Cannabinoid Receptor 2 Agonism is Capable of Preventing Lipopolysaccharide Induced Decreases of Cochlear Microcirculation – A Potential Approach for Inner Ear Pathologies

Abstract

Hypothesis:The ability of JWH-133, an agonist at the cannabinoid receptor 2, to abrogate the effects of lipopolysaccharide on cochlear microcirculation was investigated. Background: Cochlear inflammation and subsequent impairment of microcirculation is part of numerous pathologies affecting inner ear function, including suppurative labyrinthitis, noise trauma, and sudden sensorineural hearing loss. One way of causing cochlear inflammation is exposing the cochlea to lipopolysaccharide, a bacterial endotoxin. Methods: Twenty Dunkin-hartley guinea pigs were divided into four groups of five animals each. Two groups received topic treatment with JWH-133 and two received treatment with placebo. One group that had been treated with JWH-133 and one with placebo were then exposed to lipopolysaccharide or placebo, respectively. Cochlear microcirculation was quantified before, in between and after treatments by in vivo fluorescence microscopy. Results: Significantly different changes in cochlear blood flow were only seen in the group that was treated with placebo and subsequently lipopolysaccharide. Every other group showed no significant change in cochlear blood flow. Conclusion: JWH-133 is capable of abrogating the effects of lipopolysaccharide on cochlear microcirculation. It may therefore be clinical interest in treating numerous inflammation associated cochlear pathologies.

Resveratrol Ameliorates Lipopolysaccharide-Induced Sudden Sensorineural Hearing Loss in In Vitro Model through Multitarget Antiapoptotic Mechanism Based on Network Pharmacology and Molecular Docking

“…The etiology of SSNHL remains unclear, which may be related to hair cell apoptosis and damage caused by inflammatory responses, viral infection, microcirculation disturbance, and other factors, because inflammation can result in microvascular damage [ 25 ], atherosclerosis [ 26 ], and cochlear immune responses [ 27 ]; in vivo experiments have shown that LPS-stimulated guinea pigs have severe cochlear microcirculation disturbance [ 28 ]. Therefore, inflammation is considered to be an important cause of SSNHL.…”

Understanding the role of inflammation in sensorineural hearing loss: Current goals and future prospects

“…For example, Weiss et al. found that the cannabinoid receptor 2 (CNR2) agonist (JWH‐133) prevented LPS‐induced reductions in the cochlear microcirculation, thereby reducing inflammation in guinea pigs [103] . Kim et al.…”

“…For example, Weiss et al found that the cannabinoid receptor 2 (CNR2) agonist (JWH-133) prevented LPS-induced reductions in the cochlear microcirculation, thereby reducing inflammation in guinea pigs. [103] Kim et al found that immune checkpoints are crucial in regulating immune activation, which is a promising strategy for treating chronic inflammation. Programmed Cell Death Protein-1 (PD-1) monocytes are novel biomarkers and therapeutic targets for cerebral vasospasm following aneurysmal subarachnoid hemorrhages.…”

Potential effects of cannabinoids on audiovestibular function: A narrative review

“…CB2 antagonists reverse this effect ( Ghosh et al, 2018 ). Furthermore, another pharmacological agonist (JWH-133) activates CB2 receptors, produces an anti-inflammatory effect in the inner ear, and increases microcirculation following exposure to bacterial endotoxins ( Weiss et al, 2021 ). Although these results appear promising, they were performed in animal models, and therefore the translational implications for humans are quite limited given the absence of studies in this regard.…”