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Identification of new therapeutic targets by genome-wide analysis of gene expression in the ipsilateral cortex of aged rats after stroke

ABSTRACT: Because most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions. We employed the Affymetrix platform to analyze the whole-gene transcriptome following temporary ligation of the middle cerebral artery in aged and young rats.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE55260 | GEO | 2014/04/22

SECONDARY ACCESSION(S): PRJNA239008

REPOSITORIES: GEO

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Identification of new therapeutic targets by genome-wide analysis of gene expression in the ipsilateral cortex of aged rats after stroke

Project description:Because most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions. We employed the Affymetrix platform to analyze the whole-gene transcriptome following temporary ligation of the middle cerebral artery in aged and young rats. Expression profiling of periinfarcted brain areas of young and aged rats, as well as healthy tissue from naive animals.

2014-04-22 | E-GEOD-55260 | biostudies-arrayexpress

Photothrombotic Cerebral Stroke as a Model of Post-Stroke Seizures/Epilepsy in aged mice

Project description:Stroke is a prevalent disorder representing the third leading cause of death and major cause of disability. Post-stroke epilepsy (PSE) has been recognized as a common clinical issue after stroke, accounting for 30-40% of the causes of epilepsy among older adults. In this study, we determined GABAA receptor-mediated seizure susceptibility after PT cerebral stroke in aged mice. Young adult mice around 10 weeks of age are widely used in stroke experiments. However, as most strokes are diagnosed in the elderly and PSE has been recognized as a common clinical incidence after stroke, we utilized photothrombosis (PT) model of cerebral ischemia and examined seizure susceptibility and brain injury using combined behavioral (video) and EEG monitoring and histological (MRI) assessments. To investigate GABAA receptor-mediated convulsive/non-convulsive seizures, lower-doses of pentylenetetrazol (PTZ) was injected. PTZ susceptibility in aging mice increased compared to young adults. One month after PT stroke, aged PT stroke mice exhibited severe convulsive seizures (late-onset). These findings exhibited the increase of GABAA receptor-mediated seizures susceptibility in PT stroke aging mice, but not in young adults.

2023-11-27 | GSE241528 | GEO

Transcriptomic and Functional Studies Reveal Undermined Chemotactic and Angiostimulatory Properties of Aged Microglia During Stroke Recovery

Project description:Age-dependent alterations in microglia behavior have been implicated in neurodegeneration and CNS injuries. Here, we compared the transcriptional profiles of young versus aged microglia during stroke recovery. CD45intermediateCD11b+ microglia were FACS-isolated from the brains of young (10-week-old) and aged (18-month-old) male mice 14 days after distal middle cerebral artery occlusion (dMCAO) or sham operation and subjected to RNA-sequencing analysis. Functional groups enriched in young microglia are indicative of upregulation in cell movement, cell interactions, inflammatory responses and angiogenesis, while aged microglia exhibited a reduction or no change in these features. We confirmed reduced chemoattractive capacities of aged microglia toward ischemic brain tissue in organotypic slide co-cultures, and delayed accumulation of aged microglia around dead neurons injected into the striatum in vivo. In addition, aging is associated with an overall failure to increase the expression of microglial genes involved in cell-cell interactions, such as CXCL10. Finally, impaired upregulation of pro-angiogenic genes in aged microglia was associated with a decline in neovascularization in aged mice compared to young mice after dMCAO. This study provides a new resource to understand the mechanisms underlying microglial alterations in the aged brain milieu and sheds light on new strategies to improve microglial functions in aged stroke victims.

2020-01-31 | GSE142361 | GEO

Levetiracetam normalized E/I imbalance in the hippocampus after cortical stroke in aged mice

Project description:Stroke is a prevalent disorder representing the third leading cause of death and major cause of disability. Post-stroke epilepsy (PSE) has been recognized as a common clinical issue after stroke, accounting for 30-40% of the causes of epilepsy among older adults. In this study, we determined GABAA receptor-mediated seizure susceptibility after PT cerebral stroke in aged mice. Young adult mice around 10 weeks of age are widely used in stroke experiments. However, as most strokes are diagnosed in the elderly and PSE has been recognized as a common clinical incidence after stroke, we utilized photothrombosis (PT) model of cerebral ischemia and examined seizure susceptibility. To investigate in vitro drug-induced seizure susceptibility (E/I imbalance) of GABAA receptor antagonist, gabazine (GZ), voltage-sensitive dye (VSD) imaging techniques were used in hippocampal brain slices. One month after PT stroke, in vivo aged PT stroke mice exhibited severe convulsive seizures (late-onset). in vitro GZ-induced E/I imbalance in hippocampus of aging mice increased compared to young adults. In addition, Anti-seizure medication (levetiracetam) normalized in vitro GZ-induced E/I imbalance in hippocampus of aging mice. These findings exhibited that GABAA receptor-mediated seizures susceptibility (E/I imbalance) in hippocampus after cortical PT stroke in aging mice, but not in young adults.

