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1.
Virus Res ; 155(1): 35-41, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20727376

RESUMEN

Oropouche virus (OROV), of the family Bunyaviridae, is the second most frequent arbovirus causing febrile disease in Brazil. In spite of this, little is known about pathogenesis of OROV infection. This report describes an experimental model of OROV in golden hamster (Mesocricetus auratus). Following subcutaneous inoculation of OROV, over 50% of the animals developed disease characterized by lethargy, ruffled fur, shivering, paralysis, and approximately one third died. Animals were sacrificed on days 1, 3, 5, 8 and 11 post-inoculation to collect tissue samples from brain, heart, liver, lung, spleen, muscle and blood for virus titration, histology and OROV immunohistochemistry. OROV was detected in high titers in blood, liver and brain, but not in the other organs. Histopathology revealed meningoencephalitis and hepatitis, with abundant OROV antigen detected in liver and brain. Diffuse galectin-3 immunostaining in brain and liver supports microglial and Kupfer cells activation. This is the first description of an experimental model for OROV infection and should be helpful to study pathogenesis and possibly to test antiviral interventions such as drugs and vaccine candidates.


Asunto(s)
Infecciones por Bunyaviridae/veterinaria , Modelos Animales de Enfermedad , Orthobunyavirus/patogenicidad , Enfermedades de los Roedores/patología , Enfermedades de los Roedores/virología , Estructuras Animales/patología , Estructuras Animales/virología , Animales , Brasil , Infecciones por Bunyaviridae/patología , Infecciones por Bunyaviridae/virología , Cricetinae , Hepatitis Viral Animal/patología , Hepatitis Viral Animal/virología , Histocitoquímica , Masculino , Meningoencefalitis/patología , Meningoencefalitis/veterinaria , Meningoencefalitis/virología , Mesocricetus/virología , Microscopía
2.
Arch Toxicol ; 83(5): 439-49, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-18836702

RESUMEN

Lead exposure increases blood pressure (BP) by unknown mechanisms. Many recent studies have shown the involvement of matrix metalloproteinases (MMPs) in hypertension, particularly MMP-2. In this work, we have examined whether MMP-2 levels increase with lead-induced increase in BP. We have also investigated whether doxycycline (an MMP inhibitor) affects these alterations. To this end, rats were exposed to lead (90 ppm) and treated with doxycycline or vehicle for 8 weeks. Similar aortic and whole blood lead levels were found in lead-exposed rats treated with either doxycycline or vehicle. Lead-induced increases in BP and aortic MMP-2 levels (activity, protein, and mRNA) were blunted by doxycycline. Doxycycline also prevented lead-induced increases in the MMP-2/TIMP-2 mRNA ratio. No significant changes in vascular reactivity or morphometric parameters were found. In conclusion, lead exposure increases BP and vascular MMP-2, which is blunted by doxycycline. This observation suggests that MMP-2 may play a role in lead-induced increases in BP.


Asunto(s)
Hipertensión/fisiopatología , Plomo/farmacología , Metaloproteinasa 2 de la Matriz/metabolismo , Animales , Aorta Torácica/enzimología , Aorta Torácica/metabolismo , Presión Sanguínea/efectos de los fármacos , Determinación de la Presión Sanguínea/métodos , Relación Dosis-Respuesta a Droga , Doxiciclina/farmacología , Inhibidores Enzimáticos/farmacología , Expresión Génica , Plomo/sangre , Masculino , Metaloproteinasa 2 de la Matriz/genética , Inhibidores de la Metaloproteinasa de la Matriz , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Wistar , Estándares de Referencia , Factores de Tiempo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo
3.
Epilepsy Res ; 79(2-3): 166-72, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18378119

RESUMEN

Zinc is present in high concentration in many structures of the limbic circuitry, however the role of zinc as a neuromodulator in such synapses is still uncertain. In this work, we verified the effects of zinc chelation in an animal model of epileptogenesis induced by amygdala rapid kindling. The basolateral amygdala was electrically stimulated ten times per day for 2 days. A single stimulus was applied on the third day. Stimulated animals received injections of PBS or the zinc chelator diethildythiocarbamate acid (DEDTC) before each stimulus series. Animals were monitored with video-EEG and were perfused 3h after the last stimulus for subsequent neo-Timm and Fluoro-Jade B analysis. Zinc chelation decreased the duration of both behavioral seizures and electrical after-discharges, and also decreased the EEG spikes frequency, without changing the progression of behavioral seizure severity. These results indicate that the zinc ion may have a facilitatory role during kindling progression.


Asunto(s)
Amígdala del Cerebelo/fisiopatología , Quelantes/farmacología , Excitación Neurológica/fisiología , Convulsiones/fisiopatología , Zinc/fisiología , Animales , Ditiocarba/farmacología , Electroencefalografía/efectos de los fármacos , Electrofisiología , Fluoresceínas , Inmunohistoquímica , Excitación Neurológica/efectos de los fármacos , Modelos Lineales , Masculino , Compuestos Orgánicos , Ratas , Ratas Wistar , Convulsiones/clasificación
4.
Brain Res ; 1165: 126-34, 2007 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-17662262

RESUMEN

Here, we describe dentate gyrus newly born granule cells morphology in rats' temporal lobe epilepsy pilocarpine model. Digital reconstruction of doublecortin-positive neurons revealed that apical dendrites had the same total length and number of nodes in epileptic and control animals. Nonetheless, concentric spheres analyses revealed that apical dendrites spatial distribution was radically altered in epileptic animals. The apical dendrites had more bifurcations inside the granular cell layer and more terminations in the inner molecular layer of epileptic dentate gyrus. Branch order analyses showed that second- and third-order dendrites were shorter in epileptic animals. Apical dendrites were concentrated in regions like the inner molecular layer where granular neuron axons, named mossy fibers, sprout in epileptic animals. The combination of altered dendritic morphology and number enhancement of the new granular neurons suggests a deleterious role of hippocampal neurogenesis in epileptogenesis. Being more numerous and with dendrites concentrated in regions where aberrant axon terminals sprout, the new granular neurons could contribute to the slow epileptogenesis at hippocampal circuits commonly observed in temporal lobe epilepsy.


