| First Author | Lipsanen A | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 3 | Pages | e60235 |
| PubMed ID | 23555933 | Mgi Jnum | J:200158 |
| Mgi Id | MGI:5507740 | Doi | 10.1371/journal.pone.0060235 |
| Citation | Lipsanen A, et al. (2013) Non-selective calcium channel blocker bepridil decreases secondary pathology in mice after photothrombotic cortical lesion. PLoS One 8(3):e60235 |
| abstractText | Experimental studies have identified a complex link between neurodegeneration, beta-amyloid (Abeta) and calcium homeostasis. Here we asked whether early phase beta-amyloid pathology in transgenic hAPPSL mice exaggerates the ischemic lesion and remote secondary pathology in the thalamus, and whether a non-selective calcium channel blocker reduces these pathologies. Transgenic hAPPSL (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, Abeta and calcium accumulation in the thalamus. Cortical photothrombosis resulted in a small infarct, which was associated with atypical Abeta 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 Abeta 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 hAPPSL transgenic mice after ischemic cortical injury. Bepridil particularly decreased calcium pathology in the thalamus following ischemia. |
