RESUMEN
Pereskia sacharosa Griseb. is a plant used in traditional herbal medicine to treat inflammation. We analyzed the phenolic content of P. sacharosa leaves (EEPs) by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and investigated the anti-inflammatory properties of EEPs and its flavonoid fraction (F10) in animal models subjected to acute neuroinflammation induced by bacterial lipopolysaccharide (LPS). Coronal brain sections of C57BL/6JN male mice or Wistar male rats administered with EEPs or F10 before LPS were subjected to in situ hybridization to determine c-fos and CD14 mRNA levels in the hypothalamus or GABAA γ2 mRNA levels in the hippocampus. Theta oscillations were recorded every 6 h in the hippocampus of Wistar rats. In total, five flavonoids and eight phenolic acids were identified and quantified in P. sacharosa leaves. Either EEPs or F10 crossed the blood-brain barrier (BBB) into the brain and reduced the mRNA expression of c-fos, CD14, and GABAA γ2. A decrease in theta oscillation was observed in the hippocampus of the LPS group, while the F10 + LPS group overrode the LPS effect on theta activity. We conclude that the bioactive compounds of P. sacharosa reduce the central response to inflammation, allowing the early return of ambulatory activity and well-being of the animal.
RESUMEN
Orexins-A (OrxA) and -B (OrxB) neuropeptides are synthesized by a group of neurons located in the lateral hypothalamus and adjacent perifornical area, which send their projections to the mesolimbic dopaminergic (DAergic) system including ventral tegmental area and nucleus accumbens (NAc), where orexin receptors are expressed. NAc plays a central role in reward-seeking behavior and drug abuse. NAc-neurons express dopamine-1 (D1R) and dopamine-2 (D2R) receptors. Orexins bind to their two cognate G-protein-coupled receptors, orexin-receptor type-1 (Orx1R) and type-2 (Orx2R). Orexin receptor signaling is involved in behaviors such as motivation and addiction. Orexin-containing neurons modulate DAergic activity that is key in synaptic plasticity induced by addictive drugs. However, the effect of OrxA on expression and content of DAergic receptors in NAc is unknown. The purpose of this study was to investigate whether OrxA can alter gene expression and protein levels of D1R/D2R in NAc. Gene expression was evaluated by real-time PCR analysis and protein levels by western blot in rats. The results show that intracerebroventricular (i.c.v.) injection of OrxA increases both gene transcription and protein content of D2R but fails to modify D1R. This effect was also confirmed with OrxA infusion in NAc/Shell. Our results demonstrate for the first time that OrxA induces up-regulation of gene and protein of D2R in NAc. These findings support the hypothesis that OrxA modulates the DAergic transmission and this may serve to understand how orexin signaling enhances DA responses at baseline conditions and in response to psychostimulants.
Asunto(s)
Neuronas Dopaminérgicas/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Orexinas/farmacología , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Animales , Neuronas Dopaminérgicas/citología , Neuronas Dopaminérgicas/metabolismo , Regulación de la Expresión Génica , Inyecciones Intraventriculares , Masculino , Núcleo Accumbens/citología , Núcleo Accumbens/metabolismo , Orexinas/metabolismo , Unión Proteica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Transducción de Señal , Técnicas EstereotáxicasRESUMEN
RATIONALE: The use of electrical stimulation therapy to treat epilepsy is currently being studied in experimental animals and patients. Our study was designed to evaluate the effects of electrical stimulation applied in the thalamic reticular nucleus (TRN) on the development of pentylentetrazole-induced seizures. MATERIALS AND METHODS: Experiments were performed using male Wistar rats with electrodes stereotaxically implanted in the left TRN. Epidural EEG recording screws were implanted in the motor cortex for EEG recording. The rats were classified in seven groups: one sham group, four groups receiving either high- or low-frequency preemptive stimulation for either 10 or 60 minutes, and two groups receiving either high- or low-frequency responsive stimulation for ten minutes. All animals received a single dose of pentylentetrazole throughout five days. EEG recordings were obtained from the cortex and were evaluated to assess ictal behavior more than 45 to 90 minutes. RESULTS: Ten minutes of preemptive high-frequency stimulation in the TRN induced a significant decrease in seizure severity compared to 60 minutes of preemptive stimulation and ten minutes of responsive stimulation. Additionally, ten minutes of preemptive high-frequency stimulation protected against death as aftereffect of status epilepticus. The spike-wave complex frequency was not modified. CONCLUSIONS: These data could contribute to the characterization of the TRN in mediating the initiation and spreading of seizure activity and provide preclinical support for optimal parameters to use to obtain beneficial effects against convulsive activity.
