Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic–Ischaemic Brain Injury in Rats

(1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups w...
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Autor*in:	Madeleine J. Smith [verfasserIn] Tayla Penny [verfasserIn] Yen Pham [verfasserIn] Amy E. Sutherland [verfasserIn] Graham Jenkin [verfasserIn] Michael C. Fahey [verfasserIn] Madison C. B. Paton [verfasserIn] Megan Finch-Edmondson [verfasserIn] Suzanne L. Miller [verfasserIn] Courtney A. McDonald [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	immune system immunosuppression neonatal brain injury neuroprotection T-cells

Übergeordnetes Werk:	In: Cells - MDPI AG, 2012, 12(2023), 22, p 2659
Übergeordnetes Werk:	volume:12 ; year:2023 ; number:22, p 2659

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cells12222659

Katalog-ID:	DOAJ101261160

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520			\|a (1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups with the immunosuppressant tacrolimus at two time points: before and after hypoxic–ischaemic (HI)-induced injury. (2) Methods: To induce HI injury, postnatal day (PND) 10 rat pups underwent single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). Pups received daily tacrolimus (or a vehicle) starting either 3 days before HI on PND 7 (pre-HI), or 12 h after HI (post-HI). Four doses were tested: 0.025, 0.05, 0.1 or 0.25 mg/kg/day. Pups were euthanised at PND 17 or PND 50. (3) Results: All tacrolimus doses administered pre-HI significantly reduced brain infarct size and neuronal loss, increased the number of resting microglia and reduced cellular apoptosis (<i<p</i< < 0.05 compared to control). In contrast, only the highest dose of tacrolimus administered post-HI (0.25 mg/kg/day) reduced brain infarct size (<i<p</i< < 0.05). All doses of tacrolimus reduced pup weight compared to the controls. (4) Conclusions: Tacrolimus administration 3 days pre-HI was neuroprotective, likely mediated through neuroinflammatory and cell death pathways. Tacrolimus post-HI may have limited capacity to reduce brain injury, with higher doses increasing rat pup mortality. This work highlights the benefits of targeting neuroinflammation during the acute injurious period. More specific targeting of neuroinflammation, e.g., via T-cells, warrants further investigation.
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allfields	10.3390/cells12222659 doi (DE-627)DOAJ101261160 (DE-599)DOAJ3d4c13f9aded4afa9e7aaa537e5ae941 DE-627 ger DE-627 rakwb eng QH573-671 Madeleine J. Smith verfasserin aut Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic–Ischaemic Brain Injury in Rats 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups with the immunosuppressant tacrolimus at two time points: before and after hypoxic–ischaemic (HI)-induced injury. (2) Methods: To induce HI injury, postnatal day (PND) 10 rat pups underwent single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). Pups received daily tacrolimus (or a vehicle) starting either 3 days before HI on PND 7 (pre-HI), or 12 h after HI (post-HI). Four doses were tested: 0.025, 0.05, 0.1 or 0.25 mg/kg/day. Pups were euthanised at PND 17 or PND 50. (3) Results: All tacrolimus doses administered pre-HI significantly reduced brain infarct size and neuronal loss, increased the number of resting microglia and reduced cellular apoptosis (<i<p</i< < 0.05 compared to control). In contrast, only the highest dose of tacrolimus administered post-HI (0.25 mg/kg/day) reduced brain infarct size (<i<p</i< < 0.05). All doses of tacrolimus reduced pup weight compared to the controls. (4) Conclusions: Tacrolimus administration 3 days pre-HI was neuroprotective, likely mediated through neuroinflammatory and cell death pathways. Tacrolimus post-HI may have limited capacity to reduce brain injury, with higher doses increasing rat pup mortality. This work highlights the benefits of targeting neuroinflammation during the acute injurious period. More specific targeting of neuroinflammation, e.g., via T-cells, warrants further investigation. immune system immunosuppression neonatal brain injury neuroprotection T-cells Cytology Tayla Penny verfasserin aut Yen Pham verfasserin aut Amy E. Sutherland verfasserin aut Graham Jenkin verfasserin aut Michael C. Fahey verfasserin aut Madison C. B. Paton verfasserin aut Megan Finch-Edmondson verfasserin aut Suzanne L. Miller verfasserin aut Courtney A. McDonald verfasserin aut In Cells MDPI AG, 2012 12(2023), 22, p 2659 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:12 year:2023 number:22, p 2659 https://doi.org/10.3390/cells12222659 kostenfrei https://doaj.org/article/3d4c13f9aded4afa9e7aaa537e5ae941 kostenfrei https://www.mdpi.com/2073-4409/12/22/2659 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 22, p 2659
