A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials
Abstract Background Perinatal infection/inflammation is associated with a high risk for neurological injury and neurodevelopmental impairment after birth. Despite a growing preclinical evidence base, anti-inflammatory interventions have not been established in clinical practice, partly because of th...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-023-02911-w |
| _version_ | 1797557634856910848 |
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| author | Sharmony B. Kelly Nhi T. Tran Graeme R. Polglase Rodney W. Hunt Marcel F. Nold Claudia A. Nold-Petry David M. Olson Sylvain Chemtob Gregory A. Lodygensky Sarah A. Robertson Alistair J. Gunn Robert Galinsky |
| author_facet | Sharmony B. Kelly Nhi T. Tran Graeme R. Polglase Rodney W. Hunt Marcel F. Nold Claudia A. Nold-Petry David M. Olson Sylvain Chemtob Gregory A. Lodygensky Sarah A. Robertson Alistair J. Gunn Robert Galinsky |
| author_sort | Sharmony B. Kelly |
| collection | DOAJ |
| description | Abstract Background Perinatal infection/inflammation is associated with a high risk for neurological injury and neurodevelopmental impairment after birth. Despite a growing preclinical evidence base, anti-inflammatory interventions have not been established in clinical practice, partly because of the range of potential targets. We therefore systematically reviewed preclinical studies of immunomodulation to improve neurological outcomes in the perinatal brain and assessed their therapeutic potential. Methods We reviewed relevant studies published from January 2012 to July 2023 using PubMed, Medline (OvidSP) and EMBASE databases. Studies were assessed for risk of bias using the SYRCLE risk of bias assessment tool (PROSPERO; registration number CRD42023395690). Results Forty preclinical publications using 12 models of perinatal neuroinflammation were identified and divided into 59 individual studies. Twenty-seven anti-inflammatory agents in 19 categories were investigated. Forty-five (76%) of 59 studies reported neuroprotection, from all 19 categories of therapeutics. Notably, 10/10 (100%) studies investigating anti-interleukin (IL)-1 therapies reported improved outcome, whereas half of the studies using corticosteroids (5/10; 50%) reported no improvement or worse outcomes with treatment. Most studies (49/59, 83%) did not control core body temperature (a known potential confounder), and 25 of 59 studies (42%) did not report the sex of subjects. Many studies did not clearly state whether they controlled for potential study bias. Conclusion Anti-inflammatory therapies are promising candidates for treatment or even prevention of perinatal brain injury. Our analysis highlights key knowledge gaps and opportunities to improve preclinical study design that must be addressed to support clinical translation. |
| first_indexed | 2024-03-10T17:19:23Z |
| format | Article |
| id | doaj.art-87c87a74a2394d7895a2c8b4332b8133 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-03-10T17:19:23Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-87c87a74a2394d7895a2c8b4332b81332023-11-20T10:24:04ZengBMCJournal of Neuroinflammation1742-20942023-10-0120113210.1186/s12974-023-02911-wA systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trialsSharmony B. Kelly0Nhi T. Tran1Graeme R. Polglase2Rodney W. Hunt3Marcel F. Nold4Claudia A. Nold-Petry5David M. Olson6Sylvain Chemtob7Gregory A. Lodygensky8Sarah A. Robertson9Alistair J. Gunn10Robert Galinsky11The Ritchie Centre, Hudson Institute of Medical ResearchThe Ritchie Centre, Hudson Institute of Medical ResearchThe Ritchie Centre, Hudson Institute of Medical ResearchThe Ritchie Centre, Hudson Institute of Medical ResearchThe Ritchie Centre, Hudson Institute of Medical ResearchThe Ritchie Centre, Hudson Institute of Medical ResearchDepartment of Obstetrics and Gynaecology, University of AlbertaDepartment of Paediatrics, CHU Sainte Justine Research Centre, University of MontrealDepartment of Paediatrics, CHU Sainte Justine Research Centre, University of MontrealThe University of Adelaide, Robinson Research InstituteDepartment of Physiology, The University of AucklandThe Ritchie Centre, Hudson Institute of Medical ResearchAbstract Background Perinatal infection/inflammation is associated with a high risk for neurological injury and neurodevelopmental impairment after birth. Despite a growing preclinical evidence base, anti-inflammatory interventions have not been established in clinical practice, partly because of the range of potential targets. We therefore systematically reviewed preclinical studies of immunomodulation to improve neurological outcomes in the perinatal brain and assessed their therapeutic potential. Methods We reviewed relevant studies published from January 2012 to July 2023 using PubMed, Medline (OvidSP) and EMBASE databases. Studies were assessed for risk of bias using the SYRCLE risk of bias assessment tool (PROSPERO; registration number CRD42023395690). Results Forty preclinical publications using 12 models of perinatal neuroinflammation were identified and divided into 59 individual studies. Twenty-seven anti-inflammatory agents in 19 categories were investigated. Forty-five (76%) of 59 studies reported neuroprotection, from all 19 categories of therapeutics. Notably, 10/10 (100%) studies investigating anti-interleukin (IL)-1 therapies reported improved outcome, whereas half of the studies using corticosteroids (5/10; 50%) reported no improvement or worse outcomes with treatment. Most studies (49/59, 83%) did not control core body temperature (a known potential confounder), and 25 of 59 studies (42%) did not report the sex of subjects. Many studies did not clearly state whether they controlled for potential study bias. Conclusion Anti-inflammatory therapies are promising candidates for treatment or even prevention of perinatal brain injury. Our analysis highlights key knowledge gaps and opportunities to improve preclinical study design that must be addressed to support clinical translation.https://doi.org/10.1186/s12974-023-02911-wHypoxia–ischaemiaInfection/inflammationNewborn brainNeuroinflammationNeuroprotectionAnti-inflammatory |
| spellingShingle | Sharmony B. Kelly Nhi T. Tran Graeme R. Polglase Rodney W. Hunt Marcel F. Nold Claudia A. Nold-Petry David M. Olson Sylvain Chemtob Gregory A. Lodygensky Sarah A. Robertson Alistair J. Gunn Robert Galinsky A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials Journal of Neuroinflammation Hypoxia–ischaemia Infection/inflammation Newborn brain Neuroinflammation Neuroprotection Anti-inflammatory |
| title | A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials |
| title_full | A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials |
| title_fullStr | A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials |
| title_full_unstemmed | A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials |
| title_short | A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials |
| title_sort | systematic review of immune based interventions for perinatal neuroprotection closing the gap between animal studies and human trials |
| topic | Hypoxia–ischaemia Infection/inflammation Newborn brain Neuroinflammation Neuroprotection Anti-inflammatory |
| url | https://doi.org/10.1186/s12974-023-02911-w |
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