Asunto(s)
Estimulación Encefálica Profunda/métodos , Pentilenotetrazol/toxicidad , Convulsiones/inducido químicamente , Convulsiones/terapia , Núcleos Talámicos , Animales , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Convulsiones/fisiopatología , Núcleos Talámicos/fisiopatología , Resultado del TratamientoRESUMEN
The external globus pallidus (GP) firing rate synchronizes the basal ganglia-thalamus-cortex network controlling GABAergic output to different nuclei. In this context, two findings are significant: the activity and GABAergic transmission of the GP modulated by GABA B receptors and the presence of the GP-thalamic reticular nucleus (RTn) pathway, the functionality of which is unknown. The functional participation of GABA B receptors through this network in cortical dynamics is feasible because the RTn controls transmission between the thalamus and cortex. To analyze this hypothesis, we used single-unit recordings of RTn neurons and electroencephalograms of the motor cortex (MCx) before and after GP injection of the GABA B agonist baclofen and the antagonist saclofen in anesthetized rats. We found that GABA B agonists increase the spiking rate of the RTn and that this response decreases the spectral density of beta frequency bands in the MCx. Additionally, injections of GABA B antagonists decreased the firing activity of the RTn and reversed the effects in the power spectra of beta frequency bands in the MCx. Our results proved that the GP modulates cortical oscillation dynamics through the GP-RTn network via tonic modulation of RTn activity.
Asunto(s)
Globo Pálido , Receptores de GABA-B , Ratas , Animales , Globo Pálido/metabolismo , Receptores de GABA-B/metabolismo , Ganglios Basales , Agonistas del GABA/metabolismo , Agonistas del GABA/farmacología , Neuronas/metabolismoRESUMEN
A neonatal ventral hippocampal lesion (NVHL) in rats has been commonly used as a neurodevelopmental model to mimic schizophrenia-like behaviors. Recently, we reported that NVHL resulted in dendritic retraction and spine loss in pyramidal neurons of the prefrontal cortex (PFC). In addition, the hippocampus and PFC are important structures in the regulation of the electroencephalographic (EEG) activity. Patients with PFC lesions show deficits in the EEG activity. This study aimed to determine whether the EEG activity was altered in NVHL rats. In addition, we also analyzed the locomotor activity induced by a novel environment and exploratory behavior using the hole-board test. Consistent with the behavioral findings, the EEG analysis of the cortical regions showed that the NVHL rats displayed a lower power in cortical bands. At 1-8 Hz, 9-14 Hz, and 15-30 Hz bands, our findings showed a decrease in the absolute power of the parietal and occipital cortices recordings. In addition, the NVHL rats also showed a reduction in the exploratory behavior tested using the hole-board test. In conclusion, this study demonstrated that the EEG activity was reduced in adult NVHL rats and suggests that this may play a role in the behavioral changes observed in this neurodevelopmental model of schizophrenia.
