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INTRODUCTION AND IMPORTANCE: Acute epidural hematoma is typically managed with craniotomy. However, there are a few reports on transcatheter arterial embolization (TAE) as an adjunctive therapy. CASE PRESENTATION: A 70-year-old female with no obvious history of trauma was transported to our hospital. Computed tomography scan revealed an epidural hematoma of approximately 80 ml with a midline shift of 5 mm. We decided to perform an emergency craniotomy. However, the operating room (OR) was already occupied by a scheduled surgery and it would take 30 min to an hour to prepare it. We opted to wait for our OR, considering that, even if the patient was transferred to another hospital, it would take time for the craniotomy to commence. CLINICAL DISCUSSION: We performed TAE for the middle meningeal artery (MMA) as a palliative measure to prevent hematoma enlargement. The MMA was selectively embolized with 20 % n-butyl-2-cyanoacrylate (NBCA), resulting in no hematoma enlargement or observed complications. The criteria for endovascular treatment of acute epidural hematoma are not yet well-established. This case demonstrates the potential role of endovascular treatment for large acute epidural hematomas in carefully selected patients. CONCLUSION: If there is a time gap before craniotomy, TAE could be considered a viable option for large acute epidural hematomas as a palliative intervention before craniotomy.
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BACKGROUND: Normal posterior inferior cerebellar artery (PICA) anatomy is highly variable, but bihemispheric PICA crossing the midline to supply the vascular territory of bilateral cerebellar hemisphere is rare. Herein, the authors reported a rare case of ruptured aneurysm that was associated with bihemispheric PICA and successfully treated endovascularly. OBSERVATIONS: A 46-year-old woman presented with sudden headache and loss of consciousness because of an intraventricular hemorrhage due to a ruptured aneurysm that was associated with the bihemispheric PICA. Angiography revealed that the aneurysm was located at the bifurcation between the bihemispheric PICA and the bilateral distal PICA. The ruptured aneurysm was successfully occluded using coil embolization, which preserved the parent artery with no procedural-related complication. LESSONS: To the best of the authors' knowledge, this was the first report of a ruptured aneurysm associated with bihemispheric PICA being successfully treated endovascularly. Aneurysm formation may be accelerated by hemodynamic stress and vascular fragility. For neurosurgeons and neurointerventionalists, it is important to understand the anatomical variation of PICA, especially bihemispheric PICA, which is a potential risk factor for a fatal stroke.
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We report a 55-year-old man with Cryptococcus neoformans meningitis who showed refractory deterioration twice with an increased cerebrospinal fluid cryptococcal antigen titer during the course of treatment. Although the initial deterioration was temporarily improved by placement of a ventriculoperitoneal shunt, he experienced deterioration again. However, he improved after administration of systemic corticosteroids. The present case suggests that systemic corticosteroid can be a choice of treatment to rescue immunocompetent patients with Cryptococcus neoformans meningitis and severe deterioration, even if cerebrospinal fluid analysis shows an increased cryptococcal antigen titer.
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Corticoesteroides/uso terapéutico , Antígenos Fúngicos/efectos de los fármacos , Meningitis Criptocócica/tratamiento farmacológico , Encéfalo/diagnóstico por imagen , Cryptococcus neoformans , Humanos , Masculino , Meningitis Criptocócica/diagnóstico por imagen , Persona de Mediana Edad , Prótesis e Implantes , Derivación VentriculoperitonealRESUMEN
Traumatic brain injury (TBI) has a complex and heterogeneous pathology. It is frequently difficult to predict the neurological deterioration of patients with TBI, and unpredictable change may occur even when TBI is mild to moderate. When computed tomography (CT) findings are considered to be inconsistent with the traumatic origin or with the neurological deterioration of patients observed on admission, magnetic resonance imaging (MRI) is employed based on the standards of our ethical committee. In this retrospective study, we compared CT and diffusion weighted imaging (DWI) of patients with mild to moderate TBI in the very acute phase. When the high-intensity lesions on DWI are larger than the high-density lesions on CT images, we defined the imaging finding as a 'CT-DWI mismatch'. Between January 2010 and December 2013, 92 patients were inspected using both CT and MRI at admission, and we detected a CT-DWI mismatch in 35 patients. CT-DWI mismatch was 92.6% (95% confidence interval 79.8-97.9) sensitive and 84.6% (95% confidence interval 79.3-86.3) specific for the prediction of enlargement of the hemorrhagic lesions on repeat CT. CT-DWI mismatch is considered to be useful as one of the predictors of the enlargement of hemorrhagic lesions in patients with mild to moderate TBI.
