Investigating Pathways of Ventilation Induced Brain Injury on Cerebral White Matter Inflammation and Injury After 24 h in Preterm Lambs
Initiation of respiratory support in the delivery room increases the risk and severity of brain injury in preterm neonates through two major pathways: an inflammatory pathway and a haemodynamic pathway. The relative contribution of each pathway on preterm brain injury is not known. We aimed to asses...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.904144/full |
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| author | Kyra YY Chan Kyra YY Chan Nhi T. Tran Nhi T. Tran Paris C. Papagianis Valerie A. Zahra Ilias Nitsos Ilias Nitsos Alison M. Moxham Domenic A. LaRosa Domenic A. LaRosa Courtney McDonald Courtney McDonald Suzanne L. Miller Suzanne L. Miller Robert Galinsky Robert Galinsky Dhafer M. Alahmari Dhafer M. Alahmari Dhafer M. Alahmari Vanesa Stojanovska Vanesa Stojanovska Graeme R. Polglase Graeme R. Polglase |
| author_facet | Kyra YY Chan Kyra YY Chan Nhi T. Tran Nhi T. Tran Paris C. Papagianis Valerie A. Zahra Ilias Nitsos Ilias Nitsos Alison M. Moxham Domenic A. LaRosa Domenic A. LaRosa Courtney McDonald Courtney McDonald Suzanne L. Miller Suzanne L. Miller Robert Galinsky Robert Galinsky Dhafer M. Alahmari Dhafer M. Alahmari Dhafer M. Alahmari Vanesa Stojanovska Vanesa Stojanovska Graeme R. Polglase Graeme R. Polglase |
| author_sort | Kyra YY Chan |
| collection | DOAJ |
| description | Initiation of respiratory support in the delivery room increases the risk and severity of brain injury in preterm neonates through two major pathways: an inflammatory pathway and a haemodynamic pathway. The relative contribution of each pathway on preterm brain injury is not known. We aimed to assess the role of the inflammatory and haemodynamic pathway on ventilation-induced brain injury (VIBI) in the preterm lamb. Fetal lambs (125 ± 1 day gestation) were exteriorised, instrumented and ventilated with a high tidal-volume (VT) injurious strategy for 15 min either with placental circulation intact to induce the inflammatory pathway only (INJINF; n = 7) or umbilical cord occluded to induce both the inflammatory and haemodynamic pathways (INJINF+HAE; n = 7). Sham controls were exteriorised but not ventilated (SHAM; n = 5) while unoperated controls (UNOP; n = 7) did not undergo fetal instrumentation. Fetuses were returned in utero following intervention and the ewe allowed to recover. Arterial blood gases and plasma were sampled periodically. Twenty-four hours following intervention, lambs were delivered and maintained on non-injurious ventilation for ∼40 min then brains were collected post-mortem for immunohistochemistry and RT-qPCR to assess inflammation, vascular pathology and cell death within white matter regions. Compared to INJINF lambs, INJINF+HAE lambs achieved a consistently higher VT during injurious ventilation and carotid blood flow was significantly lower than baseline by the end of ventilation. Throughout the 24 h recovery period, systemic arterial IL-6 levels of INJINF+HAE lambs were significantly higher than SHAM while there was no difference between INJINF and SHAM animals. At 24 h, mRNA expression levels of pro-inflammatory cytokines, tight junction proteins, markers of cell death, and histological injury indices of gliosis, blood vessel protein extravasation, oligodendrocyte injury and cell death were not different between groups. Injurious ventilation, irrespective of strategy, did not increase brain inflammation or injury 24 h later when compared to control animals. However, the haemodynamic pathway did influence carotid blood flow adaptations during injurious ventilation and increased systemic arterial IL-6 that may underlie long-term pathology. Future studies are required to further characterise the pathways and their long-term effects on VIBI. |
| first_indexed | 2024-04-13T21:58:43Z |
| format | Article |
| id | doaj.art-e2325f45e7b043978331bc6b943fff3a |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-13T21:58:43Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-e2325f45e7b043978331bc6b943fff3a2022-12-22T02:28:11ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-07-011310.3389/fphys.2022.904144904144Investigating Pathways of Ventilation Induced Brain Injury on Cerebral White Matter Inflammation and Injury After 24 h in Preterm LambsKyra YY Chan0Kyra YY Chan1Nhi T. Tran2Nhi T. Tran3Paris C. Papagianis4Valerie A. Zahra5Ilias Nitsos6Ilias Nitsos7Alison M. Moxham8Domenic A. LaRosa9Domenic A. LaRosa10Courtney McDonald11Courtney McDonald12Suzanne L. Miller13Suzanne L. Miller14Robert Galinsky15Robert Galinsky16Dhafer M. Alahmari17Dhafer M. Alahmari18Dhafer M. Alahmari19Vanesa Stojanovska20Vanesa Stojanovska21Graeme R. Polglase22Graeme R. Polglase23The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaMonash