RESUMEN
The GABAergic system is critically involved in the modulation of anxiety levels, and dysfunction of GABAergic neurotransmission appears to be involved in the development of generalized anxiety disorder. Precursor cells from the medial ganglionic eminence (MGE) have the ability to migrate and differentiate into inhibitory GABAergic interneurons after being transplanted into the mouse brain. Thus, transplantation of interneuronal precursor cells derived from the MGE into a postnatal brain could modify the neuronal circuitry, increasing GABAergic tone and decreasing anxiety-like behavior in animals. Our aim was to verify the in vivo effects of transplanted MGE cells by evaluating anxiety-like behavior in mice. MGE cells from 14-day green fluorescent protein (GFP) embryos were transplanted into newborn mice. At 15, 30, and 60 days posttransplant, the animals were tested for anxiety behavior with the elevated plus maze (EPM) test. Our results show that transplanted cells from MGE were able to migrate to different regions of the brain parenchyma and to differentiate into inhibitory interneurons. The neuronal precursor cell transplanted animals had decreased levels of anxiety, indicating a specific function of these cells in vivo. We suggested that transplantation of MGE-derived neuronal precursors into neonate brain could strengthen the inhibitory function of the GABAergic neuronal circuitry related to anxiety-like behavior in mice.
Asunto(s)
Trastornos de Ansiedad/fisiopatología , Interneuronas/trasplante , Animales , Animales Recién Nacidos , Trastornos de Ansiedad/metabolismo , Conducta Animal/fisiología , Neuronas GABAérgicas/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Interneuronas/citología , Eminencia Media/citología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Trasplante HomólogoRESUMEN
Sickle cell disease is a rare condition in italian patients and even rarer are its complications, in particular Salmonella osteomyelitis. We describe a case of a Ghanaian child with sickle cell disease who developed osteomyelitis due to Salmonella panama, treated successfully with surgical debridement, followed by a prolonged period of specific antibiotic therapy.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Fémur/microbiología , Fémur/cirugía , Osteomielitis/complicaciones , Osteomielitis/microbiología , Infecciones por Salmonella/complicaciones , Antibacterianos , Terapia Combinada , Quimioterapia Combinada/uso terapéutico , Femenino , Humanos , Lactante , Osteomielitis/terapia , Infecciones por Salmonella/tratamiento farmacológico , Procedimientos Quirúrgicos OperativosRESUMEN
Dentate granule cells are generally considered to be relatively resistant to excitotoxicity and have been associated with robust synaptogenesis after neuronal damage. Synaptic reorganization of dentate granule cell axons, the mossy fibers, has been suggested to be relevant for hyperexcitability in human temporal lobe epilepsy and animal models. A recent hypothesis suggested that mossy-fiber sprouting is dependent on newly formed dentate granule cells. However, we recently demonstrated that cycloheximide (CHX) can block the mossy-fiber sprouting that would otherwise be induced by different epileptogenic agents and does not interfere with epileptogenesis in those models. Here, we investigated cell damage and neurogenesis in the dentate gyrus of pilocarpine- or kainate-treated animals with or without coadministration of CHX. Dentate granule cells were highly vulnerable to pilocarpine induced-status epilepticus (SE), but were hardly damaged by kainate-induced SE. CHX pretreatment markedly reduced the number of injured neurons after pilocarpine-induced SE. Induction of SE dramatically increased the mitotic rate of KA- and KA + CHX-treated animals. Induction of SE in animals injected with pilocarpine alone led to 2-7-fold increases in the mitotic rate of dentate granule cells as compared to 5- and 30-fold increases for pilocarpine + CHX animals. We suggest that such increased mitotic rates might be associated with a protection of a vulnerable precursor cell population that would otherwise degenerate after pilocarpine-induced SE. We further suggest that mossy-fiber sprouting and neurogenesis of granule cells are not necessarily linked to one another.
