Poster Sessions

Neu-1

Saba Aid

S. Aid, A. C. Silva, F. Bosetti

Cyclooxygenase-2 Exerts a Neuroprotective Role during Acute Neuroinflammation

Cyclooxygenases (COX) -1 and -2 play a key role in inflammation. COX-2 is generally inducible by inflammatory stimuli, however, in the brain, COX-2 is constitutively expressed and may be involved in the production of neuroprotective lipid mediators. To clarify the role of COX-2 in neuroinflammation, we subjected mice with a genetic deletion in COX-2 (COX-2-/-) to a single intracerebroventricular injection of lipopolysaccharide (LPS). 24 h after LPS, COX-2-/- showed increased neuronal damage, increased glial activation and increased expression of markers of inflammation and oxidative stress, such as cytokines, chemokines and NADPH oxidase subunit p67phox. Mice treated for 6 weeks with celecoxib, a selective COX-2 inhibitor, prior to LPS also exhibited higher brain levels of IL-1beta and p67phox compared to non-treated mice. COX-1 expression was similar in all groups, suggesting that the effects we observed are not mediated by COX-1. Since chemokines are involved in the trafficking and the recruitment of leukocytes into the inflamed brain, we examined Blood-Brain Barrier (BBB) integrity using quantitative Magnetic Resonance Imaging. We found that LPS-induced BBB disruption was increased in COX-2-/- compared to wild-type mice. In summary, COX-2 inhibition worsens the neuroinflammatory response to LPS, suggesting a neuroprotective function of COX-2 derived products.