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Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Penetrating brain injury(PBI)is very rare in Japan. Because there is a very wide variety of pathological condition of PBI, the guideline for the treatment of PBI has not been established yet. We report the unique case of PBI caused by a steel wire piece completely embedded in the brain parenchyma. A 75-year-old man was brought to the emergency department due to ocular injury caused by a steel wire piece. Neurological examination revealed only left visual disturbance. CT scan revealed a steel wire piece located intraparenchymally between the left frontal lobe and the ventricles, but digital subtraction angiography showed no significant vascular injury in the surrounding structures. We performed an open surgery and removed the steel wire piece. Because the steel wire piece was completely embedded in the brain, we used intraoperative X-ray fluoroscopy to choose a less invasive approach for the brain. The patient suffered no additional neurological deficit and no sign of cerebral infection or seizure after surgery. He was discharged after a 4-week administration of antibiotics. In most cases of PBI caused by low velocity injury, foreign bodies are not completely embedded in the brain except for remnants after surgical removal. This is the first report of low velocity PBI caused by a foreign body completely embedded in the brain.
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Hemorragia Cerebral/cirugía , Traumatismos Penetrantes de la Cabeza/cirugía , Acero , Heridas Penetrantes/cirugía , Anciano , Angiografía de Substracción Digital/métodos , Traumatismos Penetrantes de la Cabeza/diagnóstico , Humanos , Masculino , Resultado del Tratamiento , Heridas Penetrantes/diagnósticoRESUMEN
Sinonasal neuroendocrine carcinomas (NECs) are rare tumors. We present a rare case of intracranial invasion of sinonasal small-cell NEC. A 61-year-old woman with nasal obstruction and bleeding was referred to our hospital. Computed tomography showed a polyp-like tumor occupying her left nasal cavity and extending to the paranasal sinuses and anterior cranial fossa. The tumor was removed using a transfacial approach by otolaryngologists and a bifrontal cranial approach by neurosurgeons. In histopathological analyses, we found that the tumor presented with both an epithelial and neuroendocrine nature, and was diagnosed as a small-cell NEC. Post-surgery, she received localized radiation therapy and chemotherapy, and is alive, 18 months after diagnosis. In cases where it is difficult to perform a differential diagnosis of tumors arising from the frontal cranial base and extending to the nasal and cranial sides, NEC should be considered as a possibility.
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Carcinoma Neuroendocrino/cirugía , Neoplasias de los Senos Paranasales/cirugía , Carcinoma Neuroendocrino/radioterapia , Decorticación Cerebral , Terapia Combinada , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/radioterapia , Tomografía Computarizada por Rayos XRESUMEN
Electron-beam-induced soft-X-ray emission spectroscopy (SXES) that uses a grating spectrometer has been introduced to a conventional scanning electron microscope (SEM) for characterizing desired specimen areas of bulk materials. The spectrometer was designed as a grazing incidence flat-field optics by using aberration corrected (varied line spacing) gratings and a multichannel plate detector combined with a charge-coupled device camera, which has already been applied to a transmission electron microscope. The best resolution was confirmed as 0.13 eV at Mg L-emission (50 eV), which is comparable with that of recent dedicated electron energy-loss spectroscopy instruments. This SXES-SEM instrument presents density of states of simple metals of bulk Mg and Li. Apparent band-structure effects have been observed in Si L-emission of Si wafer, P L-emission of GaP wafer, and Al L-emissions of intermetallic compounds of AlCo, AlPd, Al2Pt, and Al2Au.
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Primary leptomeningeal lymphoma(PLML)is a neoplastic meningitis of lymphomatous origin without parenchymal central nervous system(CNS)disease or a systemic tumor. We report a case of PLML that presented with epileptic seizure, and review relevant literature. A 27-year-old man was brought to the emergency department with an epileptic seizure. Two months later, he was again brought to the emergency department with an epileptic seizure. MRI showed enhanced lesions on the surface of the right cerebellar hemisphere, right parietal sulci, and interhemispheric surface of the frontal lobes. We performed an open biopsy and diagnosed the patient with diffuse large B-cell lymphoma of the leptomeninges on the basis of histological findings. The patient was initially treated with chemotherapy including high-dose methotrexate(MTX). Because remission was not achieved by chemotherapy, the patient was treated with whole-brain radiation therapy. After onset, the patient survived for 2 years without recurrence. PLML is a particularly rare type of primary CNS lymphoma. The outcome of PLML, compared with general primary CNS lymphoma, is reported to be very poor because chemotherapy including MTX is ineffective.
