Lipopolysaccharide decreases cochlear blood flow dose dependently in a guinea pig animal model via TNF signaling

Abstract

Acute otitis media is one of the most common infectious diseases, affecting up to 11% of the worldwide population, reflecting between 300 and 700 million patients per year. 1 About half the patients affected are children, 1 and otitis media (including its chronic forms) is responsible for up to 3.200 deaths per year. 2 About 140 million patients retain a hearing impairment after acute otitis media each year, which can be caused by persisting perforation of the tympanic membrane or suppurative labyrinthitis and subsequent sensorineural hearing loss. 3

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

“…Firstly, we have been able to show that lipopolysaccharide may significantly decrease cochlear blood flow. This is in line with previous similar observations (12). The changes observed in cochlear blood flow are similar to those observed in noise-damaged cochlea (6), which supports the view that the changes observed in the experiment at hand are physiologically significant.…”

“…These observations further support the concept of a vicious cycle that has been put forward previously (12). In brief, impairment of microcirculation causes a drop in partial oxygen pressure (4) which in turn is lacking as an acceptor for electrons, causing formation of reactive oxygen species (29).…”

“…Moreover, we were able to show that agonism at the CB2-Receptor is capable of abrogating those effects of LPS on cochlear microcirculation, which is a key step in long-term inflammatory damage to the cochlea (12). This is most likely by downregulation of the TNF pathway, as CB 2 -Agonism has shown to reduce TNF secretion in inner hair cells in vitro (16).…”

“…JWH-133 had been chosen as it is one of the most potent selective CB2-agonists commercially available. The LPS concentration was chosen since it had shown a significant decrease in cochlear microcirculation after a 20-minute application in a different experiment (12).…”

“…Moreover, it has been shown that the tumor necrosis factor (TNF) pathway plays a major role in cochlear inflammation. In turn, there are numerous observation that inhibition of TNF may be beneficial in several inner ear pathologies, like acoustic trauma (6) and suppurative labyrinthitis (12).…”