Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models.

Summary

Noise-induced hearing loss triggered a neuroinflammatory response, elevated proinflammatory cytokines and microglial activation, in the primary auditory cortex of rodents. Genetically deleting or pharmacologically blocking tumour necrosis factor alpha (TNF-α) prevented both the inflammation and the behavioural signs of tinnitus, while infusing TNF-α directly into the auditory cortex produced tinnitus even in normal-hearing animals. Pharmacologically depleting microglia also prevented tinnitus. At the synaptic level, noise increased excitatory and decreased inhibitory currents onto cortical pyramidal neurons, an imbalance fully prevented by blocking TNF-α, implicating neuroinflammation as a causal driver and a therapeutic target.

Key findings

• Noise-induced hearing loss caused proinflammatory cytokine release and microglial activation in the primary auditory cortex.
• Knocking out or pharmacologically blocking TNF-α prevented tinnitus; infusing TNF-α into the cortex induced tinnitus even in normal-hearing mice (necessity and sufficiency).
• Depleting microglia also prevented noise-induced tinnitus.
• Noise shifted cortical synapses toward excitation (more excitatory, less inhibitory input); blocking TNF-α fully prevented this imbalance.