S100 protein is expressed primarily by astroglia in the brain, and accumulates in and around the ischemic lesions.
Arundic acid, a novel astroglia-modulating agent, is neuroprotective in acute
cerebral infarction, whereas the protective effects remain unknown during chronic cerebral hypoperfusion. Rats undergoing chronic cerebral hypoperfusion were subjected to a bilateral
ligation of the common carotid arteries, and were allowed to survive for 3, 7 and 14 days. The animals received a daily
intraperitoneal injection of 5.0, 10.0 or 20.0 mg/kg of
arundic acid, or vehicle, for 14 days. Alternatively, other groups of rats received a delayed
intraperitoneal injection of 20.0 mg/kg of
arundic acid or vehicle, which started from 1, 3 or 7 days after
ligation and continued to 14 days. The degree of white matter (WM) lesions and the numerical density of
S100 protein-immunoreactive astroglia were estimated. In the WM of rats with vehicle
injections, the number of
S100 protein-immunoreactive astroglia increased significantly after chronic cerebral hypoperfusion as compared to the
sham-operation. A dosage of 10.0 and 20.0 mg/kg of
arundic acid suppressed the numerical increase in
S100 protein-immunoreactive astroglia and the WM lesions. These pathological changes were suppressed with
delayed treatment up to 7 days in terms of astroglial activation, and up to 3 days in terms of the WM lesions. The protective effects of
arundic acid against WM lesions were demonstrated in a dose-dependent manner, and even after postischemic treatments. These results suggest the potential usefulness of
arundic acid in the treatment of cerebrovascular WM lesions.