Cannabinoids to treat spinal cord injury

Arévalo-Martı́n, Ángel; Molina‐Holgado, Eduardo; Garcı́a-Ovejero, Daniel

doi:10.1016/j.pnpbp.2015.03.008

Cited by 22 publications

(11 citation statements)

References 155 publications

(196 reference statements)

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“…Although the impact of cannabinoid extracts on MS disease progression remains inconclusive ( Pertwee, 2007 ; Pryce et al, 2015 ), the outlook is optimistic ( Arévalo-Martin et al, 2008 ; Chiurchiu et al, 2015 , 2018 ). Evidence of cannabinoid agonist effects on oligodendrocyte survival and OPC lifecycle suggests their usefulness in CNS pathologies such as demyelination ( Popescu and Lucchinetti, 2012 ; Kutzelnigg and Lassmann, 2014 ), neurodegeneration ( Ettle et al, 2016 ; Tauheed et al, 2016 ), ischemia ( Dewar et al, 2003 ; Mifsud et al, 2014 ), epilepsy ( Friedman and Devinsky, 2015 ; Stockings et al, 2018 ), and traumatic injuries to spinal cord ( Alizadeh and Abdolrezaee-Karimi, 2016 ; Levine, 2016 ; Arevalo-Martin et al, 2016 ) and brain ( Armstrong et al, 2016 ; Takase et al, 2018 ).…”

Section: Perspectivesmentioning

confidence: 99%

The Endocannabinoid System and Oligodendrocytes in Health and Disease

et al. 2018

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Cannabinoid-based interventions are being explored for central nervous system (CNS) pathologies such as neurodegeneration, demyelination, epilepsy, stroke, and trauma. As these disease states involve dysregulation of myelin integrity and/or remyelination, it is important to consider effects of the endocannabinoid system on oligodendrocytes and their precursors. In this review, we examine research reports on the effects of the endocannabinoid system (ECS) components on oligodendrocytes and their precursors, with a focus on therapeutic implications. Cannabinoid ligands and modulators of the endocannabinoid system promote cell signaling in oligodendrocyte precursor survival, proliferation, migration and differentiation, and mature oligodendrocyte survival and myelination. Agonist stimulation of oligodendrocyte precursor cells (OPCs) at both CB1 and CB2 receptors counter apoptotic processes via Akt/PI3K, and promote proliferation via Akt/mTOR and ERK pathways. CB1 receptors in radial glia promote proliferation and conversion to progenitors fated to become oligodendroglia, whereas CB2 receptors promote OPC migration in neonatal development. OPCs produce 2-arachidonoylglycerol (2-AG), stimulating cannabinoid receptor-mediated ERK pathways responsible for differentiation to arborized, myelin basic protein (MBP)-producing oligodendrocytes. In cell culture models of excitotoxicity, increased reactive oxygen species, and depolarization-dependent calcium influx, CB1 agonists improved viability of oligodendrocytes. In transient and permanent middle cerebral artery occlusion models of anoxic stroke, WIN55212-2 increased OPC proliferation and maturation to oligodendroglia, thereby reducing cerebral tissue damage. In several models of rodent encephalomyelitis, chronic treatment with cannabinoid agonists ameliorated the damage by promoting OPC survival and oligodendrocyte function. Pharmacotherapeutic strategies based upon ECS and oligodendrocyte production and survival should be considered.

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Section: Perspectivesmentioning

confidence: 99%

The Endocannabinoid System and Oligodendrocytes in Health and Disease

et al. 2018

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“…In general, both dysregulation and endogenous protection are active in numerous neurodegenerative pathologies, both acute (e.g., stroke [6], brain trauma [7], spinal injury [8]) and chronic progressive disorders (e.g., Alzheimer’s disease [9], Parkinson’s disease [10], Huntington’s chorea [11,12], amyotrophic lateral sclerosis [13,14] and others [2]). Such responses have also been seen in autosomal-dominant spinocerebellar ataxias (SCAs; [15–17]), a group of inherited neurodegenerative disorders that mainly affect the cerebellum and its afferent/efferent structures, in which motor discoordination (“ataxia”) is the key symptom [18–21].…”

