RESUMEN
The phenylalanine-tyrosine-dopa-dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates levodopa (L-dopa) with tetrahydrobiopterin (BH4) as a coenzyme. Here, we show that oral berberine (BBR) might supply H⢠through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH4 from dihydrobiopterin; the increased BH4 enhances TH activity, which accelerates the production of L-dopa by the gut bacteria. Oral BBR acts in a way similar to vitamins. The L-dopa produced by the intestinal bacteria enters the brain through the circulation and is transformed to dopamine. To verify the gut-brain dialog activated by BBR's effect, Enterococcus faecalis or Enterococcus faecium was transplanted into Parkinson's disease (PD) mice. The bacteria significantly increased brain dopamine and ameliorated PD manifestation in mice; additionally, combination of BBR with bacteria showed better therapeutic effect than that with bacteria alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging of dopamine identified elevated striatal dopamine levels in mouse brains with oral Enterococcus, and BBR strengthened the imaging intensity of brain dopamine. These results demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of L-dopa in the gut. Furthermore, a study of 28 patients with hyperlipidemia confirmed that oral BBR increased blood/fecal L-dopa by the intestinal bacteria. Hence, BBR might improve the brain function by upregulating the biosynthesis of L-dopa in the gut microbiota through a vitamin-like effect.
Asunto(s)
Berberina/farmacología , Dihidroxifenilalanina/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedad de Parkinson/tratamiento farmacológico , Animales , Berberina/análogos & derivados , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/microbiología , Dopamina/metabolismo , Enterococcus faecalis/metabolismo , Enterococcus faecium/metabolismo , Humanos , Levodopa/metabolismo , Ratones , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/microbiología , Tirosina 3-Monooxigenasa/genéticaRESUMEN
There is evidence to support that an impaired energy metabolism and the excessive generation of reactive oxygen species (ROS) contribute to brain injury in neurodegenerative disorders such as Parkinson's disease (PD), whereas diets enriched in foods with an antioxidant action may modulate its progression. Several studies have proved that the antioxidant components produced by Spirulina, a microscopic blue-green alga, might prevent cell death by decreasing free radicals, inhibiting lipoperoxidation and upregulating the antioxidant enzyme systems. In our study, we investigated the protective effect of the Spirulina maxima (S. maxima) against the 6-OHDA-caused toxicity in the rat striatum. The S. maxima (700 mg/kg/day, vo) was administered for 40 days before and 20 days after a single injection of 6-OHDA (16 µg/2 µL) into the dorsal striatum. At 20-day postsurgery, the brain was removed and the striatum was obtained to evaluate the indicators of toxicity, such as nitric oxide levels, ROS formation, lipoperoxidation, and mitochondrial activity. These variables were found significantly stimulated in 6-OHDA-treated rats and were accompanied by declines in dopamine levels and motor activity. In contrast, the animals that received the chronic treatment with S. maxima had a restored locomotor activity, which is associated with the decreased levels of nitric oxide, ROS, and lipoperoxidation in the striatum, although mitochondrial functions and dopamine levels remained preserved. These findings suggest that supplementation with antioxidant phytochemicals (such as contained in S. maxima) represents an effective neuroprotective strategy against 6-OHDA-caused neurotoxicity vía free radical production to preserve striatal dopaminergic neurotransmission in vivo.