spelling	10.3390/cells12222659 doi (DE-627)DOAJ101261160 (DE-599)DOAJ3d4c13f9aded4afa9e7aaa537e5ae941 DE-627 ger DE-627 rakwb eng QH573-671 Madeleine J. Smith verfasserin aut Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic–Ischaemic Brain Injury in Rats 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups with the immunosuppressant tacrolimus at two time points: before and after hypoxic–ischaemic (HI)-induced injury. (2) Methods: To induce HI injury, postnatal day (PND) 10 rat pups underwent single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). Pups received daily tacrolimus (or a vehicle) starting either 3 days before HI on PND 7 (pre-HI), or 12 h after HI (post-HI). Four doses were tested: 0.025, 0.05, 0.1 or 0.25 mg/kg/day. Pups were euthanised at PND 17 or PND 50. (3) Results: All tacrolimus doses administered pre-HI significantly reduced brain infarct size and neuronal loss, increased the number of resting microglia and reduced cellular apoptosis (<i<p</i< < 0.05 compared to control). In contrast, only the highest dose of tacrolimus administered post-HI (0.25 mg/kg/day) reduced brain infarct size (<i<p</i< < 0.05). All doses of tacrolimus reduced pup weight compared to the controls. (4) Conclusions: Tacrolimus administration 3 days pre-HI was neuroprotective, likely mediated through neuroinflammatory and cell death pathways. Tacrolimus post-HI may have limited capacity to reduce brain injury, with higher doses increasing rat pup mortality. This work highlights the benefits of targeting neuroinflammation during the acute injurious period. More specific targeting of neuroinflammation, e.g., via T-cells, warrants further investigation. immune system immunosuppression neonatal brain injury neuroprotection T-cells Cytology Tayla Penny verfasserin aut Yen Pham verfasserin aut Amy E. Sutherland verfasserin aut Graham Jenkin verfasserin aut Michael C. Fahey verfasserin aut Madison C. B. Paton verfasserin aut Megan Finch-Edmondson verfasserin aut Suzanne L. Miller verfasserin aut Courtney A. McDonald verfasserin aut In Cells MDPI AG, 2012 12(2023), 22, p 2659 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:12 year:2023 number:22, p 2659 https://doi.org/10.3390/cells12222659 kostenfrei https://doaj.org/article/3d4c13f9aded4afa9e7aaa537e5ae941 kostenfrei https://www.mdpi.com/2073-4409/12/22/2659 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 22, p 2659
allfields_unstemmed	10.3390/cells12222659 doi (DE-627)DOAJ101261160 (DE-599)DOAJ3d4c13f9aded4afa9e7aaa537e5ae941 DE-627 ger DE-627 rakwb eng QH573-671 Madeleine J. Smith verfasserin aut Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic–Ischaemic Brain Injury in Rats 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups with the immunosuppressant tacrolimus at two time points: before and after hypoxic–ischaemic (HI)-induced injury. (2) Methods: To induce HI injury, postnatal day (PND) 10 rat pups underwent single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). Pups received daily tacrolimus (or a vehicle) starting either 3 days before HI on PND 7 (pre-HI), or 12 h after HI (post-HI). Four doses were tested: 0.025, 0.05, 0.1 or 0.25 mg/kg/day. Pups were euthanised at PND 17 or PND 50. (3) Results: All tacrolimus doses administered pre-HI significantly reduced brain infarct size and neuronal loss, increased the number of resting microglia and reduced cellular apoptosis (<i<p</i< < 0.05 compared to control). In contrast, only the highest dose of tacrolimus administered post-HI (0.25 mg/kg/day) reduced brain infarct size (<i<p</i< < 0.05). All doses of tacrolimus reduced pup weight compared to the controls. (4) Conclusions: Tacrolimus administration 3 days pre-HI was neuroprotective, likely mediated through neuroinflammatory and cell death pathways. Tacrolimus post-HI may have limited capacity to reduce brain injury, with higher doses increasing rat pup mortality. This work highlights the benefits of targeting neuroinflammation during the acute injurious period. More specific targeting of neuroinflammation, e.g., via T-cells, warrants further investigation. immune system immunosuppression neonatal brain injury neuroprotection T-cells Cytology Tayla Penny verfasserin aut Yen Pham verfasserin aut Amy E. Sutherland verfasserin aut Graham Jenkin verfasserin aut Michael C. Fahey verfasserin aut Madison C. B. Paton verfasserin aut Megan Finch-Edmondson verfasserin aut Suzanne L. Miller verfasserin aut Courtney A. McDonald verfasserin aut In Cells MDPI AG, 2012 12(2023), 22, p 2659 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:12 year:2023 number:22, p 2659 https://doi.org/10.3390/cells12222659 kostenfrei https://doaj.org/article/3d4c13f9aded4afa9e7aaa537e5ae941 kostenfrei https://www.mdpi.com/2073-4409/12/22/2659 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 22, p 2659
