Protection of ischemic rat spinal cord white matter: Dual action of KB-R7943 on Na+/Ca2+ exchange and L-type Ca2+ channels

Ouardouz, Mohamed; Zamponi, Gerald W.; Barr, Wendy; Kiedrowski, Lech; Stys, Peter K.

doi:10.1016/j.neuropharm.2004.12.007

Cited by 62 publications

(56 citation statements)

References 36 publications

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“…44,45) Na ϩ /Ca 2ϩ exchange inhibitor, KB-R7943, has been reported to attenuate ischemia-induced injury in dorsal horn neurons of spinal cord. 46) Therefore, it may be possible that inhibitory actions of pralidoxime on Na ϩ /Ca 2ϩ exchanger located on dorsal horn of spinal cord is responsible for its observed beneficial effect in neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Potential of Pralidoxime in Tibial and Sural Nerve Transection-Induced Neuropathic Pain in Rats

Kaur

Jaggi

Singh

2010

Biological & Pharmaceutical Bulletin

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The present study was designed to investigate the ameliorative potential of pralidoxime in tibial and sural nerve transection-induced neuropathy in rats. Tibial and sural nerve transection was performed by sectioning tibial and sural nerve portions (2 mm) of the sciatic nerve, and leaving the common peroneal nerve intact. The pinprick, acetone, hot and cold tail immersion tests were performed to assess the degree of motor functions, mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia respectively. Biochemically, the tissue thio-barbituric acid reactive species (TBARS), super-oxide anion contents (the markers of oxidative stress) and total calcium levels were measured. Tibial sural nerve transection resulted in the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with the rise in oxidative stress and calcium levels. However, administration of pralidoxime (10, 20 mg/kg intraperitoneally (i.p.)) for 14 d attenuated tibial and sural nerve transection-induced cold allodynia, mechanical, hot and cold hyperalgesia. Furthermore, pralidoxime also attenuated tibial and sural nerve transection induced increase in oxidative stress and calcium levels. It may be concluded that pralidoxime has ameliorative potential in attenuating the painful neuropathic state associated with tibial and sural nerve transection, which may possibly be attributed to decrease in oxidative stress and calcium levels.

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Section: Discussionmentioning

confidence: 99%

Ameliorative Potential of Pralidoxime in Tibial and Sural Nerve Transection-Induced Neuropathic Pain in Rats

Kaur

Jaggi

Singh

2010

Biological & Pharmaceutical Bulletin

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“…Bepridil [105] and KB-R7943 [106] have been reported to directly block the NMDA channels in hippocampal neurons. KB-R7943 may also exert its actions by blocking L-type Ca 2+ channels [107] or, in vivo, via lowering the body temperature [108].…”

Section: Pathological Roles For Na + /H + Exchange: Impact On [Na + ]mentioning

confidence: 99%

“…These data are of particular importance, as ischemic white matter injury is less understood and may contribute substantially to neurological deficits in human stroke [120]. However, some of the previously reported effects of NCX inhibitors have to be re-evaluated because bepridil and KB-R7943 also inhibit NMDA receptors [105,106] and L-type Ca 2+ channels [107], two pathways that may also contribute to the anoxic injury of various white matter components [14,[121][122][123][124].…”

Section: Pathological Roles For Na + /H + Exchange: Impact On [Na + ]mentioning

confidence: 99%

Disruption of ionic and cell volume homeostasis in cerebral ischemia: The perfect storm

Mongin

2007

Pathophysiology

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The mechanisms of brain tissue damage in stroke are strongly linked to the phenomenon of excitotoxicity, which is defined as damage or death of neural cells due to excessive activation of receptors for the excitatory neurotransmitters glutamate and aspartate. Under physiological conditions, ionotropic glutamate receptors mediate the processes of excitatory neurotransmission and synaptic plasticity. In ischemia, sustained pathological release of glutamate from neurons and glial cells causes prolonged activation of these receptors, resulting in massive depolarization and cytoplasmic Ca 2+ overload. The NMDA subtype of glutamate receptors is particularly important as it represents the main initial route for the Ca 2+ influx. High cytoplasmic levels of Ca 2+ activate many degradative processes that, depending on the metabolic status, cause immediate or delayed death of neural cells. This traditional view has been expanded by a number of observations that implicate Cl − channels and several types of non-channel transporter proteins, such as the Na + ,K + ,2Cl − cotransporter, Na + /H + exchanger, and Na + /Ca 2+ exchanger, in the development of glutamate toxicity. Some of these ion transporters increase tissue damage by promoting pathological cell swelling and necrotic cell death, while others contribute to a long term accumulation of cytoplasmic Ca 2+ . This brief review is aimed at illustrating how the dysregulation of various ion transport processes combine in a 'perfect storm' that disrupts neural ionic homeostasis and culminates in the irreversible damage and death of neural cells. The clinical relevance of individual transporters as targets for therapeutic intervention in stroke is also briefly discussed.

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“…Excessive intra-axonal Ca 2ϩ causes injury (Stys et al, , 1992Agrawal and Fehlings, 1996;Tekkök and Goldberg, 2001;Ouardouz et al, 2005).…”

Section: Mechanisms Of Axonal Degenerationmentioning

confidence: 99%

White Matter Axon Vulnerability to AMPA/Kainate Receptor-Mediated Ischemic Injury Is Developmentally Regulated

McCarran¹,

Goldberg²

2007

J. Neurosci.

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Periventricular white matter injury (PWMI) is the leading cause of neurodevelopmental morbidity in survivors of premature birth.Cerebral ischemia is considered a major etiologic factor in the generation of PWMI. In adult white matter (WM), ischemic axonal damage is mediated by AMPA/kainate receptors. Mechanisms of ischemic axonal injury during development are not well defined. We used a murine brain slice model to characterize mechanisms of ischemic axonal injury in developing WM. Acute coronal brain slices were prepared from thy1-yellow fluorescent protein (

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Protection of ischemic rat spinal cord white matter: Dual action of KB-R7943 on Na+/Ca2+ exchange and L-type Ca2+ channels

Cited by 62 publications

References 36 publications

Ameliorative Potential of Pralidoxime in Tibial and Sural Nerve Transection-Induced Neuropathic Pain in Rats

Ameliorative Potential of Pralidoxime in Tibial and Sural Nerve Transection-Induced Neuropathic Pain in Rats

Disruption of ionic and cell volume homeostasis in cerebral ischemia: The perfect storm

White Matter Axon Vulnerability to AMPA/Kainate Receptor-Mediated Ischemic Injury Is Developmentally Regulated

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