Asunto(s)
Antioxidantes/farmacología , Cuerpo Estriado/efectos de los fármacos , Modelos Animales , Oxidopamina/toxicidad , Spirulina , Animales , Cuerpo Estriado/microbiología , Cuerpo Estriado/patología , Masculino , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Resultado del TratamientoAsunto(s)
Infecciones Bacterianas del Sistema Nervioso Central/patología , Cuerpo Estriado/patología , Infecciones por Mycoplasma/patología , Mycoplasma pneumoniae/aislamiento & purificación , Necrosis/patología , Infecciones Bacterianas del Sistema Nervioso Central/microbiología , Preescolar , Cuerpo Estriado/microbiología , Humanos , Masculino , Necrosis/microbiologíaRESUMEN
Neural transplantation of human fetal tissue for Huntington's disease (HD) is now entering the clinical arena. The safety of the procedure has now been demonstrated in a number of studies, although the efficacy of such an approach is still being investigated. Stringent but practicable screening of the donor tissue for potential pathogens is an essential prerequisite for successful implementation of any novel transplant program that uses human fetal tissue. In this article we summarize the UK-NEST protocol for the screening of human fetal tissue being grafted to patients with mild to moderate HD. We describe the results of microbiological screening of 87 potential tissue donors in a pilot study, and of the first four donor-recipient patients included in the UK-NEST series. The rationale for the adoption and interpretation of the various tests is described and our methodology is compared with those previously used by other centers. This article therefore presents a comprehensive, logical yet pragmatic screening program that could be employed in any clinical studies that use human fetal tissue for neurotransplantation.
Asunto(s)
Trasplante de Tejido Encefálico/métodos , Cuerpo Estriado/trasplante , Trasplante de Tejido Fetal/métodos , Enfermedad de Huntington/cirugía , Comités de Monitoreo de Datos de Ensayos Clínicos , Cuerpo Estriado/embriología , Cuerpo Estriado/microbiología , Cuerpo Estriado/cirugía , Selección de Donante/métodos , Humanos , Enfermedad de Huntington/fisiopatología , Reino UnidoRESUMEN
Although the neuroprotective effects of estrogens are well recognized, the exact mechanisms involved in the ability of these sex steroids to protect the cerebral tissue still remain unclear. We tested in our study the hypothesis that estradiol (E(2)) modulates the innate immune response and expression of genes encoding proteins that a provide survival signal to neurons during infection. Mice received a single systemic or cerebral injection of LPS to trigger a robust but transient inflammatory reaction in the brain. The endotoxin increased transcriptional activation of genes encoding TLR2, TNF-alpha, and IL-12 in microglial cells. Expression of these transcripts was largely inhibited in the brain of ovariectomized mice at time 24 h postchallenge. E(2) replacement therapy totally rescued the ability of the endotoxin to trigger microglial cells and these permissive effects of E(2) are mediated via the estrogen receptor (ER)alpha. Indeed, ERalpha-deficient mice exhibited an inappropriate reaction to LPS when compared with ERbeta-deficient and wild-type mice. This defective innate immune response was also associated with a widespread viral replication and neurodegeneration in ovariectomized mice inoculated intranasally with HSV-2. These data provide evidence that interaction of E(2) with their nuclear ERalpha plays a critical role in the control of cytokines involved in the transfer from the innate to adaptive immunity. This transfer is deviant in mice lacking E(2), which allows pathogens to hide from immune surveillance and exacerbates neuronal damages during viral encephalitis.
Asunto(s)
Encéfalo/inmunología , Encefalitis Viral/inmunología , Infecciones por Escherichia coli/inmunología , Estradiol/fisiología , Herpesvirus Humano 2/inmunología , Herpesvirus Humano 2/patogenicidad , Transducción de Señal/inmunología , Animales , Encéfalo/microbiología , Encéfalo/patología , Encéfalo/virología , Cuerpo Estriado/inmunología , Cuerpo Estriado/microbiología , Modelos Animales de Enfermedad , Encefalitis Viral/genética , Encefalitis Viral/metabolismo , Encefalitis Viral/patología , Infecciones por Escherichia coli/genética , Infecciones por Escherichia coli/metabolismo , Infecciones por Escherichia coli/patología , Estradiol/metabolismo , Retroalimentación Fisiológica/genética , Retroalimentación Fisiológica/inmunología , Femenino , Inmunidad Innata/genética , Inyecciones Intraventriculares , Lipopolisacáridos/administración & dosificación , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/inmunología , Microglía/microbiología , Microglía/virología , Ovariectomía , Receptores de Estrógenos/deficiencia , Receptores de Estrógenos/genética , Receptores de Estrógenos/fisiología , Receptores Inmunológicos/biosíntesis , Receptores Inmunológicos/genética , Transducción de Señal/genética , Receptor Toll-Like 2RESUMEN
