Mechanical ventilation induces brainstem inflammation in preterm fetal sheep
BackgroundPreterm infants have immature respiratory drive and often require prolonged periods of mechanical ventilation. Prolonged mechanical ventilation induces systemic inflammation resulting in ventilation-induced brain injury, however its effect on brainstem respiratory centers is unknown. We ai...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2023.1225294/full |
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| author | Kayla Vidinopoulos Kayla Vidinopoulos Zahrah Azman Zahrah Azman Ainsley Somers Ainsley Somers Valerie A. Zahra Alison Thiel Hui Lu Yen Pham Nhi Thao Tran Nhi Thao Tran Beth J. Allison Beth J. Allison Eric Herlenius Stuart Hooper Stuart Hooper Robert Galinsky Robert Galinsky Graeme R. Polglase Graeme R. Polglase |
| author_facet | Kayla Vidinopoulos Kayla Vidinopoulos Zahrah Azman Zahrah Azman Ainsley Somers Ainsley Somers Valerie A. Zahra Alison Thiel Hui Lu Yen Pham Nhi Thao Tran Nhi Thao Tran Beth J. Allison Beth J. Allison Eric Herlenius Stuart Hooper Stuart Hooper Robert Galinsky Robert Galinsky Graeme R. Polglase Graeme R. Polglase |
| author_sort | Kayla Vidinopoulos |
| collection | DOAJ |
| description | BackgroundPreterm infants have immature respiratory drive and often require prolonged periods of mechanical ventilation. Prolonged mechanical ventilation induces systemic inflammation resulting in ventilation-induced brain injury, however its effect on brainstem respiratory centers is unknown. We aimed to determine the effects of 24 h of mechanical ventilation on inflammation and injury in brainstem respiratory centres of preterm fetal sheep.MethodsPreterm fetal sheep at 110 ± 1 days (d) gestation were instrumented to provide mechanical ventilation in utero. At 112 ± 1 d gestation, fetuses received either mechanical ventilation (VENT; n = 7; 3 ml/kg) for 24 h, or no ventilation (CONT; n = 6). At post-mortem, fetal brainstems were collected for assessment of mRNA and histological markers of inflammation and injury.ResultsIn utero ventilation (IUV) did not alter any blood-gas parameters. IUV significantly increased systemic IL-6 and IL-8 concentrations over the 24 h period compared to CONT. The number of ameboid microglia within the nucleus tractus solitarius and the raphe nucleus increased in VENT fetuses (p < 0.05 for both vs. control). The % area fraction of GFAP + staining was not significantly higher within the preBötzinger complex (p = 0.067) and retrotrapezoid nucleus and parafacial respiratory group (p = 0.057) in VENT fetuses compared to CONT. Numbers of caspase-3 and TUNEL-positive cells were similar between groups. Gene expression (mRNA) levels of inflammation, injury, cell death and prostaglandin synthesis within the brainstem were similar between groups.ConclusionMechanical ventilation induces a systemic inflammatory response with only moderate inflammatory effects within the brainstem respiratory centres of preterm fetal sheep. |
| first_indexed | 2024-03-11T16:38:05Z |
| format | Article |
| id | doaj.art-68d582654d2f4ff98d19a48637566150 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-03-11T16:38:05Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-68d582654d2f4ff98d19a486375661502023-10-23T11:20:55ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-10-011110.3389/fped.2023.12252941225294Mechanical ventilation induces brainstem inflammation in preterm fetal sheepKayla Vidinopoulos0Kayla Vidinopoulos1Zahrah Azman2Zahrah Azman3Ainsley Somers4Ainsley Somers5Valerie A. Zahra6Alison Thiel7Hui Lu8Yen Pham9Nhi Thao Tran10Nhi Thao Tran11Beth J. Allison12Beth J. Allison13Eric Herlenius14Stuart Hooper15Stuart Hooper16Robert Galinsky17Robert Galinsky18Graeme R. Polglase19Graeme R. Polglase20The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, AustraliaDepartment of Women’s and Children’s Health, Astrid Lindgren Children’s Hospital, Karolinska Institutet, Stockholm, SwedenThe Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, AustraliaThe Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, AustraliaBackgroundPreterm infants have immature respiratory drive and often require prolonged periods of mechanical ventilation. Prolonged mechanical ventilation induces systemic inflammation resulting in ventilation-induced brain injury, however its effect on brainstem respiratory centers is unknown. We aimed to determine the effects of 24 h of mechanical ventilation on inflammation and injury in brainstem respiratory centres of preterm fetal sheep.MethodsPreterm fetal sheep at 110 ± 1 days (d) gestation were instrumented to provide mechanical ventilation in utero. At 112 ± 1 d gestation, fetuses received either mechanical ventilation (VENT; n = 7; 3 ml/kg) for 24 h, or no ventilation (CONT; n = 6). At post-mortem, fetal brainstems were collected for assessment of mRNA and histological markers of inflammation and injury.ResultsIn utero ventilation (IUV) did not alter any blood-gas parameters. IUV significantly increased systemic IL-6 and IL-8 concentrations over the 24 h period compared to CONT. The number of ameboid microglia within the nucleus tractus solitarius and the raphe nucleus increased in VENT fetuses (p < 0.05 for both vs. control). The % area fraction of GFAP + staining was not significantly higher within the preBötzinger complex (p = 0.067) and retrotrapezoid nucleus and parafacial respiratory group (p = 0.057) in VENT fetuses compared to CONT. Numbers of caspase-3 and TUNEL-positive cells were similar between groups. Gene expression (mRNA) levels of inflammation, injury, cell death and prostaglandin synthesis within the brainstem were similar between groups.ConclusionMechanical ventilation induces a systemic inflammatory response with only moderate inflammatory effects within the brainstem respiratory centres of preterm fetal sheep.https://www.frontiersin.org/articles/10.3389/fped.2023.1225294/fullbrainstemmechanical ventilationventilation-induced brain injuryinflammationpreterm birth |
| spellingShingle | Kayla Vidinopoulos Kayla Vidinopoulos Zahrah Azman Zahrah Azman Ainsley Somers Ainsley Somers Valerie A. Zahra Alison Thiel Hui Lu Yen Pham Nhi Thao Tran Nhi Thao Tran Beth J. Allison Beth J. Allison Eric Herlenius Stuart Hooper Stuart Hooper Robert Galinsky Robert Galinsky Graeme R. Polglase Graeme R. Polglase Mechanical ventilation induces brainstem inflammation in preterm fetal sheep Frontiers in Pediatrics brainstem mechanical ventilation ventilation-induced brain injury inflammation preterm birth |
| title | Mechanical ventilation induces brainstem inflammation in preterm fetal sheep |
| title_full | Mechanical ventilation induces brainstem inflammation in preterm fetal sheep |
| title_fullStr | Mechanical ventilation induces brainstem inflammation in preterm fetal sheep |
| title_full_unstemmed | Mechanical ventilation induces brainstem inflammation in preterm fetal sheep |
| title_short | Mechanical ventilation induces brainstem inflammation in preterm fetal sheep |
| title_sort | mechanical ventilation induces brainstem inflammation in preterm fetal sheep |
| topic | brainstem mechanical ventilation ventilation-induced brain injury inflammation preterm birth |
| url | https://www.frontiersin.org/articles/10.3389/fped.2023.1225294/full |
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