Asunto(s)
Hipocampo/fisiopatología , Esquizofrenia/fisiopatología , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Electroencefalografía , Conducta Exploratoria , Hipocampo/crecimiento & desarrollo , Hipocampo/patología , Actividad Motora , Ratas , Ratas Sprague-Dawley , Esquizofrenia/patologíaRESUMEN
The external globus pallidus (GP) is a GABAergic node involved in motor control regulation and coordinates firing and synchronization in the basal ganglia-thalamic-cortical network through inputs and electrical activity. In Parkinson's disease, high GABA levels alter electrical activity in the GP and contribute to motor symptoms. Under normal conditions, GABA levels are regulated by GABA transporters (GATs). GAT type 1 (GAT-1) is highly expressed in the GP, and pharmacological blockade of GAT-1 increases the duration of currents mediated by GABA A receptors and induces tonic inhibition. The functional contribution of the pathway between the GP and the reticular thalamic nucleus (RTn) is unknown. This pathway is important since the RTn controls the flow of information between the thalamus and cortex, suggesting that it contributes to cortical dynamics. In this work, we investigated the effect of increased GABA levels on electrical activity in the RTn by obtaining single-unit extracellular recordings from anesthetized rats and on the motor cortex (MCx) by corticography. Our results show that high GABA levels increase the spontaneous activity rate of RTn neurons and desynchronize oscillations in the beta frequency band in the MCx. Our findings provide evidence that the GP exerts tonic control over RTn activity through the GP-reticular pathway and functionally contributes to cortical oscillation dynamics.
Asunto(s)
Globo Pálido , Núcleos Talámicos , Animales , Ganglios Basales , Globo Pálido/fisiología , Neuronas/metabolismo , Ratas , Núcleos Talámicos/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: For many centuries, Mexican Valerian (Valeriana edulis ssp. procera) has been an important plant in folk medicine. It has been considered useful to control epilepsy; however, electroencephalographic evidence of its anticonvulsant activity is missing in literature. AIM OF THE STUDY: In the present study, in situ electroencephalographic (EEG) analysis was performed along with administration of a crude ethanol extract of V. edulis and its valepotriate fraction on the pentylenetetrazole (PTZ)-induced convulsive behavior in rats. MATERIALS AND METHODS: Experiments were performed using male Wistar rats with nail-shaped electrodes implanted in the frontal and parietal cortices for EEG recording. All animals received a single dose of PTZ (35 mg/kg, i.p.) to test the anticonvulsant activity of V. edulis crude extract and valepotriate fraction (100 mg/kg, i.p.) 15 and/or 30 min after administration. EEG recordings were obtained from the cortices and were evaluated to assess ictal behavior over 60-75 min. Chromatographic analysis of the valepotriate fraction and in silico predictions of pharmacodynamic properties were also explored. The latency, frequency and duration of seizures evaluated using EEG recordings from the frontal and parietal cortices of rats showed significant changes demonstrating the inhibition of paroxystic activity. RESULTS: The spectral analysis confirmed the reduction of excitatory activity induced by V. edulis extract, which was improved in the presence of the valepotriate fraction as compared to that induced by ethosuximide (a reference anticonvulsant drug). The presence of valepotriates such as: isodihydrovaltrate (18.99%), homovaltrate (13.51%), 10-acetoxy-valtrathydrin (4%) and valtrate (1.34%) was identified by chromatographic analysis. Whereas, not only GABAA receptor participation but also the cannabinoid CB2 receptor was found to be likely involved in the anticonvulsant mechanism of action after in silico prediction. CONCLUSIONS: Our data support the anticonvulsant properties attributed to this plant in folk medicine, due to the presence of valepotriates.
Asunto(s)
Anticonvulsivantes/farmacología , Iridoides/farmacología , Extractos Vegetales/farmacología , Convulsiones/tratamiento farmacológico , Valeriana/química , Animales , Anticonvulsivantes/aislamiento & purificación , Simulación por Computador , Modelos Animales de Enfermedad , Electroencefalografía , Etosuximida/farmacología , Iridoides/aislamiento & purificación , Masculino , Pentilenotetrazol , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas , Ratas , Ratas Wistar , Convulsiones/fisiopatología , Factores de TiempoRESUMEN
BACKGROUND: Variation in the temporal patterns of electrical pulses in stimulation trains has opened a new field of opportunity for the treatment of neurological disorders, such as pharmacoresistant temporal lobe epilepsy. Whether this novel type of stimulation affects epileptogenesis remains to be investigated. OBJECTIVE: The purpose of this study was to analyze the effects of temporally irregular deep brain stimulation on kindling-induced epileptogenesis in rats. METHODS: Temporally irregular deep brain stimulation was delivered at different times with respect to the kindling stimulation. Behavioral and electrographic changes on kindling acquisition were compared with a control group and a temporally regular deep brain stimulation-treated group. The propagation of epileptiform activity was analyzed with wavelet cross-correlation analysis, and interictal epileptiform discharge ratios were obtained. RESULTS: Temporally irregular deep brain stimulation delivered in the epileptogenic focus during the interictal period shortened the daily afterdischarge duration, slowed the progression of seizure stages, diminished the generalized seizure duration and interfered with the propagation of epileptiform activity from the seizure onset zone to the ipsi- and contralateral motor cortex. We also found a negative correlation between seizure severity and interictal epileptiform discharges in rats stimulated with temporally irregular deep brain stimulation. CONCLUSION: These results provide evidence that temporally irregular deep brain stimulation interferes with the establishment of epilepsy by delaying epileptogenesis by almost twice as long in kindling animals. Thus, temporally irregular deep brain stimulation could be a preventive approach against epilepsy.
