RESUMO
Neuroblasts from the subventricular zone (SVZ) migrate to striatum following stroke, but most of them die in the ischaemic milieu and this can be related to exacerbated microglial activation. Here, we explored the effects of the non-steroidal anti-inflammatory indomethacin on microglial activation, neuronal preservation and neuroblast migration following experimental striatal stroke in adult rats. Animals were submitted to endothelin-1 (ET-1)-induced focal striatal ischaemia and were treated with indomethacin or sterile saline (i.p.) for 7 days, being perfused after 8 or 14 days. Immunohistochemistry was performed to assess neuronal loss (anti-NeuN), microglial activation (anti-Iba1, ED1) and migrating neuroblasts (anti-DCX) by counting NeuN, ED1 and DCX-positive cells in the ischaemic striatum or SVZ. Indomethacin treatment reduced microglia activation and the number of ED1+ cells in both 8 and 14 days post injury as compared with controls. There was an increase in the number of DCX+ cells in both SVZ and striatum at the same survival times. Moreover, there was a decrease in the number of NeuN+ cells in indomethacin-treated animals as compared with the control group at 8 days but not after 14 days post injury. Our results suggest that indomethacin treatment modulates microglia activation, contributing to increased neuroblast proliferation in the SVZ and migration to the ischaemic striatum following stroke.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Corpo Estriado/efeitos dos fármacos , Indometacina/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/patologia , Proliferação de Células/efeitos dos fármacos , Corpo Estriado/patologia , Proteína Duplacortina , Endotelina-1/toxicidade , Humanos , Ventrículos Laterais/efeitos dos fármacos , Ventrículos Laterais/patologia , Microglia/efeitos dos fármacos , Microglia/patologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/patologia , Neurogênese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/patologiaRESUMO
We explored whether the modulation of microglia activation with minocycline is beneficial to the therapeutic actions of bone marrow mononuclear cells (BMMCs) transplanted after experimental stroke. Male Wistar adult rats were divided in four experimental groups: ischemic control saline treated (G1, N = 6), ischemic minocycline treated (G2, N = 5), ischemic BMMC treated (G3, N = 5), and ischemic minocycline/BMMC treated (G4, N = 6). There was a significant reduction in the number of ED1+ cells in G3 animals (51.31 ± 2.41, P < 0.05), but this effect was more prominent following concomitant treatment with minocycline (G4 = 29.78 ± 1.56). There was conspicuous neuronal preservation in the brains of G4 animals (87.97 ± 4.27) compared with control group (G1 = 47.61 ± 2.25, P < 0.05). The behavioral tests showed better functional recovery in animals of G2, G3, and G4, compared with G1 and baseline (P < 0.05). The results suggest that a proper modulation of microglia activity may contribute to a more permissive ischemic environment contributing to increased neuroprotection and functional recovery following striatal ischemia.
Assuntos
Transplante de Medula Óssea , Isquemia Encefálica/terapia , Microglia/efeitos dos fármacos , Minociclina/uso terapêutico , Acidente Vascular Cerebral/terapia , Animais , Células da Medula Óssea/metabolismo , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/tratamento farmacológico , Células Cultivadas , Endotelina-1 , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Wistar , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
Operant response rate changes within the course of a typical free-operant experimental session. These changes are orderly, and reliably demonstrated with subjects from different species, responding under different experimental conditions. Killeen (1995) postulated that the response rate changes are a function of the interplay between arousal and satiation and offered a mathematical model for this hypothesis. Here we analyze Killeen's model, demonstrating that, although solid in its principles, it presents some flaws in its implementation. Then, based on the same principles, we build and test a new model of within-session motivation dynamics. We also demonstrate that, by representing arousal as a variable that ranges between 0 and 1, we can obtain a surprisingly simple model of free-operant response rate.
Assuntos
Condicionamento Operante/fisiologia , Modelos Psicológicos , Modelos Teóricos , Reforço Psicológico , Animais , Nível de Alerta/fisiologia , Ratos , Esquema de Reforço , Fatores de TempoRESUMO
The chemical composition of volatile oils from two Myrtaceae species, Myrceugenia myrcioidesand Eugenia riedeliana, both native from the Brazilian Atlantic Rain Forest, was analyzed by GC-MS. Acetylcholinesterase inhibitory activity was colorimetrically evaluated for these oils. For M. myrcioides, monoterpene hydrocarbons represented the major class in the volatile oil, with α-pinene as the most abundant component and a weak inhibitory activity was observed, whilst for E. riedeliana sesquiterpenes were found in higher amounts, being valerianol the major compound, and this oil presented a strong acetylcholinesterase inhibition.
