naloxone and Cerebral-Infarction

Although time has been recognized as a critical factor in the treatment of other arterial occlusive disorders, it has been an underemphasized variable in the treatment of acute stroke. Animal models of cerebral arterial occlusion have demonstrated that neurologic recovery is more likely the shorter the duration of occlusion. Complete recovery does not occur if the occlusion persists more than six hours. Prior trials have only rarely begun treatment within six hours of stroke onset. Over the past five years, we have participated in three stroke trials and have tried to identify factors that lead to delays in treatment. Factors that affect the time from stroke onset to arrival at the hospital include recognition of acute stroke by the patient, prehospital care personnel, and physicians. After arrival at the hospital, factors that can significantly delay treatment include the time to obtain computed tomography and the site of treatment (emergency department vs ICU). With proper attention, the time from patient arrival until treatment should be less than one hour. Future efforts should be directed toward reducing the time from stroke onset until arrival at the hospital. Education of the public, high-risk patients, prehospital care providers, and physicians may aid in these efforts.

Topics: Cerebral Infarction; Emergencies; Humans; Naloxone; Recurrence; Time Factors; Tissue Plasminogen Activator

Topics: Anticoagulants; Arterial Occlusive Diseases; Calcium Channel Blockers; Carotid Artery Diseases; Cerebral Infarction; Humans; Intracranial Embolism and Thrombosis; Naloxone

Puerarin is an important active ingredient of Radix puerariae. Puerarin is an isoflavone compound Z clinical and basic research proves that S. puerarin can increase cerebral circulation blood flow; increase cerebral perfusion; reduce blood viscosity and improve microcirculation. The present research was conducted to observe the clinical efficacy of puerarin combined with naloxone in the treatment of traumatic cerebral infarction (TCI). Methods 52 patients with TCI were randomly divided into two groups. The treatment group was treated with puerarin and naloxone and the control group was treated with conventional therapy. Results: The total effective rate was 82% in the treatment group, which was better than 61% in the control group. The difference was statistically significant (p<0.05). The efficacy of simple TCI in both groups was significantly better than that of TCI with brain contusion; the effect of intracranial hemorrhage and the effect of TCI alone in the two groups; the treatment group was significantly better than the control group (p<0.05). Conclusion: The combination of puerarin and naloxone in the treatment of TCI can improve the curative effect.

Topics: Adult; Brain Injuries, Traumatic; Cerebral Infarction; Female; Humans; Isoflavones; Male; Middle Aged; Naloxone; Perfusion Imaging; Tomography, X-Ray Computed; Treatment Outcome

Topics: Acute Disease; Adult; Aged; Brain Ischemia; Cerebral Infarction; Double-Blind Method; Female; Hemiplegia; Humans; Morphine; Naloxone; Pain

The present study was designed to investigate the possible role of opioids and K(ATP) channels in ischemic postconditioning-induced reversal of global cerebral ischemia and reperfusion (I/R) induced neuronal injury. Mice were subjected to global ischemia by bilateral carotid artery occlusion for 10 min followed by reperfusion for 24 h, to produce neuronal injury. Ischemic postconditioning was induced by three episodes of carotid artery occlusion and reperfusion of 10 s each, immediately after global ischemia. Morphine postconditioning was induced by administration of morphine (5 mg/kg i.v.), 5 min prior to reperfusion. Naloxone (5 mg/kg i.v.), opioid receptor antagonist, and glibenclamide (5 mg/kg i.v.), K(ATP) channel blocker were administered 10 min before global ischemia. Extent of cerebral injury was assessed by measuring cerebral infarct size using triphenyl tetrazolium chloride (TTC) staining. Short-term memory was evaluated using the elevated plus maze test, while degree of motor incoordination was evaluated using inclined beam-walking, rota-rod and lateral push tests. Bilateral carotid artery occlusion followed by reperfusion resulted in significant increase in infarct size, impairment in short-term memory and motor co-ordination. Ischemic/morphine postconditioning significantly attenuated I/R induced neuronal injury and behavioural alterations. Pretreatments with naloxone and glibenclamide attenuated the neuroprotective effects of ischemic/morphine postconditioning. It may be concluded that ischemic/morphine postconditioning protects I/R induced cerebral injury via activating opioid receptor and K(ATP) channel opening.