Asunto(s)
Estimulación Encefálica Profunda/métodos , Modelos Animales de Enfermedad , Epilepsia/terapia , Excitación Neurológica/fisiología , Animales , Estimulación Eléctrica/métodos , Epilepsia/fisiopatología , Masculino , Ratas , Ratas Wistar , Convulsiones/fisiopatología , Convulsiones/terapia , Factores de TiempoRESUMEN
Transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE), tripolar TFS, is proposed to treat pharmacoresistant epilepsy. We determined the effect of tripolar TFS on electrical amygdaloid kindling (AK) in freely moving cats. Fifteen cats were bilaterally implanted with electrodes in the amygdala (AM) and prefrontal cortex and assigned to three groups: the control group, which only received AK; the tripolar TFS before AK group, in which TCREs were placed over the vertex and tripolar TFS (300â¯Hz, 200⯵s biphasic equal charge, square pulses) was delivered for 40â¯min just prior to AK; and the tripolar TFS after AK group, in which the TCREs were placed over the temporal bone ipsilateral to the kindled AM, while tripolar TFS was administered for 2â¯min just after AK onset for 40â¯days, and, thereafter, only AK was applied. AK was applied daily until all animals reached kindling stage VI. A three concentric spheres finite element cat head model was developed to analyze the electric fields caused by tripolar TFS. Tripolar TFS after AK inhibited kindling development. Animals with tripolar TFS after AK remained at the focal seizure stages for 20â¯days after tripolar TFS cessation and required 80.0⯱â¯15.42 AK stimulations to reach stage VI, significantly higher than TFS before AK, and control (Pâ¯<â¯.001). Tripolar TFS before AK did not show signs of protection against epileptogenesis. The finite modeling of tripolar TFS showed that the electric field is >0.3â¯mV/mm at depths less than approximately 12.6â¯mm in the cat brain, which should be strong enough to alter brain activity. In conclusion, tripolar TFS applied via a TCRE over the ipsilateral temporal area significantly delayed AK. This taken together with other reports of tripolar TFS aborting seizures in acute seizure models suggests that tripolar TFS is a promising new modality that should be considered for further testing.
Asunto(s)
Encéfalo , Electrodos , Estimulación Transcraneal de Corriente Directa/instrumentación , Animales , Gatos , Excitación Neurológica , Masculino , Movimiento , Convulsiones/prevención & controlRESUMEN
Orexins (OXs) system has been suggested to play a key role in regulate processes related to arousal, including anxious behaviors. However, until now, the contribution of OXs in anxiogenic-like effects has not been completely clear, particularly in rats, whose results are not yet conclusive in behavioral-tests such as elevated-plus-maze test (EPM-test). The goal of this study was to explore the anxiogenic-like effect induced by orexin-A (OX-A) using two different paradigms; the EPM-test and simultaneously a quantitative index in vivo, the cortical-electroencephalographic-(EEG)-record. This index proposes that a low-frequency domain EEG, particularly 0.5-5-Hz (delta and low portion of theta-waves), is a key indicator to evaluate anxiety levels. We also explored whether the anxious effect of OX-A could be altered by an antagonist of dopamine-D2-receptor (D2R) sulpiride (SUL). Our results showed that intracerebroventricular (i.c.v.) injection of a low dose of OX-A (140 pmol) did not increase anxiety levels in rats. On the other hand, cortical-EEG-activity showed only a decrease in delta-spectral-power but no changes in theta-potency. These data suggest that the reduction in delta-power induced by OX-A only keeps the animals awake and alert without changes in anxiety levels.
