Aging brain

About: Aging brain is a research topic. Over the lifetime, 1255 publications have been published within this topic receiving 66405 citations.

Experimental Stroke and Neuroprotection in the Aging Rat Brain

Abstract: Background and Purpose Experimental stroke research has for the most part incorporated the use of young animals despite the importance of aging in cerebrovascular disease in humans. We hypothesized that age-related reductions in the density and function of cortical N -methyl-d-aspartate (NMDA) receptors might limit neuroprotective potential in the elderly. In this study, a model of occlusive stroke in the aging rat brain has been developed and used to establish the effects of age on cerebral infarction and to evaluate the scope for protecting the aging brain during ischemia. Methods Focal cerebral ischemia was produced by thermocoagulation of the left middle cerebral artery in adult (11 to 17 months) and aged (28 to 36 months) male Wistar rats. Infarcts were assessed histologically with volumetric analysis of infarct size, hemodynamically by serial cerebral blood flow measurement using the hydrogen clearance technique, and by analysis of specific gravity as an index of brain edema. Neuroprotective potential was assessed using the competitive NMDA receptor antagonist 3-(2-carboxy piperazin-4-yl)propyl-1-phosphonate (d-CPPene). Results Aging was associated with a significant increase in infarct size, with a mean infarct volume of 40.5±2.6% of the hemisphere volume in aged rats compared with 30.9±0.7% in adult rats ( P <.01). d-CPPene reduced the mean infarct volume to 33±1.8% and 20.7±3.2% in aged and adult rats, respectively ( P <.05). Cerebral blood flow fell markedly after infarction, but thereafter d-CPPene–pretreated rats maintained higher cerebral blood flow than untreated animals throughout the duration of the experiment (22.8±3.2 and 30.1±5.5 mL · 100 g−1 · min−1 in treated aged and adult rats, respectively, compared with 11.3±2.7 and 16.5±3.2 mL · 100 g−1 · min−1 in untreated aged and adult groups, 90 minutes after infarction [ P <.05]). Pretreatment also reduced cortical edema; mean cortical specific gravity 4 hours after infarction was 1.0381±0.0013 in untreated aged rats and 1.0391±0.0014 in untreated adults compared with 1.0458±0.0031 in treated aged rats and 1.0442±0.0014 in treated adult rats ( P <.05). Conclusions Under similar experimental conditions, there was an age-related increase in cerebral infarct size. However, NMDA receptor antagonism was neuroprotective in the aging brain and resulted in a significant reduction in cerebral ischemic damage, less cortical edema, and preservation of cerebral blood flow.

Exercise, antidepressant treatment, and BDNF mRNA expression in the aging brain.

Abstract: Principal mental disorders affecting the geriatric population include dementia and depression. A lack of trophic support is thought to contribute to the pathology of these disorders. Physical activity and antidepressant treatment increase the expression of brain-derived neurotrophic factor (BDNF) in the young rat hippocampus. Herein, we investigated the responsiveness of the aging rat hippocampus to antidepressant treatment and voluntary exercise. In situ hybridization revealed that, in young animals, exercise, antidepressant treatment, or their combination elevated BDNF mRNA levels in several hippocampal regions, most notably in the CA3, CA4, and dentate gyrus (DG). This effect was rapid (detectable at 2 days) and sustainable to 20 days. In aged (22-month-old) rats, hippocampal responsiveness to antidepressant treatment and exercise was also rapid and sustainable, but evident mostly in the CA1 and CA2. Daily swimming also revealed that small amounts of activity led to marked elevations in hippocampal BDNF mRNA. The differences in regional patterns of BDNF mRNA elevations between young and aged animals observed with running were maintained with this different exercise modality. Our results indicate that the aged brain is responsive to exercise and antidepressant treatment, and changes in regional response patterns may reflect shifts in hippocampal physiology during the lifespan.

Astrocyte senescence: Evidence and significance.

Abstract: Astrocytes participate in numerous aspects of central nervous system (CNS) physiology ranging from ion balance to metabolism, and disruption of their physiological roles can therefore be a contributor to CNS dysfunction and pathology. Cellular senescence, one of the mechanisms of aging, has been proposed as a central component of the age dependency of neurodegenerative disorders. Cumulative evidence supports an integral role of astrocytes in the initiation and progression of neurodegenerative disease and cognitive decline with aging. The loss of astrocyte function or the gain of neuroinflammatory function as a result of cellular senescence could have profound implications for the aging brain and neurodegenerative disorders, and we propose the term "astrosenescence" to describe this phenotype. This review summarizes the current evidence pertaining to astrocyte senescence from early evidence, in vitro characterization and relationship to age-related neurodegenerative disease. We discuss the significance of targeting senescent astrocytes as a novel approach toward therapies for age-associated neurodegenerative disease.