INTRODUCTION: Necrosis of the basal ganglia (NBG) is an uncommon condition in childhood. Cases of NBG have been reported in connection with metabolic disorders, infections, degenerative conditions, intoxications, head injuries and hypoxic-ischemic encephalopathies. The commonest clinical features include alteration of consciousness, chorea-athetoic or dystonic movements, spasticity, contractures of the limbs and convulsions. CLINICAL CASE: We describe the case of an eight year old girl, who after having clinical gastroenteritis, developed acute neurological dysfunction, associated with images on cranial computerized axial tomography (CAT) showing a possible intracranial tumour and magnetic resonance (MR) studies showing bilateral hypodensity of the basal ganglia. Three months later magnetic resonance showed that these lesions had almost completely disappeared. This supports the diagnosis of post-infectious lesions. CONCLUSIONS: The clinical course is very variable. Cases with a previous history of infection have a better prognosis. In our patient treatment was started with corticosteroids. She made a good recovery and was sent home with no sequelae five days later. The new imaging techniques (CAT and MR) have led to more cases of selective involvement of the basal ganglia being diagnosed. MR is the most specific technique for diagnosis in these patients. Although there is no effective specific treatment, treatment with biperidine, thyrotropic hormone and corticosteroids have been used with no apparent effect on the course of the disorder.
Asunto(s)
Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/patología , Enfermedades de los Ganglios Basales/complicaciones , Enfermedades de los Ganglios Basales/microbiología , Enfermedades de los Ganglios Basales/patología , Niño , Cuerpo Estriado/microbiología , Electroencefalografía , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/inmunología , Potenciales Evocados Somatosensoriales , Femenino , Humanos , Inmunoglobulina G/inmunología , Imagen por Resonancia Magnética , Necrosis , Trastornos Respiratorios/etiología , Trastornos Respiratorios/rehabilitación , Respiración Artificial , Tomografía Computarizada por Rayos XAsunto(s)
Cuerpo Estriado/microbiología , Cuerpo Estriado/patología , Infecciones por Mycoplasma/microbiología , Mycoplasma pneumoniae/aislamiento & purificación , Trastornos Parkinsonianos/microbiología , Enfermedad Aguda , Adolescente , Anticuerpos Antibacterianos/sangre , Encéfalo/diagnóstico por imagen , Encéfalo/microbiología , Encéfalo/patología , Cuerpo Estriado/diagnóstico por imagen , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Masculino , Mycoplasma pneumoniae/inmunología , Necrosis , Trastornos Parkinsonianos/diagnóstico , Trastornos Parkinsonianos/patología , Tomografía Computarizada de Emisión , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
During meningitis, the host produces a plethora of signaling agents as part of a coordinated defense mechanism against invading pathogens. Nitric oxide (NO) and prostaglandin E2 (PGE2) are two such inflammatory mediators produced in response to bacterial endotoxins. Disruption of the blood-brain barrier (BBB) is one of many pathophysiological consequences of meningitis. The present objective was to examine the time-course of NO and PGE2 production in relationship to BBB permeability alterations during experimentally-induced meningitis. Meningeal inflammation was elicited by intracisternal administration of the bacterial endotoxin, lipopolysaccharides (LPS; 200 microg), and NO, PGE2, and BBB integrity were monitored over the next 24 h. Meningeal NO production was assessed by headspace chemiluminescence; cerebrospinal fluid PGE2 was determined by enzyme-linked immunosorbent assay (ELISA) immunoassay; and BBB integrity was determined by the brain accumulation of 14C-sucrose. Similar time-course profiles for NO and PGE2 were observed, with a peak effect for both inflammatory mediators observed within 6-8 h after intracisternal LPS dosing. Statistically significant (p < 0.05) disruption of the BBB was observed in various brain regions. Strikingly similar temporal relationships were observed for NO and PGE2 production and BBB disruption. These results suggest the hypothesis that NO and PGE2 may act in conjunction to disrupt the BBB during experimental meningitis.