Asunto(s)
Electroencefalografía/efectos de los fármacos , Orexinas/farmacología , Animales , Ansiedad/inducido químicamente , Trastornos de Ansiedad/metabolismo , Nivel de Alerta/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Antagonistas de los Receptores de Dopamina D2/farmacología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Receptores de Orexina/metabolismo , Orexinas/metabolismo , Ratas , Ratas Wistar , Receptores de Dopamina D2/efectos de los fármacos , Sulpirida/farmacologíaRESUMEN
BACKGORUND: Moringa oleifera Lamarck is a species that has long been used in high demand in folk medicine, including for the treatment of epilepsy. Nevertheless, scientific studies demonstrating its anticonvulsant properties and the nature of the bioactive constituents are lacking. HYPOTHESIS/AIM: The aim of this study was to evaluate the anticonvulsant activities of the Moringa oleifera leaves in non-polar vs. polar extracts using behavioral and electroencephalographic (EEG) analyses in rodents. METHODS: First, PTZ (80â¯mg/kg, i.p.)-induced tonic-clonic seizures were assayed via a dose-response (100, 200 and 300â¯mg/kg, i.p.) evaluation in mice. Then, a dosage of the extracts (100 or 300â¯mg/kg) and one metabolite (30â¯mg/kg, i.p.) was selected to evaluate its effect on PTZ (35â¯mg/kg, i.p.)-induced EEG paroxystic activities in rats compared to the effects of ethosuximide (reference anticonvulsant drug, 100â¯mg/kg, i.p.). Latent onset of the first paroxystic spike, first seizure and frequency as well as seizure severity, were determined using Racine's scale. RESULTS: Moringa oleifera ethanol and hexane extracts produced a delay in the seizure latency in mice and rats; this effect was improved in the presence of the hexane extract containing the active metabolite hexadecanoic acid. The anticonvulsant effects were corroborated in the spectral analysis by the potency of the EEG due to a reduction in the spike frequency and amplitude, as well as in the duration and severity of the seizures. The effects of the hexane extract resembled those observed in the reference antiepileptic drug ethosuximide. CONCLUSION: Moringa oleifera leaves possess anticonvulsant activities due to the complementary of the non-polar and polar constituents. However, the non-polar constituents appear to exert an important influence via the partial participation of fatty acids, providing evidence of the effects of this plant in epilepsy therapy.
Asunto(s)
Anticonvulsivantes/farmacología , Moringa oleifera/química , Extractos Vegetales/farmacología , Convulsiones/tratamiento farmacológico , Animales , Evaluación Preclínica de Medicamentos/métodos , Electroencefalografía , Etanol/química , Hexanos/química , Masculino , Ratones , Pentilenotetrazol/toxicidad , Extractos Vegetales/química , Hojas de la Planta/química , Ratas Wistar , Convulsiones/inducido químicamenteRESUMEN
Propylparaben (PPB) induces cardioprotection after ischemia-reperfusion injury by inhibiting voltage-dependent Na+ channels. The present study focuses on investigating whether the i.p. application of 178mg/kg PPB after pilocarpine-induced status epilepticus (SE) reduces the acute and long-term consequences of seizure activity. Initially, we investigated the effects of a single administration of PPB after SE. Our results revealed that compared to rats receiving diazepam (DZP) plus vehicle after 2h of SE, animals receiving a single dose of PPB 1h after DZP injection presented 126% (p<0.001) lower extracellular levels of glutamate in the hippocampus. This effect was associated with an increased potency of low-frequency oscillations (0.1-13Hz bands, p<0.001), a reduced potency of 30-250Hz bands (p<0.001) and less neuronal damage in the hippocampus. The second experiment examined whether the subchronic administration of PPB during the post-SE period is able to prevent the long-term consequences of seizure activity. In comparison to animals that were treated subchronically with vehicle after SE, rats administered with PPB for 5 days presented lower hippocampal excitability and interictal glutamate release, astrogliosis, and neuroprotection in the dentate gyrus. Our data indicate that PPB, when applied after SE, can be used as a therapeutic strategy to reduce the consequences of seizure activity.