Topics: Analgesics, Opioid; Animals; Cerebral Infarction; Ischemic Attack, Transient; Ischemic Preconditioning; KATP Channels; Male; Memory, Short-Term; Mice; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Postural Balance; Psychomotor Performance; Reperfusion Injury

Naloxone has been advanced as a potential neuroprotectant against ischemic injury. This study examined the involvement of classical opioid receptors in the reduction of middle cerebral arterial ligation-induced cortical infarction in rats. The infarct volume was significantly reduced after infusion of (-)-naloxone, but not its inert stereoisomer (+)-naloxone. Beta-funaltrexamine (beta-FNA), a mu opioid antagonist, also reduced ischemic infarct volume. Both (-)-naloxone and beta-FNA attenuated cerebral ischemia/reperfusion (I/R)-induced increases in neutrophil-associated myeloperoxidase activity and chemokine mRNA expression, including macrophage inflammatory protein-1 alpha and -2. However, (-)-naloxone and beta-FNA failed to decrease cerebral I/R-induced brain edema. The findings suggest that naloxone, acting through a blockade of mu opioid receptor activation, is beneficial to cerebral I/R insult in terms of reducing brain infarction, neutrophil accumulation, and chemokine expression.

Topics: Animals; Carotid Artery, Common; Cerebral Infarction; Coronary Disease; Functional Laterality; Hypoxia-Ischemia, Brain; Infarction, Middle Cerebral Artery; Male; Naloxone; Naltrexone; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Time Factors

Topics: Adult; Brain Ischemia; Cerebral Infarction; Coma; Drug Therapy, Combination; Emergency Medical Services; Female; Flumazenil; GABA Modulators; Glucose; Humans; Hypertonic Solutions; Naloxone; Narcotic Antagonists; Thiamine; Vasodilator Agents

Eight kinds of neuropeptides and four kinds of neuropeptide receptors were examined in the right and left hemispheres of mongolian gerbils after unilateral carotid ligation-induced stroke and in normal controls. Five hours after ligation of the right common carotid artery, beta-endorphin concentration in the right hemisphere (ischemic side) of the stroke group was significantly increased compared with that in the contralateral hemisphere (non-ischemic side), but there were no differences between sides in other neuropeptides either with or without stroke. Furthermore, although there were no differences in [3H]naloxone binding, [3H]thyrotropin-releasing hormone binding or 125I-vasoactive intestinal polypeptide binding in the brain in this model of stroke, [3H]enkephalin binding was significantly lower on the ischemic side than on the non-ischemic side in the stroke group. These results suggest that increased activity in the beta-endorphinergic system in the brain might be partly caused by ischemic brain failure.

Topics: Animals; Brain Chemistry; Cerebral Infarction; Endorphins; Gerbillinae; Naloxone; Neuropeptides; Receptors, Neurotransmitter; Receptors, Opioid

We have examined the effects of a single injection of naloxone (5 mg/kg, i.v.) in cats with cerebral ischemia produced by transorbital occlusion of the middle cerebral artery (MCA). Cerebral blood flow (CBF) was measured and the cerebral metabolic rate of oxygen consumption (CMRO2) was estimated based on measurements of arteriovenous (A-V) oxygen difference. Six cats were treated with naloxone 30 minutes after occlusion and 8 were treated 2 hours after occlusion. In 6 control animals, naloxone produced a 10-15% increase in mean arterial blood pressure (MABP), CBF and CMRO2 lasting 30 minutes. MCA occlusion reduced CBF by 70-75% in the ipsilateral MCA territory and by 15% in the contralateral hemisphere. Naloxone increased CBF by 3.5-6% in the ischemic region and 10-22% in the contralateral hemisphere in both treatment groups to the same extent as seen in control animals. There was no significant change in A-V oxygen difference and the estimated increase in CMRO2 of non-ischemic regions of both treatment groups was similar to that of control animals. These effects were transient and lasted 15-60 minutes. We have concluded that naloxone caused a transient increase in cerebral metabolism which equals or exceeds the corresponding increase in CBF. Therefore, naloxone would not be beneficial, and may be detrimental in the treatment of cerebral ischemia.

