ROCK2 regulates microglia proliferation and neuronal survival after traumatic brain injury
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
Traumatic brain injury (TBI) results in prolonged and non-resolving activation of microglia. Forced turnover of these cells during the acute phase of TBI aids recovery, but the cell-intrinsic pathways that underpin the pro-repair phenotype of these repopulating microglia remain unclear. Here, we show that selective targeting of ROCK2 with the small molecule inhibitor KD025 impairs the proliferative response of microglia after TBI as well as during genetically induced turnover of microglia. KD025 treatment abolished the substantial neuroprotective and cognitive benefits conferred by repopulating microglia, preventing these cells from replenishing the depleted niche during the early critical time window post-injury. Delaying KD025 treatment to the subacute phase of TBI allowed microglial repopulation to occur, but this did not enhance the benefits conferred by repopulating microglia. Taken together, our data indicate that ROCK2 mediates neuronal survival and microglial population dynamics after TBI, including the emergence of repopulating microglia with a pro-repair phenotype.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:117 |
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| Enthalten in: |
Brain, behavior, and immunity - 117(2024) vom: 07. März, Seite 181-194 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Willis, Emily F [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 07.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbi.2024.01.004 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Traumatic brain injury (TBI) results in prolonged and non-resolving activation of microglia. Forced turnover of these cells during the acute phase of TBI aids recovery, but the cell-intrinsic pathways that underpin the pro-repair phenotype of these repopulating microglia remain unclear. Here, we show that selective targeting of ROCK2 with the small molecule inhibitor KD025 impairs the proliferative response of microglia after TBI as well as during genetically induced turnover of microglia. KD025 treatment abolished the substantial neuroprotective and cognitive benefits conferred by repopulating microglia, preventing these cells from replenishing the depleted niche during the early critical time window post-injury. Delaying KD025 treatment to the subacute phase of TBI allowed microglial repopulation to occur, but this did not enhance the benefits conferred by repopulating microglia. Taken together, our data indicate that ROCK2 mediates neuronal survival and microglial population dynamics after TBI, including the emergence of repopulating microglia with a pro-repair phenotype | ||
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| 700 | 1 | |a Vukovic, Jana |e verfasserin |4 aut | |
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