Section: Introductionmentioning

confidence: 99%

Altered striatal endocannabinoid signaling in a transgenic mouse model of spinocerebellar ataxia type-3

et al. 2017

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Spinocerebellar ataxia type-3 (SCA-3) is the most prevalent autosomal dominant inherited ataxia. We recently found that the endocannabinoid system is altered in the post-mortem cerebellum of SCA-3 patients, and similar results were also found in the cerebellar and brainstem nuclei of a SCA-3 transgenic mouse model. Given that the neuropathology of SCA-3 is not restricted to these two brain regions but rather, it is also evident in other structures (e.g., the basal ganglia), we studied the possible changes to endocannabinoid signaling in the striatum of these transgenic mice. SCA-3 mutant mice suffer defects in motor coordination, balance and they have an abnormal gait, reflecting a cerebellar/brainstem neuropathology. However, they also show dystonia-like behavior (limb clasping) that may be related to the malfunction/deterioration of specific neurons in the striatum. Indeed, we found a loss of striatal projecting neurons in SCA-3 mutant mice, accompanied by a reduction in glial glutamate transporters that could potentially aggravate excitotoxic damage. In terms of endocannabinoid signaling, no changes in CB2 receptors were evident, yet an important reduction in CB1 receptors was detected by qPCR and immunostaining. The reduction in CB1 receptors was presumed to occur in striatal afferent and efferent neurons, also potentially aggravating excitotoxicity. We also measured the endocannabinoid lipids in the striatum and despite a marked increase in the FAAH enzyme in this area, no overall changes in these lipids were found. Collectively, these studies confirm that the striatal endocannabinoid system is altered in SCA-3 mutant mice, adding to the equivalent changes found in other strongly affected CNS structures in this type of ataxia (i.e.: the cerebellum and brainstem). These data open the way to search for drugs that might correct these changes.

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“…The relevance of this combination of effects is that they ultimately promote neuron survival in chronic neurodegenerative disorders (Fernández‐Ruiz, 2019), a property that also can be extended to acute degeneration conditions (e.g. stroke, brain trauma and spinal injury) (Arevalo‐Martin et al, 2016; Kolb et al, 2019; Shohami et al, 2011).…”

Section: Cannabinoids and Neuroprotectionmentioning

confidence: 99%

Targeting the CB₂ receptor and other endocannabinoid elements to delay disease progression in amyotrophic lateral sclerosis

Rodríguez‐Cueto

García-Toscano

Santos‐García

et al. 2021

British J Pharmacology

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Cannabinoids form a singular group of plant‐derived compounds, endogenous lipids and synthetic derivatives with multiple therapeutic effects exerted by targeting different elements of the endocannabinoid system. One of their therapeutic applications is the preservation of neuronal integrity exerted by attenuating the multiple neurotoxic events that kill neurons in neurodegenerative disorders. In this review, we will address the potential of cannabinoids as neuroprotective agents in amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disorder characterized by muscle denervation, atrophy and paralysis, and progressive deterioration in upper and/or lower motor neurons. The emphasis will be paid on the cannabinoid type 2 (CB2) receptor, whose activation limits glial reactivity, but the potential of additional endocannabinoid‐related targets will be also addressed. The evidence accumulated so far at the preclinical level supports the need to soon move towards the patients and initiate clinical trials to confirm the potential of cannabinoid‐based medicines as disease modifiers in ALS. LINKED ARTICLES This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc

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Cannabinoids to treat spinal cord injury

Cited by 22 publications

References 155 publications

The Endocannabinoid System and Oligodendrocytes in Health and Disease

The Endocannabinoid System and Oligodendrocytes in Health and Disease

Altered striatal endocannabinoid signaling in a transgenic mouse model of spinocerebellar ataxia type-3

Targeting the CB₂ receptor and other endocannabinoid elements to delay disease progression in amyotrophic lateral sclerosis

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Cannabinoids to treat spinal cord injury

Cited by 22 publications

References 155 publications

The Endocannabinoid System and Oligodendrocytes in Health and Disease

The Endocannabinoid System and Oligodendrocytes in Health and Disease

Altered striatal endocannabinoid signaling in a transgenic mouse model of spinocerebellar ataxia type-3

Targeting the CB2 receptor and other endocannabinoid elements to delay disease progression in amyotrophic lateral sclerosis

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Targeting the CB₂ receptor and other endocannabinoid elements to delay disease progression in amyotrophic lateral sclerosis