naloxone and Brain-Diseases

Topics: Adenosine Triphosphate; Anesthesia; Anesthetics; Aneurysm; Animals; Barbiturates; Brain; Brain Diseases; Brain Ischemia; Cerebrovascular Circulation; Electroencephalography; Energy Metabolism; Humans; Hypothermia, Induced; Intraoperative Complications; Isoflurane; Naloxone; Phenytoin; Thiopental

In previous studies, large-dose fentanyl produced electrographic seizure activity and histologically evident brain damage. We assessed whether fentanyl-induced brain damage is attenuated by using anticonvulsant drugs. Using halothane/nitrous oxide anesthesia, 40 Sprague-Dawley rats underwent tracheal intubation, arterial and venous cannulation, and insertion of biparietal electroencephalogram electrodes and a rectal temperature probe. Halothane was discontinued. The dose of IV fentanyl shown previously to cause maximal brain damage was given to all animals and N(2)O was discontinued. Control rats were given fentanyl only. Rats in the three study groups also received midazolam, phenytoin, or N(2)O/naloxone. After characteristic seizure activity began with fentanyl loading the study drug was started. After a 2-h infusion, wounds were closed, and animals recovered overnight and underwent cerebral perfusion-fixation. Neuropathologic alterations were ranked on a scale of 0-5 for both neuronal death (0 = normal, 5 = more than 75% neuronal death) and for malacia. Significantly fewer rats in the N(2)O/Naloxone, Phenytoin, and Midazolam Groups sustained any brain damage compared with controls. Protection against opioid neurotoxicity is achieved with midazolam, naloxone, and phenytoin. If opioid neurotoxicity is clinically relevant, a small change in anesthetic practice might reduce any potential neurologic morbidity.. Narcotics in large doses can cause brain damage in rats. This brain damage is attenuated by a narcotic antagonist, a sedative, and an antiepileptic drug.

Topics: Analgesics, Opioid; Animals; Anticonvulsants; Blood Gas Analysis; Body Weight; Brain Diseases; Electroencephalography; Fentanyl; GABA Modulators; Male; Midazolam; Naloxone; Narcotic Antagonists; Phenytoin; Rats; Rats, Sprague-Dawley

We report the case of a 61-year-old diabetic woman with end-stage renal disease who was on hemodialysis and who developed an encephalopathy and episodes of hypotension and hypoventilation, all of which showed rapid and dramatic responses on multiple occasions to the administration of the opiate antagonist naloxone. Improvement in encephalopathy was confirmed by electroencephalography. The patient had received no exogenous opiates and had a normal beta-endorphin level. She subsequently developed myoclonus and was treated for possible aluminum overload that was of borderline magnitude. We conclude that this patient had an encephalopathy that responded to opiate receptor blockade. Because of cerebrovascular disease, episodes of diminished blood pressure due to a state of increased opiate receptor stimulation may have unmasked this underlying encephalopathy. These effects may have been secondary to increased opiate-binding sites or to elevated central nervous system levels of endogenous opiates.

Topics: Brain Diseases; Diabetes Mellitus, Type 2; Electroencephalography; Female; Humans; Kidney Failure, Chronic; Middle Aged; Naloxone; Renal Dialysis

Single-cell activity was recorded in the locus coeruleus (LC) of morphine-dependent, halothane-anesthetized rats. Systemic administration of the opiate antagonist naloxone (0.1 mg/kg, i.v.) robustly increased the activity of LC neurons. Local microinjection of naloxone or of its hydrophilic derivative, naloxone methiodide, into LC (10 mM, 20-40 nl) did not activate LC neurons in dependent rats. Intracerebroventricular or intracoerulear injection of kynurenate, a broad-spectrum antagonist of excitatory amino acids (EAAs), substantially but incompletely attenuated the activation of LC cells induced by intravenous naloxone-precipitated withdrawal (more than 50% blockade). Intracoerulear microinjections of the non-NMDA-receptor antagonist 6-cyano-7-dinitroquinoxaline-2,3-dione (CNQX) or the selective NMDA-receptor antagonist AP5 significantly reduced the withdrawal-induced excitation. AP5 was the least effective among all antagonists tested. Similar microinjections of kynurenate or CNQX almost completely suppressed the excitation of LC neurons induced by electrical stimulation of a rear footpad. LC responses to footpad stimulation (mediated by endogenous EAAs) or iontophoretically applied glutamate were not modified by the chronic morphine treatment. These results indicate that a substantial part of LC hyperactivity during opiate withdrawal is mediated by an augmented EAA input to LC.

Topics: Amino Acids; Animals; Brain Diseases; Electric Stimulation; Glutamates; Glutamic Acid; Infusion Pumps, Implantable; Kynurenic Acid; Locus Coeruleus; Male; Microinjections; Morphine; Naloxone; Neurons; Rats; Rats, Inbred Strains; Substance Withdrawal Syndrome

To assess whether endogenous opioids participate in respiratory depression due to brain hypoxia, we determined the ventilatory response to progressive carboxyhemoglobinemia (1% CO, 40% O2) before and after administration of naloxone (NLX, 0.1 mg/kg iv). Minute ventilation (VI) and ventral medullary surface pH (Vm pH) were measured in six anesthetized, peripherally chemodenervated cats. NLX consistently increased base-line hyperoxic VI from 618 +/- 99 to 729 +/- 126 ml/min (P less than 0.05). Although NLX did not alter the Vm pH response to CO [initial alkalosis, Vm pH +0.011 +/- 0.003 pH units, followed by acidosis, Vm pH -0.082 +/- 0.036 at carboxyhemoglobin (HbCO) 55%], NLX attenuated the amount of ventilatory depression; increasing HbCO to 55% decreased VI to 66 +/- 6% of base line before NLX and to 81 +/- 9% of base line after NLX (P less than 0.05). The difference in response after NLX was primarily the result of a linear increase in tidal volume (VT) with decreasing Vm pH (delta VT = 60.3 ml/-pH unit) which was absent before NLX. To assess whether the site of action of the endogenous opioid effect was the central chemosensors, the ventilatory and Vm pH response to progressive HbCO was determined in three additional cats before and after topical application of NLX (3 X 10(-4) M) to the ventral medullary surface. The effect of topical NLX was similar to systemic NLX; significant attenuation of the reduction in VI with increasing HbCO. We conclude that 1) endogenous opioids mediate a portion of the depression of ventilation due to acute brain hypoxia, and 2) this effect is probably at the central chemosensitive regions.

Topics: Administration, Topical; Animals; Brain Diseases; Cats; Hypoxia; Injections, Intravenous; Naloxone; Respiration

Topics: Ataxia; Brain; Brain Chemistry; Brain Diseases; Cerebrospinal Fluid; Diagnosis, Differential; Endorphins; Enkephalins; Humans; Infant; Injections, Intravenous; Intellectual Disability; Male; Morphine; Naloxone; Necrosis; Spinal Cord Diseases; Syndrome

Topics: Brain Chemistry; Brain Diseases; Cerebrospinal Fluid; Endorphins; Enkephalins; Humans; Infant; Injections, Intravenous; Male; Naloxone; Necrosis; Spinal Cord Diseases