Opiate Antagonist Improves Neurologic Recovery after Spinal Injury

Faden, Alan I.; Jacobs, Thomas P.; Holaday, John W.; Coonan, Thomas

doi:10.1097/00132586-198204000-00004

Cited by 18 publications

(25 citation statements)

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“…Moreover, their significance in the pathophysiology of CNS trauma or stroke must be supported by experimental observations that pharmacological antagonism of either oxygen radical generation and/or lipid peroxidation results in therapeutic effects. [1][2][3][4][5][6][7][8][9]11,17,28,35,36 Work by Fujimoto et al 5 showed that potent protective effects of melatonin on experimental trauma induced on rat spinal cords at T12 showed increased MDA levels after the injury. This work showed that melatonin facilitated recovery of the damaged spinal cord.…”

Section: Discussionmentioning

confidence: 99%

“…The extent of lipid peroxidation is a useful parameter for evaluating the cellular disturbances caused by spinal cord injury caused by ischemia/reperfusion (IR) in experimental conditions. [1][2][3][4][5][6][7][8][9][10] Free oxygen radicals have been implicated in postischemic cell injury and cellular death, while free radical scavengers such as superoxide dismutase (SOD) and catalase (CAT) are associated with an amelioration of ischemic injury. 11 To prevent such damage, a variety of biological defense systems are activated in normal cells.…”

Section: Introductionmentioning

confidence: 99%

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Protective effect of melatonin on experimental spinal cord ischemia

et al. 2003

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Study design: Experimental animal model to assess ischemic spinal cord injury following occlusion of the thoraco-abdominal aorta. Objectives: To measure whether melatonin administered to rabbits before and after occlusion exerts an effect on the repair of ischemia-reperfusion (IR) injury. Setting: Medical Biology Laboratory, Inonu University, Malatya, Turkey Methods: Rabbits were divided into three IR treatment groups and one sham-operated (ShOp) control group. The three treatment groups had their infrarenal aorta temporarily occluded for 25 min, while the ShOp group had laparotomy without aortic occlusion. Melatonin was administered either 10 min before aortic occlusion or 10 min after the clamp was removed. Physiologic saline was administered to the control animals. After treatment, the animals were euthanized and lumbosacral spinal cord tissue was removed for the determination of relevant enzyme activities. Results: Malondialdehyde levels, indicating the extent of lipid peroxidation, were found to be significantly increased in the nonmelatonin treated (IR) group when compared to the ShOp group. Melatonin, whether given to pre-or post occlusion groups, suppressed malondialdehyde levels below that of the ShOp group. Catalase (CAT) and glutathione peroxidase (GSH-Px) enzyme activities were increased in the IR group compared to the ShOp group. Melatonin given preocclusion resulted in a significant decrease in both CAT and GSH-Px enzyme levels. The superoxide dismutase (SOD) enzyme activity was decreased in the ischemia-reperfusion treatment group. However, the melatonin treatment increased SOD enzyme activity to levels approximating that of the ShOp group. Conclusion: To our knowledge, this is the first study that shows the effects of melatonin administered both pre-and postischemia on induced oxidative damage to injured spinal cords. Our data also expands on reports that melatonin administration may significantly reduce the incidence of spinal cord injury following temporary aortic occlusion.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective effect of melatonin on experimental spinal cord ischemia

et al. 2003

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“…In an experimental hemorrhage model, intracisternal administration of the opioid receptor blocker naloxone was effective in preventing hypotension. 53 However, this effect was not demonstrable with peripheral naloxone administration during study of neurally mediated syncope in humans. 54 Possibly, then, endorphins may contribute to the evolving faint, and agents capable of blunting this effect may have therapeutic utility.…”

Section: Potential Novel Pharmacological Approachesmentioning

confidence: 99%

“…In this regard, ␤-endorphin levels are increased in both vasovagal syncope and the analogous second stage of hemorrhagic shock. [52][53][54] The trigger for this increase and its precise timing are not known. However, as endorphin levels increase, their central action would be expected to accentuate efferent parasympathetic activity and possibly diminish efferent sympathetic activity.…”

Section: Potential Novel Pharmacological Approachesmentioning

confidence: 99%

Pharmacotherapy of Neurally Mediated Syncope

et al. 1999

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Abstract-A wide variety of pharmacological agents are currently used for prevention of recurrent neurally mediated syncope, especially the vasovagal faint. None, however, have unequivocally proven long-term effectiveness based on adequate randomized clinical trials. At the present time, ␤-adrenergic receptor blockade, along with agents that increase central volume (eg, fludrocortisone, electrolyte-containing beverages), appear to be favored treatment options. The antiarrhythmic agent disopyramide and various serotonin reuptake blockers have also been reported to be beneficial. Finally, vasoconstrictor agents such as midodrine offer promise and remain the subject of clinical study. Ultimately, though, detailed study of the pathophysiology of these syncopal disorders and more aggressive pursuit of carefully designed placebo-controlled treatment studies are essential if pharmacological prevention of recurrent neurally mediated syncope is to be placed on a firm foundation. (Circulation. 1999;100:1242-1248.)Key Words: syncope Ⅲ nervous system Ⅲ pharmacology Ⅲ Cardiovascular Drugs N eurally mediated (neurocardiogenic) syncope comprises a number of clinical conditions in which symptomatic systemic hypotension occurs as a result of a transient disturbance of neural reflex cardiovascular control (Table 1). [1][2][3] The vasovagal faint, carotid sinus syndrome, and postmicturition syncope are the most common forms of the neurally mediated faint. Others, including cough syncope and postexertional syncope, are less frequently encountered.This communication focuses on the pharmacological options that have been proposed for preventing neurally mediated faints, and especially the vasovagal faint, because it has been the most thoroughly studied. The objective is to provide an overview of the pharmacology and pertinent proposed modes of action of those agents that may be of benefit. Drug Therapy of Neurally Mediated Syncope: Basic PrinciplesMost individuals who experience a neurally mediated faint (particularly vasovagal fainters) require no additional therapy beyond education (ie, recognition of premonitory symptoms, avoidance of triggering events, and awareness of useful evasive actions) and reassurance regarding the non-lifethreatening nature of the condition. On occasion, stress and anxiety management may be warranted. Various more aggressive nonpharmacological (eg, support hose, extended exposure to upright posture, pacemakers) and pharmacological treatment options are usually reserved for those relatively few individuals who experience frequent syncope and/or when symptoms cause excessive lifestyle difficulties, threaten employment, or result in unacceptable risk of physical injury to the patient or others.Currently, drugs are used for both diagnostic and therapeutic purposes in the patient with neurally mediated syncope. [1][2][3] In terms of diagnostic applications, agents such as isoproterenol, edrophonium, nitroglycerin, and adenosine have been reported to be helpful during tilt-table testing (ie, so-called pharmacolog...

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“…Naloxone was included in the study, as some earlier studies had found that it improved systemic hypotension, spinal cord blood flow, and neurologic recovery in laboratory animals. [5][6][7][8] In the NASCIS 2 study, patients, physicians, and researchers were blinded as to which patients were receiving which therapy. They found that patients who received high-dose MP had ''significant improvement'' compared with those in the other two study groups.…”

Section: Reviewmentioning

confidence: 99%