Experimental Spinal Cord Injury

Flamm, Eugene S.; Young, Wise; Demopoulos, Harry B.; DeCrescito, Vincent; Tomasula, John J.

doi:10.1227/00006123-198202000-00009

Cited by 68 publications

(14 citation statements)

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“…Thereafter, in va rious experimental models, naloxone has been shown to ameliorate spinal cord blood flow, motor functions and electrophysiological activities after spinal cord trauma (8)(9)(10). Similarly, after ischemic injury of the spinal cord, naloxone also preserves motor functions and elec trophysiological activities (11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

Effects of Naloxone and Levallorphan on the Spinal Cord Reflex Potentials under the Spinal Ischemic Condition in Cats

Okamoto

Suzuki

Murayama

1992

Japanese Journal of Pharmacology

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ABSTRACT-The spinal reflex potentials elicited by electrical stimulation of the tibial nerve were re corded from the lumbo-sacral ventral root in spinal cats. When the thoracic aorta and the bilateral in ternal mammary arteries were occluded for 10 min, the potentials were completely depressed. Reap pearance of these potentials could be observed at about 10 min after removal of the occlusion and they gradually recovered. Intravenous injection of naloxone (1 or 10 mg/kg) or levallorphan (0.1 mg/kg) together with removal of occlusion significantly promoted the recovery of the polysynaptic reflex poten tial. Morphine (5 mg/kg) showed no particular effect on the recovery of potentials. Furthermore, pre treatment with morphine (5 mg/kg) did not influence the effects of these opioid antagonists. These re sults suggest that naloxone and levallorphan may preserve or potentiate the interneuronal activities of the lumbo-sacral spinal cord under the ischemic condition and that the effects may not be mediated through morphine-like opioid receptors.

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Section: Discussionmentioning

confidence: 99%

Effects of Naloxone and Levallorphan on the Spinal Cord Reflex Potentials under the Spinal Ischemic Condition in Cats

Okamoto

Suzuki

Murayama

1992

Japanese Journal of Pharmacology

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“…As discussed above, the opiate receptor antagonist naloxone was shown many years ago to be neuroprotective in models of acute SCI 40,41 and showed evidence of some efficacy in the NASCIS II trial. 46 This has been interpreted as an indication that opiate receptor mechanisms are involved in the acute pathophysiology of SCI.…”

Section: Thyrotropin-releasing Hormone and Trh Analogsmentioning

confidence: 96%

Neuroprotection and acute spinal cord injury: A reappraisal

2004

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Summary: It has long been recognized that much of the posttraumatic degeneration of the spinal cord following injury is caused by a multi-factorial secondary injury process that occurs during the first minutes, hours, and days after spinal cord injury (SCI). A key biochemical event in that process is reactive oxygeninduced lipid peroxidation (LP). In 1990 the results of the Second National Acute Spinal Cord Injury Study (NASCIS II) were published, which showed that the administration of a high-dose regimen of the glucocorticoid steroid methylprednisolone (MP), which had been previously shown to inhibit post-traumatic LP in animal models of SCI, could improve neurological recovery in spinal-cord-injured humans. This resulted in the registration of high-dose MP for acute SCI in several countries, although not in the U.S. Nevertheless, this treatment quickly became the standard of care for acute SCI since the drug was already on the U.S. market for many other indications. Subsequently, it was demonstrated that the non-glucocorticoid 21-aminosteroid tirilazad could duplicate the antioxidant neuroprotective efficacy of MP in SCI models, and evidence of human efficacy was obtained in a third NASCIS trial (NASCIS III). In recent years, the use of high-dose MP in acute SCI has become controversial largely on the basis of the risk of serious adverse effects versus what is perceived to be on average a modest neurological benefit. The opiate receptor antagonist naloxone was also tested in NASCIS II based upon the demonstration of its beneficial effects in SCI models. Although it did not a significant overall effect, some evidence of efficacy was seen in incomplete (i.e., paretic) patients. The monosialoganglioside GM1 has also been examined in a recently completed clinical trial in which the patients first received high-dose MP treatment. However, GM1 failed to show any evidence of a significant enhancement in the extent of neurological recovery over the level afforded by MP therapy alone. The present paper reviews the past development of MP, naloxone, tirilazad, and GM1 for acute SCI, the ongoing MP-SCI controversy, identifies the regulatory complications involved in future SCI drug development, and suggests some promising neuroprotective approaches that could either replace or be used in combination with high-dose MP.

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“…Many studies have indicated that naloxone improves neurologic recovery after spinal cord injuries produced by contusion or ischemia (6)(7)(8)(9)(10). Mechanisms of the beneficial effect of naloxone have been postulated to be the antagonism of neurotoxicity produced by excitatory amino acids (20) and the inhibition of transmembrane Ca 2t influx (8,21).…”

Section: Effects Of Gabaergic Drugs On the Recovery Of Spinal Reflex mentioning

confidence: 99%

“…Several experimental studies have shown that the opioid antagonist naloxone accelerates neurological recovery after traumatic or ischemic spinal cord injury (6)(7)(8)(9)(10). We have previously reported that not only naloxone but also levallorphan promoted the recovery of the polysynaptic reflex (PSR) potentials after spinal cord ischemia in spinal cats (11).…”

mentioning

confidence: 99%

Effects of GABAergic Drugs on the Recovery of Reflex Potentials after Spinal Cord Ischemia in Cats

Suzuki¹,

Okamoto

Sekikawa

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-Effectsof GABAergic drugs on the recovery of reflex potentials after spinal cord ischemia were examined in anesthethized spinal cats. Monosynaptic reflex (MSR) and polysynaptic reflex (PSR) potentials, elicited by electrical stimulation of the tibial nerve in spinal cats, were recorded from the Jumbo-sacral ventral root. The spinal reflex potentials were immediately depressed by occlusion of the thoracic aorta and the bilateral mammary arteries for 10 min. The potentials recovered gradually to the control level within 90 min after reperfusion. Pretreatment with bicuculline (0.3 mg/kg, i.v.), a GABA antagonist, or semicarbazide (200 mg/kg, i.v.), an inhibitor of GABA synthesis, accelerated the recovery of PSR potentials after the removal of the arterial occlusion. In contrast, pretreatment with aminooxyacetic acid (10 mg/kg, i.v.), an inhibitor of GABA degradation, retarded the recovery of PSR potentials, and this effect was overcome by the addition of the opioid antagonist naloxone (10 mg/kg, i.v.). These results suggest that the GABAergic system retards the recovery of PSR potentials after a brief spinal cord ischemia, which can be antagonized by naloxone.

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Experimental Spinal Cord Injury

Cited by 68 publications

References 0 publications

Effects of Naloxone and Levallorphan on the Spinal Cord Reflex Potentials under the Spinal Ischemic Condition in Cats

Effects of Naloxone and Levallorphan on the Spinal Cord Reflex Potentials under the Spinal Ischemic Condition in Cats

Neuroprotection and acute spinal cord injury: A reappraisal

Effects of GABAergic Drugs on the Recovery of Reflex Potentials after Spinal Cord Ischemia in Cats

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