Palabras clave
Cannabidiol
Fenobarbital
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Resumen
Objetivo: Evaluar los efectos de la administración transdérmica de cannabidiol (CBD), solo o en combinación con fenobarbital, sobre los cambios conductuales, histopatológicos y oxidativos en un modelo experimental de epilepsia inducida por pilocarpina. Métodos: Setenta y dos ratas Wistar se dividieron en ocho grupos experimentales, se les indujo epilepsia por pilocarpina y se trataron transdérmicamente durante 30 días con formulaciones que contenían CBD y/o fenobarbital. Se realizaron pruebas de comportamiento en un laberinto elevado en cruz y en un campo abierto, junto con análisis histopatológicos e histomorfométricos del hipocampo, así como la evaluación de marcadores de estrés oxidativo. Las formulaciones nanoestructuradas también se caracterizaron por su estabilidad fisicoquímica. Resultados: Los grupos tratados con CBD mostraron una reducción de la hiperexcitabilidad neuronal, una mejoría conductual y una disminución de la actividad locomotora. Se observó una menor mortalidad neuronal, una reducción de la gliosis y una preservación parcial de la arquitectura del hipocampo, especialmente en el grupo CBD35. Este grupo también demostró una mejor respuesta antioxidante, con mayor actividad de la superóxido dismutasa y mantenimiento parcial de la catalasa. Conclusión: La administración transdérmica de CBD, particularmente en combinación con fenobarbital, demostró potencial neuroprotector y antioxidante en el modelo experimental de epilepsia, lo que la convierte en una estrategia terapéutica prometedora.
Referencias
AEBI H. Oxygen radicals in biological systems. Methods Enzymology, 1984; 105: 121-126.
AGRAWAL S, et al. Hippocampal neuronal loss and cognitive decline in LATE-NC and ADNC among community-dwelling older persons. Alzheimer’s & Dementia, 2025; 21(2): e14500.
ARSHAD MN, NAEGELE JR. Aberrant adult neurogenesis in intractable epilepsy: can GABAergic progenitor transplantation normalize this process? Neural Regeneration Research, 2024; 19(7): 1419-1420.
ASSADPOUR E, et al. Cannabidiol-Loaded Nanocarriers and Their Therapeutic Applications. Pharmaceuticals (Basel). 2023 Mar 24;16(4):487. doi: 10.3390/ph16040487.
BENZIE IF, STRAIN JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Analytical Biochemistry, 1996; 239(1): 70-76.
BLESSING EM, et al. Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics, 2015; 12(4): 825-836.
CAMPOS AC, et al. Cannabidiol, neuroprotection and neuropsychiatric disorders. Pharmacological Research, 2016; 112: 119-127.
CASTILLO-ARELLANO J, et al. The polypharmacological effects of cannabidiol. Molecules, 2023; 28: 3271.
DIAS FCR, et al. Hydroalcoholic extract of Pfaffia glomerata alters the organization of the seminiferous tubules by modulating the oxidative state and the microstructural reorganization of the mice testes. Journal of Ethnopharmacology, 2019; 233: 179-189.
DO VAL-DA SILVA RA, et al. Protective effects of cannabidiol against seizures and neuronal death in a rat model of mesial temporal lobe epilepsy. Frontiers in Pharmacology, 2017; 8: 131.
GHOSH S, et al. Pharmacological and therapeutic approaches in the treatment of epilepsy. Biomedicines, 2021; 9(5): 470.
GUTTERRIDGE JMC, HALLIWELL B. The measurement and mechanism of lipid peroxidation in biological systems. Trends in Biochemical Sciences, 1990; 15: 129-135.
HABIG WH, et al. Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry, 1974; 249(22): 7130-7139.
HAMPSON AJ, et al. Cannabidiol and (-)Δ9-tetrahydrocannabinol are neuroprotective antioxidants. Proceedings of the National Academy of Sciences, 1998; 95(14): 8268-8273.