allfieldsGer	10.3390/cells12222659 doi (DE-627)DOAJ101261160 (DE-599)DOAJ3d4c13f9aded4afa9e7aaa537e5ae941 DE-627 ger DE-627 rakwb eng QH573-671 Madeleine J. Smith verfasserin aut Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic–Ischaemic Brain Injury in Rats 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups with the immunosuppressant tacrolimus at two time points: before and after hypoxic–ischaemic (HI)-induced injury. (2) Methods: To induce HI injury, postnatal day (PND) 10 rat pups underwent single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). Pups received daily tacrolimus (or a vehicle) starting either 3 days before HI on PND 7 (pre-HI), or 12 h after HI (post-HI). Four doses were tested: 0.025, 0.05, 0.1 or 0.25 mg/kg/day. Pups were euthanised at PND 17 or PND 50. (3) Results: All tacrolimus doses administered pre-HI significantly reduced brain infarct size and neuronal loss, increased the number of resting microglia and reduced cellular apoptosis (<i<p</i< < 0.05 compared to control). In contrast, only the highest dose of tacrolimus administered post-HI (0.25 mg/kg/day) reduced brain infarct size (<i<p</i< < 0.05). All doses of tacrolimus reduced pup weight compared to the controls. (4) Conclusions: Tacrolimus administration 3 days pre-HI was neuroprotective, likely mediated through neuroinflammatory and cell death pathways. Tacrolimus post-HI may have limited capacity to reduce brain injury, with higher doses increasing rat pup mortality. This work highlights the benefits of targeting neuroinflammation during the acute injurious period. More specific targeting of neuroinflammation, e.g., via T-cells, warrants further investigation. immune system immunosuppression neonatal brain injury neuroprotection T-cells Cytology Tayla Penny verfasserin aut Yen Pham verfasserin aut Amy E. Sutherland verfasserin aut Graham Jenkin verfasserin aut Michael C. Fahey verfasserin aut Madison C. B. Paton verfasserin aut Megan Finch-Edmondson verfasserin aut Suzanne L. Miller verfasserin aut Courtney A. McDonald verfasserin aut In Cells MDPI AG, 2012 12(2023), 22, p 2659 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:12 year:2023 number:22, p 2659 https://doi.org/10.3390/cells12222659 kostenfrei https://doaj.org/article/3d4c13f9aded4afa9e7aaa537e5ae941 kostenfrei https://www.mdpi.com/2073-4409/12/22/2659 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 22, p 2659
allfieldsSound	10.3390/cells12222659 doi (DE-627)DOAJ101261160 (DE-599)DOAJ3d4c13f9aded4afa9e7aaa537e5ae941 DE-627 ger DE-627 rakwb eng QH573-671 Madeleine J. Smith verfasserin aut Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic–Ischaemic Brain Injury in Rats 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups with the immunosuppressant tacrolimus at two time points: before and after hypoxic–ischaemic (HI)-induced injury. (2) Methods: To induce HI injury, postnatal day (PND) 10 rat pups underwent single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). Pups received daily tacrolimus (or a vehicle) starting either 3 days before HI on PND 7 (pre-HI), or 12 h after HI (post-HI). Four doses were tested: 0.025, 0.05, 0.1 or 0.25 mg/kg/day. Pups were euthanised at PND 17 or PND 50. (3) Results: All tacrolimus doses administered pre-HI significantly reduced brain infarct size and neuronal loss, increased the number of resting microglia and reduced cellular apoptosis (<i<p</i< < 0.05 compared to control). In contrast, only the highest dose of tacrolimus administered post-HI (0.25 mg/kg/day) reduced brain infarct size (<i<p</i< < 0.05). All doses of tacrolimus reduced pup weight compared to the controls. (4) Conclusions: Tacrolimus administration 3 days pre-HI was neuroprotective, likely mediated through neuroinflammatory and cell death pathways. Tacrolimus post-HI may have limited capacity to reduce brain injury, with higher doses increasing rat pup mortality. This work highlights the benefits of targeting neuroinflammation during the acute injurious period. More specific targeting of neuroinflammation, e.g., via T-cells, warrants further investigation. immune system immunosuppression neonatal brain injury neuroprotection T-cells Cytology Tayla Penny verfasserin aut Yen Pham verfasserin aut Amy E. Sutherland verfasserin aut Graham Jenkin verfasserin aut Michael C. Fahey verfasserin aut Madison C. B. Paton verfasserin aut Megan Finch-Edmondson verfasserin aut Suzanne L. Miller verfasserin aut Courtney A. McDonald verfasserin aut In Cells MDPI AG, 2012 12(2023), 22, p 2659 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:12 year:2023 number:22, p 2659 https://doi.org/10.3390/cells12222659 kostenfrei https://doaj.org/article/3d4c13f9aded4afa9e7aaa537e5ae941 kostenfrei https://www.mdpi.com/2073-4409/12/22/2659 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2023 22, p 2659
