ABSTRACT
The neuroprotective effect of epidermal growth factor (EGF) has been documented in different contexts, but its potential benefits in peripheral neuropathies have been little studied. We investigated the neuroprotective action of EGF in experimental neuropathy induced by acrylamide (ACR). Mice and rats were treated chronically with acrylamide for 6 and 8 weeks, respectively. Concurrently they received EGF in daily doses of 1 and 5 mg/kg in mice and 3 mg/kg in rats, or saline (PBS). ACR severely affected the neurological score, the muscle strength, and the muscle potential M, in mice, as well as F-waves (F-Wii), sensory potentials (SPii), and apomorphine-induced penile erection, in rats. EGF reduced the ACR effects in both species. A dose-dependent effect of EGF was manifested in the proportion of diseased animals at the end of treatments, as well as in the reduction of M amplitude throughout the treatment. F-Wii parameters were less protected by EGF than SP. The results show a protective effect of EGF in acrylamide-induced neuropathy and support previous studies concerning the neuroprotective action of this peptide.
Subject(s)
Acrylamide/toxicity , Epidermal Growth Factor/therapeutic use , Neuroprotective Agents/therapeutic use , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/drug therapy , Action Potentials/physiology , Animals , Apomorphine/pharmacology , Disease Models, Animal , Dopamine Agonists/pharmacology , Electric Stimulation , Epidermal Growth Factor/chemistry , Hand Strength/physiology , Male , Mice , Mice, Inbred C57BL , Neurologic Examination , Neuroprotective Agents/chemistry , Penile Erection/drug effects , Rats , Rats, Wistar , Time FactorsABSTRACT
BACKGROUND: Combined therapy with epidermal growth factor (EGF) and growth hormone-releasing peptide 6 (GHRP-6) in stroke models has accumulated evidence of neuroprotective effects from several studies, but needs further support before clinical translation. Comparing EGF + GHRP-6 to hypothermia, a gold neuroprotection standard, may contribute to this purpose. OBJECTIVES: The aims of this study were to compare the neuroprotective effects of a combined therapy based on EGF + GHRP-6 with hypothermia in animal models of (a) global ischemia representing myocardial infarction and (b) focal brain ischemia representing ischemic stroke. METHODS: (a) Global ischemia was induced in Mongolian gerbils by a 15-min occlusion of both carotid arteries, followed by reperfusion. (b) Focal brain ischemia was achieved by intracerebral injection of endothelin 1 in Wistar rats. In each experiment, three ischemic treatment groups - vehicle, EGF + GHRP-6, and hypothermia - were compared to each other and to a sham-operated control group. End points were survival, neurological scores, and infarct volume. RESULTS: (a) In global ischemia, neurological score at 48-72 h, infarct volume, and neuronal density of hippocampal CA1 zone in gerbils treated with EGF + GHRP-6 were similar to the hypothermia-treated group. (b) In focal ischemia, the neurologic score and infarct volume of rats receiving EGF + GHRP-6 were also similar to animals in the hypothermia group. DISCUSSION: With hypothermia being a good standard neuroprotectant reference, these results provide additional proof of principle for EGF and GHRP-6 co-administration as a potentially neuroprotective stroke therapy.
Subject(s)
Growth Hormone-Releasing Hormone/therapeutic use , Hypothermia, Induced/methods , Neuroprotective Agents/therapeutic use , Oligopeptides/therapeutic use , Stroke/therapy , Analysis of Variance , Animals , Body Temperature/drug effects , Cerebrovascular Circulation/drug effects , Disease Models, Animal , Drug Therapy, Combination , Gerbillinae , Male , Neurologic Examination , Rats , Rats, Wistar , Severity of Illness Index , Time Factors , Treatment OutcomeABSTRACT
INTRODUCTION: Certain compounds belonging to the family of the 2-aryl oxazolines have been reported to act on the central nervous system with a number of different effects and applications, which make them useful as depressants, anaesthetics, anticonvulsants, and so on. AIMS: Our aim was to study the possible effect of 4,4-bis(hydroxymethyl)-2-phenyl-2-oxazoline (OX), obtained by chemical synthesis using microwaves, in two experimental models of epilepsy. MATERIALS AND METHODS: Two models were used: one involving (repeated stimulation) electroconvulsive shock in mice and the other consisted in inducing audiogenic seizures in Mongolian gerbils. Recordings were performed of the potentials in the dentate gyrus (DG) generated in response to electrical stimulation of the entorhinal cortex in anaesthetised gerbils, using the stereotactic technique. RESULTS: A 150 mg/kg dose of OX lowered the number of electrical pulses required to induce the tonic seizures triggered by the electroshock, as well as their duration. This same dose blocked the seizures induced by audiogenic stimuli in the gerbils and significantly reduced their severity (degrees of seizures) and occurrence. OX diminished, in a dose-dependent manner, the amplitude of the excitatory post-synaptic potential and that of the population spike, triggered by stimulating the entorhinal cortex in the DG. CONCLUSIONS: OX acts as an antiepileptic agent and its mechanism of action could be related to the inhibiting effect it exerts on the entorhinal cortex-DG synapses in the hippocampus.
