintenance and the inhibition of its oligomerization protects spinal cord from demyelination and facilitates locomotor function recovery after spinal cord injury

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Vera Paschon ◽  
Beatriz Cintra Morena ◽  
Felipe Fernandes Correia ◽  
Giovanna Rossi Beltrame ◽  
Gustavo Bispo dos Santos ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Conformational Changes ◽  
Secondary Response ◽  
Disulfonic Acid ◽  
Function Recovery ◽  
Cord Injury

Abstract During the progression of the neurodegenerative process, mitochondria participates in several intercellular signaling pathways. Voltage-dependent anion-selective channel 1 (VDAC1) is a mitochondrial porin involved in the cellular metabolism and apoptosis intrinsic pathway in many neuropathological processes. In spinal cord injury (SCI), after the primary cell death, a secondary response that comprises the release of pro-inflammatory molecules triggers apoptosis, inflammation, and demyelination, often leading to the loss of motor functions. Here, we investigated the functional role of VDAC1 in the neurodegeneration triggered by SCI. We first determined that in vitro targeted ablation of VDAC1 by specific morpholino antisense nucleotides (MOs) clearly promotes neurite retraction, whereas a pharmacological blocker of VDAC1 oligomerization (4, 4′-diisothiocyanatostilbene-2, 2′-disulfonic acid, DIDS), does not cause this effect. We next determined that, after SCI, VDAC1 undergoes conformational changes, including oligomerization and N-terminal exposition, which are important steps in the triggering of apoptotic signaling. Considering this, we investigated the effects of DIDS in vivo application after SCI. Interestingly, blockade of VDAC1 oligomerization decreases the number of apoptotic cells without interfering in the neuroinflammatory response. DIDS attenuates the massive oligodendrocyte cell death, subserving undisputable motor function recovery. Taken together, our results suggest that the prevention of VDAC1 oligomerization might be beneficial for the clinical treatment of SCI.

Acute upregulation of bone morphogenetic protein-4 regulates endogenous cell response and promotes cell death in spinal cord injury

2020 ◽  
Vol 325 ◽  
pp. 113163 ◽  
Author(s):  
Christopher G. Hart ◽  
Scott M. Dyck ◽  
Hardeep Kataria ◽  
Arsalan Alizadeh ◽  
Pandian Nagakannan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Bone Morphogenetic Protein ◽  
Cell Response ◽  
Bone Morphogenetic Protein 4 ◽  
Morphogenetic Protein ◽  
Cord Injury

Neuroprotection and functional recovery after application of the caspase-9 inhibitor z-LEHD-fmk in a rat model of traumatic spinal cord injury

2005 ◽  
Vol 2 (3) ◽  
pp. 327-334 ◽  
Author(s):  
Ahmet Çolak ◽  
Alper Karaoǧlan ◽  
Şeref Barut ◽  
Sibel Köktürk ◽  
Aysşenur Iǧdem Akyildiz ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Rat Model ◽  
Caspase 9 ◽  
Content Type ◽  
Cord Injury ◽  
Group 3 ◽  
Group 2 ◽  
Fine Print

Object. Apoptosis is considered one of the most significant mechanisms in the pathogenesis of neuronal damage after spinal cord injury (SCI). This form of cell death occurs via mediators known as caspases. The aim of this study was to evaluate the neuroprotective effect of the caspase-9 inhibitor, z-LEHD-fmk, in a rat model of spinal cord trauma. Methods. Fifty-four Wistar albino rats were studied in the following three groups of 18 animals each: sham-operated controls (Group 1); trauma-only controls (Group 2); and trauma combined with z-LEHD-fmk—treated animals (0.8 µM/kg; Group 3). Spinal cord injury was produced at the thoracic level by using the weight-drop technique. Responses to SCI and the efficacy of z-LEHD-fmk treatment were determined on the basis of terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick—end labeling staining and light and electron microscopy findings in cord tissue at 24 hours and 7 days posttrauma. Six rats from each group were also assessed for functional recovery at 3 and 7 days after SCI. This was conducted using the inclined-plane technique and a modified version of the Tarlov motor grading scale. At 24 hours postinjury, light microscopic examination of Group 2 tissue samples showed hemorrhage, edema, necrosis, polymorphonuclear leukocyte infiltration, and vascular thrombi. Those obtained in Group 3 rats at this stage showed similar features. At 24 hours postinjury, the mean apoptotic cell count in Group 2 was significantly higher than that in Group 3 (90.25 ± 2.6 and 50.5 ± 1.9, respectively; p < 0.05). At 7 days postinjury, the corresponding mean apoptotic cell counts were 49 ± 2.1 and 17.7 ± 2.6, also a significant difference (p < 0.05). Electron microscopy findings confirmed the occurrence of programmed cell death in different cell types in the spinal cord and showed that z-LEHD-fmk treatment protected neurons, glia, myelin, axons, and intracellular organelles. Conclusions. Examination of the findings in this rat model of SCI revealed that apoptosis occurs not only in neurons and astrocytes but also in oligodendrocytes and microglia. Furthermore, immediate treatment with the caspase-9 inhibitor z-LEHD-fmk blocked apoptosis effectively and was associated with better functional outcome. More in-depth research of the role of programmed cell death in spinal cord trauma and further study of the ways in which caspases are involved in this process may lead to new strategies for treating SCI.

scholarly journals Changes in Expression of Receptor-Interacting Protein Kinase 1 in Secondary Neural Tissue Damage Following Spinal Cord Injury

2020 ◽  
Vol 15 ◽  
pp. 263310552090640
Author(s):  
Haruo Kanno ◽  
Hiroshi Ozawa ◽  
Kyoichi Handa ◽  
Taishi Murakami ◽  
Eiji Itoi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Tissue Damage ◽  
Time Course ◽  
Apoptotic Cell ◽  
Neural Tissue ◽  
Apoptotic Cell Death ◽  
Neural Cells ◽  
Cord Injury

Introduction: Necroptosis is a form of programmed cell death that is different from apoptotic cell death. Receptor-interacting protein kinase 1 (RIPK1) plays a particularly important function in necroptosis execution. This study investigated changes in expression of RIPK1 in secondary neural tissue damage following spinal cord injury in mice. The time course of the RIPK1 expression was also compared with that of apoptotic cell death in the lesion site. Methods and Materials: Immunostaining for RIPK1 was performed at different time points after spinal cord injury. The protein expressions of RIPK1 were determined by western blot. The RIPK1 expressions in various neural cells were investigated using immunohistochemistry. To investigate the time course of apoptotic cell death, TUNEL-positive cells were counted at the different time points. To compare the incidence of necroptosis and apoptosis, the RIPK1-labeled sections were co-stained with TUNEL. Results: The RIPK1 expression was significantly upregulated in the injured spinal cord. The upregulation of RIPK1 expression was observed in neurons, astrocytes, and oligodendrocytes. The increase in RIPK1 expression started at 4 hours and peaked at 3 days after injury. Time course of the RIPK1 expression was similar to that of apoptosis detected by TUNEL. Interestingly, the increased expression of RIPK1 was rarely observed in the TUNEL-positive cells. Furthermore, the number of RIPK1-positive cells was significantly higher than that of TUNEL-positive cells. Conclusions: This study demonstrated that the expression of RIPK1 increased in various neural cells and peaked at 3 days following spinal cord injury. The temporal change of the RIPK1 expression was analogous to that of apoptosis at the lesion site. However, the increase in RIPK1 expression was barely seen in the apoptotic cells. These findings suggested that the RIPK1 might contribute to the pathological mechanism of the secondary neural tissue damage after spinal cord injury.

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