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Linfoma/terapia , Neoplasias Meníngeas/terapia , Recurrencia Local de Neoplasia/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Humanos , Linfoma/complicaciones , Linfoma/diagnóstico , Masculino , Neoplasias Meníngeas/complicaciones , Neoplasias Meníngeas/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Convulsiones/etiología , Resultado del TratamientoRESUMEN
Epilepsy is a chronic neurological disorder, which presents with various forms of seizures. Traditional treatments, including medication using antiepileptic drugs, remain the treatment of choice for epilepsy. Recent development in surgical techniques and approaches has improved treatment outcomes. However, several epileptic patients still suffer from intractable seizures despite the advent of the multimodality of therapies. In this article, we initially provide an overview of clinical presentation of epilepsy then describe clinically relevant animal models of epilepsy. Subsequently, we discuss the concepts of regenerative medicine including cell therapy, neuroprotective agents, and electrical stimulation, which are reviewed within the context of our data.
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Epilepsia/terapia , Medicina Regenerativa , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Tratamiento Basado en Trasplante de Células y Tejidos , Estimulación Eléctrica , Epilepsia/metabolismo , Epilepsia/patología , Humanos , Células-Madre Neurales/citología , Células-Madre Neurales/trasplante , Fármacos Neuroprotectores/uso terapéuticoRESUMEN
A new multilayer-coated varied line-spaced grating, JS4000, was fabricated and tested for extending the upper limit of a grating X-ray spectrometer for electron microscopy. This grating was designed for 2-3.8 keV at a grazing incidence angle of 1.35°. It was revealed that this new multilayer structure enables us to take soft-X-ray emission spectra continuously from 1.5 to 4.3 keV at the same optical setting. The full-width at half maximum of Te-L(α1,2) (3.8 keV) emission peak was 27 eV. This spectrometer was applied to indium tin oxide particles and clearly resolved Sn-L(α) (3444 eV) and In-L(ß1) (3487 eV) peaks, which could not be resolved by a widely used energy-dispersive X-ray spectrometer.
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Espectrometría por Rayos X/instrumentación , Compuestos de Estaño/análisis , Diseño de Equipo , Análisis de Falla de EquipoRESUMEN
Laminar and blazed type holographic varied-line-spacing spherical gratings for use in a versatile soft x-ray flat-field spectrograph attached to an electron microscope are designed, fabricated, and evaluated. The absolute diffraction efficiencies of laminar (or blazed) master and replica gratings at 86.00° incidence evaluated by synchrotron radiation show over 5% (or 8%) in the 50-200 eV range with the maxima of 22% (or 26%-27%). Also the resolving power evaluated by a laser produced plasma source is in excess of 700 at the energy near the K emission spectrum of lithium (~55 eV) for all gratings. Moreover, the K emission spectrum of metallic Li with high spectral resolution is successfully observed with the spectrograph attached to a transmission electron microscope.
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OBJECTIVE: Patients with lung cancer harboring epidermal growth factor receptor (EGFR) mutation respond remarkably well to tyrosine kinase inhibitors of the EGFR (EGFR-TKI). We examined the relation of the EGFR mutation and the efficacy of EGFR-TKI for metastatic brain tumors from lung cancer. MATERIALS AND METHODS: Forty-one patients with brain metastases from lung cancer were treated in our hospital from January 2007 to October 2010. Among them, 9 patients were examined on their EGFR mutation of tumors using the PNA-LNA PCR clamp method, and were treated with gefitinib, given orally at a daily dose of 250 mg. The drug efficacy for brain tumors was evaluated with MRI and CT. RESULTS: Seven patients had EGFR mutation (4 in exon 19, and 3 in exon 21). Five patients showed partial response, 3 remained stable, and one had progressive disease. All 5 patients who showed partial response had EGFR mutation. One patient who had progressive disease had no EGFR mutation. Three patients (case 1, 2 and 6) among 5 patients who showed partial response were well controlled only with gefitinib (without radiation). CONCLUSION: This study suggests that the efficacy of EGFR-TKI for metastatic brain tumors from lung cancer is related to the EGFR mutation of tumor.
