ArticlePloS one2012
Autophagy and apoptosis are differentially induced in neurons and astrocytes treated with an in vitro mimic of the ischemic penumbra.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- The effect of astrocyte depletion and repopulation approaches in pathological condition of CNS.Acta neurologica Belgica · 2026Review
- An aldehyde-crosslinking mitochondrial probe for STED imaging in fixed cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Herpes Simplex Virus type 1 inhibits autophagy in glial cells but requires ATG5 for the success of viral replication.Frontiers in microbiology · 2024Article
- Review
- Research progress on astrocyte autophagy in ischemic stroke.Frontiers in neurology · 2022Review
- Modulation of the IGF1R-MTOR pathway attenuates motor neuron toxicity of human ALS SOD1Autophagy · 2021Article
- Differential regulation of autophagy during metabolic stress in astrocytes and neurons.Autophagy · 2020Article
- Review
- The excretory/secretory products of fifth-stage larval Angiostrongylus cantonensis induces autophagy via the Sonic hedgehog pathway in mouse brain astrocytes.PLoS neglected tropical diseases · 2020Article
- The Contribution of Astrocyte Autophagy to Systemic Metabolism.International journal of molecular sciences · 2020Review
- Peroxisomal Dysfunction in Neurological Diseases and Brain Aging.Frontiers in cellular neuroscience · 2020Article
- Modulator of apoptosis-1 is a potential therapeutic target in acute ischemic injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Immune Cells After Ischemic Stroke Onset: Roles, Migration, and Target Intervention.Journal of molecular neuroscience : MN · 2018Review
- Sphingosine kinase 1-associated autophagy differs between neurons and astrocytes.Cell death & disease · 2018Article
- Cell Death Mechanisms in Stroke and Novel Molecular and Cellular Treatment Options.Current neuropharmacology · 2018Review
- Effects of Hydroxyurea Exposure on the Rat Cerebellar Neuroepithelium: an Immunohistochemical and Electron Microscopic Study Along the Anteroposterior and Mediolateral Axes.Neurotoxicity research · 2017Article
- Inhibition of autophagy blocks cathepsins-tBid-mitochondrial apoptotic signaling pathway via stabilization of lysosomal membrane in ischemic astrocytes.Cell death & disease · 2017Article
- Oxygen-Glucose Deprivation (OGD) Modulates the Unfolded Protein Response (UPR) and Inflicts Autophagy in a PC12 Hypoxia Cell Line Model.Cellular and molecular neurobiology · 2016Article
- Dynamic changes in neuronal autophagy and apoptosis in the ischemic penumbra following permanent ischemic stroke.Neural regeneration research · 2016Article
- Sirtuin 3 mediates neuroprotection of ketones against ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The development of clinical stroke therapies remains elusive. The neuroprotective efficacies of thousands of molecules and compounds have not yet been determined; however, screening large volumes of potential targets in vivo is severely rate limiting. High throughput screens (HTS) may be used to discover promising candidates, but this approach has been hindered by the lack of a simple in vitro model of the ischemic penumbra, a clinically relevant region of stroke-afflicted brain. Recently, our laboratory developed such a mimic (ischemic solution: IS) suitable for HTS, but the etiology of stress pathways activated by this model are poorly understood. The aim of the present study was to determine if the cell death phenotype induced by IS accurately mimics the in vivo penumbra and thus whether our model system is suitable for use in HTS. We treated cultured neuron and astrocyte cell lines with IS for up to 48 hrs and examined cellular energy state ([ATP]), cell and organelle morphology, and gene and molecular profiles related to stress pathways. We found that IS-treated cells exhibited a phenotype of mixed apoptosis/autophagy characteristic of the in vivo penumbra, including: (1) short-term elevation of [ATP] followed by progressive ATP depletion and Poly ADP Ribose Polymerase cleavage, (2) increased vacuole number in the cytoplasm, (3) mitochondrial rupture, decreased mitochondrial and cristae density, release of cytochrome C and apoptosis inducing factor, (4) chromatin condensation, nuclear lamin A and DNA cleavage, fragmentation of the nuclear envelope, and (5) altered expression of mRNA and proteins consistent with autophagy and apoptosis. We conclude that our in vitro model of the ischemic penumbra induces autophagy and apoptosis in cultured neuron and astrocyte cell lines and that this mimic solution is suitable for use in HTS to elucidate neuroprotective candidates against ischemic penumbral cell death.
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