VASCULAR FACTORS IN THE NEUROTOXIC DAMAGE CAUSED BY 1,3-DINITROBENZENE IN THE RAT

Using a 3 x 10 mg/kg dose schedule of 1,3-dinitrobenzene(DNB) over two days in Fischer rats, we have found the following changes in vascular function and structure during the early phase of the symmetrical brain stem lesions. 1 Marked increase in cerebral blood flow generally but especially in the inferior colliculi, from 6 h after the final dose of DNB. 2 Increasing incidence of petechial haemorrhages in inferior colliculi, cerebellar roof, vestibular and superior olivary nuclei from 12 h. 3 Focal leakage of horseradish peroxidase and many sleeve-like arteriolar haemorrhages seen in vibratome sections and by scanning electron microscopy (SEM) in these regions from 12 h. 4 Periarteriolar oedema and protein leakage present in step-serial sections in these regions from 12 h, with astrocyte swelling and occasional small infarcts. These changes suggest that the vascular bed may play an important role in the pathogenesis of these lesions, perhaps in parallel with early astroglial damage. They are discussed in relation to (i) the known presence of xanthine oxidase in the vascular bed of the brain and the likelihood of 'useless redox cycling' with free radical generation from this enzyme's interaction with nitroheterocyclic compounds, and (ii) the possible role of free radical damage to endothelial cells in this intoxication and in the analogous lesions of natural and experimental Wernicke's encephalopathy.