Non-Selective Calcium Channel Blocker Bepridil Decreases Secondary Pathology in Mice after Photothrombotic Cortical Lesion

作者：Lipsanen Anu; Flunkert Stefanie; Kuptsova Kristina; Hiltunen Mikko; Windisch Manfred; Hutter Paier Birgit; Jolkkonen Jukka^*

来源：PLos One, 2013, 8(3): e60235.

DOI：10.1371/journal.pone.0060235

Experimental studies have identified a complex link between neurodegeneration, beta-amyloid (A beta) and calcium homeostasis. Here we asked whether early phase beta-amyloid pathology in transgenic hAPP(SL) mice exaggerates the ischemic lesion and remote secondary pathology in the thalamus, and whether a non-selective calcium channel blocker reduces these pathologies. Transgenic hAPP(SL) (n = 33) and non-transgenic (n = 30) male mice (4-5 months) were subjected to unilateral cortical photothrombosis and treated with the non-selective calcium channel blocker bepridil (50 mg/kg, p.o., once a day) or vehicle for 28 days, starting administration 2 days after the operation. Animals were then perfused for histological analysis of infarct size, A beta and calcium accumulation in the thalamus. Cortical photothrombosis resulted in a small infarct, which was associated with atypical A beta and calcium accumulation in the ipsilateral thalamus. Transgenic mice had significantly smaller infarct volumes than non-transgenic littermates (P<0.05) and ischemia-induced rodent A beta accumulation in the thalamus was lower in transgenic mice compared to non-transgenic mice (P<0.01). Bepridil decreased calcium load in the thalamus (P<0.01). The present data suggest less pronounced primary and secondary pathology in hAPP(SL) transgenic mice after ischemic cortical injury. Bepridil particularly decreased calcium pathology in the thalamus following ischemia.

• 出版日期2013-3-26