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1.
Epilepsy Res ; 181: 106873, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35180639

RESUMO

PURPOSE: Curcumin is known for its neuroprotective, anti-inflammatory and anti-oxidant properties and has been investigated as a potential therapeutic drug for Temporal Lobe Epilepsy (TLE). We previously found anti-epileptogenic properties of curcumin in an in vitro brain slice model for epileptogenesis, and inhibitory effects on the MAPK-pathway in vivo after intracerebrally applying curcumin in post-status epilepticus rats. Here, we investigated whether the intracerebral application of curcumin could be anti-epileptogenic in the rapid kindling rat model for TLE. METHODS: Curcumin or vehicle was injected directly into the brain through an intracerebral ventricular cannula at 5 consecutive days during the kindling process. Kindling consisted of repeated electrical stimulations of the angular bundle (12 times a day with a 30 min interval) every other day, until rats were fully kindled or until 36 stimulations were administered. One week after kindling acquisition, additional kindling stimulations were applied in a re-test in the absence of curcumin- or vehicle treatment. RESULTS: Curcumin-treated rats required more stimulations compared to vehicle-treated rats to reach Racine stage IV seizures, indicating that curcumin delayed seizure development. However, it did not prevent the fully kindled state as shown in the re-test. Increasing the dose of curcumin did not produce a delay in seizure development. Immunohistochemistry showed that kindling produced cell loss, astrogliosis, mossy fiber sprouting and neurogenesis in the dentate gyrus, which were not different between vehicle- and curcumin-treated groups. CONCLUSION: Although curcumin's effects on neuropathology were not detected and the delay of kindling development was transient, the data warrant further exploration of its anti-epileptogenic potential using formulations that further increase its bioavailability.


Assuntos
Curcumina , Epilepsia do Lobo Temporal , Excitação Neurológica , Estado Epiléptico , Animais , Curcumina/farmacologia , Curcumina/uso terapêutico , Modelos Animais de Doenças , Epilepsia do Lobo Temporal/tratamento farmacológico , Ratos , Convulsões/tratamento farmacológico , Estado Epiléptico/tratamento farmacológico
2.
Dev Neurobiol ; 76(4): 357-74, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26097169

RESUMO

Developing networks in the immature nervous system and in cellular cultures are characterized by waves of synchronous activity in restricted clusters of cells. Synchronized activity in immature networks is proposed to regulate many different developmental processes, from neuron growth and cell migration, to the refinement of synapses, topographic maps, and the mature composition of ion channels. These emergent activity patterns are not present in all cells simultaneously within the network and more immature "silent" cells, potentially correlated with the presence of silent synapses, are prominent in different networks during early developmental periods. Many current network analyses for detection of synchronous cellular activity utilize activity-based pixel correlations to identify cellular-based regions of interest (ROIs) and coincident cell activity. However, using activity-based correlations, these methods first underestimate or ignore the inactive silent cells within the developing network and second, are difficult to apply within cell-dense regions commonly found in developing brain networks. In addition, previous methods may ignore ROIs within a network that shows transient activity patterns comprising both inactive and active periods. We developed analysis software to semi-automatically detect cells within developing neuronal networks that were imaged using calcium-sensitive reporter dyes. Using an iterative threshold, modulation of activity was tracked within individual cells across the network. The distribution pattern of both inactive and active, including synchronous cells, could be determined based on distance measures to neighboring cells and according to different anatomical layers.


Assuntos
Imageamento Tridimensional/métodos , Potenciais da Membrana/fisiologia , Neurônios/fisiologia , Reconhecimento Automatizado de Padrão/métodos , Software , Imagens com Corantes Sensíveis à Voltagem/métodos , Animais , Cálcio/metabolismo , Células Cultivadas , Células-Tronco Embrionárias/fisiologia , Córtex Entorrinal/efeitos dos fármacos , Córtex Entorrinal/crescimento & desenvolvimento , Córtex Entorrinal/fisiologia , Antagonistas de Receptores de GABA-A/farmacologia , Humanos , Potenciais da Membrana/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Vias Neurais/efeitos dos fármacos , Vias Neurais/crescimento & desenvolvimento , Vias Neurais/fisiologia , Neurônios/efeitos dos fármacos , Periodicidade , Piridazinas/farmacologia , Técnicas de Cultura de Tecidos
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