Subject(s)
Anticonvulsants/therapeutic use , Epilepsy, Reflex/drug therapy , Oxazoles/therapeutic use , Seizures/drug therapy , Animals , Anticonvulsants/administration & dosage , Anticonvulsants/chemical synthesis , Anticonvulsants/pharmacology , Dentate Gyrus/drug effects , Dentate Gyrus/physiopathology , Diazepam/therapeutic use , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Electroshock , Entorhinal Cortex/drug effects , Entorhinal Cortex/physiopathology , Epilepsy, Reflex/genetics , Gerbillinae , Mice , Mice, Inbred Strains , Oxazoles/administration & dosage , Oxazoles/chemical synthesis , Oxazoles/pharmacology , Perforant Pathway/drug effects , Perforant Pathway/physiology , Seizures/etiology , Seizures/geneticsABSTRACT
Introduction. Certain compounds belonging to the family of the 2-aryl oxazolines have been reported to act on the central nervous system with a number of different effects and applications, which make them useful as depressants, anaesthetics, anticonvulsants, and so on. Aims. Our aim was to study the possible effect of 4,4-bis(hydroxymethyl)-2-phenyl-2-oxazoline (OX), obtained by chemical synthesis using microwaves, in two experimental models of epilepsy. Materials and methods. Two models were used: one involving (repeated stimulation) electroconvulsive shock in mice and the other consisted in inducing audiogenic seizures in Mongolian gerbils. Recordings were performed of the potentials in the dentate gyrus (DG) generated in response to electrical stimulation of the entorhinal cortex in anaesthetised gerbils, using the stereotactic technique. Results. A 150 mg/kg dose of OX lowered the number of electrical pulses required to induce the tonic seizures triggered by the electroshock, as well as their duration. This same dose blocked the seizures induced by audiogenic stimuli in the gerbils and significantly reduced their severity (degrees of seizures) and occurrence. OX diminished, in a dose-dependent manner, the amplitude of the excitatory post-synaptic potential and that of the population spike, triggered by stimulating the entorhinal cortex in the DG. Conclusions. OX acts as an antiepileptic agent and its mechanism of action could be related to the inhibiting effect it exerts on the entorhinal cortex-DG synapses in the hippocampus (AU)
Introducción. Algunos compuestos de la familia de las 2- aril-oxazolinas se han descrito como sustancias activas sobre el sistema nervioso central, con efectos y aplicaciones diversas, como depresores, anestésicos, anticonvulsionantes, etc. Objetivo. Estudiar el posible efecto de la 2-fenil-4,4-bis (hidroximetil)-2-oxazolina (OX) obtenida por síntesis química bajo microondas en dos modelos de epilepsia experimental. Materiales y métodos. Se emplearon el modelo de choque electroconvulsivo por estimulación repetitiva en ratones y el de crisis audiogénica en el gerbo mongol. Se incluyó el registro de los potenciales del giro dentado (GD) en respuesta a la estimulación eléctrica de la corteza entorrinal en el gerbo anestesiado mediante la técnica estereotáctica. Resultados. La dosis de 150 mg/kg de OX redujo el número de pulsos eléctricos necesarios para inducir la crisis tónica producida por el choque eléctrico, así como su duración. Esta misma dosis bloqueó las crisis inducidas por el estímulo audiogénico en el gerbo y disminuyó significativamente su gravedad (grados de crisis) y aparición. La OX redujo, en forma dependiente de la dosis, la amplitud del potencial postsináptico excitatorio y de la espiga de población, provocada por la estimulación de la corteza entorrinal en el GD. Conclusiones. La OX posee un efecto antiepiléptico cuyo mecanismo podría estar relacionado con su acción inhibitoria sobre la sinapsis corteza entorrinal-GD en el hipocampo (AU)
Subject(s)
Animals , Rats , Epilepsy/drug therapy , Anticonvulsants/pharmacokinetics , Epilepsy, Reflex/drug therapy , Dentate Gyrus , Disease Models, Animal , Perforant Pathway , ElectroshockABSTRACT
Certain compounds belonging to the family of the 2-aryl oxazolines have been reported to act on the central nervous system with a number of different effects and applications, which make them useful as depressants, anaesthetics, anticonvulsants, and so on. AIMS. Our aim was to study the possible effect of 4,4-bis(hydroxymethyl)-2-phenyl-2-oxazoline (OX), obtained by chemical synthesis using microwaves, in two experimental models of epilepsy...(AU)
Subject(s)
Anticonvulsants/therapeutic use , Epilepsy, Reflex/drug therapy , OxazolesABSTRACT
