How does toluene inhalation damage the brain? We just had a discussion about toluene abuse. It is known, that people inhaling toluene for a long time have significant brain damage, including decreased intelligence. I found that toluene is a lipid solvent, and that it can damage the myelin. However, myelin is only present in the white matter, but intelligence is related to the grey matter which does not contain myelin. Is there any indirect damage, or did we miss some important point in this case? Second, how does toluene get to the brain? Is it able to infiltrate from the nose through the mucous membrane, or is it carried in the blood? I am just curious.

> After crossing the blood-brain barrier, toluene, along with other volatile anesthetic agents, had been previously thought to inhibit neuronal transmission by causing a change in membrane or membrane protein conformation. Recent research has shown that interactions with several key brain neurotransmitters, mainly γ-aminobutyric acidA (GABA), to a lessor degree glycine, and possibly dopamine, are responsible for the clinical effects seen. Postmortem studies along with magnetic resonance imaging (MRI) findings have shown diffuse white matter demyelination and gliosis (solvent vapor/toluene leukoencephalopathy), which is postulated to be the end product by which chronic toxicity occurs, although the exact mechanism by which this occurs remains unclear

(McKeown at al. Toluene Toxicity).