Nitric oxide (NO) and
reactive oxygen species are both implicated in neuronal death due to
cerebral ischemia.
BN 80933, an original compound associating an inhibitor of neuronal
NO synthase with an
antioxidant, has been shown to reduce functional and histological damage in rat submitted to
cerebral ischemia. The aim of the present study was to confirm these results in mice and to further examine the effects of
BN 80933 on inflammatory response, including blood-brain barrier (BBB) disruption,
brain edema, and neutrophil infiltration after transient
middle cerebral artery occlusion (MCAO).
Intravenous administration of
BN 80933 at 3 and 10 mg/kg 3 h after MCAO significantly reduced by 26 to 36% the
infarct volume evaluated 24 and 48 h after
ischemia, and improved the neurological score. Furthermore,
BN 80933 at both dosages decreased by 42 to 75% the extravasation of
Evans blue in brain parenchyma observed 24 h after
ischemia. This reduction in BBB disruption was associated with decreased
brain edema as demonstrated by the 37% reduction in brain water content induced by
BN 80933 at 3 mg/kg 24 h after MCAO. Neutrophil infiltration in brain parenchyma, evaluated by the
myeloperoxidase activity, was also reduced by 45 to 56% in animals treated with
BN 80933 at 3 and 10 mg/kg. Together, these results extend the protective capacity of
BN 80933 against brain ischemic injury and confirm that
BN 80933 represents a promising treatment for
stroke.