Introducción. Algunos compuestos de la familia de las 2- aril-oxazolinas se han descrito como sustancias activas sobre el sistema nervioso central, con efectos y aplicaciones diversas, comodepresores, anestésicos, anticonvulsionantes, etc. Objetivo. Estudiar el posible efecto de la 2-fenil-4,4-bis (hidroximetil)-2-oxazolina (OX)obtenida por síntesis química bajo microondas en dos modelos deepilepsia experimental. Materiales y métodos. Se emplearon el modelode choque electroconvulsivo por estimulación repetitivaen ratones y el de crisis audiogénica en el gerbo mongol. Se incluyó el registro de los potenciales del giro dentado (GD) en respuesta a la estimulación eléctrica de la corteza entorrinal en el gerbo anestesiado mediante la técnica estereotáctica. Resultados. La dosis de 150 mg/kg de OX redujo el número de pulsos eléctricos necesarios parainducir la crisis tónica producida por el choque eléctrico, así comosu duración. Esta misma dosis bloqueó las crisis inducidas por el estímulo audiogénico en el gerbo y disminuyó significativamente su gravedad (grados de crisis) y aparición. La OX redujo, en forma dependiente de la dosis, la amplitud del potencial postsináptico excitatorio y de la espiga de población, provocada por la estimulación dela corteza entorrinal en el GD. Conclusiones. La OX posee un efectoantiepiléptico cuyo mecanismo podría estar relacionado con su acción inhibitoria sobre la sinapsis corteza entorrinal-GD en el hipocampo(AU)
Introduction. Certain compounds belonging to the family of the 2-aryl oxazolines have been reported to act on the central nervous system with a number of different effects and applications, which make them useful as depressants, anaesthetics, anticonvulsants, and so on. Aims. Our aim was to study the possible effect of 4,4-bis(hydroxymethyl)-2-phenyl-2-oxazoline (OX), obtained by chemical synthesis using microwaves, in two experimental models of epilepsy. Materials and methods. Two models were used: one involving (repeated stimulation) electroconvulsive shock in mice and the other consistedin inducing audiogenic seizures in Mongolian gerbils. Recordings were performed of the potentials in the dentate gyrus (DG) generated in response to electrical stimulation of the entorhinal cortex in anaesthetised gerbils, using the stereotactictechnique. Results. A 150 mg/kg dose of OX lowered the number of electrical pulses required to induce the tonic seizures triggered by the electroshock, as well as their duration. This same dose blocked the seizures induced by audiogenic stimuli in the gerbils and significantly reduced their severity (degrees of seizures) and occurrence. OX diminished, in a dose-dependentmanner, the amplitude of the excitatory post-synaptic potential and that of the population spike, triggered by stimulating the entorhinal cortex in the DG. Conclusions. OX acts as an antiepileptic agent and its mechanism of action could be related to the inhibiting effect it exerts on the entorhinal cortex-DG synapses in the hippocampus(AU)
Subject(s)
Animals , Mice , Anticonvulsants/administration & dosage , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use , Epilepsy, Reflex/drug therapy , Epilepsy, Reflex/genetics , Oxazoles/administration & dosage , Oxazoles/pharmacology , Oxazoles/therapeutic useABSTRACT
No disponible
Subject(s)
Child , Child, Preschool , Adult , Male , Infant , Humans , Translocation, Genetic , Translocation, Genetic , Syndrome , Microtubule-Associated Proteins , Chromosome Aberrations , Cerebral Cortex , Abnormalities, Multiple , In Situ Hybridization, FluorescenceABSTRACT
The influence of drugs affecting different neurotransmitter systems on an acute abstinence head-shaking (AHS) model induced by nalorphine or naloxone was studied in 9-day-old rat pups pretreated (3 h before) with morphine (10 mg/kg, i.p.). One hour after the injection of nalorphine (10 mg/ kg, i.p.) AHS was stopped by a second dose of morphine (10 mg/kg, i.p.) and reinitiated 1 h later by a higher dose of nalorphine (20 mg/kg, i.p.). In other groups AHS was blocked by spiroperidol (0.1 mg/kg, i.p.), clonidine (0.01 mg/kg, i.p.) or scopolamine (50 mg/kg, i.p.). In these groups a second injection of nalorphine did not reinitiate AHS. In dose-effect curve experiments the AHS induced by naloxone or nalorphine was significantly reduced by previous injections of scopolamine, spiroperidol, metergoline or phentolamine in the corresponding groups. Scopolamine was the only antagonist which displaced the AHS dose-effect curves to the right without affecting the maximal response. Since no common receptors exist for a direct competitive interaction between opiate antagonists and scopolamine, these experiments suggest that a direct molecular relationship exists between the tissue concentration of nalorphine (or naloxone) and the endogenous ACh release during abstinence. Thus, the AHS model in 9-day-old rats clearly differentiates specific from non-specific blockade of the abstinence syndrome, and confirms a distinct or primary role of cholinergic neurotransmission in morphine abstinence.
