Blood-brain barrier dysfunction developed during normal aging is associated with inflammation and loss of tight junctions but not with leukocyte recruitment
MetadataShow full item record
This open access article is distributed under the Creative Commons license http://creativecommons.org/licenses/by/4.0
Background: Functional loss of blood–brain barrier (BBB) is suggested to be pivotal to pathogenesis and pathology of vascular-based neurodegenerative disorders such as Alzheimer’s disease. We recently reported in wild-type mice maintained on standard diets, progressive deterioration of capillary function with aging concomitant with heightened neuroinflammation. However, the mice used in this study were relatively young (12 months of age) and potential mechanisms for loss of capillary integrity were not investigated per se. The current study therefore extended the previous finding to investigate the effect of aging on BBB integrity in aged mice at 24 months and its potential underlying molecular mechanisms. Results: Immunomicroscopy analyses confirmed significantly increased capillary permeability with heightened neuroinflammation in naturally aged 24-month old mice compared to young control at 3 months of age. Aged mice showed significant attenuation in the expression of BBB tight junction proteins, occludin-1 and to lesser extent ZO-1 compared to young mice. In addition, TNF-α in cerebral endothelial cells of aged mice was significantly elevated compared to controls and this was associated with heightened peripheral inflammation. The expression of ICAM-1 and VCAM-1 remained unelevated, and no sign of leukocyte recruitment was observed in aged mice. Conclusion: The BBB breakdown that occurs during ordinary aging is associated with inflammation and disruption of tight junction complex assembly but not through leukocyte trafficking.
Showing items related by title, author, creator and subject.
Disruption of blood-brain barrier function by chronic intake of saturated fat and cholesterol : implications for Alzheimer’s disease riskTakechi, Ryusuke (2010)It has been reported that lifestyle including diet is associated with Alzheimer’s disease (AD) risk and progression. Population studies indicate that the chronic consumption of diets enriched in saturated fats (SFA) and ...
Macrophage Depletion in Elderly Mice Improves Response to Tumor Immunotherapy, Increases Anti-tumor T Cell Activity and Reduces Treatment-Induced CachexiaDuong, L.; Radley-Crabb, H.; Gardner, J.; Tomay, F.; Dye, D.; Grounds, M.; Pixley, F.; Nelson, Delia; Jackaman, Connie (2018)Most cancers emerge in the elderly, including lung cancer and mesothelioma, yet the elderly remain an underrepresented population in pre-clinical cancer studies and clinical trials. The immune system plays a critical role ...
Takechi, Ryusuke; Pallebage-Gamarallage, Menuka; Lam, Virginie; Giles, Cory; Mamo, John (2012)Background: Disturbances in blood-brain barrier (BBB) integrity contribute to the onset and progression of neurodegenerative diseases including Alzheimer’s disease (AD) and vascular dementia (VaD). Aging is positively ...