naloxone and Brain-Edema

Topics: Animals; Brain Edema; Cerebrovascular Circulation; Dipeptides; Hepatic Encephalopathy; Humans; Naloxone

Although approximately 500,000 patients suffer from a stroke each year in the United States, treatment of these patients to date has consisted primarily of prevention, supportive measures, and rehabilitation. The modification of experimental cerebral infarction by new pharmacologic agents, along with encouraging results from the restoration of blood flow to areas of focal ischemia in both laboratory and clinical trials, suggests that a more aggressive approach might be considered in selected patients with acute stroke.

Topics: Anticoagulants; Barbiturates; Brain Edema; Brain Ischemia; Calcium Channel Blockers; Cerebral Revascularization; Cerebrovascular Circulation; Fluorocarbons; Hemodilution; Humans; Mannitol; Microcirculation; Naloxone

Topics: Acidosis; Adrenal Cortex Hormones; Anticoagulants; Barbiturates; Blood Viscosity; Brain Edema; Calcium Channel Blockers; Carbon Dioxide; Cerebrovascular Disorders; Dextrans; Hemodilution; Humans; Hypothermia, Induced; Lactates; Naloxone; Vasodilator Agents

Topics: Animals; Blood-Brain Barrier; Body Temperature; Brain; Brain Edema; Cerebrovascular Circulation; Heat Stress Disorders; Male; Naloxone; Naltrexone; Narcotic Antagonists; Rats; Rats, Wistar

Centrally released arginine vasopressin (AVP) has been implicated in the regulation of the brain water content and is elevated in the cerebrospinal fluid of patients with ischaemic and traumatic brain injuries. The protective effect of RU51599, which is a selective kappa opioid agonist as an AVP release inhibitor, on brain oedema was examined. Male Wistar rats, weighing 300 to 400 g each, were used. The cortical cryogenic injury was produced by application of a previously prepared metal probe cooled with dry ice to the dura of the right patietal region. Animals were separated into three groups. Group 1: sham operated rats without lesion production. Group 2: saline-treated rats with lesion production. Group 3: RU51599-treated rats with lesion production. In Group 3, rats were treated with RU51599 (0.1-3 mg/kg) at 30 minutes before lesion production, 1 hour, 2 hours, and 4 hours after lesion production. After 6 hours, animals were decapitated and brain water contents were measured using the dry-wet weight method. The extent of blood brain barrier (BBB) disruption was determined by assessment of Evans blue uptake based on extraction from tissue using dimethylformamide. The primary injured infarcted area was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Sodium and potassium contents in serum and brain tissue were measured using atomic absorption spectrophotometry. The antagonism of naloxone against protective effects of RU51599 on cryogenic induced brain oedema and on antinociceptive effects in acetic-acid treated animals was examined. Statistical analysis was performed using Dunnett-test and U-test following Kruskal-Wallis test. RU51599 significantly reduced the brain water contents on the injured side and the contralateral non-injured side (p < 0.01) after 4 administration of 1 and 3 mg/kg. RU51599 neither significantly inhibited BBB disruption nor reduced the primary injured infarcted area. RU51559 significantly increased brain sodium and potassium contents in the injured brain and also increased serum sodium levels (p < 0.01). Naloxone antagonized the anti-oedema effects and anti-nociceptive effects of RU51599. These findings indicate that the AVP release inhibitor, RU51599 possibly mediated by opioid receptors, has a potential protective effect on cryogenic-induced brain oedema and that centrally released AVP plays an important role in the progression of vasogenic brain oedema.

Topics: Animals; Arginine Vasopressin; Benzeneacetamides; Blood-Brain Barrier; Brain Chemistry; Brain Edema; Brain Injuries; Cold Temperature; Diuretics; Evans Blue; Male; Naloxone; Potassium; Pyrrolidines; Rats; Rats, Wistar; Receptors, Opioid, kappa; Sodium; Spectrophotometry, Atomic

Experiments in rats showed i. p. injections of a dose of 0.1 mg/kg of highly mu-selective agonist DAGO, relatively selective delta-receptor agonist DSLET and Tyr-D-Ala-Gly-MePhe-Leu-Arg-NH-Et to attenuate markedly the development of cerebral edema 24 hours after brain injury. The same effect was found with administration of DSLET 4 days after trauma. Naloxone (1 mg/kg, i. p.) had no effect on this process, but completely blocked protective effect of peptides. These data demonstrate that both mu and delta opioid receptors are involved in the pathogenesis of traumatic cerebral edema.

