Cannabinoids as Glial Cell Modulators in Ischemic Stroke: Implications for Neuroprotection

Vicente-Acosta, Andrés; Ceprián, María; Sobrino, Pilar; Pazos, M. Ruth; Loría, Frida

doi:10.3389/fphar.2022.888222

Cited by 6 publications

(3 citation statements)

References 290 publications

(481 reference statements)

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“…These effects are mediated through cell‐autonomous or non‐cell‐autonomous mechanisms after ischemic stroke. [ 158 , 159 ] These dynamic changes depend on astrocyte interaction with microglia, neurons, and oligodendrocytes. [ 159 , 160 ] Furthermore, reactive astrocytes release pro‐inflammatory cytokines, such as IL‐1β, IL‐6, and TNF‐α, actively participating in the inflammatory process after an ischemic stroke.…”

Section: Pathophysiological Mechanisms Following Stroke‐heart Interac...mentioning

confidence: 99%

Stroke Related Brain–Heart Crosstalk: Pathophysiology, Clinical Implications, and Underlying Mechanisms

Fan,

Cao,

et al. 2024

Advanced Science

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The emergence of acute ischemic stroke (AIS) induced cardiovascular dysfunctions as a bidirectional interaction has gained paramount importance in understanding the intricate relationship between the brain and heart. Post AIS, the ensuing cardiovascular dysfunctions encompass a spectrum of complications, including heart attack, congestive heart failure, systolic or diastolic dysfunction, arrhythmias, electrocardiographic anomalies, hemodynamic instability, cardiac arrest, among others, all of which are correlated with adverse outcomes and mortality. Mounting evidence underscores the intimate crosstalk between the heart and the brain, facilitated by intricate physiological and neurohumoral complex networks. The primary pathophysiological mechanisms contributing to these severe cardiac complications involve the hypothalamic‐pituitary‐adrenal (HPA) axis, sympathetic and parasympathetic hyperactivity, immune and inflammatory responses, and gut dysbiosis, collectively shaping the stroke‐related brain–heart axis. Ongoing research endeavors are concentrated on devising strategies to prevent AIS‐induced cardiovascular dysfunctions. Notably, labetalol, nicardipine, and nitroprusside are recommended for hypertension control, while β‐blockers are employed to avert chronic remodeling and address arrhythmias. However, despite these therapeutic interventions, therapeutic targets remain elusive, necessitating further investigations into this complex challenge. This review aims to delineate the state‐of‐the‐art pathophysiological mechanisms in AIS through preclinical and clinical research, unraveling their intricate interplay within the brain–heart axis, and offering pragmatic suggestions for managing AIS‐induced cardiovascular dysfunctions.

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Section: Pathophysiological Mechanisms Following Stroke‐heart Interac...mentioning

confidence: 99%

Stroke Related Brain–Heart Crosstalk: Pathophysiology, Clinical Implications, and Underlying Mechanisms

Fan,

Cao,

et al. 2024

Advanced Science

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“…Activation of CB1R in astrocytes has been linked to the regulation of metabolic activities, enhancing processes crucial for supplying energy to the brain, such as glucose oxidation and ketogenesis. Considering the role of perivascular astrocytes in delivering energy to neurons, the activation of astrocytic CB1R may have implications for regulating the energy supply to neurons [ 146 , 147 , 148 , 149 ].…”

Section: Ecs–glia Axis: Molecular Mechanisms and Cellular Interactionsmentioning

confidence: 99%

Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders

Camberos-Barraza,

Camacho-Zamora,

Bátiz-Beltrán

et al. 2024

IJMS

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The relationship between sleep, glial cells, and the endocannabinoid system represents a multifaceted regulatory network with profound implications for neuroinflammation and cognitive function. The molecular underpinnings of sleep modulation by the endocannabinoid system and its influence on glial cell activity are discussed, shedding light on the reciprocal relationships that govern these processes. Emphasis is placed on understanding the role of glial cells in mediating neuroinflammatory responses and their modulation by sleep patterns. Additionally, this review examines how the endocannabinoid system interfaces with glia-immune signaling to regulate inflammatory cascades within the central nervous system. Notably, the cognitive consequences of disrupted sleep, neuroinflammation, and glial dysfunction are addressed, encompassing implications for neurodegenerative disorders, mood disturbances, and cognitive decline. Insights into the bidirectional modulation of cognitive function by the endocannabinoid system in the context of sleep and glial activity are explored, providing a comprehensive perspective on the potential mechanisms underlying cognitive impairments associated with sleep disturbances. Furthermore, this review examines potential therapeutic avenues targeting the endocannabinoid system to mitigate neuroinflammation, restore glial homeostasis, and normalize sleep patterns. The identification of novel therapeutic targets within this intricate regulatory network holds promise for addressing conditions characterized by disrupted sleep, neuroinflammation, and cognitive dysfunction. This work aims to examine the complexities of neural regulation and identify potential avenues for therapeutic intervention.

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“…Although recombinant tissue plasminogen activator (rtPA) is the most common drug used for treating ischemic stroke, its effectiveness on thrombolysis and neuroprotection is limited due to a narrow time window and potential risks ( 2 ). Despite extensive research, many neuroprotective drugs have failed in clinical trials due to poor targeting, a lack of effectiveness and potential off-target effects ( 3 ). Therefore, new therapeutic strategies are required to enhance neuronal cell survival and regeneration following ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

Netrin-1 controls inflammation in response to ischemic stroke through altering microglia phenotype

et al. 2023

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IntroductionThe current approaches that are used to treat ischemic stroke suffer from poor targeting, lack of effectiveness, and potential off-target effects, necessitating the development of new therapeutic strategies to enhance neuronal cell survival and regeneration. This study aimed to investigate the role of microglial Netrin-1 in ischemic stroke, a topic that has not been fully understood.MethodsNetrin-1 levels and its primary receptor expressions were investigated in cerebral microglia from acute ischemic stroke patients and age-matched control subjects. A public database (GEO148350), which supplied RNAseq results for rat cerebral microglia in a middle cerebral artery occlusion (MCAO) model, was analyzed to assess the expression of Netrin-1, its major receptors, and genes related to macrophage function. A microglia-specific gene targeting approach and a delivery system allowing for crossing the blood-brain barrier were applied in a mouse model for ischemic stroke to investigate the role of microglial Netrin-1. Netrin-1 receptor signaling in microglia was observed and the effects on microglial phenotype, apoptosis, and migration were analyzed.ResultsAcross human patients, rat and mouse models, activation of Netrin-1 receptor signaling was mainly conducted via its receptor UNC5a in microglia, which resulted in a shift in microglial phenotype towards an anti-inflammatory or M2-like state, leading to a reduction in apoptosis and migration of microglia. Netrin-1-induced phenotypic change in microglia exerted protective effects on neuronal cells in vivo during ischemic stroke.ConclusionOur study highlights the potential of targeting Netrin-1 and its receptors as a promising therapeutic strategy for promoting post-ischemic survival and functional recovery.

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Cannabinoids as Glial Cell Modulators in Ischemic Stroke: Implications for Neuroprotection

Cited by 6 publications

References 290 publications

Stroke Related Brain–Heart Crosstalk: Pathophysiology, Clinical Implications, and Underlying Mechanisms

Stroke Related Brain–Heart Crosstalk: Pathophysiology, Clinical Implications, and Underlying Mechanisms

Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders

Netrin-1 controls inflammation in response to ischemic stroke through altering microglia phenotype

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