Topics: Animals; Blood Flow Velocity; Blood Pressure; Brain Ischemia; Carbon Dioxide; Cats; Cerebral Cortex; Cerebral Infarction; Cerebrovascular Circulation; Endorphins; Energy Metabolism; Female; Hydrogen-Ion Concentration; Male; Naloxone; Oxygen

The effects of high dose naloxone in humans have not been studied extensively. We treated 36 patients who had acute ischemic cerebral infarction with high doses of naloxone to evaluate potential efficacy and toxicity. All patients were treated with a 160-mg/m2 (4-mg/kg) loading dose followed by 80 mg/m2.h (2 mg/kg.h) x 24 h. There were no statistically significant changes in group mean arterial pressure, respiratory rate, or heart rate in response to the loading dose or infusion, although clinically significant changes did occur in four patients. Twenty-three patients had adverse reactions possibly related to naloxone, the most common of which were nausea (n = 20), bradycardia and/or hypotension (n = 3), myoclonus (n = 1), and hypertension (n = 1). Seven patients had naloxone discontinued for possible adverse reactions. All adverse reactions abated with discontinuation of naloxone and/or pharmacologic therapy when indicated. No deaths were attributable to naloxone treatment. High dose naloxone appears to be well tolerated in the majority of elderly patients with acute cerebral infarction.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Cerebral Infarction; Female; Humans; Male; Middle Aged; Naloxone; Nausea

The authors examined the effect of the opiate antagonists naloxone and thyrotropin-releasing hormone (TRH) on neurological outcome and the size of areas of cerebral infarction in a rat model of focal cerebral ischemia. The middle cerebral artery (MCA) was permanently occluded in 66 adult Sprague-Dawley rats. The rats were randomly divided into three groups. In 20 Group I rats, TRH in normal saline was administered initially as a 2-mg/kg bolus followed by continuous infusion of 2 mg/kg/hr for 4 hours. In 20 Group II rats, naloxone in normal saline was administered initially as a 2-mg/kg bolus followed by continuous infusion of 2-mg/kg/hr for 4 hours. In 26 Group III rats, physiological saline was administered as an initial 0.5-cc bolus followed by continuous infusion of 0.5 cc/hr for 4 hours. All solutions were given in volumes of 0.5 cc for the bolus and 0.5 cc/hr for continuous infusion, and all infusions were begun within 10 minutes of MCA occlusion. Twenty-four hours after treatment, the rats underwent a careful neurological examination and were then sacrificed immediately. The size of areas of cerebral infarction was evaluated using 2,3,5-triphenyltetrazolium chloride staining techniques. The neurological grade of the rats correlated with the size of infarcted areas among all grades, irrespective of treatment (p less than 0.01). Neither naloxone nor TRH improved neurological function or reduced the size of infarction compared to saline-treated control rats. Treatment with TRH caused a significant increase in mean arterial blood pressure during infusion, but naloxone had no effect. These results suggest that neither TRH nor naloxone are effective in the treatment of acute focal cerebral ischemia.

Topics: Animals; Arterial Occlusive Diseases; Blood Pressure; Cerebral Arteries; Cerebral Infarction; Male; Naloxone; Narcotic Antagonists; Nervous System; Rats; Rats, Inbred Strains; Thyrotropin-Releasing Hormone

We studied the ability of serum glucose concentration and neurologic deficits at admission in predicting the outcome of acute cerebral ischemia in 65 patients given naloxone. Among our patients, the volume of infarction on computed tomograms and outcome were strongly related to the severity of neurologic deficits found at admission. Neither a history of diabetes nor hyperglycemia when added to the results of the initial neurologic assessment improved prediction of outcome after acute cerebral infarction.

Topics: Acute Disease; Adult; Aged; Blood Glucose; Cerebral Infarction; Diagnostic Tests, Routine; Female; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Naloxone; Nervous System; Neurologic Examination; Osmolar Concentration; Prospective Studies

Endorphins have been implicated in the pathophysiology of both spinal cord injury and cerebral ischemia. This review examines the nature of the experimental evidence to support this hypothesis. Present studies suggest that naloxone administration improves neurological function and outcome in the setting of the spinal cord trauma by centrally inhibiting an opiate receptor-mediated diminution of spinal cord flow. In the setting of spinal shock, naloxone administration is associated with improvement in vital sign and cardiovascular parameters as measured by mean arterial pressure, cardiac output, body temperature, and ventilation. Experiments using a variety of animal stroke models similarly support the notion that naloxone improves neurological function in the setting of cerebral ischemia by a stereospecific opiate receptor-mediated effect, but this improvement does not seem to be accompanied by augmentation of blood flow to affected areas of the brain or by any improvement in vital signs or cardiovascular parameters as seen in spinal cord trauma. A variety of mechanisms are discussed to explain these observations. The therapeutic implications of administering opiate agonists and antagonists in the setting of neurological deficits are outlined for the neurosurgeon.

