Cannabidiol Exerts a Neuroprotective and Glia-Balancing Effect in the Subacute Phase of Stroke

Pharmacological agents limiting secondary tissue loss and improving functional outcomes after stroke are still limited. Cannabidiol (CBD), the major non-psychoactive component of Cannabis sativa, has been proposed as a neuroprotective agent against experimental cerebral ischemia. The effects of CBD mostly relate to the modulation of neuroinflammation, including glial activation. To investigate the effects of CBD on glial cells after focal ischemia in vivo, we performed time-lapse imaging of microglia and astroglial Ca2+ signaling in the somatosensory cortex in the subacute phase of stroke by in vivo two-photon laser-scanning microscopy using transgenic mice with microglial EGFP expression and astrocyte-specific expression of the genetically encoded Ca2+ sensor GCaMP3. CBD (10 mg/kg, intraperitoneally) prevented ischemia-induced neurological impairment, reducing the neurological deficit score from 2.0 ± 1.2 to 0.8 ± 0.8, and protected against neurodegeneration, as shown by the reduction (more than 70%) in Fluoro-Jade C staining (18.8 ± 7.5 to 5.3 ± 0.3). CBD reduced ischemia-induced microglial activation assessed by changes in soma area and total branch length, and exerted a balancing effect on astroglial Ca2+ signals. Our findings indicate that the neuroprotective effects of CBD may occur in the subacute phase of ischemia, and reinforce its strong anti-inflammatory property. Nevertheless, its mechanism of action on glial cells still requires further studies

<b>Avaliação da atividade ansiolítica e antidepressiva do extrato fluido e fração aquosa de folhas de <em>Passiflora alata</em> Curtis em camundongos</b> - DOI: 10.4025/actascihealthsci.v28i2.1100

O extrato fluido (EF), preparado segundo a Farmacopéia Brasileira, e sua fração aquosa (FA) obtidos de folhas de Passiflora alata foram administrados por via oral em camundongos. Seus efeitos comportamentais foram avaliados por modelos que detectam a atividade ansiolítica e antidepressiva de drogas, tais como: o labirinto em cruz elevado (LCE) e o teste da suspensão pela cauda (TSC). Efeitos sobre a atividade locomotora geral dos animais foram monitorados no campo aberto. Efeitos sedativos foram observados com EF (100 e 300 mg kg-1) e EA (100, 300 e 600 mg kg-1), caracterizados por uma diminuição do número de entradas nos braços fechados do LCE e uma diminuição no número de cruzamentos e levantamentos no campo aberto. No TSC, a administração de EF (100 mg kg-1) ou FA (100 e 300 mg kg-1) resultou em aumento do tempo de imobilidade. Esses resultados são relevantes, pois contribuem para validar o uso popular dessa plant

Avaliação da atividade ansiolítica e antidepressiva do extrato fluido e fração aquosa de folhas de Passiflora alata Curtis em camundongos = Evaluation of anxiolytic and antidepressant activities in mice with fluid extracts and aqueous fraction obtained from the leaves of Passiflora alata

O extrato fluido (EF), preparado segundo a Farmacopéia Brasileira, e sua fração aquosa (FA) obtidos de folhas de Passiflora alata foram administrados por via oral em camundongos. Seus efeitos comportamentais foram avaliados por modelos que detectam a atividade ansiolítica e antidepressiva de drogas, tais como: o labirinto em cruz elevado (LCE) e o teste da suspensão pela cauda (TSC). Efeitos sobre a atividade locomotora geral dos animais foram monitorados no campo aberto. Efeitos sedativos foram observados com EF (100 e 300 mg kg-1) e EA (100, 300 e 600 mg kg-1), caracterizados por uma diminuiçãodo número de entradas nos braços fechados do LCE e uma diminuição no número de cruzamentos e levantamentos no campo aberto. No TSC, a administração de EF (100 mg kg-1) ou FA (100 e 300 mg kg-1) resultou em aumento do tempo de imobilidade. Esses resultados são relevantes, pois contribuem para validar o uso popular dessa planta.The fluid extract (FE), prepared according to the Brazilian Pharmacopoea, obtained from the leaves of Passiflora alata and its aqueous fraction (AF), were administered by oral route to mice, and the behavioural effects were evaluated using animal models that detect anxiolytic and antidepressant activities, such as the elevated plus maze (EPM) and the tail suspension test (TST). Effects on general motor activity were monitored in the open field. Sedativeeffects were observed with FE (100 and 300 mg kg-1) and AF (100, 300 and 600 mg kg-1) and were characterized by a decreased number of entries in the enclosed arms of the EPM and a decrease in the number of crossings and rearing in the open field. In the TST, FE (100 mgkg-1) and AF (100 and 300 mg kg-1) induced an increase in the immobility time. These results are relevant because they contribute to validate the traditional use of this plant

