RESUMEN
OBJECTIVE: Identification of the role of oxidative stress in the development of disorders that occur in hemorrhagic stroke (HS, post-traumatic intracerebral hematoma), and the study of the effects of Mexidol on neurological and cognitive deficits in HS with an analysis of the relationship between the therapeutic effects of the drug in HS with its antioxidant effect. MATERIAL AND METHODS: The study was carried out on mature outbred male rats weighing 260-280 g. HS was created by destruction of the brain tissue in the area of the capsula interna, with the introduction of blood into the site of injury. On the 1st, 7th, and 14th days after HS modeling, death, neurological deficits (McGrow scale, rotating rod), convulsive manifestations, and cognitive impairment were recorded in rats; blood plasma and homogenates of the cerebral cortex of rats. Mexidol was administered after the HS operation: first at a dose of 150 mg/kg, intraperitoneally, for 3 days and then 75 mg/kg, orally (from the 4th to the 14th day). RESULTS: Mexidol in rats with HS significantly increases the survival rate of animals, reduces the manifestations of neurological deficits according to the McGrow scale (playpen movements, paresis of 1-4 limbs, paralysis of the lower limbs, lateral position), eliminates individual motor convulsive manifestations, restores impaired coordination of movements (rotating rod test) and improves, impaired HS, learning and memory processes. Mexidol normalizes the concentration of TBA-active products in the blood of animals and homogenates of the cerebral cortex of rats, both a day and 7 days after HS modeling. CONCLUSION: The data obtained indicate the involvement of oxidative stress as a chain of pathogenesis in the development of disorders in HS and the ability of Mexidol to alleviate neurological deficits, convulsive manifestations and cognitive impairment in HS, which is accompanied by a decrease in oxidative stress. All this justifies the importance of the use of Mexidol in patients with hemorrhagic stroke, posttraumatic intracerebral hematoma and determines the features of its therapeutic effects.
Asunto(s)
Accidente Cerebrovascular Hemorrágico , Animales , Hematoma , Masculino , Estrés Oxidativo , Picolinas , RatasRESUMEN
The effects of GSB-106, a low-molecular mimetic of BDNF loop 4, that represents a substituted dimeric dipeptide bis (N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide, on cognitive and motor impairments in a model of a depressive-like state in rats caused by unavoidable electric foot-shock were studied using active avoidance and open-field tests. GSB-106 (0.5 mg/kg, per os, 10 days) completely restored the number of avoidance reactions that was reduced in rats exposed to foot-shock and the percentage of trained rats in active avoidance training. In the open-field test, the peptide restored reduced horizontal activity and the number of explored holes. Thus, GSB-106 corrected impaired learning and memory, as well as locomotor activity and exploratory behavior in a model of depression in rats.
Asunto(s)
Antidepresivos/química , Antidepresivos/farmacología , Factor Neurotrófico Derivado del Encéfalo/química , Dipéptidos/química , Animales , Antidepresivos/uso terapéutico , Reacción de Prevención/efectos de los fármacos , Depresión/tratamiento farmacológico , Masculino , Distribución Aleatoria , RatasRESUMEN
The protective effects of a new low-molecular-weight mimetic of nerve growth factor hexamethylene diamide bis-(N-monosuccinyl-L-glutamine-L-lysine; GK-2) were studied on the experimental model of hemorrhagic stroke (intracerebral posttraumatic hematoma) in rats. Intraperitoneal injections of GK-2 in a dose of 1 mg/kg 4 and 24 h after surgery and 24 h before testing the CNS function on days 3, 7, and 14 prevent death of experimental animals, reduce the neurological deficit, and normalized behavior.
Asunto(s)
Dipéptidos/uso terapéutico , Hemorragias Intracraneales/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Hemorragias Intracraneales/mortalidad , Masculino , Factor de Crecimiento Nervioso , Ratas , Accidente Cerebrovascular/mortalidadRESUMEN
Effects of the novel antiparkinsonian drug himantane and amantadin were studied in rats with intracerebral posttraumatic hematoma. Drugs were administered first at 3.5 hours after surgery and then for 4 consecutive days. Effects were registered on days 1, 3, 7 and 14 after surgery. It was shown that both drugs significantly decreased mortality and improved motor activity, exploratory behavior and memory. Amantadin was more effective in tests for motor activity and exploratory behavior. Himantane 5 mg/kg i.p demonstrated the more pronounced activity in restoring memory. The results obtained testify for neuroprotective properties of the novel antiparkinsonian drug himantane.
