Abstract
Neurological disorders such as neurodegenerative diseases or traumatic brain injury are associated with cognitive, motor and behavioural changes that influence the quality of life of the patients. Although different therapeutic strategies have been developed and tried until now to decrease the neurological decline, no treatment has been found to cure these pathologies. In the last decades, the implication of the endocannabinoid system in the neurological function has been extensively studied, and the cannabinoids have been tried as a new promising potential treatment. In this study, we aimed to overview the recent available literature regarding in vivo potential of natural and synthetic cannabinoids with underlying mechanisms of action for protecting against cognitive decline and motor impairments. The results of studies on animal models showed that cannabinoids in traumatic brain injury increase neurobehavioral function, working memory performance, and decrease the neurological deficit and ameliorate motor deficit through down-regulation of pro-inflammatory markers, oedema formation and blood–brain barrier permeability, preventing neuronal cell loss and up-regulating the levels of adherence junction proteins. In neurodegenerative diseases, the cannabinoids showed beneficial effects in decreasing the motor disability and disease progression by a complex mechanism targeting more signalling pathways further than classical receptors of the endocannabinoid system. In light of these results, the use of cannabinoids could be beneficial in traumatic brain injuries and multiple sclerosis treatment, especially in those patients who display resistance to conventional treatment.
Highlights
Neurological disorders that affect different subsets of neurons such as neurodegenerative diseases (NDs) are associated with several cognitive, motor and behavioural changes that influence the quality of life of patients and the evolution and prognosis of the disease [1,2,3]
We aimed to review the recent available literature regarding the in vivo potential of cannabinoids in protecting against cognitive decline and motor impairments that appear in acute brain injury and chronic brain injury
We identify 13 studies that evaluate the protective effects of synthetic cannabinoids active as CB2R agonists as HU-910 and HU-914 [44], JWH133 [45,46,54], GP1a [47], SMM-189 [1,49,51], ACEA [52], 0-1966 [57,60], KN38-7271 [59], ACEA [52] in Traumatic Brain Injury (TBI) animal models, 2 studies that evaluated the protective effect of natural cannabinoid CBD [48,58] in TBI animal models, 1 study that evaluated the beneficial effect of exogenous administration of the AraS endocannabinoid in TBI animal models [56] and 2 studies that evaluated the protective effect of increasing the endocannabinoid levels in TBI animal models by inhibiting the enzymes that metabolize the endocannabinoids as fatty acid amide hydrolase (FAAH) [53] and ABHD6 [55]
Summary
Neurological disorders that affect different subsets of neurons such as neurodegenerative diseases (NDs) are associated with several cognitive, motor and behavioural changes that influence the quality of life of patients and the evolution and prognosis of the disease [1,2,3]. Cognitive decline and motor impairments are usually associated with patients affected by neurodegeneration [6]. The cognitive, behavioural and motor impairment is determined by the death of neurons in different regions of the central nervous system (CNS), and it cannot be treated. Even if a lot of progress has been made to understand the mechanism implicated in the pathogenesis of cognitive and motor impairment in neurodegenerative and brain injuries [9,10,11], no treatment has been found to cure these pathologies. Several strategies and therapies have been developed and tried until now to treat some symptoms and to decrease the neurological decline in order to improve the quality of life of patients [12], and many others underwent preclinical testing [13,14]
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