Topics: Animals; Brain Edema; Brain Injuries; Dose-Response Relationship, Drug; Enkephalins; Female; Male; Naloxone; Rats; Receptors, Opioid; Time Factors

Opioid receptors blocker naloxone potentiated edematous effect of GABA-receptors blockers in experiments on rats. In combination with bicuculline and picrotoxine that agent leads to increased content of water in the brain and decreased brain tissue density. At the same time naloxone prevented GABA-antagonists activation of oxidative processes in brain mitochondria.

Topics: Animals; Bicuculline; Brain; Brain Edema; Female; Male; Mitochondria; Naloxone; Oxidative Phosphorylation; Picrotoxin; Rats; Receptors, GABA-A; Receptors, Opioid; Semicarbazides

Excitotoxic neurodegeneration in the rat striatum was induced by direct injection of quinolinic acid. The degree of damage was evaluated in vivo 1 day later by quantitative magnetic resonance imaging (MRI) and 7 days later in the same animals by measuring the activities of the neuronal marker enzymes choline acetyltransferase and glutamic acid decarboxylase. Striatal damage assessed using the two approaches was highly correlated. Moreover the cerebroprotective efficacy of the N-methyl-D-aspartate receptor antagonist CGP 40116 was indistinguishable based on all analytical parameters. MRI, however, was more reproducible than the enzymatic methods and was faster and simpler for routine analyses of excitotoxic damage and cerebroprotection in vivo.

Topics: 2-Amino-5-phosphonovalerate; Animals; Brain; Brain Edema; Choline O-Acetyltransferase; Corpus Striatum; Glutamate Decarboxylase; Magnetic Resonance Imaging; Male; Naloxone; Nerve Degeneration; Quinolinic Acid; Rats; Rats, Inbred Strains; Receptors, N-Methyl-D-Aspartate

Trauma to the spinal cord induces a series of electrophysiological, immunological and biochemical events, but it is still unclear how such reactions are initiated and maintained. Most likely release of neurochemicals, breakdown of microvascular permeability and the formation of vasogenic edema play important roles in the pathophysiology of spinal cord trauma. In an animal model we have focused the attention to the possible involvement of endogenous serotonin, prostaglandins and opioid peptides in the formation of edema and associated disturbances of vascular permeability. The trauma was produced in anesthetized rats by making a focal lesion in the right dorsal horn at the T10-11 segments. This injury resulted in a profound increase in the microvascular permeability to 131I-sodium and an elevation of water content in the rostral T9 and caudal T12 segments as measured 5 h after the onset of the injury. Light microscopy of the perifocal changes in the T9-T12 segments using Nissl stain and immunohistochemistry to glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) showed profound cellular changes which were most severe in the ipsilateral ventral horn. Many nerve cell bodies were shrunken and the tissue had a spongy edematous appearance. There was a marked increase of GFAP immunoreactivity as well as a significant diminution of MBP staining. Pre-treatment with p-chlorophenylalanine (p-CPA, an endogenous serotonin depletor and synthesis inhibitor) or indomethacin (an endogenous prostaglandin synthesis inhibitor) or naloxone (an opioid receptor antagonist) significantly reduced the permeability changes and the edema formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Pressure; Body Water; Brain Edema; Capillary Permeability; Carbon Dioxide; Fenclonine; Glial Fibrillary Acidic Protein; Indomethacin; Male; Myelin Basic Protein; Naloxone; Oxygen; Partial Pressure; Rats; Rats, Wistar; Spinal Cord; Spinal Cord Injuries

Endogenous opioids have been shown to produce beneficial effects in experimental stroke. To evaluate both neurophysiological and biochemical parameters, we induced massive cerebral ischemia in 11 rabbits according to the method standardized in our laboratory, using microspheres injected through the internal carotid artery. Binding studies were performed in the 11 embolized, in nine control, and in five sham-operated rabbits using the appropriate concentration of [3H]dynorphin A (1-8). Neurophysiological parameters were evaluated under baseline conditions and 1 hour after embolization, surgical preparation, or sham operation in 17 rabbits. Comparison of visual readings of the electroencephalograms and analyses of the quantified electroencephalograms under baseline conditions and after embolization indicated a marked and statistically significant (p less than 0.01) increase in bilateral delta activity; histologic examination confirmed bilateral brain edema. Binding studies on kappa-opioid receptors indicate that 1 hour after embolization there were significantly more (28%) kappa-opioid receptors (Bmax) in six embolized rabbits than in five sham-operated animals. No significant changes were observed in the affinity parameters, particularly in the dissociation constant (Kd). Our results indicate a role for endogenous dynorphin peptides in the pathogenesis of stroke.

Topics: Animals; Brain Edema; Brain Ischemia; Electroencephalography; Naloxone; Rabbits; Receptors, Opioid; Receptors, Opioid, kappa