2023-11-27 | GSE241525 | GEO

Central nervous system-associated macrophages modulate the immune response following stroke in aged mice

Project description:To study the differential role of central nervous system-associated macrophages (CAMs) in neuroinflammation after stroke between young and aged mice, we FACS sorted CD3-CD11b+CD45+CD206+ CAMs from brains of C57BL/6 mice aged 2 months (young) and 18 months (old)

2024-05-22 | GSE267623 | GEO

Expression data from the cortex after middle cerebral artery occlusion (MCAO) between young and aged rats

Project description:Elderly patients suffer more brain damage in comparison with young patients from the same ischemic stroke. In that regard, it is imperative to investigate the factors responsible for decreased resistance to anti-ischemic/hypoxic injury in the aged brain. We conducted analysis of the gene expression pattern on our samples (Transient MCAO for 60 minutes established acute ischemic stroke followed by 3 days reperfusion) by the Affymetrix rat 230 2.0 chip.

2021-03-16 | GSE166162 | GEO

Microglia renewal in old mice enhances the cellular fitness to cope with stroke

Project description:Microglial cells of the aged brain manifest signs of dysfunction that could contribute to the worst neurological outcome of stroke in the elderly. Treatment with colony-stimulating factor 1 receptor antagonists enables microglia depletion that is followed by microglia repopulation after interruption of the treatment, without any known harm to the mice. We used this strategy aiming to rejuvenate microglia function and ameliorate stroke outcome in aged mice. Cerebral ischemia/reperfusion induced strong innate immune responses in microglia highlighted by prominent type-I interferon signalling, together with cellular metabolic perturbances and lipid droplet biogenesis. Old age increased innate immune responses in microglia, which also showed more lipid droplets than microglia of young mice. Microglia renewal in old mice prevented the exaggerated type I interferon response observed in microglia after stroke, reduced the lipid droplet content, and improved the neurological outcome of stroke. This study shows that microglia renewal in old mice rejuvenates some features of old microglia and improves stroke outcome.

2022-11-29 | GSE196737 | GEO

RNA-Seq of ischemic stroke in young and aged mice

Project description:RNA-Seq of ischemic stroke in young and aged mice

| PRJNA565703 | ENA

Exploring the Biological Mechanisms of Severe COVID-19 in the Elderly: Insights from an Aged Mouse

Project description:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global health crisis, particularly affecting the elderly, who are more susceptible to severe outcomes. However, definitive parameters or mechanisms underlying the severity of COVID-19 in elderly people remain confused. Thus, this study seeks to elucidate the mechanism behind the increased vulnerability of elderly individuals to severe COVID-19. We employed an aged mouse model with a mouse-adapted SARS-CoV-2 strain to mimic the severe symptoms observed in elderly patients with COVID-19. Comprehensive analyses of the whole lung were performed using transcriptome and proteome sequencing, comparing data from aged and young mice. For transcriptome analysis, bulk RNA sequencing was conducted using an Illumina sequencing platform. Proteomic analysis was performed using mass spectrometry following protein extraction, digestion, and peptide labeling. We analyzed the transcriptome and proteome profiles of young and aged mice and discovered that aged mice exhibited elevated baseline levels of inflammation and tissue damage repair. After SARS-CoV-2 infection, aged mice showed increased antiviral and inflammatory responses; however, these responses were weaker than those in young mice, with significant complement and coagulation cascade responses. In summary, our study demonstrates that the increased vulnerability of the elderly to severe COVID-19 can be attributed to an attenuated antiviral response and the overactivation of complement and coagulation cascades.

2024-09-24 | PXD055174 | Pride

Enhanced functional recovery from spinal cord injury in aged mice after stem cell transplantation through HGF induction

Project description:The number of elderly patients with spinal cord injury (SCI) is increasing worldwide, representing a serious burden for both the affected patients and the community. Previous studies have demonstrated that neural stem cell (NSC) transplantation is an effective treatment for SCI in young animals. Here we show that NSC transplantation is as effective in aged mice as it is in young mice, even though aged mice exhibit more severe neurological deficits after SCI. NSCs grafted into aged mice exhibited better survival than did those grafted into young mice. Furthermore, we show that the neurotrophic factor HGF plays a key role in the enhanced functional recovery after NSC transplantation observed in aged mice with SCI. The unexpected results of the present study suggest that NSC transplantation is a potential therapeutic modality for SCI, even in elderly patients.

2017-01-13 | GSE93561 | GEO

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