Asunto(s)
Barrera Hematoencefálica/inmunología , Dinoprostona/metabolismo , Meningitis Bacterianas/fisiopatología , Óxido Nítrico/metabolismo , Sacarosa/farmacocinética , Animales , Radioisótopos de Carbono , Cerebelo/irrigación sanguínea , Cerebelo/microbiología , Cerebelo/fisiopatología , Cuerpo Estriado/irrigación sanguínea , Cuerpo Estriado/microbiología , Cuerpo Estriado/fisiopatología , Modelos Animales de Enfermedad , Lóbulo Frontal/irrigación sanguínea , Lóbulo Frontal/microbiología , Lóbulo Frontal/fisiopatología , Hipocampo/irrigación sanguínea , Hipocampo/microbiología , Hipocampo/fisiopatología , Recuento de Leucocitos , Leucocitos/inmunología , Lipopolisacáridos/inmunología , Masculino , Meningitis Bacterianas/inmunología , Ratas , Ratas Sprague-DawleyAsunto(s)
Absceso Encefálico/diagnóstico por imagen , Criptococosis/diagnóstico por imagen , Enfermedades Pulmonares Fúngicas/diagnóstico por imagen , Adulto , Enfermedades de los Ganglios Basales/diagnóstico por imagen , Enfermedades de los Ganglios Basales/microbiología , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/microbiología , Ventrículos Cerebrales/microbiología , Ventriculografía Cerebral , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/microbiología , Femenino , Humanos , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/microbiología , Tomografía Computarizada por Rayos XRESUMEN
Av01 is a variant of the challenge virus standard strain of fixed rabies virus that was selected with a neutralizing anti-glycoprotein monoclonal antibody, and has a single amino acid change in the glycoprotein. It is avirulent after both intracerebral and peripheral routes of inoculation in adult mice. In this study, Av01 was found to be neurovirulent with stereotaxic brain inoculation in either the striatum or cerebellum of adult mice. Mice that had been inoculated simultaneously with Av01 by the intracerebral and intrastriatal routes recovered. More infectious virus was present in the brains of mice inoculated intrastriatally than intracerebrally, and more neurons contained rabies virus antigen. However, the topographical distribution of infected neurons was similar with both routes. Serum neutralizing antibodies against rabies virus were produced later and in smaller quantities after intrastriatal inoculation. Av01 is probably neurovirulent after stereotaxic brain inoculation because this route produces both a direct site of viral entry into the central nervous system and a low level of immune stimulation.
Asunto(s)
Encéfalo/microbiología , Neuronas/microbiología , Virus de la Rabia/patogenicidad , Rabia/patología , Animales , Anticuerpos Antivirales/análisis , Antígenos Virales/análisis , Encéfalo/patología , Cuerpo Estriado/microbiología , Cuerpo Estriado/patología , Femenino , Ratones , Ratones Endogámicos , Especificidad de Órganos , Rabia/mortalidad , Virus de la Rabia/crecimiento & desarrollo , VirulenciaRESUMEN
Stereotaxic inoculation of rabies virus into specific nuclei in the central nervous system has been used for the investigation of the central neural transport mechanisms of viral information. The infection was monitored by specific fluorescence and peroxidase studies and the titration of viral infectivity in dissected brain areas. Twenty-four hours after inoculation into the striatum, cortex, or substantia nigra, infected neurons were detected only in cells from areas and nuclei which were related to the site of inoculation. The distribution of infected neurons showed that retrograde axoplasmic flow plays a determining role in the transport of rabies virus 24 hours after delivery of virus to specific target nuclei. Local destruction of neurons by kainic acid at the site of viral inoculation did not prevent the uptake and subsequent retrograde axonal transport of virus. There was an overall correlation between the major neural connections of the inoculated areas (e.g. the striatum) and the infected areas 24 hours later (e.g. the substantia nigra).