Asunto(s)
Adamantano/análogos & derivados , Amantadina/uso terapéutico , Antiparkinsonianos/uso terapéutico , Hemorragia Cerebral Traumática/tratamiento farmacológico , Adamantano/uso terapéutico , Animales , Hemorragia Cerebral Traumática/psicología , Hemorragia Cerebral Traumática/rehabilitación , Modelos Animales de Enfermedad , Conducta Exploratoria/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Tono Muscular/efectos de los fármacos , RatasRESUMEN
Intraperitoneal administration of afobazole in a dose of 0.1 mg/kg over 2 weeks after repeated modeling of intracerebral post-traumatic hematoma reduces animal mortality, decreases motor coordination disturbances, and improves learning and memory processes in rats.
Asunto(s)
Ataxia/tratamiento farmacológico , Bencimidazoles/farmacología , Hemorragia Cerebral Traumática/tratamiento farmacológico , Aprendizaje/efectos de los fármacos , Memoria/efectos de los fármacos , Morfolinas/farmacología , Fármacos Neuroprotectores/farmacología , Factores de Edad , Animales , Ataxia/etiología , Bencimidazoles/administración & dosificación , Bencimidazoles/uso terapéutico , Hemorragia Cerebral Traumática/complicaciones , Hemorragia Cerebral Traumática/mortalidad , Inyecciones Intraperitoneales , Masculino , Morfolinas/administración & dosificación , Morfolinas/uso terapéutico , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/uso terapéutico , RatasRESUMEN
The model of posttraumatic hematoma was used to imitate the condition of hemorrhagic stroke in rats. Afobazole (5-ethoxy-2-[2-(morpholino)-ethylthio] benzimidazole dihydrochloride) administered in doses of 0.1 and 1.0 mg/kg intraperitoneally for 14 days was shown to be able to decrease the pathological manifestations of this model. Afobazole administration decreased mortality and the neurological deficits, including motor discoordination, and improve the learning and memory.
Asunto(s)
Conducta Animal/efectos de los fármacos , Bencimidazoles/farmacología , Hemorragias Intracraneales/tratamiento farmacológico , Morfolinas/farmacología , Fármacos Neuroprotectores/farmacología , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Bencimidazoles/uso terapéutico , Masculino , Morfolinas/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , RatasRESUMEN
Changes in proline-specific peptidase activity in the frontal cortex and hippocampus were studied using the experimental model of retrograde amnesia in rats. In one group, the amnesia was produced by a single injection of M-cholinergic antagonist scopolamine and the other group received the maximal electroconvulsive stimulation (MES). The amnesic effect was evaluated in passive avoidance test. In the amnesia models under consideration, the activity of prolylendopeptidase was significantly increased in both frontal cortex and hippocampus. The activity of dipeptidyl peptidase IV was significantly decreased in the cortex, whereas in the hippocampus it remained unchanged. Pyracetam inhibited prolylendopeptidase in the cortex and hippocampus, whereas dipeptidyl peptidase IV activity remained unchanged.
Asunto(s)
Amnesia Retrógrada/enzimología , Dipeptidil Peptidasa 4/metabolismo , Serina Endopeptidasas/metabolismo , Amnesia Retrógrada/inducido químicamente , Animales , Dipeptidil Peptidasa 4/análisis , Modelos Animales de Enfermedad , Estimulación Eléctrica , Lóbulo Frontal/enzimología , Hipocampo/enzimología , Masculino , Antagonistas Muscarínicos/toxicidad , Nootrópicos/farmacología , Piracetam/farmacología , Prolil Oligopeptidasas , Ratas , Ratas Wistar , Escopolamina/toxicidad , Serina Endopeptidasas/análisisRESUMEN
An efficacy of mexidol, a Russian drug of the new generation, used in 100 mkg during 7 days has been demonstrated in rats in the model of experimentally caused intracerebral posttraumatic hematoma (hemorrhagic stroke). The drug significantly reduced the number of neurological impairments (paresis, riding-arena movements) and increased the animal's survival rate. Mexidol improved learning and memory in rats with hemorrhagic stroke in the passive avoidance test and exerted influence on the locomotor activity in the open field test.