Cannabidiol Exerts a Neuroprotective and Glia-Balancing Effect in the Subacute Phase of Stroke

Pharmacological agents limiting secondary tissue loss and improving functional outcomes after stroke are still limited. Cannabidiol (CBD), the major non-psychoactive component of Cannabis sativa, has been proposed as a neuroprotective agent against experimental cerebral ischemia. The effects of CBD mostly relate to the modulation of neuroinflammation, including glial activation. To investigate the effects of CBD on glial cells after focal ischemia in vivo, we performed time-lapse imaging of microglia and astroglial Ca2+ signaling in the somatosensory cortex in the subacute phase of stroke by in vivo two-photon laser-scanning microscopy using transgenic mice with microglial EGFP expression and astrocyte-specific expression of the genetically encoded Ca2+ sensor GCaMP3. CBD (10 mg/kg, intraperitoneally) prevented ischemia-induced neurological impairment, reducing the neurological deficit score from 2.0 &plusmn; 1.2 to 0.8 &plusmn; 0.8, and protected against neurodegeneration, as shown by the reduction (more than 70%) in Fluoro-Jade C staining (18.8 &plusmn; 7.5 to 5.3 &plusmn; 0.3). CBD reduced ischemia-induced microglial activation assessed by changes in soma area and total branch length, and exerted a balancing effect on astroglial Ca2+ signals. Our findings indicate that the neuroprotective effects of CBD may occur in the subacute phase of ischemia, and reinforce its strong anti-inflammatory property. Nevertheless, its mechanism of action on glial cells still requires further studies

Subchronic administration of Trichilia catigua ethyl-acetate fraction promotes antidepressant-like effects and increases hippocampal cell proliferation in mice

AbstractEthnopharmacological relevanceTrichilia catigua preparations have been popularly used in Brazil as a tonic for the treatment of fatigue, stress, impotence, and memory deficits. We recently demonstrated an antidepressant-like effect of acute administration of the Trichilia catigua ethyl-acetate fraction (EAF) in mice. The aim of the present study was to evaluate whether subchronic Trichilia catigua EAF administration maintains its antidepressant-like effects and whether these effects are related to hippocampal neurogenesis.Material and methodsTrichilia catigua EAF (200 and 400mg/kg) was orally administered to mice for 14 day. The animals were tested in the forced swim test (FST) or tail suspension test (TST). After behavioral testing, the animals received bromodeoxyuridine (BrdU; 200mg/kg, i.p.) and were euthanized 24h, 7 day, or 15 day later. The brains were assayed for BrdU and doublecortin (DCX) immunohistochemistry to detect cell proliferation/survival and neurogenesis, respectively.ResultsSubchronic administration of 400mg/kg Trichilia catigua EAF promoted antidepressant-like effects in mice in both the FST and TST. The antidepressant-like effect was accompanied by an increase in cell proliferation in the dentate gyrus (DG) of the hippocampus 24h after the treatments were discontinued. This proliferative effect, however, did not influence cell survival or neurogenesis because no change in the number of BrdU- or DCX-positive cells was detected 7 or 15 day after the last EAF administration compared with controls.ConclusionsTrichilia catigua EAF produced antidepressant-like effects and induced hippocampal cell proliferation in mice. The results contribute information on the pharmacological and molecular mechanisms involved in the antidepressant-like effect of Trichilia catigua EAF