The role of nonneuronal cells in the resolution of cerebral ischemia remains to be fully understood. To decode key molecular and cellular processes that occur after ischemia, we performed spatial and single-cell transcriptomic profiling of the male mouse brain during the first week of injury. Cortical gene expression was severely disrupted, defined by inflammation and cell death in the lesion core, and glial scar formation orchestrated by multiple cell types on the periphery. The glial scar was identified as a zone with intense cell-cell communication, with prominent ApoE-Trem2 signaling pathway modulating microglial activation. For each of the three major glial populations, an inflammatory-responsive state, resembling the reactive states observed in neurodegenerative contexts, was observed. The recovered spectrum of ischemia-induced oligodendrocyte states supports the emerging hypothesis that oligodendrocytes actively respond to and modulate the neuroinflammatory stimulus. The findings are further supported by analysis of other spatial transcriptomic datasets from different mouse models of ischemic brain injury. Collectively, we present a landmark transcriptomic dataset accompanied by interactive visualization that provides a comprehensive view of spatiotemporal organization of processes in the postischemic mouse brain.

• Klíčová slova
• glia, ischemic stroke, neuroinflammation, single-cell transcriptomics, spatial transcriptomics,
• MeSH
• ischemie mozku * genetika   metabolismus   patologie   MeSH
• membránové glykoproteiny metabolismus   genetika   MeSH
• mikroglie metabolismus   MeSH
• modely nemocí na zvířatech * MeSH
• mozek metabolismus   patologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neuroglie * metabolismus   MeSH
• oligodendroglie metabolismus   MeSH
• receptory imunologické MeSH
• signální transdukce MeSH
• stanovení celkové genové exprese MeSH
• transkriptom * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• membránové glykoproteiny MeSH
• receptory imunologické MeSH
• Trem2 protein, mouse MeSH Prohlížeč

The changes in the necrotic core and the penumbra following induction of focal ischemia have been the focus of attention for some time. However, evidence shows, that ischemic injury is not confined to the primarily affected structures and may influence the remote areas as well. Yet many studies fail to probe into the structures beyond the penumbra, and possibly do not even find any significant results due to their short-term design, as secondary damage occurs later. This slower reaction can be perceived as a therapeutic opportunity, in contrast to the ischemic core defined as irreversibly damaged tissue, where the window for salvation is comparatively short. The pathologies in remote structures occur relatively frequently and are clearly linked to the post-stroke neurological outcome. In order to develop efficient therapies, a deeper understanding of what exactly happens in the exo-focal regions is necessary. The mechanisms of glia contribution to the ischemic damage in core/penumbra are relatively well described and include impaired ion homeostasis, excessive cell swelling, glutamate excitotoxic mechanism, release of pro-inflammatory cytokines and phagocytosis or damage propagation via astrocytic syncytia. However, little is known about glia involvement in post-ischemic processes in remote areas. In this literature review, we discuss the definitions of the terms "ischemic core", "penumbra" and "remote areas." Furthermore, we present evidence showing the array of structural and functional changes in the more remote regions from the primary site of focal ischemia, with a special focus on glia and the extracellular matrix. The collected information is compared with the processes commonly occurring in the ischemic core or in the penumbra. Moreover, the possible causes of this phenomenon and the approaches for investigation are described, and finally, we evaluate the efficacy of therapies, which have been studied for their anti-ischemic effect in remote areas in recent years.

• Klíčová slova
• NG2-glia, astrocyte, future outlooks, microglia, oligodendrocytes, remote areas, stroke, therapy,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Ischemic brain injury and Alzheimer's disease (AD) both lead to cell death in the central nervous system (CNS) and thus negatively affect particularly the elderly population. Due to the lack of a definitive cure for brain ischemia and AD, it is advisable to carefully study, compare, and contrast the mechanisms that trigger, and are involved in, both neuropathologies. A deeper understanding of these mechanisms may help ameliorate, or even prevent, the destructive effects of neurodegenerative disorders. In this review, we deal with ischemic damage and AD, with the main emphasis on the common properties of these CNS disorders. Importantly, we discuss the Wnt signaling pathway as a significant factor in the cell fate determination and cell survival in the diseased adult CNS. Finally, we summarize the interesting findings that may improve or complement the current sparse and insufficient treatments for brain ischemia and AD, and we delineate prospective directions in regenerative medicine.

• Klíčová slova
• Alzheimer’s disease, Wnt signaling, amyloid beta, central nervous system, dementia, ischemic brain injury, neurodegeneration, stroke,
• MeSH
• Alzheimerova nemoc etiologie   metabolismus   patologie   MeSH
• amyloidní beta-protein metabolismus   MeSH
• biologické markery MeSH
• degenerace nervu MeSH
• ischemie mozku etiologie   metabolismus   patologie   MeSH
• lidé MeSH
• náchylnost k nemoci * MeSH
• neurony metabolismus   MeSH
• poranění mozku etiologie   metabolismus   patologie   MeSH
• signální dráha Wnt MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• amyloidní beta-protein MeSH
• biologické markery MeSH