Asunto(s)
Fibras Musgosas del Hipocampo/patología , Estado Epiléptico/patología , Animales , Antimetabolitos/análisis , Bromodesoxiuridina/análisis , Cicloheximida/farmacología , Agonistas de Aminoácidos Excitadores , Ácido Kaínico , Masculino , Mitosis/efectos de los fármacos , Fibras Musgosas del Hipocampo/química , Agonistas Muscarínicos , Pilocarpina , Inhibidores de la Síntesis de la Proteína/farmacología , Ratas , Ratas Wistar , Coloración y Etiquetado , Estado Epiléptico/inducido químicamenteRESUMEN
In a recent report we have shown that a protein synthesis inhibitor, cycloheximide (CHX), is able to block the mossy fiber sprouting (MFS) that would otherwise be triggered by pilocarpine (Pilo)-induced status epilepticus (SE), and also gives relative protection against hippocampal neuronal death. Under this condition animals still showed spontaneous recurrent seizures (SRS) which led us to question the role played by sprouted mossy fibers in generating those seizures. In both patients and animal models of epilepsy the relative contribution of SE (when present) and/or SRS for the development of MFS is not known. In the present study we investigated the relationship between MFS, SE and SRS, and evaluated whether the CHX-induced blockade of MFS was transient or permanent in nature. We performed a chronic study which included animals subject to Pilo-induced SE in the presence of CHX and sacrificed between 8 and 10 months later, and animals that were subject to Pilo-induced SE in the presence of CHX and underwent a reinduction of SE with Pilo, 45 days after the first induction, but this time in the absence of CHX. Re-induction of SE or a long period of chronic seizures, were able to trigger supragranular MFS even in animals where the first (or only) SE event was triggered in the presence of CHX. MFS did not show any association with the frequency of SRS, and thus seemed to depend more critically on time. Our current findings allow us to suggest that MFS are neither the cause nor the consequence of SRS in the pilocarpine model.
Asunto(s)
Fibras Musgosas del Hipocampo/fisiología , Convulsiones/fisiopatología , Estado Epiléptico/fisiopatología , Animales , Cicloheximida/uso terapéutico , Masculino , Fibras Musgosas del Hipocampo/efectos de los fármacos , Agonistas Muscarínicos , Pilocarpina , Inhibidores de la Síntesis de la Proteína/uso terapéutico , Ratas , Ratas Wistar , Convulsiones/inducido químicamente , Estado Epiléptico/inducido químicamente , Estado Epiléptico/tratamiento farmacológicoRESUMEN
In a previous study, we suggested a dissociation between spontaneous recurrent epileptic seizures (SRS) and hippocampal supragranular mossy fiber sprouting (MFS) in the pilocarpine model of epilepsy (PILO). One possible explanation, would be that SRS in the PILO model do not originate in the hippocampus and thus would not depend on MFS. In the present study, we investigated whether MFS is necessary for the SRS that develop after a small intrahippocampal dose of kainic acid (KA), a model where seizures are more likely to start in the hippocampus. Intrahippocampal injections of KA were performed in rats, with and without the concomitant administration of cycloheximide (CHX) (0.5 microg of KA and 6 microg of CHX). After injection, recording electrodes were positioned in the same stereotaxic location. Here again, CHX was able to completely block (5/8 animals) MFS, visualized by neo-Timm staining, without altering the frequency and intensity of spontaneous ictal and interictal EEG events. From these data, we can conclude that, in the intra-hippocampal KA model, MFS is not necessary for the occurrence of ictal events. We suggest that CHX can be used together with classic epileptogenic agents, as a means to study temporal lobe epilepsy (TLE) without the contributing effect of MFS--as seen in TLE patients with mass lesions in the lateral temporal lobe.
Asunto(s)
Electroencefalografía , Epilepsia/fisiopatología , Hipocampo/fisiopatología , Fibras Nerviosas/fisiología , Convulsiones/fisiopatología , Animales , Cicloheximida/farmacología , Modelos Animales de Enfermedad , Electroencefalografía/efectos de los fármacos , Epilepsia/inducido químicamente , Epilepsia/patología , Potenciales Evocados/efectos de los fármacos , Proteína GAP-43/genética , Hipocampo/efectos de los fármacos , Hipocampo/patología , Ácido Kaínico/farmacología , Fibras Nerviosas/efectos de los fármacos , Fibras Nerviosas/patología , Proteínas Proto-Oncogénicas c-fos/genética , Ratas , Ratas Wistar , Convulsiones/inducido químicamente , Convulsiones/patología , Transcripción Genética/efectos de los fármacosRESUMEN
Post-injury sprouting of hippocampal mossy fibers has been suggested to be a causal mechanism underlying the development of temporal lobe epilepsy. However, this hypothesis rests entirely on indirect correlational evidence. Here we demonstrate that cycloheximide, a protein synthesis inhibitor, blocked pilocarpine- and kainate-induced mossy fiber sprouting in rats, but did not prevent the subsequent development of spontaneous seizures or affect their frequency. These results provide direct evidence against a causal role for mossy fiber sprouting in temporal lobe epileptogenesis.