Topics: Animals; beta-Endorphin; Brain Ischemia; Cats; Cerebral Infarction; Cerebrovascular Circulation; Endorphins; Evoked Potentials, Somatosensory; Hemodynamics; Naloxone; Rats; Receptors, Opioid; Respiration; Spinal Cord; Spinal Cord Injuries

Topics: Anticoagulants; Bloodletting; Cerebral Infarction; Cerebrovascular Disorders; Fibrinolytic Agents; Heparin; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Naloxone; Recurrence; Vasodilator Agents; Warfarin

beta-Endorphin was measured in cerebrospinal fluid (CSF) and plasma in patients with cerebral infarction at acute (4 to 48 hours) and chronic (1 month) stages. Only CSF samples obtained in the acute stage showed beta-endorphin values that were statistically higher than those measured in a control population. This finding suggests that infarction at its acute stage gives rise to an increased release of beta-endorphin. Such a mechanism is consistent with the possibility that the reported therapeutic effect of naloxone in cerebral ischemic lesions may result in part from the antagonism of the centrally released endorphin, beta-endorphin.

Topics: Adult; Aged; beta-Endorphin; Cerebral Infarction; Endorphins; Humans; Middle Aged; Naloxone

Naloxone has recently been reported to be of benefit in the treatment of central nervous system ischemia. To study the effect of naloxone in an experimental stroke model, we subjected 40 awake monkeys to middle cerebral artery (MCA) occlusion 2 weeks after the placement of a MCA ligature by a transorbital technique. Cerebral blood flow (CBF) was monitored with stereotactically placed H2 electrodes, and the neurological course was serially recorded. Infarct size was determined 2 weeks after MCA occlusion. Twenty animals served as control and received no naloxone; 10 of these underwent permanent occlusion, and 10 underwent 4-hour MCA occlusion. In 25 treatment animals, naloxone was administered in three different intravenous dosages: (a) naloxone, 2-mg/kg bolus 20 minutes postocclusion and 2 mg/kg/hour X 4 hours, in 10 animals with permanent MCA occlusion; (b) naloxone, 10-mg/kg bolus 20 minutes postocclusion and 10 mg/kg/hour X 4 hours, in 10 animals with 4-hour MCA occlusion; and (c) naloxone, 20-mg/kg bolus, in 5 animals with various neurological deficits. MCA occlusion typically produced a moderate deficit: hemiparesis, hemianopsia, and facial paresis. In most instances, naloxone in the 2- and 10-mg/kg dose regimens produced little or no change in the neurological function. CBF decreased after MCA occlusion and was unaffected by naloxone in most cases. Infarct size was not significantly different between the control and treated groups. However, the 20-mg/kg dose consistently produced a nonfunctional, transient increase in total body motor tone in normal and hemiparetic animals. Naloxone did not significantly improve useful neurological function, CBF, or infarct size in an experimental primate stroke model.

Topics: Animals; Brain Ischemia; Cerebral Infarction; Cerebrovascular Circulation; Cerebrovascular Disorders; Macaca fascicularis; Male; Models, Biological; Naloxone

Focal incomplete cerebral ischemia was created in 20 adult cats by retro-orbital middle cerebral artery (MCA) occlusion under halothane anesthesia. Arterial blood flow (CBF), bilateral electroencephalographic (EEG) recordings, and systemic arterial blood pressure (SABP) were monitored for the 1st hour of occlusion. Ten animals were treated with 10 mg/kg of naloxone within 10 minutes of MCA clipping, followed by a continuous infusion of naloxone at 2 mg/kg/hr for the duration of the occlusion (8 hours). Ten animals were treated in a similar fashion with physiological saline (control). Blood flow was restored after 8 hours. The brains were examined at the time of death or 7 days after the occlusion period. There was no difference between the two groups regarding cerebral infarction size or distribution, neurological outcome, SABP, PaCO2, or CBF. Minor changes in EEG amplitude observed in the naloxone-treated group appear to represent interaction of the drug with halothane after prolonged administration. The authors conclude that naloxone did not modify the outcome of focal cerebral ischemia in the cat.

Topics: Animals; Brain; Cats; Cerebral Infarction; Cerebrovascular Circulation; Collateral Circulation; Electroencephalography; Female; Ischemic Attack, Transient; Male; Naloxone