Production of nitric oxide and transforming growth factor-beta in developing and adult rat brain

Nitric oxide (NO) has been suggested to have a neurotoxic role in the brain, while transforming growth factor-beta (TGF-beta) has been considered to be a suppressor of inflammatory cytokine release. The amounts of these modulators that are released by rat brain cultures were measured for tissue obtained from rats of different maturational age groups: weanling (3 weeks), young (3 months), and middle-aged (12 months) rats. Basal levels of brain-derived NO increased with age. This was attributed to brain microglial-derived NO. Culturing of the brain tissue with LPS or PGE2 further increased the amount of NO elaborated from brain cultures of 3-week-old and 3-month-old rats to a level that was similar to the high amounts detected in unstimulated brain cultures from 12-month-old rats. Stimulation of brain cultures from 12-month-old rats did not further enhance NO levels. In contrast to the maturation-associated increase in NO production, levels of brain-derived bioactive TGF-beta declined with age. LPS and PGE2 increased the amount of bioactive TGF-beta released by brain cultures of each rat age group, but there nevertheless remained an age-related reduction in active TGF-beta levels. These results suggest a possible developmental association between an enhancement of brain-derived NO and a concomitant decline in brain TGF-beta.