Delayed Antagonism of AMPA/Kainate Receptors Reduces Long-Term Functional Deficits Resulting from Spinal Cord Trauma

Wrathall, Jean R.; Teng, Yang D.; Marriott, Robert A.

doi:10.1006/exnr.1997.6506

Cited by 100 publications

(70 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several lines of evidence have suggested that glutamate excitotoxicity plays a key role not only in neuronal cell death but also in delayed post traumatic spinal cord white matter degeneration (Faden and Simon, 1988;Wrathall et al, 1994;Agrawal and Fehlings, 1997;Wrathall et al, 1997). Oligodendrocytes are highly vulnerable to excitotoxic signals mediated by glutamate receptors of the AMPA and kainate classes compared to astrocytes (Oka et al, 1993;Yoshioka et al, 1996;Agrawal and Fehlings, 1997;Matute -27 -et al, 1997;McDonald et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

et al. 2007

View full text Add to dashboard Cite

Abbreviations: SCI, spinal cord injury; DIG, digoxigenin; APC, adenomatus polyposis coli; MBP, myelin basic protein; TUNEL, TdT-mediated dUTP-fluorescein nick end labeling -3 - AbstractPrevious studies indicated that the expression of neuropsin, a serine protease, is induced in mature oligodendrocytes after injury to the central nervous system (CNS). The pathophysiology of spinal cord injury (SCI) involves primary and secondary mechanisms, the latter contributing further to permanent losses of function. To explore the role of neuropsin after SCI, histochemical and behavioral analyses were performed in wild-type (WT) and neuropsin-deficient (neuropsin -/-) mice using a crush injury model, a well-characterized and consistently reproducible model of SCI. In situ hybridization revealed that neuropsin mRNA expression was induced in the spinal cord white matter from WT mice after crush SCI, peaking at day 4. Neuropsin -/-mice showed attenuated demyelination, oligodendrocyte death, and axonal damage after SCI.Although axonal degeneration in the corticospinal tract was obvious caudal to the lesion site in both strains of mice after SCI, the number of surviving nerve fibers caudal to the lesion was significantly larger in neuropsin -/-mice than WT mice. Behavioral analysis revealed that the recovery at days 10-42 was significantly improved in neuropsin -/-mice compared to WT mice in spite of the severe initial hindlimb impairments due to SCI in both strains. These observations suggest that neuropsin is involved in the secondary phase of the pathogenesis of SCI mediated by demyelination, oligodendrocyte death, and axonal degeneration.-4 -

show abstract

Section: Discussionmentioning

confidence: 99%

Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

et al. 2007

View full text Add to dashboard Cite

show abstract

“…AMPAR antagonists are neuroprotective in models of spinal cord injury; NBQX is effective in limiting both gray and white matter damage after spinal cord contusions in rats (Wrathall et al, 1997). Contusion injury to the cord rapidly increases levels of TNFα (Bethea et al, 1999;Pan et al, 1999), other inflammatory cytokines (McTigue et al, 1998;McTigue et al, 2000) and extracellular glutamate.…”

Section: Interplay Between Tnf α and Ampar Trafficking After Acute Nementioning

confidence: 99%

TNFα-induced AMPA-receptor trafficking in CNS neurons; relevance to excitotoxicity?

Leonoudakis

Braithwaite²,

Beattie

et al. 2004

Neuron Glia Biol.