language	English
source	In Cells 12(2023), 22, p 2659 volume:12 year:2023 number:22, p 2659
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format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	immune system immunosuppression neonatal brain injury neuroprotection T-cells Cytology
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container_title	Cells
authorswithroles_txt_mv	Madeleine J. Smith @@aut@@ Tayla Penny @@aut@@ Yen Pham @@aut@@ Amy E. Sutherland @@aut@@ Graham Jenkin @@aut@@ Michael C. Fahey @@aut@@ Madison C. B. Paton @@aut@@ Megan Finch-Edmondson @@aut@@ Suzanne L. Miller @@aut@@ Courtney A. McDonald @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
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spellingShingle	Madeleine J. Smith misc QH573-671 misc immune system misc immunosuppression misc neonatal brain injury misc neuroprotection misc T-cells misc Cytology Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic–Ischaemic Brain Injury in Rats
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topic_title	QH573-671 Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic–Ischaemic Brain Injury in Rats immune system immunosuppression neonatal brain injury neuroprotection T-cells
topic	misc QH573-671 misc immune system misc immunosuppression misc neonatal brain injury misc neuroprotection misc T-cells misc Cytology
topic_unstemmed	misc QH573-671 misc immune system misc immunosuppression misc neonatal brain injury misc neuroprotection misc T-cells misc Cytology
topic_browse	misc QH573-671 misc immune system misc immunosuppression misc neonatal brain injury misc neuroprotection misc T-cells misc Cytology
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title	Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic–Ischaemic Brain Injury in Rats
ctrlnum	(DE-627)DOAJ101261160 (DE-599)DOAJ3d4c13f9aded4afa9e7aaa537e5ae941
title_full	Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic–Ischaemic Brain Injury in Rats
author_sort	Madeleine J. Smith
journal	Cells
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author_browse	Madeleine J. Smith Tayla Penny Yen Pham Amy E. Sutherland Graham Jenkin Michael C. Fahey Madison C. B. Paton Megan Finch-Edmondson Suzanne L. Miller Courtney A. McDonald
container_volume	12
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author-letter	Madeleine J. Smith
doi_str_mv	10.3390/cells12222659
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title_sort	neuroprotective action of tacrolimus before and after onset of neonatal hypoxic–ischaemic brain injury in rats
callnumber	QH573-671
title_auth	Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic–Ischaemic Brain Injury in Rats
abstract	(1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups with the immunosuppressant tacrolimus at two time points: before and after hypoxic–ischaemic (HI)-induced injury. (2) Methods: To induce HI injury, postnatal day (PND) 10 rat pups underwent single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). Pups received daily tacrolimus (or a vehicle) starting either 3 days before HI on PND 7 (pre-HI), or 12 h after HI (post-HI). Four doses were tested: 0.025, 0.05, 0.1 or 0.25 mg/kg/day. Pups were euthanised at PND 17 or PND 50. (3) Results: All tacrolimus doses administered pre-HI significantly reduced brain infarct size and neuronal loss, increased the number of resting microglia and reduced cellular apoptosis (<i<p</i< < 0.05 compared to control). In contrast, only the highest dose of tacrolimus administered post-HI (0.25 mg/kg/day) reduced brain infarct size (<i<p</i< < 0.05). All doses of tacrolimus reduced pup weight compared to the controls. (4) Conclusions: Tacrolimus administration 3 days pre-HI was neuroprotective, likely mediated through neuroinflammatory and cell death pathways. Tacrolimus post-HI may have limited capacity to reduce brain injury, with higher doses increasing rat pup mortality. This work highlights the benefits of targeting neuroinflammation during the acute injurious period. More specific targeting of neuroinflammation, e.g., via T-cells, warrants further investigation.
