Expression of Na–K–Cl cotransporter and edema formation are age dependent after ischemic stroke

Akella, Padmastuti; Benashski, Sharon E.; Xu, Yan; McCullough, Louise D.

doi:10.1016/j.expneurol.2010.04.010

Cited by 35 publications

(29 citation statements)

References 31 publications

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“…Declining levels of oestrogen with age may also underlie the larger infarct volume observed in middle-aged and older female rats [16]. With respect to age, disparity in stroke outcomes has been associated with age-related down-regulation of several proteins including NKCC (Na + –K + –Cl − co-transporter) [33], BDNF (brain-derived neurotrophic factor), bFGF (basic fibroblast growth factor) [34] and neuron-specific intermediate filaments, NFs (neurofilaments) [35]. In clinical studies, NO was shown to be reduced in serum of aged stroke patients compared with younger patients, whereas IL-6 (interleukin-6) was elevated in aged patients with a poor outcome [36].…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNA profiles provide a biomarker for severity of stroke outcomes associated with age and sex in a rat model

et al. 2014

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Small non-coding RNA [miRNA (microRNA)] found in the circulation have been used successfully as biomarkers and mechanistic targets for chronic and acute disease. The present study investigated the impact of age and sex on miRNA expression following ischaemic stroke in an animal model. Adult (6 month) and middle-aged (11–12 months) female and male rats were subject to MCAo (middle cerebral artery occlusion) using ET-1 (endothelin-1). Circulating miRNAs were analysed in blood samples at 2 and 5 days post-stroke, and brain miRNAs were analysed at 5 days post-stroke. Although stroke-associated infarction was observed in all groups, infarct volume and sensory-motor deficits were significantly reduced in adult females compared with middle-aged females, adult males or middle-aged males. At 2 days post-stroke, 21 circulating miRNAs were differentially regulated and PCA (principal component analysis) confirmed that most of the variance was due to age. At 5 days post-stroke, 78 circulating miRNAs exhibited significantly different regulation, and most of the variance was associated with sex. A small cohort (five) of miRNAs, miR-15a, miR-19b, miR-32 miR-136 and miR-199a-3p, were found to be highly expressed exclusively in adult females compared with middle-aged females, adult males and middle-aged males. Predicted gene targets for these five miRNAs analysed for KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed that the top ten KEGG pathways were related to growth factor signalling, cell structure and PI3K (phosphoinositide 3-kinase)/Akt and mTOR (mammalian target of rapamycin) signalling. Overall, the pattern of circulating miRNA expression suggests an early influence of age in stroke pathology, with a later emergence of sex as a factor for stroke severity.

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Section: Discussionmentioning

confidence: 99%

Circulating miRNA profiles provide a biomarker for severity of stroke outcomes associated with age and sex in a rat model

et al. 2014

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“…Immunohistochemical staining of frozen fixed sections (30 μm) was performed as described previously 6, 16, 17 . Briefly, brain slices were mounted onto gelatin-coated slides, allowed to air dry and then blocked in 0.1 M phosphate buffer (PB) with 0.3% TritonX-100 (sigma) and 10% donkey serum (PBTDS) for an hour.…”

Section: Methodsmentioning

confidence: 99%

Perfusion of Ischemic Brain in Young and Aged Animals

Manwani

Friedler

Verma

et al. 2014

Stroke

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Background and Purpose Aging is an important determinant of ischemic stroke outcomes. Both clinical and experimental stroke studies have shown that aging negatively correlates with infarct volumes but is associated with worsened functional recovery after stroke. This may correspond to a differing cellular and molecular response to stroke in the aged vs. young brain. It was hypothesized in this study that the smaller injury seen in the aged ischemic brain is due to structural differences in microvasculature with aging or differences in intra-ischemic tissue perfusion. Methods Both young and aged C57BL6 mice were subject to middle cerebral artery occlusion (MCAO) modeling. Laser Speckle Flowmetry (LSF) was utilized to study the functional dynamics of cerebral perfusion, and FITC-dextran staining was performed to examine the structural change in microvasculature. In separate cohorts, Cresyl violet (CV) staining and immunohistochemistry with CD31 and IgG antibodies were applied to further assess the microvascular density and blood brain barrier breakdown after stroke. Results No difference in cerebral blood flow was seen at the baseline, intra-ischemically and post-reperfusion in young vs. aged mice. FITC-dextran and CD31 staining did not show significant differences in the microvascular density between young and aged ischemic brains. More extravasation of IgG through the BBB was found in the young vs. aged cohort at both 24 and 72 hours after stroke. Conclusions Cerebrovascular dynamics and perfusion are not responsible for the different stroke phenotypes seen in the young vs. aged animals, which may be more related to different levels of BBB breakdown.

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“…The total number of cells was averaged across the four fields of view for each animal. The average number of cells/field of view was used for statistical analysis as described previously (Liu et al, 2010). …”

Section: Methodsmentioning

confidence: 99%

Functional recovery in aging mice after experimental stroke

Manwani

Liu

et al. 2011

Brain, Behavior, and Immunity

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Aging is a non modifiable risk factor for stroke. Since not all strokes can be prevented, a major emerging area of research is the development of effective strategies to enhance functional recovery after stroke. However, in the vast majority of pre-clinical stroke studies, the behavioral tests used to assess functional recovery have only been validated for use in young animals, or are designed for rats. Mice are increasingly utilized in stroke models but well validated behavioral tests designed for rats are not necessarily reproducible in mice. We examined a battery of behavioral tests to evaluate functional recovery in an aging murine model of stroke. We found that the vertical pole, hanging wire and open field can accurately assess acute behavioral impairments after stroke in both young and aging male mice, but animals recover rapidly on these tasks. The corner test can accurately and repeatedly differentiate stroke from sham animals up to 30 days post stroke and can be performed reliably in aging mice. Aging male mice had significantly worse behavioral impairment compared to young male mice in the first two weeks after stroke but eventually recovered to the same degree as young mice. In contrast, chronic infarct size, as measured by ipsilateral cerebral atrophy, was significantly lower in aging male mice compared to young male mice. Reactive gliosis, formation of glial scar, and an enhanced innate immune response was seen in the aging brain and may contribute to the delayed behavioral recovery seen in aged animals.

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Expression of Na–K–Cl cotransporter and edema formation are age dependent after ischemic stroke

Cited by 35 publications

References 31 publications

Circulating miRNA profiles provide a biomarker for severity of stroke outcomes associated with age and sex in a rat model

Circulating miRNA profiles provide a biomarker for severity of stroke outcomes associated with age and sex in a rat model

Perfusion of Ischemic Brain in Young and Aged Animals

Functional recovery in aging mice after experimental stroke

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