Naloxone therapy during focal cerebral ischemia evaluation in a primate model.

Abstract

Conflicting reports have appeared in the literature regarding the effect of the opiate antagonist naloxone on ischemic neurologic deficits. We report the results of a study using naloxone in our model of focal cerebral ischemia in the awake primate. A total of 14 adult baboons were subjected to six-hour occlusion of the left middle cerebral artery (MCA). Seven animals served as controls and seven received treatment with naloxone (5 mg/kg) beginning 30 min after MCA occlusion and continuing until two hours after reperfusion. All animals developed profound hemiparesis and homonymous hemianopsia within seconds of inflating the MCA occluder. Acutely, therapy with naloxone partially reversed ischemic neurologic deficits in five of the seven treatment animals. Within minutes of receiving the loading dose of naloxone, responding animals were more alert and demonstrated improvements in motor function. Naloxone did not affect mortality: Three animals in the treatment group and two in the naloxone group died secondary to malignant intracranial pressure within 48 hours of the ischemic episode. In animals surviving the ischemic insult however, treatment with naloxone significantly improved neurologic outcome at 10 days (p less than 0.05). Neuropathologic examinations in these animals revealed amelioration of ischemic tissue damage, with three of the five suffering only small focal areas of infarction. (All control animals suffered large infarcts of the MCA territory.) Our results verify that naloxone can reverse ischemic deficits, and more importantly may improve the outcome from focal ischemic insults.

High-dose intravenous naloxone for the treatment of acute ischemic stroke.

“…Neurologic parameters assessed included National Institutes of Health stroke scale score, 30 level of consciousness, orientation, response to commands, visual fields, gaze, pupillary responses, sensory responses, motor function, limb coordination, plantar reflex, presence of neglect, language, and articulation. The patients' baseline, completion of loading dose, and 3 -month neurologic conditions were categorized as normal (stroke scale score of 0) or mild (1-10), moderate (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), or severe (^30) deficit.…”

“…12 Finally, naloxone may attenuate cerebral edema. 13 The potential value of opiate antagonists in treating acute ischemic stroke is suggested by the results of some animal studies 14 - 16 and a few human studies. 17 " 27 In other small clinical studies, results have ranged from complete reversal of 18 -19 to temporary reversal of 20 to no effect on 21 -22 ischemic neurologic deficits.…”

Intravenously and iontophoretically administered naloxone reverses ischemic changes in rat hippocampus.

“…Several previous articles reporting a beneficial effect of naloxone on cerebral ischemia studied the concomitant changes in cerebral blood flow, 20 23 and found no significant change in these parameters. Accordingly, naloxone was thought to act at the neuronal or microcirculatory level.…”

Thrombotic Stroke in the Anesthetized Monkey <b><i>(Macaca mulatta)</i></b>: Characterization by MRI – A Pilot Study

“…There are several models of stroke that have been used in nonhuman primates; some are more severe than others in terms of the degree of neuropathological changes. Experimental techniques to occlude the middle cerebral artery (MCA) involve mechanical occlusions by using either electrocoagulation [6,7], a filament model [8,9], an intravascular balloon or cuff [2,10,11,12], microvascular clips [13,14,15,16,17,18], or ligatures [19,20,21]. Other approaches use the intravascular route to inject autologous or heterologous preformed fibrin, blood clots [3,22,23], microemboli [24,25,26], or, in some cases, by in situ clot formation by photothrombosis [27,28,29].…”