INTRODUCTION: Modification of the extracellular matrix (ECM) is one of the major processes in the pathology of brain damage following an ischemic stroke. However, our understanding of how age-related ECM alterations may affect stroke pathophysiology and its outcome is still very limited. METHODS: We conducted an ECM-targeted re-analysis of our previously obtained RNA-Seq dataset of aging, ischemic stroke and their interactions in young adult (3-month-old) and aged (18-month-old) mice. The permanent middle cerebral artery occlusion (pMCAo) in rodents was used as a model of ischemic stroke. Altogether 56 genes of interest were chosen for this study. RESULTS: We identified an increased activation of the genes encoding proteins related to ECM degradation, such as matrix metalloproteinases (MMPs), proteases of a disintegrin and metalloproteinase with the thrombospondin motifs (ADAMTS) family and molecules that regulate their activity, tissue inhibitors of metalloproteinases (TIMPs). Moreover, significant upregulation was also detected in the mRNA of other ECM molecules, such as proteoglycans, syndecans and link proteins. Notably, we identified 8 genes where this upregulation was enhanced in aged mice in comparison with the young ones. Ischemia evoked a significant downregulation in only 6 of our genes of interest, including those encoding proteins associated with the protective function of ECM molecules (e.g., brevican, Hapln4, Sparcl1); downregulation in brevican was more prominent in aged mice. The study was expanded by proteome analysis, where we observed an ischemia-induced overexpression in three proteins, which are associated with neuroinflammation (fibronectin and vitronectin) and neurodegeneration (link protein Hapln2). In fibronectin and Hapln2, this overexpression was more pronounced in aged post-ischemic animals. CONCLUSION: Based on these results, we can conclude that the ratio between the protecting and degrading mechanisms in the aged brain is shifted toward degradation and contributes to the aged tissues' increased sensitivity to ischemic insults. Altogether, our data provide fresh perspectives on the processes underlying ischemic injury in the aging brain and serve as a freely accessible resource for upcoming research.
- Publikační typ
- časopisecké články MeSH
- MeSH
- domácí ošetřování MeSH
- lidé MeSH
- manželé MeSH
- osoby pečující o pacienty * psychologie MeSH
- sociální práce MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- domácí ošetřování MeSH
- lidé MeSH
- osoby pečující o pacienty * psychologie MeSH
- rodiče MeSH
- smrt rodiče psychologie MeSH
- vztahy mezi rodiči a dětmi MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
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- MeSH
- dějiny 21. století MeSH
- domácí ošetřování MeSH
- domácí ošetřovatelství MeSH
- osoby pečující o pacienty MeSH
- péče o sebe MeSH
- zátěž pečovatele MeSH
- Check Tag
- dějiny 21. století MeSH
- Publikační typ
- kazuistiky MeSH
- sborníky MeSH
- Konspekt
- Druhy sociální pomoci a služeb
- NLK Obory
- sociologie
- psychologie, klinická psychologie
- NLK Publikační typ
- informační publikace
- brožury
The proper function of the nervous system is dependent on the balance of ions and water between the intracellular and extracellular space (ECS). It has been suggested that the interaction of aquaporin-4 (AQP4) and the transient receptor potential vaniloid isoform 4 (TRPV4) channels play a role in water balance and cell volume regulation, and indirectly, of the ECS volume. Using the real-time iontophoretic method, we studied the changes of the ECS diffusion parameters: ECS volume fraction α (α = ECS volume fraction/total tissue volume) and tortuosity λ (λ2 = free/apparent diffusion coefficient) in mice with a genetic deficiency of AQP4 or TRPV4 channels, and in control animals. The used models of cytotoxic edema included: mild and severe hypotonic stress or oxygen-glucose deprivation (OGD) in situ and terminal ischemia/anoxia in vivo. This study shows that an AQP4 or TRPV4 deficit slows down the ECS volume shrinkage during severe ischemia in vivo. We further demonstrate that a TRPV4 deficit slows down the velocity and attenuates an extent of the ECS volume decrease during OGD treatment in situ. However, in any of the cytotoxic edema models in situ (OGD, mild or severe hypotonic stress), we did not detect any alterations in the cell swelling or volume regulation caused by AQP4 deficiency. Overall, our results indicate that the AQP4 and TRPV4 channels may play a crucial role in severe pathological states associated with their overexpression and enhanced cell swelling. However, detailed interplay between AQP4 and TRPV4 channels requires further studies and additional research.
- MeSH
- akvaporin 4 nedostatek metabolismus MeSH
- draslík metabolismus MeSH
- edém mozku metabolismus MeSH
- elektrokardiografie MeSH
- extracelulární prostor metabolismus MeSH
- hypoglykemie metabolismus MeSH
- kationtové kanály TRPV nedostatek metabolismus MeSH
- modely nemocí na zvířatech MeSH
- mozková hypoxie a ischemie metabolismus MeSH
- myši knockoutované MeSH
- myši transgenní MeSH
- myši MeSH
- somatosenzorické korové centrum metabolismus MeSH
- srdeční zástava metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
online
Odborné články. Krizové situace. Léčba, rehabilitace. Slovník odborných termínů. Odborná literatura. Sociální zabezpečení rodiny. Zdravotní pomůcky a protetika. Školství a vzdělávání. Volný čas. Lázně, léčebny. Bydlení.
- Publikační typ
- populární práce MeSH
- Konspekt
- Sociologie
- NLK Obory
- zdravotně postižení
- NLK Publikační typ
- portály
