Regional brain bioamine levels under hyperbaric oxygen in two unequally susceptible strains of mice

Background: Hyperbaric oxygen (HBO) increases monoamine deamination with re lated toxic products which aggravates hyperbaric oxygen (HBO) neurotoxicity . However, the possibility of some protective action of monoamines balanced by the toxicity of their metabolites have received little attention. Hypot hesis: To try to unmask this protective action, we compared brain monoamine levels in two strains of mice differing in HBO-sensitivity and their sensi tivity to HBO after norepinephrine (NE) depletion by N-(2-chloroethyl)-N-et hyl-2-bromo benzylamine (DSP4). Methods: Mice were exposed to 6 ATA O-2 for 90 min (C57 strain) and 24 min (HBO-sensitive CD1 strain) so that 50% of m ice of each strain had preconvulsive symptoms when decompressed and 50% had one generalized convulsion. After microwave sacrifice, monoamines in the c erebral cortex, the striatum and the brainstem were analyzed. Another serie s studied the effect of DSP4 on the delay to symptoms of these HBO-exposed mice. Results: NE normoxic levels in the striatum were greater in the HBO-s ensitive CD1 than in the C57 strain. Under HBO, NE levels in the striatum a nd the cortex of CD1 fell without any concomitant increase in its metabolit e whereas in the C57 strain, NE decreased less and its metabolite increased . There was no strain difference and little change in the NE levels in the brainstem. The increase in toxicity induced by DSP4 was highly significant in both strains; moreover C57 strain was more affected than CD1. Conclusion : Monoamine depletion before HBO aggravates HBO neurotoxicity. As monoamine deamination is known to be toxic, this demonstrates that monoaminergic act ivation is protective. The greater toxicity of DSP4 in the C57 strain sugge sts the involvement of monoamines in the strain-differential susceptibility to HBO. The lower sensitivity of CD1 mice to DSP4 may be related to a comb ination of less NE activation under HBO that in C57 and greater activation of peroxidation and amino acids in CD1 sensitive strain.