We investigated the effects of the combination of
idebenone, an energy metabolism enhancer, and
manidipine 2HCl, a
dihydropyridine-derivative
calcium antagonist, on neurological deficits and histological changes in the brain and kidneys of
stroke-prone spontaneously hypertensive rats (SHRSP) with cerebrovascular lesions (
stroke). The SHRSP were kept on a 1% NaCl
solution as their
drinking water to synchronize the onset of
stroke. After the onset of
stroke symptoms, the
salt solution was replaced with tap water. On the day following the onset of
stroke,
idebenone (50 mg/kg),
manidipine 2HCl (2 mg/kg) or a combination of
idebenone (50 mg/kg) and
manidipine 2HCl (2 mg/kg) was administered orally once a day for 3 weeks. In the combination group and
manidipine 2HCl-treated group, the neurological deficits after the onset of
stroke were ameliorated during the entire experimentalperiod. Especially, the combination significantly decreased the number of days with severe neurological deficits as compared to the control group. The combination and
manidipine 2HCl significantly recovered the decrease in
body weight and ameliorated the increase of brain weight, which was mainly caused by
edema, significantly as compared to the control group.
Manidipine 2HCl ameliorated the histological changes in the brain. In the combination group, the histological changes in both the brain and the kidneys were ameliorated. In conclusion, the combination of
idebenone and
manidipine 2HCl significantly ameliorated the neurological deficits and the histological changes in the brain and the kidney of SHRSP with
stroke as compared to each individual treatment. We concluded that
manidipine 2HCl enhances the
therapeutic effect of
idebenone in the treatment of
cerebrovascular diseases.