FK506 Treatment Inhibits Caspase-3 Activation and Promotes Oligodendroglial Survival Following Traumatic Spinal Cord Injury

Nottingham, Stephanie A.

doi:10.1006/exnr.2002.7975

Cited by 61 publications

(42 citation statements)

References 66 publications

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“…Work in other neural systems has demonstrated that calcineurin activation initiates downstream events including dephosphorylation and activation of BAD (a Bcl-2 family protein which activates apoptotic cell death pathways), release of cytochrome c, activation of caspases 9 and 3, and cell death (Springer et al, 2000;Nottingham et al, 2002;Agostinho and Oliveira, 2003;Almeida et al, 2004;Shou et al, 2004;Watabe and Nakaki, 2004;Cardoso and Oliveira, 2005;Grosskreutz et al, 2005;Jayanthi et al, 2005). Inhibiting calcineurin activation reduces BAD dephosphorylation and improves cell survival (Wang et al, 1999a;Springer et al, 2000;Uchino et al, 2002;Berthier et al, 2004;Mano et al, 2004;Shou et al, 2004;Watabe and Nakaki, 2004;Yang et al, 2004a;Biswas et al, 2005;Cardoso and Oliveira, 2005;Huang et al, 2005).…”

Section: Bcl-2 Anti-apoptotic Proteinsmentioning

confidence: 99%

Mechanisms of noise-induced hearing loss indicate multiple methods of prevention

et al. 2007

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Recent research has shown the essential role of reduced blood flow and free radical formation in the cochlea in noise-induced hearing loss (NIHL). The amount, distribution, and time course of free radical formation have been defined, including a clinically significant late formation 7-10 days following noise exposure, and one mechanism underlying noise-induced reduction in cochlear blood flow has finally been identified. These new insights have led to the formulation of new hypotheses regarding the molecular mechanisms of NIHL; and, from these, we have identified interventions that prevent NIHL, even with treatment onset delayed up to 3 days post-noise. It is essential to now assess the additive effects of agents intervening at different points in the cell death pathway to optimize treatment efficacy. Finding safe and effective interventions that attenuate NIHL will provide a compelling scientific rationale to justify human trials to eliminate this single major cause of acquired hearing loss.

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Section: Bcl-2 Anti-apoptotic Proteinsmentioning

confidence: 99%

Mechanisms of noise-induced hearing loss indicate multiple methods of prevention

et al. 2007

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“…Studies of apoptosis in white matter after dorsal cordotomy or after transection suggest that glial apoptosis occurs, at least in part, as a consequence of axonal degeneration (10,11). Several studies have implicated the apoptotic role of caspases in the injured spinal cord (12)(13)(14)(15)(16)(17)(18)(19)(20)(21). An increase in the number of cells expressing Fas was observed within 72 hours of SCI (22).…”

Section: Introductionmentioning

confidence: 99%

Umbilical Cord Blood Stem Cell Mediated Downregulation of Fas Improves Functional Recovery of Rats after Spinal Cord Injury

Dasari

Spomar

et al. 2007

Neurochem Res

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Human umbilical cord blood stem cells (hUCB), due to their primitive nature and ability to develop into nonhematopoietic cells of various tissue lineages, represent a potentially useful source for cellbased therapies after spinal cord injury (SCI). To evaluate their therapeutic potential, hUCB were stereotactically transplanted into the injury epicenter, one week after SCI in rats. Our results show the presence of a substantial number of surviving hUCB in the injured spinal cord up to five weeks after transplantation. Three weeks after SCI, apoptotic cells were found especially in the dorsal white matter and gray matter, which are positive for both neuron and oligodendrocyte markers. Expression of Fas on both neurons and oligodendrocytes was efficiently downregulated by hUCB. This ultimately resulted in downregulation of caspase-3 extrinsic pathway proteins involving increased expression of FLIP, XIAP and inhibition of PARP cleavage. In hUCB-treated rats, the PI3K/Akt pathway was also involved in antiapoptotic actions. Further, structural integrity of the cytoskeletal proteins α-tubulin, MAP2A&2B and NF-200 has been preserved in hUCB treatments. The behavioral scores of hind limbs of hUCB-treated rats improved significantly than those of the injured group, showing functional recovery. Taken together, our results indicate that hUCB-mediated downregulation of Fas and caspases leads to functional recovery of hind limbs of rats after SCI.

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“…Apoptosis in white matter after dorsal cordotomy or after transection suggest that glial apoptosis occurs, at least in part, as a consequence of axonal degeneration (10,11). Several studies have implicated the apoptotic role of caspases in the injured spinal cord (12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Fas expression, activation of caspases 3 and 8, and apoptosis occur in a temporally similar fashion after SCI (22).…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells from Rat Bone Marrow Downregulate Caspase-3-mediated Apoptotic Pathway After Spinal Cord Injury in Rats

et al. 2007

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Mesenchymal stem cells have been intensively studied for their potential use in reparative strategies for neurodegenerative diseases and traumatic injuries. We used mesenchymal stem cells (rMSC) from rat bone marrow to evaluate the therapeutic potential after spinal cord injury (SCI). Immunohistochemistry confirmed a large number of apoptotic neurons and oligodendrocytes in caudal segments 2mm away from the lesion site. Expression of caspase-3 on both neurons and oligodendrocytes after SCI was significantly downregulated by rMSC. Caspase-3 downregulation by rMSC involves increased expression of FLIP and XIAP in the cytosol and inhibition of PARP cleavage in the nucleus. Animals treated with rMSC had higher BBB scores and better recovery of hind limb sensitivity. Treatment with rMSC had a positive effect on behavioral outcome and histopathological assessment after SCI. The ability of rMSC to incorporate into the spinal cord, differentiate and to improve locomotor recovery hold promise for a potential cure after SCI.

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FK506 Treatment Inhibits Caspase-3 Activation and Promotes Oligodendroglial Survival Following Traumatic Spinal Cord Injury

Cited by 61 publications

References 66 publications

Mechanisms of noise-induced hearing loss indicate multiple methods of prevention

Mechanisms of noise-induced hearing loss indicate multiple methods of prevention

Umbilical Cord Blood Stem Cell Mediated Downregulation of Fas Improves Functional Recovery of Rats after Spinal Cord Injury

Mesenchymal Stem Cells from Rat Bone Marrow Downregulate Caspase-3-mediated Apoptotic Pathway After Spinal Cord Injury in Rats

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