Asunto(s)
Dendritas/patología , Epilepsia del Lóbulo Temporal/patología , Hipocampo/patología , Proteínas Asociadas a Microtúbulos/metabolismo , Neuronas/patología , Neuronas/fisiología , Neuropéptidos/metabolismo , Animales , Dendritas/ultraestructura , Modelos Animales de Enfermedad , Proteínas de Dominio Doblecortina , Proteína Doblecortina , Epilepsia del Lóbulo Temporal/inducido químicamente , Hipocampo/efectos de los fármacos , Masculino , Pilocarpina , Ratas , Ratas Wistar , Tinción con Nitrato de Plata
6.
Epilepsia ; 46 Suppl 5: 134-41, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15987268

RESUMEN

Central nervous system synapses have an intrinsic plastic capacity to adapt to new conditions with rapid changes in their structure. Such activity-dependent refinement occurs during development and learning, and shares features with diseases such as epilepsy. Quantitative ultrastructural studies based on serial sectioning and reconstructions have shown various structural changes associated with synaptic strength involving both dendritic spines and postsynaptic densities (PSDs) during long-term potentiation (LTP). In this review, we focus on experimental studies that have analyzed at the ultrastructural level the consequences of LTP in rodents, and plastic changes in the hippocampus of experimental models of epilepsy and human tissue obtained during surgeries for intractable temporal lobe epilepsy (TLE). Modifications in spine morphology, increases in the proportion of synapses with perforated PSDs, and formation of multiple spine boutons arising from the same dendrite are the possible sequence of events that accompany hippocampal LTP. Structural remodeling of mossy fiber synapses and formation of aberrant synaptic contacts in the dentate gyrus are common features in experimental models of epilepsy and in human TLE. Combined electrophysiological and ultrastructural studies in kindled rats and chronic epileptic animals have indicated the occurrence of seizure- and neuron loss-induced changes in the hippocampal network. In these experiments, the synaptic contacts on granule cells are similar to those described for LTP. Such changes could be associated with enhancement of synaptic efficiency and may be important in epileptogenesis.


Asunto(s)
Epilepsia del Lóbulo Temporal/patología , Hipocampo/ultraestructura , Plasticidad Neuronal/fisiología , Sinapsis/ultraestructura , Animales , Espinas Dendríticas/patología , Espinas Dendríticas/ultraestructura , Modelos Animales de Enfermedad , Epilepsia del Lóbulo Temporal/fisiopatología , Hipocampo/fisiopatología , Humanos , Excitación Neurológica/patología , Excitación Neurológica/fisiología , Potenciación a Largo Plazo/fisiología , Fibras Musgosas del Hipocampo/fisiopatología , Fibras Musgosas del Hipocampo/ultraestructura , Técnicas de Placa-Clamp , Ratas , Sinapsis/fisiología
7.
Epilepsy Behav ; 6(3): 328-36, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15820339

RESUMEN

Wet dog shakes (WDS) and head shakes (HS) are associated with experimentally induced convulsive seizures. We sought to determine whether these behaviors are correlated or not with major (status epilepticus (SE) or fully kindled animals) or minor (non-SE or partially kindled animals) seizure severity. WDS are directly correlated with SE induced by intracerebral star fruit extract (Averrhoa carambola) injection and with kindled animals in the amygdala fast kindling model. On the other hand, WDS are inversely correlated with SE induced by intracerebral bicuculline and pilocarpine injections. Systemic pilocarpine in animals pretreated with methyl-scopolamine barely induced WDS or HS. The role of shaking behaviors may vary from ictal to anticonvulsant depending on the experimental seizure model, circuitries involved, and stimulus intensity. The physical presence of acrylic helmets may per se inhibit the HS response. Also, methyl-scopolamine, a drug incapable of crossing the blood-brain barrier, can induce HS in animals without acrylic helmets.


Asunto(s)
Conducta Animal/fisiología , Modelos Animales de Enfermedad , Excitación Neurológica/fisiología , Convulsiones/fisiopatología , Amígdala del Cerebelo/efectos de la radiación , Análisis de Varianza , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/efectos de la radiación , Bicuculina/toxicidad , Estimulación Eléctrica/métodos , Electroencefalografía/métodos , Lateralidad Funcional/fisiología , Antagonistas del GABA/toxicidad , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Excitación Neurológica/efectos de los fármacos , Excitación Neurológica/efectos de la radiación , Masculino , Microscopía de Interferencia/métodos , Agonistas Muscarínicos/toxicidad , Antagonistas Muscarínicos/toxicidad , Pilocarpina/toxicidad , Ratas , Ratas Wistar , Escopolamina/toxicidad , Convulsiones/inducido químicamente , Técnicas Estereotáxicas , Factores de Tiempo
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