RESUMEN
INTRODUCTION: Paclitaxel (PTX) cannot effectively treat glioma because it cannot cross the bloodbrain barrier (BBB). A specific mode electroacupuncture stimulation (SMES) can temporarily open the BBB, thereby improving drug delivery to the brain. This study aimed to observe SMES-mediated accumulation of PTX in the brain and its anti-glioma effect and explore the role of the Hedgehog pathway. METHODS: The acupoint selectivity of SMES in opening the BBB was examined in normal rats. The penetration and anti-glioma activity were determined in a C6-Luc glioma rat model. SMES was performed using 2/100â¯Hz, 3â¯mA, 6-6â¯s, and 40â¯min The survival curve was analysed by the KaplanMeier method, brain tumour pathology and size was observed by HE staining, and in vivo imaging system respectively. RESULTS: SMES-induced BBB opening had acupoint selectivity. SMES could improve PTX accumulation in brain and SMES-mediated PTX delivery showed enhanced anti-glioma activity due to better brain penetration. Hedgehog pathway was involved in SMES-mediated PTX delivery by regulating Occludin expression. CONCLUSION: SMES at the head acupoints to deliver PTX is a feasible and effective method for treating glioma. The Hedgehog pathway may play a key role in SMES-mediated PTX delivery across the BBB.
Asunto(s)
Antineoplásicos Fitogénicos , Barrera Hematoencefálica , Neoplasias Encefálicas , Electroacupuntura , Glioma , Proteínas Hedgehog , Paclitaxel , Animales , Electroacupuntura/métodos , Paclitaxel/farmacología , Proteínas Hedgehog/metabolismo , Glioma/terapia , Glioma/metabolismo , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/metabolismo , Antineoplásicos Fitogénicos/farmacología , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Masculino , Ratas , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Ratas Sprague-Dawley , Línea Celular Tumoral , Encéfalo/metabolismo , Encéfalo/efectos de los fármacosRESUMEN
Cognitive impairment frequently presents as a prevalent consequence following stroke, imposing significant burdens on patients, families, and society. The objective of this study was to assess the effectiveness and underlying mechanism of nerve growth factor (NGF) in treating post-stroke cognitive dysfunction in rats with cerebral ischemia-reperfusion injury (MCAO/R) through delivery into the brain using specific mode electroacupuncture stimulation (SMES). From the 28th day after modeling, the rats were treated with NGF mediated by SMES, and the cognitive function of the rats was observed after treatment. Learning and memory ability were evaluated using behavioral tests. The impact of SMES on blood-brain barrier (BBB) permeability, the underlying mechanism of cognitive enhancement in rats with MCAO/R, including transmission electron microscopy, enzyme-linked immunosorbent assay, immunohistochemistry, immunofluorescence, and TUNEL staining. We reported that SMES demonstrates a safe and efficient ability to open the BBB during the cerebral ischemia repair phase, facilitating the delivery of NGF to the brain by the p65-VEGFA-TJs pathway.