A composição química dos óleos voláteis de duas espécies de Myrtaceae, Myrceugenia myrcioidese Eugenia riedeliana, ambas nativas da Mata Atlântica, foi analisada por CG-EM. A atividade inibidora de acetilcolinesterase foi determinada colorimetricamente para estes óleos. Em M. myrcioides, hidrocarbonetos monoterpênicos representaram a classe majoritária de compostos presentes no óleo volátil, sendo α-pineno o componente mais abundante e a atividade inibidora de acetilcolinesterase foi baixa, enquanto para E. riedelianaos sesquiterpenos foram observados em maiores concentrações, sendo o valerianol o componente majoritário, e este óleo apresentou uma forte atividade inibidora da enzima.
RESUMO
The volatile oil composition and anti-acetyl cholinesterase activity were analyzed in two specimens of Marlierea racemosa growing in different areas of the Atlantic Rain Forest (Cananéia and Caraguatatuba, SP, Brazil). Component identifications were performed by GC/MS and their acetyl cholinesterase inhibitory activity was measured through colorimetric analysis. The major constituent in both specimens was spathulenol (25.1% in Cananéia and 31.9% in Caraguatatuba). However, the first one also presented monoterpenes (41.2%), while in the Carguatatuba plants, this class was not detected. The oils from the plants collected in Cananéia were able to inhibit the acetyl cholinesterase activity by up to 75%, but for oils from the other locality the maximal inhibition achieved was 35%. These results suggested that the monoterpenes are more effective in the inhibition of acetyl cholinesterase activity than sesquiterpenes as these compounds are present in higher amounts in the M. racemosa plants collected in Cananéia.
Assuntos
Inibidores da Colinesterase/isolamento & purificação , Myrtaceae/química , Óleos Voláteis/isolamento & purificação , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Brasil , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Colorimetria/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Óleos Voláteis/farmacologia , Clima TropicalRESUMO
A anemia falciforme é uma doença genética caracterizada pelo alto índice de morbimortalidade, considerada como a mais grave entre as doenças falciformes. As opções terapêuticas mais eficazes atualmente disponíveis para tratamento desta hemoglobinopatia são transplante de medula óssea (TMO) e hidroxiuréia (HU). O TMO apesar de ser a medida curativa é considerado de alto risco por apresentar diversos graus de complicações e significativo nível de mortalidade. O uso de HU em crianças portadoras de anemia falciforme tem proporcionado redução de complicações clínicas e aumento significativo na expectativa de vida, por promover elevação dos níveis de hemoglobina fetal, da concentração de hemoglobina e do VCM, bem como redução da hemólise e de eventos vaso-oclusivos. Desse modo, a HU é considerada como melhor opção terapêutica atualmente disponível. Porém, por ser apontada como droga potencialmente carcinogênica, há questionamentos quanto aos benefícios e toxicidades quando utilizada por longo período. Este trabalho teve como proposta, avaliar por meio da revisão literária, os riscos, benefícios e efeitos adversos da hidroxiuréia em crianças.
Sickle cell anemia is a genetic disease characterized by a high morbimortality rate, it is considered as the most serious among all sickle cell diseases. The most effective therapeutic options available nowadays for the treatment of this hemoglobinopathy are bone morrow transplantation (BMT) and hydroxyurea (HU). BMT is considered a high risk procedure due to the different complications and significant mortality rates. The use of HU for children with sickle cell anemia has reduced the clinical complications and given a significant increase in life expectancy by augmenting the fetal hemoglobin levels and hemoglobin concentrations and reducing cytomegalovirus, as well as reducing hemolysis and vaso-occlusive events. Thus, HU is considered the best therapeutic option currently available. However, as HU has been identified as a potentially carcinogenic drug, there are questions related to the benefits and toxicities when it is used over long periods of time. This work aimed at evaluating, through a review of the literature, the risks, benefits and adverse effects of the use of hydroxyurea in children.