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A systematic review of immune-based interventions for perinatal neuroprotection: closing the gap between animal studies and human trials

Authors :
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
Source :
Journal of Neuroinflammation, Vol 20, Iss 1, Pp 1-32 (2023)
Publication Year :
2023
Publisher :
BMC, 2023.

Abstract

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.

Details

Language :
English
ISSN :
17422094
Volume :
20
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Neuroinflammation
Publication Type :
Academic Journal
Accession number :
edsdoj.87c87a74a2394d7895a2c8b4332b8133
Document Type :
article
Full Text :
https://doi.org/10.1186/s12974-023-02911-w