Biomedicine Discovery Institute and Department of Medical Imaging and Radiation Sciences, Monash University, Clayton, VIC, AustraliaMonash Biomedical Imaging, Monash University, Clayton, VIC, AustraliaDepartment of Diagnostic Imaging, King Saud Medical City, Riyadh, Saudi ArabiaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, AustraliaInitiation of respiratory support in the delivery room increases the risk and severity of brain injury in preterm neonates through two major pathways: an inflammatory pathway and a haemodynamic pathway. The relative contribution of each pathway on preterm brain injury is not known. We aimed to assess the role of the inflammatory and haemodynamic pathway on ventilation-induced brain injury (VIBI) in the preterm lamb. Fetal lambs (125 ± 1 day gestation) were exteriorised, instrumented and ventilated with a high tidal-volume (VT) injurious strategy for 15 min either with placental circulation intact to induce the inflammatory pathway only (INJINF; n = 7) or umbilical cord occluded to induce both the inflammatory and haemodynamic pathways (INJINF+HAE; n = 7). Sham controls were exteriorised but not ventilated (SHAM; n = 5) while unoperated controls (UNOP; n = 7) did not undergo fetal instrumentation. Fetuses were returned in utero following intervention and the ewe allowed to recover. Arterial blood gases and plasma were sampled periodically. Twenty-four hours following intervention, lambs were delivered and maintained on non-injurious ventilation for ∼40 min then brains were collected post-mortem for immunohistochemistry and RT-qPCR to assess inflammation, vascular pathology and cell death within white matter regions. Compared to INJINF lambs, INJINF+HAE lambs achieved a consistently higher VT during injurious ventilation and carotid blood flow was significantly lower than baseline by the end of ventilation. Throughout the 24 h recovery period, systemic arterial IL-6 levels of INJINF+HAE lambs were significantly higher than SHAM while there was no difference between INJINF and SHAM animals. At 24 h, mRNA expression levels of pro-inflammatory cytokines, tight junction proteins, markers of cell death, and histological injury indices of gliosis, blood vessel protein extravasation, oligodendrocyte injury and cell death were not different between groups. Injurious ventilation, irrespective of strategy, did not increase brain inflammation or injury 24 h later when compared to control animals. However, the haemodynamic pathway did influence carotid blood flow adaptations during injurious ventilation and increased systemic arterial IL-6 that may underlie long-term pathology. Future studies are required to further characterise the pathways and their long-term effects on VIBI.https://www.frontiersin.org/articles/10.3389/fphys.2022.904144/fullventilation-induced brain injurymechanical ventilationpretermwhite matter injurymechanismscerebral inflammation |
| spellingShingle | Kyra YY Chan Kyra YY Chan Nhi T. Tran Nhi T. Tran Paris C. Papagianis Valerie A. Zahra Ilias Nitsos Ilias Nitsos Alison M. Moxham Domenic A. LaRosa Domenic A. LaRosa Courtney McDonald Courtney McDonald Suzanne L. Miller Suzanne L. Miller Robert Galinsky Robert Galinsky Dhafer M. Alahmari Dhafer M. Alahmari Dhafer M. Alahmari Vanesa Stojanovska Vanesa Stojanovska Graeme R. Polglase Graeme R. Polglase Investigating Pathways of Ventilation Induced Brain Injury on Cerebral White Matter Inflammation and Injury After 24 h in Preterm Lambs Frontiers in Physiology ventilation-induced brain injury mechanical ventilation preterm white matter injury mechanisms cerebral inflammation |
| title | Investigating Pathways of Ventilation Induced Brain Injury on Cerebral White Matter Inflammation and Injury After 24 h in Preterm Lambs |
| title_full | Investigating Pathways of Ventilation Induced Brain Injury on Cerebral White Matter Inflammation and Injury After 24 h in Preterm Lambs |
| title_fullStr | Investigating Pathways of Ventilation Induced Brain Injury on Cerebral White Matter Inflammation and Injury After 24 h in Preterm Lambs |
| title_full_unstemmed | Investigating Pathways of Ventilation Induced Brain Injury on Cerebral White Matter Inflammation and Injury After 24 h in Preterm Lambs |
| title_short | Investigating Pathways of Ventilation Induced Brain Injury on Cerebral White Matter Inflammation and Injury After 24 h in Preterm Lambs |
| title_sort | investigating pathways of ventilation induced brain injury on cerebral white matter inflammation and injury after 24 h in preterm lambs |
| topic | ventilation-induced brain injury mechanical ventilation preterm white matter injury mechanisms cerebral inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.904144/full |
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