Asunto(s)
Hemorragia Cerebral/tratamiento farmacológico , Picolinas/administración & dosificación , Psicotrópicos/administración & dosificación , Animales , Lesiones Encefálicas/complicaciones , Hemorragia Cerebral/etiología , Hemorragia Cerebral/psicología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Aprendizaje/efectos de los fármacos , Locomoción/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Ratas , Resultado del TratamientoRESUMEN
An ischemic cerebral affection zone amounting to 22.51 +/- 3.0% of the ipsilateral hemisphere volume was found on the frontal brain sections in the frontoparietal cortex of rats 72 h after occlusion of the distal branch of the medial cerebral artery. The new nootropic drug nooglutyl [N-(5-hydroxynicotinoyl)-L-glutamic acid] in a dose of 10 mg/kg, as well as mexidol or phenyl-tert-butylnitrone (PBN) in a dose of 100 mg/kg, introduced into the vein at the moment of occlusion and intraperitoneally for two days after operation, effectively restricted the affected zone: nooglutyl, up to 7.6 +/- 2.28%; mexidol, up to 9.55 +/- 1.9%; and PBN, up to 12.8 +/- 1.7% of the ipsilateral hemisphere volume. On the third day after operation, animals preliminarily learnt to the passive avoidance conditioned reflex exhibited violated memory retrieval. The retrieval was significantly improved in the test animals treated with mexidol and especially nooglutyl.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Depuradores de Radicales Libres/uso terapéutico , Glutamatos/uso terapéutico , Memoria/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Ácidos Nicotínicos/uso terapéutico , Óxidos de Nitrógeno/uso terapéutico , Picolinas/uso terapéutico , Animales , Arteriopatías Oclusivas/complicaciones , Isquemia Encefálica/etiología , Isquemia Encefálica/patología , Enfermedades Arteriales Cerebrales/complicaciones , Óxidos N-Cíclicos , Masculino , Ratas , Ratas WistarRESUMEN
The effect of the new nootropic drug nooglutyl, a positive modulator of AMPA-subtype glutamatergic receptors, was studied in rats with a model hemorrhagic stroke (HS)--posttraumatic hematoma induced by cerebral tissue destruction in the capsule interna region. Single intraperitoneal injections of nooglutyl (10 and 20 mg/kg) 3-4 h after operation decreased the HS-induced neurological deficiency, restored the coordination of movements, improved the passive avoidance reaction retrieval, and prevented the loss of experimental animals. The results show evidence of a pronounced neuroprotector action of nooglutyl in rats with the HS model.
Asunto(s)
Hemorragia Cerebral Traumática/tratamiento farmacológico , Glutamatos/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Ácidos Nicotínicos/uso terapéutico , Animales , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Hemorragia Cerebral Traumática/mortalidad , Hemorragia Cerebral Traumática/fisiopatología , Condicionamiento Psicológico/efectos de los fármacos , Aprendizaje/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , RatasRESUMEN
Proproten contains ultra-low doses of affinity purified antibodies to S-100 protein dynamized according to the rules of homeopathy. S-100 is regulator of brain integrative activity and takes part in synaptic processes. In experiment on outbred rats proproten demonstrates significant anxiolytic, antidepressant and antiamnestic effects after single and repeated administration. Proproten is similar to the well-known reference preparations diazepam, amitriptyline and piracetam in activity. Proporten's advantage over these drugs is no sedative, myorelaxation and amnestic effects. Psychotropic effects of proproten are likely to result from modulation of synaptic transmission in limbic structures of brain.