Asunto(s)
Sistema Nervioso Central/fisiología , Virus de la Rabia/inmunología , Vacunas Virales/administración & dosificación , Animales , Antígenos Virales/análisis , Transporte Axonal , Axones/microbiología , Encéfalo/microbiología , Encéfalo/patología , Sistema Nervioso Central/inmunología , Sistema Nervioso Central/microbiología , Corteza Cerebral/microbiología , Cuerpo Estriado/microbiología , Técnica del Anticuerpo Fluorescente , Técnicas para Inmunoenzimas , Inyecciones , Ácido Kaínico/farmacología , Rabia/microbiología , Ratas , Ratas Endogámicas , Técnicas Estereotáxicas , Sustancia Negra/microbiologíaRESUMEN
A microinjection of a homogenate of scrapie agent-infected brain (strain 263 K) into the nigrostriatal system in the golden hamster is followed by the progressive development of the disease which terminates by the death of animals around the 4th month postinoculation. These intracerebral inoculations induce more rapid changes in neuronal activity which can be revealed by the assessment of the specific synthesizing enzymes of neurotransmitter systems. The microinoculation of a homogenate of an infected brain unilaterally into the substantia nigra (SN) provokes a decrease in tyrosine hydroxylase (TH), the synthesizing enzyme for dopamine in the dopaminergic neurones, in the striatum ipsilateral to the injected SN. This biochemical response, specifically induced by the active pathogen, is detectable as soon as the 5th day postinoculation and is detectable towards the 80th day. A return of TH levels to control values is detected after this period. At the end of the incubation period and towards the death of the animals, TH is not different from control TH measured from intact animals. The decrease in TH is concomitant with an increase in striatal glutamic acid decarboxylase (GAD), the synthesizing enzyme for gamma-aminobutyric acid (GABA), measured 20 days postinoculation with no change in choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine. Studies of the biochemical responses associated locally to the scrapie agent inoculation have been performed at the striatal level. The intrastriatal administration of the infective agent induces 20 days postinoculation an increase in GAD with no change in TH and ChAT. Ninety days postinoculation, a decrease in GAD was detected associated with an increase in TH with no change in ChAT.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Colina O-Acetiltransferasa/metabolismo , Cuerpo Estriado/enzimología , Glutamato Descarboxilasa/metabolismo , Priones , Sustancia Negra/enzimología , Tirosina 3-Monooxigenasa/metabolismo , Animales , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/microbiología , Cricetinae , Femenino , Hidroxidopaminas/farmacología , Ácido Kaínico/farmacología , Masculino , Mesocricetus , Oxidopamina , Sustancia Negra/efectos de los fármacos , Sustancia Negra/microbiologíaAsunto(s)
Enfermedad de Alzheimer/metabolismo , Glucemia/metabolismo , Scrapie/metabolismo , Enfermedad de Alzheimer/microbiología , Animales , Encéfalo/metabolismo , Cuerpo Estriado/microbiología , Cricetinae , Desoxiglucosa/sangre , Modelos Animales de Enfermedad , Humanos , Mesocricetus , Priones/patogenicidad , Scrapie/microbiología , Ovinos , Sustancia Negra/microbiologíaRESUMEN
Light and electron microscopic observation 3--4 days after microinjection of Herpes simplex virus (HSV) into the left neostriatum of rat demonstrated the following results. (1) Virus labeled nerve cells were found in the ipsilateral substantia nigra; a large number of infected neurons were in the zona compacta and some were in the zona reticulata. No virus infection was evident in the contralateral side. (2) Virus labeled neurons were found in the cortex, a greater number ipsilaterally than contralaterally, and in the dorsal raphé nuclei. Cortical microinjection of HSV led to infection of some cortical cells but no neostriatal cells. We conclude, therefore, that spread of the virus to the cortex, the substantia nigra and the dorsal raphé following neostriatal injection was by retrograde axonal transport. (3) The left neostriatum, where HSV was injected, showed a surprisingly small number of virus infected neurons. The infected neurons were mostly the large neurons; the majority of medium sized neurons were well preserved. There was massive degeneration of nerve terminals throughout the neuropil. Most of these degenerating nerve terminals are considered to be afferent fibers.