Asunto(s)
Potenciales de Acción/efectos de los fármacos , Anticonvulsivantes/uso terapéutico , Ácido Glutámico/metabolismo , Hipocampo/efectos de los fármacos , Parabenos/uso terapéutico , Estado Epiléptico/tratamiento farmacológico , Animales , Recuento de Células , Diazepam/uso terapéutico , Modelos Animales de Enfermedad , Estimulación Eléctrica , Fluoresceínas/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Agonistas Muscarínicos/toxicidad , Fosfopiruvato Hidratasa/metabolismo , Pilocarpina/toxicidad , Ratas , Ratas Wistar , Estado Epiléptico/inducido químicamente , Estado Epiléptico/patologíaRESUMEN
Dysfunction of thalamo-cortical networks involving particularly the thalamic reticular nucleus (TRN) is implicated in schizophrenia. In the neonatal ventral hippocampal lesion (NVHL), a heuristic animal model of schizophrenia, brain oscillation changes similar to those of schizophrenic patients have been reported. The aim of this study was to analyze the effects of short-term deep brain stimulation (DBS) in the thalamic reticular nucleus on electroencephalographic (EEG) activity in the NVHL. Male and female Sprague-Dawley rats were used and the model was prepared by excitotoxicity damage of the ventral hippocampus on postnatal day 7 (PD-7). Chronic bilateral stainless steel electrodes were implanted in the TRN, thalamic dorsomedial nucleus and prelimbic area at PD-90. Rats were classified as follows: sham and NVHL groups, both groups received bilateral DBS in the TRN for one hour (100Hz, 100µs pulses, 200µA). All animals showed a sudden behavioral arrest accompanied by widespread symmetric bilateral spike-wave discharges, this activity was affected by DBS-TRN. Additionally, the power spectra of 0.5-100Hz and the coherence of 0.5-4.5 and 35-55Hz frequencies were modified by DBS-TRN. Our results suggest that DBS in the TRN may modify functional connectivity between different parts of the thalamo-cortical network. Additionally, our findings may suggest a beneficial effect of DBS-TRN on some preclinical aberrant oscillatory activities in a neurodevelopmental model of schizophrenia.
Asunto(s)
Ondas Encefálicas/fisiología , Esquizofrenia/fisiopatología , Esquizofrenia/terapia , Núcleos Talámicos/fisiopatología , Animales , Estimulación Encefálica Profunda , Modelos Animales de Enfermedad , Electrocorticografía , Femenino , Hipocampo/crecimiento & desarrollo , Hipocampo/fisiopatología , Ácido Iboténico , Masculino , Actividad Motora/fisiología , Distribución Aleatoria , Ratas Sprague-Dawley , Núcleos Talámicos/crecimiento & desarrolloRESUMEN
Deep brain stimulation (DBS) is used as an alternative therapeutic procedure for pharmacoresistant psychiatric disorders. Recently the thalamic reticular nucleus (TRN) gained attention due to the description of a novel pathway from the amygdala to this nucleus suggesting that may be differentially disrupted in mood disorders. The limbic system is implicated in the regulation of these disorders that are accompanied by neuroplastic changes. The hippocampus is highly plastic and shows the generation of new neurons, process affected by stress but positively regulated by antidepressant drugs. We explored the impact of applying acute DBS to the TRN (DBS-TRN) in male Wistar rats exposed to acute stress caused by the forced-swim Porsolt's test (FST) and on initial events of hippocampal neurogenesis. After the first session of forced-swim, rats were randomly subdivided in a DBS-TRN and a Sham group. Stimulated rats received 10min of DBS, thus the depressant-like behavior reflected as immobility was evaluated in the second session of forced-swim. Locomotricity was evaluated in the open field test. Cell proliferation and doublecortin-associated cells were quantified in the hippocampus of other cohorts of rats. No effects of electrode implantation were found in locomotricity. Acute DBS-TRN reduced immobility in comparison to the Sham group (p<0.001). DBS-TRN increased cell proliferation (Ki67 or BrdU-positive cells; p=0.02, p=0.02) and the number of doublecortin-cells compared to the Sham group (p<0.02). Similar effects were found in rats previously exposed to the first session of forced-swim. Our data could suggest that TRN brain region may be a promising target for DBS to treat intractable depression.