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Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Genes erbB-1/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Quinazolinas/uso terapéutico , Anciano , Femenino , Gefitinib , Humanos , Persona de Mediana EdadRESUMEN
Increased oxidative stress contributes to pathogenesis of Parkinson's disease (PD). 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the oxidation product most frequently measured as an indicator of oxidative DNA damage. Several studies have shown increased 8-OHdG in PD patients. There are few basic laboratory data examining 8-OHdG levels in animal models of PD. In this study, we utilized hemiparkinsonian model of rats induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA). The urinary 8-OHdG level was measured in relation to behavioral and pathological deficits arising from 6-OHDA-induced neurotoxic effects on the nigrostriatal dopaminergic pathway. All rats were subjected to a series of behavioral tests for 42 days after 6-OHDA injection. We collected urine samples with subsequent measurement of 8-OHdG level using ELISA kits. For immunohistochemical evaluation, tyrosine hydroxylase (TH) staining was performed. Significant increments in urinary 8-OHdG level were observed continuously from day 7 until day 35 compared to control group, which showed a trend of elevation as early as day 3. Such elevated urinary 8-OHdG level significantly correlated with all of the behavioral deficits measured here, suggesting that urinary 8-OHdG level provides a good index of severity of parkinsonism. Urinary 8-OHdG level also had a significant positive correlation with the survival rate of dopaminergic fibers or neurons, advancing the concept that oxidative stress during the early phase of 6-OHDA neurotoxicity may correspond to disease progression closely approximating neuronal degeneration in the nigrostriatal dopaminergic system. The present results demonstrate that alterations in urinary 8-OHdG level closely approximate onset and disease progression in PD.
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Ganglios Basales/metabolismo , Conducta Animal , Encéfalo/metabolismo , Desoxiguanosina/análogos & derivados , Dopamina/metabolismo , Degeneración Nerviosa/metabolismo , Trastornos Parkinsonianos/metabolismo , Sustancia Negra/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Ganglios Basales/patología , Biomarcadores/orina , Encéfalo/patología , Desoxiguanosina/orina , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Inmunohistoquímica , Inyecciones , Actividad Motora , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/patología , Degeneración Nerviosa/psicología , Degeneración Nerviosa/orina , Estrés Oxidativo , Oxidopamina/administración & dosificación , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/patología , Trastornos Parkinsonianos/psicología , Trastornos Parkinsonianos/orina , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad , Sustancia Negra/patología , Factores de Tiempo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Brain-derived neurotrophic factor (BDNF) is a well neurotrophic factor with neuroprotective potentials for various diseases in the central nervous system. However several previous studies demonstrated that BDNF might deteriorate symptoms for epilepsy model of animals by progression of abnormal neurogenesis. We hypothesized that continuous administration of BDNF at low dose might be more effective for epilepsy model of animals because high dose of BDNF was used in many studies. BDNF-secreting cells were genetically made and encapsulated for transplantation. Rats receiving BDNF capsule showed significant amelioration of seizure stage and reduction of the number of abnormal spikes at 7 days after kainic acid administration, compared to those of control group. The number of BrdU and BrdU/doublecortin positive cells in the hippocampus of BDNF group significantly increased, compared to that of control group. NeuN positive cells in the CA1 and CA3 of BDNF group were significantly preserved, compared to control group. In conclusion, low dose administration using encapsulated BDNF-secreting cells exerted neuroprotective effects with enhanced neurogenesis on epilepsy model of rats. These results might suggest the importance of the dose and administrative way of this neurotrophic factor to the epilepsy model of animals.
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Factor Neurotrófico Derivado del Encéfalo/farmacología , Epilepsia/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Neuronas/efectos de los fármacos , Animales , Factor Neurotrófico Derivado del Encéfalo/administración & dosificación , Bromodesoxiuridina/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Proteína Doblecortina , Epilepsia/metabolismo , Hipocampo/metabolismo , Ácido Kaínico , Masculino , Neuronas/metabolismo , Ratas , Ratas Endogámicas F344RESUMEN
Deep brain stimulation (DBS) is used to treat a variety of neurological disorders including Parkinson's disease. In this study, we explored the effects of striatal stimulation (SS) in a rat model of chronic-phase ischemic stroke. The stimulation electrode was implanted into the ischemic penumbra at 1 month after middle cerebral artery occlusion (MCAO) and thereafter continuously delivered SS over a period of 1 week. Rats were evaluated behaviorally coupled with neuroradiological assessment of the infarct volumes using magnetic resonance imaging (MRI) at pre- and post-SS. The rats with SS showed significant behavioral recovery in the spontaneous activity and limb placement test compared to those without SS. MRI visualized that SS also significantly reduced the infarct volumes compared to that at pre-SS or without SS. Immunohistochemical analyses revealed a robust neurogenic response in rats that received SS characterized by a stream of proliferating cells from the subventricular zone migrating to and subsequently differentiating into neurons in the ischemic penumbra, which exhibited a significant GDNF upregulation. In tandem with this SS-mediated neurogenesis, enhanced angiogenesis was also recognized as revealed by a significant increase in VEGF levels in the penumbra. These results provide evidence that SS affords neurorestoration at the chronic phase of stroke by stimulating endogenous neurogenesis and angiogenesis.
