scholarly journals A Mapping Study of Caspase-3 Activation Following Acute Spinal Cord Contusion in Rats

2005 ◽  
Vol 53 (7) ◽  
pp. 809-819 ◽  
Author(s):  
Melanie L. McEwen ◽  
Joe E. Springer
Keyword(s):  
Spinal Cord ◽  
Cell Death ◽  
Cellular Localization ◽  
Time Course ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Early Time ◽  
Apoptotic Cell Death ◽  
Biphasic Pattern ◽  
Cord Injury

Spinal cord injury (SCI) initiates a cascade of biochemical changes that results in necrotic and apoptotic cell death. There is evidence that caspase-3 activation and apoptotic cell death occur within hours after SCI. However, the time course and cellular localization of activated caspase-3 has not been examined. Such information is essential because caspase-3–independent apoptotic pathways do exist. In this experiment, we describe the distribution of and cell types containing activated caspase-3 at 4 hr, 1 day, 2 days, 4 days, and 8 days following SCI in rats. Numerous caspase-3–positive cells were observed at 4 hr and 1 day postinjury and colocalized most often with CC1, a marker for oligodendroglia. Both markers disappeared near the injury epicenter over the next several days. Activated caspase-3 was again present in the injured spinal cord on postoperative day 8, which coincided with a reemergence of CC1-positive cells. Many of these CC1-positive cells again colocalized activated caspase-3. NeuN-positive neurons of the dorsal horn were occasionally immunopositive for activated caspase-3 at early time points. OX42-positive microglia/macrophages rarely contained activated caspase-3. The results indicate a biphasic pattern of caspase-3 activation during the first 8 days postinjury, suggesting that at least two mechanisms activate caspase-3 following SCI. This time-course study provides a framework for investigating and understanding the different signaling events contributing to this biphasic pattern of caspase-3 activation.

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.

Rapid Upregulation of Caspase-3 in Rat Spinal Cord after Injury: mRNA, Protein, and Cellular Localization Correlates with Apoptotic Cell Death

2000 ◽  
Vol 166 (2) ◽  
pp. 213-226 ◽  
Author(s):  
Bruce A. Citron ◽  
Paul M. Arnold ◽  
Cyril Sebastian ◽  
Fan Qin ◽  
Sundaravalli Malladi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cell Death ◽  
Cellular Localization ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Rat Spinal Cord

scholarly journals Inhibition of Apoptotic Cell Death by Ghrelin Improves Functional Recovery after Spinal Cord Injury

Endocrinology ◽  
2010 ◽  
Vol 151 (8) ◽  
pp. 3815-3826 ◽  
Author(s):  
Jee Y. Lee ◽  
Hyunju Chung ◽  
Young S. Yoo ◽  
Young J. Oh ◽  
Tae H. Oh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Functional Recovery ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Cord Injury

scholarly journals Suppression of TRPM7 by carvacrol protects against injured spinal cord by inhibiting blood-spinal cord barrier disruption

2021 ◽  
Author(s):  
Chan Sol Park ◽  
Jee Youn Lee ◽  
Hae Young Choi ◽  
Bong Gun Ju ◽  
Tae Young Yune
Keyword(s):  
Spinal Cord ◽  
Cell Death ◽  
Transient Receptor Potential ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Apoptotic Cell Death ◽  
Therapeutic Drug ◽  
Transient Receptor Potential Melastatin ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier

Abstract When the blood-spinal cord barrier (BSCB) is disrupted after a spinal cord injury (SCI), several pathophysiological cascades occur, including inflammation and apoptotic cell death of neurons and oligodendrocytes, resulting in permanent neurological deficits. Transient receptor potential melastatin 7 (TRPM7) is involved in the pathological processes in many neuronal diseases, including traumatic brain injury, amyotrophic lateral sclerosis, parkinsonism dementia, and Alzheimer’s disease. Furthermore, carvacrol (CAR), a TRPM7 inhibitor, is known to protect against SCI by reducing oxidative stress and inhibiting the endothelial nitric oxide synthase pathway. However, the functions of TRPM7 in the regulation of BSCB homeostasis after SCI have not been examined. Here, we demonstrated that TRPM7, a calcium-mediated non-selective divalent cation channel, plays a critical role after SCI in rat. Rats were contused at T9 and given CAR (50 mg/kg) via intraperitoneally immediately and 12 hours after SCI, and then given the same dose once a day for 7 days. TRPM7 was found to be up-regulated after SCI in both in vitro and in vivo studies, and it was expressed in blood vessels alongside neurons and oligodendrocytes. Additionally, CAR treatment suppressed BSCB disruption by inhibiting the loss of TJ proteins and preserved TJ integrity. CAR also reduced apoptotic cell death and improved functional recovery after SCI by preventing BSCB disruption caused by blood infiltration and inflammatory responses. Based on these findings, we propose that blocking the TRPM7 channel can inhibit the destruction of the BSCB and it is a potential target in therapeutic drug development for use in SCI.

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