Bepridil decreases Aβ and calcium levels in the thalamus after middle cerebral artery occlusion in rats.
Bottom Line: A 27-day bepridil treatment (50 mg/kg, p.o.) initiated 2 days after MCAO significantly decreased the levels of soluble Aβ40, Aβ42 and calcium in the ipsilateral thalamus, as compared with vehicle-treated MCAO rats.Bepridil treatment did not significantly affect heme oxygenase-1- or NAD(P)H quinone oxidoreductase-1-mediated oxidative stress or inflammatory responses in the ipsilateral thalamus of MCAO rats.These findings suggest that bepridil is a plausible therapeutic candidate in AD or stroke owing to its multifunctional role in key cellular events that are relevant for the pathogenesis of these diseases.
Affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.Show MeSH
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Mentions: The sensorimotor impairment and recovery of function after MCAO was assessed by three behavioural tests. Spontaneous forelimb use was measured by the cylinder test at baseline (1 day before the operation) and at 14 and 28 days after MCAO (Fig. 7). All the animals used both forelimbs for postural support prior to surgery and MCAO rats showed decreased use of their impaired forelimb (i.e. contralateral to lesion) at 14 and 28 days after the operation. There was no significant group effect in forelimb use. However, ANOVA for repeated measures showed a significant group × time interaction (P < 0.05), indicating that sensorimotor recovery was different between the groups. A more detailed analysis revealed that bepridil-treated MCAO rats significantly increased the use of the impaired forelimb on post-operative day 28 as compared with vehicle-treated MCAO rats. The limb-placing test was used to assess forelimb and hindlimb responses to tactile and proprioceptive stimulation. The test showed that MCAO rats were initially severely impaired but then made a partial recovery. A significant overall group effect was explained by the difference between sham-operated and MCAO rats throughout the follow up (P < 0.01). MCAO groups with or without bepridil treatment did not differ from each other (data not shown). The tapered/ledged beam-walking test was used as a measure of hindlimb function. The special feature of this test is that the ledge allows the rat to display a deficit normally hidden by compensatory adjustment. All rats showed an increase in slips (foot faults) with no apparent recovery after MCAO. A significant overall group effect resulted from the fact that MCAO rats made significantly more slips compared with sham-operated rats (P < 0.05). There was no difference between vehicle- and bepridil-treated MCAO rats during the follow up (data not shown).
Affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.