PMID- 38240014
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 16
DP  - 2023
TI  - Blocking of microglia-astrocyte proinflammatory signaling is beneficial following 
      stroke.
PG  - 1305949
LID - 10.3389/fnmol.2023.1305949 [doi]
LID - 1305949
AB  - Microglia and astrocytes play an important role in the neuroinflammatory response 
      and contribute to both the destruction of neighboring tissue as well as the 
      resolution of inflammation following stroke. These reactive glial cells are 
      highly heterogeneous at both the transcriptomic and functional level. Depending 
      upon the stimulus, microglia and astrocytes mount a complex, and specific 
      response composed of distinct microglial and astrocyte substates. These substates 
      ultimately drive the landscape of the initiation and recovery from the adverse 
      stimulus. In one state, inflammation- and damage-induced microglia release tumor 
      necrosis factor (TNF), interleukin 1alpha (IL1alpha), and complement component 1q (C1q), 
      together "TIC." This cocktail of cytokines drives astrocytes into a neurotoxic 
      reactive astrocyte (nRA) substate. This nRA substate is associated with loss of 
      many physiological astrocyte functions (e.g., synapse formation and maturation, 
      phagocytosis, among others), as well as a gain-of-function release of neurotoxic 
      long-chain fatty acids which kill neighboring cells. Here we report that 
      transgenic removal of TIC led to reduction of gliosis, infarct expansion, and 
      worsened functional deficits in the acute and delayed stages following stroke. 
      Our results suggest that TIC cytokines, and likely nRAs play an important role 
      that may maintain neuroinflammation and inhibit functional motor recovery after 
      ischemic stroke. This is the first report that this paradigm is relevant in 
      stroke and that therapies against nRAs may be a novel means to treat patients. 
      Since nRAs are evolutionarily conserved from rodents to humans and present in 
      multiple neurodegenerative diseases and injuries, further identification of 
      mechanistic role of nRAs will lead to a better understanding of the 
      neuroinflammatory response and the development of new therapies.
CI  - Copyright (c) 2024 Prescott, Munch, Brahms, Weigel, Inoue, Buckwalter, Liddelow and 
      Peterson.
FAU - Prescott, Kimberly
AU  - Prescott K
AD  - Department of Psychology, University of North Carolina Wilmington, Wilmington, 
      NC, United States.
FAU - Munch, Alexandra E
AU  - Munch AE
AD  - Neuroscience Department, Stanford University, Stanford, CA, United States.
FAU - Brahms, Evan
AU  - Brahms E
AD  - Department of Neurology and Neurological Sciences, Stanford School of Medicine, 
      Stanford, CA, United States.
FAU - Weigel, Maya K
AU  - Weigel MK
AD  - Neuroscience Department, Stanford University, Stanford, CA, United States.
FAU - Inoue, Kenya
AU  - Inoue K
AD  - Department of Psychology, University of North Carolina Wilmington, Wilmington, 
      NC, United States.
FAU - Buckwalter, Marion S
AU  - Buckwalter MS
AD  - Department of Neurology and Neurological Sciences, Stanford School of Medicine, 
      Stanford, CA, United States.
AD  - Department of Neurosurgery, Stanford School of Medicine, Stanford, CA, United 
      States.
FAU - Liddelow, Shane A
AU  - Liddelow SA
AD  - Neuroscience Institute, NYU Grossman School of Medicine, New York, NY, United 
      States.
AD  - Department of Neuroscience and Physiology, NYU Grossman School of Medicine, New 
      York, NY, United States.
AD  - Department of Ophthalmology, NYU Grossman School of Medicine, New York, NY, 
      United States.
AD  - Parekh Center for Interdisciplinary Neurology, NYU Grossman School of Medicine, 
      New York, NY, United States.
FAU - Peterson, Todd C
AU  - Peterson TC
AD  - Department of Psychology, University of North Carolina Wilmington, Wilmington, 
      NC, United States.
AD  - Department of Neurology and Neurological Sciences, Stanford School of Medicine, 
      Stanford, CA, United States.
LA  - eng
GR  - F32 NS089162/NS/NINDS NIH HHS/United States
GR  - R01 EY033353/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20240104
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC10794541
OTO - NOTNLM
OT  - astrocyte
OT  - infarct volume reduction
OT  - macrophage
OT  - recovery of function
OT  - stroke
COIS- SL declares ownership in AstronauTx Ltd, and sits on the Scientific Advisory 
      Board of the Global BioAccess Fund, Tamborine, and Synapticure. The remaining 
      authors declare that the research was conducted in the absence of any commercial 
      or financial relationships that could be construed as a potential conflict of 
      interest. The author(s) declared that they were an editorial board member of 
      Frontiers, at the time of submission. This had no impact on the peer review 
      process and the final decision.
EDAT- 2024/01/19 06:42
MHDA- 2024/01/19 06:43
PMCR- 2023/01/01
CRDT- 2024/01/19 03:50
PHST- 2023/10/02 00:00 [received]
PHST- 2023/12/01 00:00 [accepted]
PHST- 2024/01/19 06:43 [medline]
PHST- 2024/01/19 06:42 [pubmed]
PHST- 2024/01/19 03:50 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2023.1305949 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2024 Jan 4;16:1305949. doi: 10.3389/fnmol.2023.1305949. 
      eCollection 2023.