abstractGer	(1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups with the immunosuppressant tacrolimus at two time points: before and after hypoxic–ischaemic (HI)-induced injury. (2) Methods: To induce HI injury, postnatal day (PND) 10 rat pups underwent single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). Pups received daily tacrolimus (or a vehicle) starting either 3 days before HI on PND 7 (pre-HI), or 12 h after HI (post-HI). Four doses were tested: 0.025, 0.05, 0.1 or 0.25 mg/kg/day. Pups were euthanised at PND 17 or PND 50. (3) Results: All tacrolimus doses administered pre-HI significantly reduced brain infarct size and neuronal loss, increased the number of resting microglia and reduced cellular apoptosis (<i<p</i< < 0.05 compared to control). In contrast, only the highest dose of tacrolimus administered post-HI (0.25 mg/kg/day) reduced brain infarct size (<i<p</i< < 0.05). All doses of tacrolimus reduced pup weight compared to the controls. (4) Conclusions: Tacrolimus administration 3 days pre-HI was neuroprotective, likely mediated through neuroinflammatory and cell death pathways. Tacrolimus post-HI may have limited capacity to reduce brain injury, with higher doses increasing rat pup mortality. This work highlights the benefits of targeting neuroinflammation during the acute injurious period. More specific targeting of neuroinflammation, e.g., via T-cells, warrants further investigation.
abstract_unstemmed	(1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups with the immunosuppressant tacrolimus at two time points: before and after hypoxic–ischaemic (HI)-induced injury. (2) Methods: To induce HI injury, postnatal day (PND) 10 rat pups underwent single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). Pups received daily tacrolimus (or a vehicle) starting either 3 days before HI on PND 7 (pre-HI), or 12 h after HI (post-HI). Four doses were tested: 0.025, 0.05, 0.1 or 0.25 mg/kg/day. Pups were euthanised at PND 17 or PND 50. (3) Results: All tacrolimus doses administered pre-HI significantly reduced brain infarct size and neuronal loss, increased the number of resting microglia and reduced cellular apoptosis (<i<p</i< < 0.05 compared to control). In contrast, only the highest dose of tacrolimus administered post-HI (0.25 mg/kg/day) reduced brain infarct size (<i<p</i< < 0.05). All doses of tacrolimus reduced pup weight compared to the controls. (4) Conclusions: Tacrolimus administration 3 days pre-HI was neuroprotective, likely mediated through neuroinflammatory and cell death pathways. Tacrolimus post-HI may have limited capacity to reduce brain injury, with higher doses increasing rat pup mortality. This work highlights the benefits of targeting neuroinflammation during the acute injurious period. More specific targeting of neuroinflammation, e.g., via T-cells, warrants further investigation.
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container_issue	22, p 2659
title_short	Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic–Ischaemic Brain Injury in Rats
url	https://doi.org/10.3390/cells12222659 https://doaj.org/article/3d4c13f9aded4afa9e7aaa537e5ae941 https://www.mdpi.com/2073-4409/12/22/2659 https://doaj.org/toc/2073-4409
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author2	Tayla Penny Yen Pham Amy E. Sutherland Graham Jenkin Michael C. Fahey Madison C. B. Paton Megan Finch-Edmondson Suzanne L. Miller Courtney A. McDonald
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up_date	2024-07-03T19:38:12.356Z
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