Subject(s)
Acetylcholine/physiology , Head/physiology , Morphine Dependence , Movement/drug effects , Narcotic Antagonists/adverse effects , Synaptic Transmission/drug effects , Animals , Animals, Newborn , Rats , Rats, WistarABSTRACT
In an attempt to develop a technique which would allow early assessment of the functional state of explanted brain tissue, (K+)e was measured in the CA1 region of rat hippocampal slices using K+-selective microelectrodes. In slices (450 micron) maintained at the boundary between the incubation medium and 95% O2/5% CO2 atmosphere, (K+)e was highest (up to 25-30 mmol/l) immediately below the exposed surface and gradually decreased with depth to (K+) of the bathing fluid (5 mmol/l). (K+)e below the exposed surface remained high throughout the 2 h of incubation. In submersed slices, (K+)e was the highest in the center of the slice (200 micron, 10 mmol/l) and decreased towards both surfaces. During 2 h incubation, (K+)e decreased in the center of the slice to 6 mmol/l in viable preparations remaining high in the deteriorating ones. Electrical stimulation of Schaffer's collaterals (15 V; 0.2 ms; 10 Hz) increased (K+)e of viable slices 200 micron below the surface by 2-3 mmol/l. Similar but slower (K+)e changes were elicited by brief (3 min) anoxic episodes (perfusion with incubation medium equilibrated with 95% N2/5% CO2). It is concluded that submersed slices have a more uniform (K+)e profile as compared to the exposed ones and that low (K+)e in the early phase of incubation is a good predictor of slice viability.
Subject(s)
Hippocampus/metabolism , Potassium/metabolism , Animals , Electric Stimulation , Hypoxia/metabolism , In Vitro Techniques , Male , Oxygen Consumption , Rats , SolutionsABSTRACT
Electroconvulsive shock (ECS) decreases fascia dentata responses to entorhinal stimulation by 50% in unanesthetized rats. Synaptic potentials and population spikes return to pre-ECS level during 1 h and 3 h, respectively. This recovery rate is compared with the dynamics of ECS-induced anterograde amnesia.
Subject(s)
Amnesia/physiopathology , Hippocampus/physiopathology , Action Potentials , Animals , Electroshock , Humans , Male , Memory/physiology , Rats , Time FactorsSubject(s)
Disease Models, Animal , Motor Activity/drug effects , Opioid-Related Disorders/physiopathology , Substance Withdrawal Syndrome/physiopathology , Animals , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Fentanyl/pharmacology , Male , Morphine/pharmacology , Nalorphine/pharmacology , Naloxone/pharmacology , Rats , Rats, Inbred StrainsABSTRACT
Mice treated with morphine (100 mg/kg SC) and 3 hr later with naloxone (30 mg/kg) developed an acute abstinence syndrome characterized by escape attempts (rearing, wall-climbing, jumping) and unconditioned motor (head-shaking, jerking) and visceral signs. Functional decortication by spreading depression (SD), elicited 15 min before naloxone injection by epidural application of 25% KCl, abolished the escape behaviour without interfering with other abstinence signs. Electrophysiological recording confirmed reliable generation of cortical SD waves under the conditions of the experiment. The SD effect indicates that the escape behaviour of morphine dependent mice is a conditioned compensatory response to the unconditioned effects of the drugs.
Subject(s)
Cortical Spreading Depression , Escape Reaction/drug effects , Morphine/pharmacology , Naloxone/pharmacology , Animals , Caudate Nucleus/physiology , Cerebral Cortex/physiology , Cortical Spreading Depression/drug effects , Electric Conductivity , Electric Stimulation , Male , Mice , Mice, Inbred StrainsABSTRACT
The pharmacological activity of vitamin C and the antiallergic drug disodium cromoglycate are compared in models of rat mast cell degranulation and histamine release, and in protracted anaphylactic shock in the guinea pig. Our results demonstrate that ascorbic acid has a very weak inhibitory effect on degranulation and histamine release from mast cells, and therefore cannot be considered a prophylactic antiallergic drug such as disodium cromoglycate.