View full text Add to dashboard Cite

Injury and disease in the CNS increases the amount of tumor necrosis factor α (TNFα) that neurons are exposed to. This cytokine is central to the inflammatory response that occurs after injury and during prolonged CNS disease, and contributes to the process of neuronal cell death. Previous studies have addressed how long-term apoptotic-signaling pathways that are initiated by TNFα might influence these processes, but the effects of inflammation on neurons and synaptic function in the timescale of minutes after exposure are largely unexplored. Our published studies examining the effect of TNFα on trafficking of AMPA-type glutamate receptors (AMPARs) in hippocampal neurons demonstrate that glial-derived TNFα causes a rapid (<15 minute) increase in the number of neuronal, surface-localized, synaptic AMPARs leading to an increase in synaptic strength. This indicates that TNFα-signal transduction acts to facilitate increased surface localization of AMPARs from internal postsynaptic stores. Importantly, an excess of surface localized AMPARs might predispose the neuron to glutamate-mediated excitotoxicity and excessive intracellular calcium concentrations, leading to cell death. This suggests a new mechanism for excitotoxic TNFα-induced neuronal death that is initiated minutes after neurons are exposed to the products of the inflammatory response.Here we review the importance of AMPAR trafficking in normal neuronal function and how abnormalities that are mediated by glial-derived cytokines such as TNFα can be central in causing neuronal disorders. We have further investigated the effects of TNFα on different neuronal cell types and present new data from cortical and hippocampal neurons in culture. Finally, we have expanded our investigation of the temporal profile of the action of this cytokine relevant to neuronal damage. We conclude that TNFα-mediated effects on AMPAR trafficking are common in diverse neuronal cell types and very rapid in their onset. The abnormal AMPAR trafficking elicited by TNFα might present a novel target to aid the development of new neuroprotective drugs.

show abstract

“…6 From this point of view, it has been proposed that agents that block glutamate receptors may improve functional outcomes and reduce damage to traumatized spinal cord tissue. 2-amino-5-phosphonovaleric acid (APV), the agent used in our experiment, is an NMDA receptor blocker [7][8][9][10][11] and acts on the glutamate transmitter recognition site of NMDA receptors, preventing receptor activation by competing with agonists for the transmitter-binding site. 12 In this study, we aimed at determining the effects of different doses of APV on oxidative stress after an experimental SCI in rats.…”

Section: Introductionmentioning

confidence: 99%

NMDA receptor blockage with 2-amino-5-phosphonovaleric acid improves oxidative stress after spinal cord trauma in rats

et al. 2009

View full text Add to dashboard Cite

Study design: 2-amino-5-phosphonovaleric acid (APV) is an N-methyl-D-aspartate (NMDA) receptor blocker and has neuroprotective properties. This study is aimed at evaluating the effect of APV treatment on oxidative status after spinal cord injury (SCI). Methods: The experiment was carried out on the following five groups: Group1: sham operated, non-traumatized; Group2: with injured spinal cord, no treatment; Group3: with SCI, injected with 100 mg kg À1 APV; Group4: with SCI, injected with 200 mg kg À1 APV; and Group5: with SCI, injected with 400 mg kg À1 APV. SCI was inflicted by epidural compression with a cerebral vascular clip after T9-11 laminectomy. The experiments were completed after 12 h of trauma. Spinal cords were excised for evaluation of superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and malonyldialdehyde (MDA) levels. Results: After SCI, SOD and GSH levels decreased and the MDA level increased significantly. APV treatment decreased the MDA level and increased SOD, catalase and GSH levels. The maximum decrease in MDA was detected in the group treated with 100 mg kg À1 APV compared with the other groups. The GSH level was significantly increased in the group treated with 200 mg kg À1 APV. The SOD level was significantly increased in the group treated with 200 mg kg À1 APV. Conclusion:The results of this study have shown that APV treatment creates a dose-dependent antioxidant effect in rats with SCI and may be used for the treatment of SCIs.

show abstract

Delayed Antagonism of AMPA/Kainate Receptors Reduces Long-Term Functional Deficits Resulting from Spinal Cord Trauma

Cited by 100 publications

References 39 publications

Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

TNFα-induced AMPA-receptor trafficking in CNS neurons; relevance to excitotoxicity?

NMDA receptor blockage with 2-amino-5-phosphonovaleric acid improves oxidative stress after spinal cord trauma in rats

Contact Info

Product

Resources

About