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Isquemia Encefálica/terapia , Estimulación Encefálica Profunda , Neovascularización Fisiológica/fisiología , Neurogénesis , Accidente Cerebrovascular/terapia , Animales , Conducta Animal , Encéfalo/irrigación sanguínea , Encéfalo/fisiopatología , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Enfermedad Crónica , Modelos Animales de Enfermedad , Electrodos , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Imagen por Resonancia Magnética , Masculino , Ratas , Ratas Wistar , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/patología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Recent studies demonstrate that rehabilitation ameliorates physical and cognitive impairments of patients with stroke, spinal cord injury, and other neurological diseases and that rehabilitation also has potencies to modulate brain plasticity. Here we examined the effects of compulsive exercise on Parkinson's disease model of rats. Before 6-hydroxydopamine (6-OHDA, 20 microg) lesion into the right striatum of female SD rats, bromodeoxyuridine (BrdU) was injected to label the proliferating cells. Subsequently, at 24 h after the lesion, the rats were forced to run on the treadmill (5 days/week, 30 min/day, 11 m/min). As behavioral evaluations, cylinder test was performed at 1, 2, 3, and 4 weeks and amphetamine-induced rotational test was performed at 2 and 4 weeks with consequent euthanasia for immunohistochemical investigations. The exercise group showed better behavioral recovery in cylinder test and significant decrease in the number of amphetamine-induced rotations, compared to the non-exercise group. Correspondingly, significant preservation of tyrosine hydroxylase (TH)-positive fibers in the striatum and TH-positive neurons in the substantia nigra pars compacta (SNc) was demonstrated, compared to the non-exercise group. Additionally, the number of migrated BrdU- and Doublecortin-positive cells toward the lesioned striatum was increased in the exercise group. Furthermore, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor increased in the striatum by exercise. The results suggest that exercise exerts neuroprotective effects or enhances the neuronal differentiation in Parkinson's disease model of rats with subsequent improvement in deteriorated motor function.
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Enfermedad de Parkinson Secundaria/rehabilitación , Condicionamiento Físico Animal/métodos , Anfetamina/farmacología , Animales , Ácido Ascórbico , Conducta Animal , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Bromodesoxiuridina/metabolismo , Proliferación Celular , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/fisiología , Modelos Animales de Enfermedad , Proteínas de Dominio Doblecortina , Proteína Doblecortina , Prueba de Esfuerzo , Femenino , Factores Neurotróficos Derivados de la Línea Celular Glial/metabolismo , Proteínas Asociadas a Microtúbulos , Movimiento/efectos de los fármacos , Neuropéptidos , Oxidopamina , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/patología , Enfermedad de Parkinson Secundaria/fisiopatología , Ratas , Ratas Sprague-Dawley , Rotación , Sustancia Negra/efectos de los fármacos , Sustancia Negra/fisiopatología , Factores de Tiempo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
We explored the effects of exogenous and endogenous erythropoietin (EPO) in a seizure model of rat. Adult male Fischer 344 rats received continuous intraventricular infusion of EPO dissolved in saline containing 1mg/ml of rat serum albumin, anti-EPO antibody, saline containing 1mg/ml of rat serum albumin or combined EPO and neuropeptide Y (NPY) Y2-receptor antagonist. Animals were behaviorally evaluated for seizure development over 6h after kainic acid injection followed by immunohistochemical assays. Mortality rate, seizure severity, apoptotic cell death and abnormal cell proliferation in the hippocampus of EPO-treated epileptic rats were significantly attenuated, compared to control rats. Anti-EPO antibody in non-EPO-treated animals worsened seizures and CA1 neuronal cell death, while NPY Y2-receptor antagonist cancelled the therapeutic effects of exogenous EPO. Both exogenous and endogenous EPO might modulate seizure severity and protect the hippocampal neurons in epileptic rats, via novel mechanistic pathways involving blockade of epileptogenic cell formation coupled with NPY receptor modulation in the hippocampus.