Asunto(s)
Antidepresivos/farmacología , Estimulación Encefálica Profunda , Hipocampo/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Animales , Estimulación Encefálica Profunda/métodos , Proteína Doblecortina , Sistema Límbico/efectos de los fármacos , Masculino , Neuronas/efectos de los fármacos , Ratas Wistar , Estrés Fisiológico/fisiologíaRESUMEN
Vagus nerve stimulation (VNS) is an adjunctive therapy for treating pharmacoresistant epilepsy. The present study analyze the effect of VNS on the epileptic activity of amygdala kindling (AK) in different seizure severity stages in freely moving cats. Fourteen adult male cats were used and were stereotaxically implanted in both amygdalae, in thalamic reticular nuclei and in prefrontal cortices. AK was developed by the application of 60Hz pulse trains that were one second in duration. VNS was applied the following day after the first stages were reached. This stimulation consisted of 10 pulse trains in the one-hour period (1min on/5min off) prior to AK. AK stimulation continued until all animals reached stage VI. The behavioral changes induced by VNS were transient and bearable. The animals showed relaxation of the nictitating membrane, ipsilateral anisocoria, swallowing and licking. Intermittent VNS application in stage I induced a delay in AK progression. The effect of VNS on the amygdala afterdischarge duration (AD) did not change progressively. VNS in stages II, III, and IV does not have an inhibitory effect on AK, and the AD further exhibited a progressive development. At the end of the generalized seizures, the animals presented with synchronized bilateral discharges of the spike-wave type (3Hz) and a behavioral "staring spell". Our results show that VNS applied during the different stages of seizure severity exerts an anti-epileptogenic effect in stage I but no anti-epileptogenic effect in stages II, III, and IV. These results suggest that VNS applied at stage I of kindling induces a delay of generalized convulsive activity.
Asunto(s)
Excitación Neurológica/fisiología , Movimiento/fisiología , Convulsiones/prevención & control , Convulsiones/fisiopatología , Índice de Severidad de la Enfermedad , Estimulación del Nervio Vago/métodos , Animales , Gatos , MasculinoRESUMEN
The vagus nerve participates in the control and regulation of important autonomous functions, emotional tasks, and neural activity. Electrical vagus nerve stimulation (VNS) is an approved procedure for the treatment of refractory epilepsy in humans. VNS has also been shown to improve mood complaints and cognitive function in both human patients and animals. Thus, the purpose of this study was to analyse and describe the effects of VNS on the development and establishment of sensory habituation and electrographic activity of the visual pathway in freely moving cats. Six cats had implants placed in the optic chiasm (OC), lateral geniculate body (LGB), mesencephalic reticular formation (MRF), primary visual cortex (VC) of the left hemisphere, and left vagus nerve. Immediately after surgery, all cats presented anisocoria and relaxation of the left nictitant membrane. Also showed vegetative-type responses such as myosis, licking, and swallowing during VNS. Animals were then subjected to repeated luminous stimuli at intervals of 1 and 3s to cause habituation. The effect of VNS on the frequency and latency of the habituation episodes and the electrographic changes in the registered brain structures were analysed. Latency analysis showed that VNS delayed the first habituation episode. VNS had transitory effects on the neural activity of the primary visual pathway structures, which caused a small but measurable delay in the establishment of habituation. In conclusion, VNS interferes with the development and establishment of visual habituation, an elementary form of non-associative learning, in freely moving cats.