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

Autor: Kristina Kuptsova, Birgit Hutter-Paier, Jukka Jolkkonen, Anu Lipsanen, Manfred Windisch, Stefanie Flunkert, Mikko Hiltunen
Rok vydání: 2013
Předmět:
Male
Pathology
Anatomy and Physiology
Light
Mouse
lcsh:Medicine
Calcium channel blocker
Brain Ischemia
Brain ischemia
Mice
Thalamus
Molecular Cell Biology
Homeostasis
lcsh:Science
Neuropathology
Multidisciplinary
Voltage-dependent calcium channel
Chemistry
Neurodegenerative Diseases
Animal Models
Calcium Channel Blockers
Signaling Cascades
Neurology
Bepridil
Medicine
Research Article
Signal Transduction
medicine.drug
medicine.medical_specialty
Histology
Clinical Research Design
medicine.drug_class
Cerebrovascular Diseases
Ischemia
chemistry.chemical_element
Mice
Transgenic
Calcium
Model Organisms
Diagnostic Medicine
Alzheimer Disease
medicine
Animals
Animal Models of Disease
Biology
Calcium metabolism
Amyloid beta-Peptides
lcsh:R
medicine.disease
Anatomical Pathology
Calcium Signaling Cascade
Dementia
lcsh:Q
Intracranial Thrombosis
Physiological Processes
Zdroj: PLoS ONE, Vol 8, Iss 3, p e60235 (2013)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0060235
Popis: Experimental studies have identified a complex link between neurodegeneration, β-amyloid (Aβ) and calcium homeostasis. Here we asked whether early phase β-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, Aβ and calcium accumulation in the thalamus. Cortical photothrombosis resulted in a small infarct, which was associated with atypical Aβ and calcium accumulation in the ipsilateral thalamus. Transgenic mice had significantly smaller infarct volumes than non-transgenic littermates (P
Databáze: OpenAIRE
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