Research ReportProtection against ischemic stroke damage by synergistic treatment with amlodipine plus atorvastatin in Zucker metabolic rat

Ischemic stroke is a major neurologic disorder and a leading cause of disability and death in the world. We compared neuroprotective effects of single or combination therapy of amlodipine (AM) and atorvastatin (AT) in such a metabolic syndrome model Zucker rat. The animals were pretreated with vehicle, AM, AT, or the combination of AM plus AT for 28 days, and physical and serum parameters were analyzed, then 90 min of transient middle cerebral artery occlusion (tMCAO), was performed followed by immunohistochemical analyses at 24 h. Without affecting serum levels of lipids, adiponectin, and leptin, the combination therapy of AM plus AT ameliorated the post-ischemic brain weight increase. The single treatment with AM or AT itself exerted neuroprotective effects with reducing inductions of MMP-9 and AT2R, as well as with preserving collagen IV, and the combination therapy of AM plus AT showed a further synergistic benefit against acute ischemic neural damages. Single AT was more protective on these 3 molecules than single AM at this time point of 24 h after tMCAO. Thus, the combination therapy with AM plus AT extended the neuroprotectives effect of single treatment with AM or AT on a part of neurovascular unit and a hypertension-related receptor.

Research Highlights► MMP-9, collagen IV, and AT2R are strongly related to the pathophysiology of stroke. ► Synergistic effect of AM plus AT combination. ► The combination of AM plus AT treatment decreased the ischemic damage.