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 consi dered to be a suppressor of inflammatory cytokine release. The amounts of these modulators that are released by rat brain cultures were meas ured for tissue obtained from rats of different maturational age group s: weanling (3 weeks), young (3 months), and middle-aged (12 months) r ats. Basal levels of brain-derived NO increased with age. This was att ributed to brain microglial-derived NO. Culturing of the brain tissue with LPS or PGE(2) 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 fr om 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 bioactiv e TGF-beta declined with age. LPS and PGE(2) increased the amount of b ioactive TGF-beta released by brain cultures of each rat age group, bu t there nevertheless remained an age-related reduction in active TGF-b eta levels. These results suggest a possible developmental association . between an enhancement of brain-derived NO and a concomitant decline in brain TGF-beta.