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Región CA1 Hipocampal/fisiopatología , Giro Dentado/fisiopatología , Eritropoyetina/metabolismo , Neuronas/fisiología , Neuropéptido Y/metabolismo , Convulsiones/fisiopatología , Animales , Apoptosis/fisiología , Autoanticuerpos/metabolismo , Región CA1 Hipocampal/patología , Proliferación Celular , Giro Dentado/patología , Modelos Animales de Enfermedad , Eritropoyetina/inmunología , Hematopoyesis/fisiología , Ácido Kaínico , Masculino , Neuronas/patología , Ratas , Ratas Endogámicas F344 , Receptores de Neuropéptido Y/antagonistas & inhibidores , Receptores de Neuropéptido Y/metabolismo , Convulsiones/inducido químicamente , Convulsiones/mortalidad , Índice de Severidad de la Enfermedad , Transducción de Señal , Regulación hacia Arriba/fisiologíaRESUMEN
The relationship between neurogenesis and epilepsy remains to be solved so far, although aberrant electric circuit recognized in epilepsy might be involved in neurogenesis. In this study, neurogenesis and the proliferation of astrocytes in the subgranular zone of the hippocampus were explored using unilateral amygdala-kindled rats with or without muscimol, a gamma-aminobutyric acid a (GABAa) agonist injection into the bilateral anterior thalamic nuclei (AN). Muscimol injection significantly ameliorated the behavioral scores of epilepsy without any significant alteration on the electroencephalography recorded at the stimulated basolateral amygdala, thus suggesting that muscimol injection might affect the secondary generalization, but not the initial discharge itself. The number of bromodeoxyuridine (BrdU), BrdU/doublecortin and BrdU/glial fibrillary acidic protein-positive cells in the subgranular zone of kindled animals increased markedly. Muscimol injection significantly suppressed neurogenesis, but not the proliferation of astrocyte, in the subgranular zone of the non-stimulated side, probably through the suppression of secondary generalization via AN. The results might indicate the underlying relationships between neurogenesis and epilepsy, that epileptic propagation in unilateral amygdala-kindled rats might go through AN into the contralateral side with subsequent neurogenesis, although further studies need to clarify the hypothesis.
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Núcleos Talámicos Anteriores/efectos de los fármacos , Agonistas del GABA/farmacología , Hipocampo/fisiología , Excitación Neurológica/efectos de los fármacos , Muscimol/farmacología , Neurogénesis/efectos de los fármacos , Amígdala del Cerebelo , Animales , Núcleos Talámicos Anteriores/fisiología , Bromodesoxiuridina/metabolismo , Recuento de Células , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Proteínas de Dominio Doblecortina , Proteína Doblecortina , Estimulación Eléctrica/efectos adversos , Electroencefalografía/métodos , Epilepsia/tratamiento farmacológico , Epilepsia/patología , Epilepsia/fisiopatología , Lateralidad Funcional , Proteína Ácida Fibrilar de la Glía/metabolismo , Indoles , Excitación Neurológica/fisiología , Masculino , Proteínas Asociadas a Microtúbulos/metabolismo , Neuropéptidos/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Metabotropic glutamate receptors (mGluRs) have been recently implicated as robust therapeutic targets for Parkinson's disease (PD). Here, we explored how activation of mGluRs in globus pallidus (GP) affected the amphetamine-induced rotational behavior in the unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of PD. The amphetamine-induced rotations were completely suppressed by the ipsilateral intrapallidal injection of the non-selective mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (ACPD) and the selective group I mGluR agonist, (R,S)-3,5-dihydroxyphenylglycine (DHPG), but not the selective group III mGluR agonist, l-2-amino-4-phosphonobutyric acid (l-AP4). The suppressive effects were detected at 2, 4, 6, 8, and 12 h after ACPD injection, but returned to the control level at 24 h. A remarkable c-fos expression was found in the lesioned side of GP, subthalamic nucleus (STN), and substantia nigra pars reticulata (SNr) of rats that received the ACPD or DHPG injection, compared to rats treated with L-AP-4 or phosphate buffer-injection. The results indicate that the blockade of amphetamine-induced rotations might be at least partially mediated by group I mGluR activation. This study advances the use of selective group I mGluRs directed toward the GP for PD treatment.