Asunto(s)
Anticuerpos/farmacología , Psicotrópicos/farmacología , Proteínas S100/inmunología , Amitriptilina/farmacología , Animales , Antidepresivos/farmacología , Conducta Animal/efectos de los fármacos , Condicionamiento Operante/efectos de los fármacos , Diazepam/farmacología , Relación Dosis-Respuesta a Droga , Masculino , Piracetam/farmacología , Ratas , Proteínas S100/efectos de los fármacosRESUMEN
The administration of neurotoxin thiolactone homocysteine in rats with cobalt-induced epileptogenic focus in the sensomotor cortical region led to the development of secondary generalized convulsions and epileptic state. The pattern was analogous to the manifestation of convulsions in epileptic state in humans. Fenitoin (50 mg/kg) inhibited the development of convulsions, arrested the epileptic state, reduced the number and duration of the secondary generalized tonic--clonic attacks, decreased the behavioral manifestations (focal convulsions, lateral position etc.), normalized EEG, and prevented fatal outcome. An increase in the fenitoin dose to 100 mg/kg decreased the antiepileptic activity, enhanced side effects, and increased the lethality in test animals.
Asunto(s)
Anticonvulsivantes/farmacología , Epilepsia/fisiopatología , Homocisteína/análogos & derivados , Fenitoína/farmacología , Convulsiones/fisiopatología , Animales , Conducta Animal/efectos de los fármacos , Cobalto , Convulsivantes , Electroencefalografía , Epilepsia/inducido químicamente , Epilepsia/mortalidad , Masculino , Ratas , Convulsiones/inducido químicamente , Convulsiones/mortalidad , Estado Epiléptico/inducido químicamente , Estado Epiléptico/mortalidad , Estado Epiléptico/fisiopatologíaRESUMEN
Ondansetron (GR38032F, zofran)--a specific blocker of 5-HT3-receptors in a dose range of 0.05 to 0. mg/kg causes an anxiolytic effect in experiments on mice and rats on a model of elevated plus maze. The drug does not produce a sedative and myorelaxant effect. A 0.05 mg/kg dose of ondansetron reduces the level of anxiety and convulsive manifestations which are induced by discontinuation of long-term diazepam administration. The results of the study bear evidence of selectivity of the anxiolytic effect of ondansetron in intact animals and its effectiveness in rats with diazepam abstinence.
Asunto(s)
Ansiolíticos/efectos adversos , Ansiolíticos/uso terapéutico , Diazepam/efectos adversos , Ondansetrón/uso terapéutico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Animales , Ansiolíticos/farmacología , Conflicto Psicológico , Convulsivantes , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Conducta Exploratoria/efectos de los fármacos , Masculino , Ratones , Ondansetrón/farmacología , Pentilenotetrazol , Ratas , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Factores de TiempoAsunto(s)
Ansiolíticos/toxicidad , Ansiedad/prevención & control , Bloqueadores de los Canales de Calcio/farmacología , Diazepam/toxicidad , Nifedipino/farmacología , Convulsiones/prevención & control , Síndrome de Abstinencia a Sustancias/prevención & control , Adaptación Fisiológica , Animales , Ansiolíticos/administración & dosificación , Ansiedad/inducido químicamente , Canales de Calcio/fisiología , Convulsivantes/toxicidad , Diazepam/administración & dosificación , Excitación Neurológica , Masculino , Pentilenotetrazol/toxicidad , Ratas , Ratas Wistar , Convulsiones/inducido químicamente , Trastornos Relacionados con Sustancias/fisiopatologíaRESUMEN
The effects of new selective catechol-O-methyltransferase (COMT) inhibitors entacapone (mainly peripheral effect) and tolcapone (acting also in the brain) on normal and impaired cognitive functions were studied in aversively motivated inhibitory avoidance using a single-trial passive avoidance paradigm in young adult rats. Passive avoidance retention latency was shortened by either scopolamine (1.0 mg/kg) or bilateral lesions to nucleus basalis magnocellularis (NBM) caused by infusions of ethylcholine aziridinium (AF64A). Entacapone (30 mg/kg) administered once before training or before the retention test, 24 h after training, prevented the effect of scopolamine but did not alter extinction in these rats. However, entacapone (30 mg/kg) prolonged lag time when given during the extinction process to intact rats after training. Tolcapone administered once before training (10 mg/kg) counteracted the effect of scopolamine. It prolonged retention latency of the intact rats when given after training (10 mg/kg). Tolcapone (3 mg/kg) also prolonged lag time when given during extinction to rats bearing NBM lesions. The effect of scopolamine on extinction and retrieval was not prevented by tolcapone. Only entacapone improved memory storage. Collectively, the present results indicate that COMT inhibitors prolong retention latencies in a single-trial passive avoidance test assessed at several memory phases.