Analysis of Small Ischemic Lesions in the Examinees of a Brain Dock and Neurological Examination of Animals Subjected to Cortical or Basal Ganglia Photothrombotic Infarction

Kuroiwa, Toshihiko; Tabata, Hitoshi; Xi, Guohua; Hua, Ya; Keep, Richard F.

doi:10.1007/978-3-319-18497-5_16

Cited by 5 publications

(4 citation statements)

References 8 publications

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“…The primary insult to which brain cells are exposed during ischemia is the decrease on substrates such as glucose and oxygen. A critical event, considering that brain cells require a continuous supply of oxygen and energetic substrates for maintenance of its functional and structural integrity (Castelló-Ruiz et al, 2014 ; Kuroiwa et al, 2016 ). Astrocytes have multiple functions in several metabolic aspects of ischemic brain damage, because they are capable of protecting neurons against numerous insults, and in that way promoting neuronal survival.…”

Section: Discussionmentioning

confidence: 99%

Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network

Martin-Jimenez

Salazar-Barreto

Barreto

et al. 2017

Front. Aging Neurosci.

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Astrocytes are the most abundant cells of the central nervous system; they have a predominant role in maintaining brain metabolism. In this sense, abnormal metabolic states have been found in different neuropathological diseases. Determination of metabolic states of astrocytes is difficult to model using current experimental approaches given the high number of reactions and metabolites present. Thus, genome-scale metabolic networks derived from transcriptomic data can be used as a framework to elucidate how astrocytes modulate human brain metabolic states during normal conditions and in neurodegenerative diseases. We performed a Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network with the purpose of elucidating a significant portion of the metabolic map of the astrocyte. This is the first global high-quality, manually curated metabolic reconstruction network of a human astrocyte. It includes 5,007 metabolites and 5,659 reactions distributed among 8 cell compartments, (extracellular, cytoplasm, mitochondria, endoplasmic reticle, Golgi apparatus, lysosome, peroxisome and nucleus). Using the reconstructed network, the metabolic capabilities of human astrocytes were calculated and compared both in normal and ischemic conditions. We identified reactions activated in these two states, which can be useful for understanding the astrocytic pathways that are affected during brain disease. Additionally, we also showed that the obtained flux distributions in the model, are in accordance with literature-based findings. Up to date, this is the most complete representation of the human astrocyte in terms of inclusion of genes, proteins, reactions and metabolic pathways, being a useful guide for in-silico analysis of several metabolic behaviors of the astrocyte during normal and pathologic states.

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Section: Discussionmentioning

confidence: 99%

Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network

Martin-Jimenez

Salazar-Barreto

Barreto

et al. 2017

Front. Aging Neurosci.

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“…Photothrombosis was initially developed in rats to study cortical ischemia (Watson et al, 1985) and was soon adapted to other small animals such as mice and Mongolian gerbils (Kuroiwa et al, 2016). The benefit of inducing photothrombosis in smaller animals is minimal invasiveness (no need for craniotomy); however, additional live brain imaging with modalities such as intravital microscopy would still necessitate bone removal (Nowak et al, 2022).…”

Section: Photothrombosis Modelmentioning

confidence: 99%

Animal models of focal ischemic stroke: brain size matters

et al. 2023

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Stroke remains the second leading cause of death worldwide and the third cause of disability-adjusted life-years. Most strokes are ischemic in nature, meaning they are caused by the disruption of cerebral blood flow resulting from obstructed blood vessels. Reperfusion therapies such as thrombolysis with tissue plasminogen activator and endovascular mechanical thrombectomy are very effective and are becoming game changers for eligible patients. Despite these advances, the achieved effects are insufficient from the perspective of the entire population of stroke patients. Therefore, there is an urgent need to expand eligibility for reperfusion therapies and implement adjuvant therapeutic measures. Animal stroke models are at the forefront of these efforts, helping to untangle complex pathophysiology and providing valuable preclinical data to guide further clinical trials. Various stroke models are available, including direct blocking of cerebral arteries or using other means to recapitulate stroke pathophysiology. International advisory boards recommend initial in vivo experiments be performed in smaller animals, such as rodents. However, second testing would be more desirable in larger animals such as cats, pigs, dogs, and non-human primates. Due to larger cerebral volume, gyrencephalization, and higher white/gray matter ratio, large animals are crucial in translational stroke research. Animal stroke models differ in the time and complexity of the stroke induction procedure, the reproducibility rate, the level of similarity to the human condition, and the possibilities for analysis, imaging, and follow-up studies. The choice of the most appropriate stroke model may translate to better bench-to-bedside translation of preclinical stroke research; ideally, this choice should be based solely on scientific merit.

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“…It is important to note that gliosis plays a role in responding to brain insults, but their inflammatory response and their activity in the regulation of immune cells is controversial (Lapuente-Chala and Céspedes-Rubio, 2018 ). Astrogliosis is a defensive reaction that involves both morphological and molecular changes as a response to injury, where astrocytes increase at the lesion site with an altered morphology (Kuroiwa et al, 2016 ). The proliferation of adjacent astrocytes implies an increased expression of the intermediate glial filaments such as vimentin, GFAP, nestin, and chondroitin sulfate proteoglycans (Hamby and Sofroniew, 2010 ; Bylicky et al, 2018 ).…”

Section: Astrocytes Are Important For Brain Homeostasismentioning

confidence: 99%

Advances in Astrocyte Computational Models: From Metabolic Reconstructions to Multi-omic Approaches

González

Pinzón

Angarita-Rodríguez

et al. 2020

Front. Neuroinform.

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The growing importance of astrocytes in the field of neuroscience has led to a greater number of computational models devoted to the study of astrocytic functions and their metabolic interactions with neurons. The modeling of these interactions demands a combined understanding of brain physiology and the development of computational frameworks based on genomic-scale reconstructions, system biology, and dynamic models. These computational approaches have helped to highlight the neuroprotective mechanisms triggered by astrocytes and other glial cells, both under normal conditions and during neurodegenerative processes. In the present review, we evaluate some of the most relevant models of astrocyte metabolism, including genome-scale reconstructions and astrocyte-neuron interactions developed in the last few years. Additionally, we discuss novel strategies from the multi-omics perspective and computational models of other glial cell types that will increase our knowledge in brain metabolism and its association with neurodegenerative diseases.

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Analysis of Small Ischemic Lesions in the Examinees of a Brain Dock and Neurological Examination of Animals Subjected to Cortical or Basal Ganglia Photothrombotic Infarction

Cited by 5 publications

References 8 publications

Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network

Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network

Animal models of focal ischemic stroke: brain size matters

Advances in Astrocyte Computational Models: From Metabolic Reconstructions to Multi-omic Approaches

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