HILL MN, et al. Cannabidiol and its potential therapeutic effects: a review of the neurobiological mechanisms. Journal of Neuroscience Research, 2021; 41(2): 148-161.
IBEAS BIH C, et al. Molecular targets of cannabidiol in neurological disorders. Journal of Neuroinflammation, 2015; 12: 71.
KREZYMON A, et al. Modifications of hippocampal circuits and early disruption of adult neurogenesis in the Tg2576 mouse model of Alzheimer’s disease. PLoS One, 2013; 8(9): e76497.
KREZYMON A, et al. Modifications of hippocampal circuits and early disruption of adult neurogenesis in the Tg2576 mouse model of Alzheimer’s disease. PLoS One, 2013; 8(9): e76497.
LODZKI M, et al. Cannabidiol-transdermal delivery and anti-inflammatory effect in a murine model. Journal of Controlled Release, 2003; 93(3): 377-387.
LOWRY OH, et al. Protein measurement with the folin phenol reagent. Analytical Biochemistry, 1951; 193: 265-275.
MAHMOUDINOODEZH H, et al. The transdermal delivery of therapeutic cannabinoids. Pharmaceutics, 2022; 14(2): 438.
MILLAR SA, et al. A systematic review on the pharmacokinetics of cannabidiol in humans. Frontiers in Pharmacology, 2018; 9: 1365.
PARENT JM, LOWENSTEIN DH. Seizure-induced neurogenesis: are more new neurons good for an adult brain? Progress in Brain Research, 2002; 135: 121-131.
RICART-JANÉ D, et al. Anticoagulants and other preanalytical factors interfere in plasma nitrate/nitrite quantification by the Griess method. Nitric Oxide - Biology and Chemistry, 2002; 6: 178-185.
SEIBENHENER ML, WOOTEN MC. Use of the open field maze to measure locomotor and anxiety-like behavior in mice. Journal of Visualized Experiments, 2015; 96: e52434.
SIDDIQUI IA, et al. Protective effects of black tea extract on testosterone induced oxidative damage in prostate. Cancer Letters, 2005; 227: 125-132.
SIERRA A, et al. Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell, 2010; 7(4): 483-495.
TASKER RC. Hippocampal selective regional vulnerability and development. Developmental Medicine & Child Neurology, 2008; 43: 6-7.
TOMSON T, et al. The pharmacological treatment of epilepsy in adults. Epileptic Disorders, 2023.
VERHEIJEN ME, et al. The pharmacology of cannabidiol in neurological disorders. Journal of Psychopharmacology, 2020; 34: 418-429.
WEN X, MA H. Cytoplasmic vacuolization: a fascinating morphological alteration from cellular stress to cell death. Cancer Science, 2025; 116(5): 1181-1192.
BERG AT, et al. FDA patient-focused drug development guidances: considerations for trial readiness in rare developmental and epileptic encephalopathies. Neurology, 2024; 102: e207958.
CAVALHEIRO EA, et al. Estudos sobre epilepsia experimental e neuroproteção. Revista Brasileira de Neurologia, 1991; 30: 12-20.
LISTER RG. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology, 1987; 92: 180-185.
MAKARIEVA LM, et al. Morphological and morphometric description of neurons of the sensorimotor cortex of the rat brain after ligation of the common carotid arteries. Journal of Anatomy and Histopathology, 2022; 11(1): 49-58.
MCCLEMENTS DJ. Nanoemulsions versus microemulsions: terminology, differences, and similarities. Soft Matter, 2012; 8: 1719-1729.
TISHKINA AO, et al. Chronic stress induces nonapoptotic neuronal death in the rat hippocampus. Doklady Biological Sciences, 2009; 428(1): 403-406.
VERHEIJEN ME, et al. The pharmacology of cannabidiol in the treatment of neurological disorders. Journal of Psychopharmacology, 2020; 34(4): 418-429.
ZULFIQAR NS. Pyramidal layer thinning, shrunken neurons and deep vacuolation in hippocampus due to organic lead-induced toxicity. 2014.