Abstract
Background
Therapeutic hypothermia (TH) is the standard of care for neonates with hypoxic–ischemic encephalopathy, but it is not fully protective in the clinical setting. Hypoxia–ischemia (HI) may cause white matter injury (WMI), leading to neurological and cognitive dysfunction.
Methods
P9 mice were subjected to HI as previously described. Pups underwent 3.5 h of systemic hypothermia or normothermia. Cresyl violet and Perl’s iron staining for histopathological scoring of brain sections was completed blindly on all brains. Immunocytochemical (ICC) staining for myelin basic protein (MBP), microglia (Iba1), and astrocytes (glia fibrillary acidic protein (GFAP)) was performed on adjacent sections. Volumetric measurements of MBP coverage were used for quantitative analysis of white matter.
Results
TH provided neuroprotection by injury scoring for the entire group (n=44; P<0.0002). ICC analysis of a subset of brains showed that the lateral caudate was protected from WMI (P<0.05). Analysis revealed decreased GFAP and Iba1 staining in hippocampal regions, mostly CA2/CA3. GFAP and Iba1 directly correlated with injury scores of normothermic brains.
Conclusion
TH reduced injury, and qualitative data suggest that hippocampus and lateral caudate are protected from HI. Mildly injured brains may better show the benefits of TH. Overall, these data indicate regional differences in WMI susceptibility and inflammation in a P9 murine HI model.
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Acknowledgements
EK was sponsored by the American Pediatric Society & Society for Pediatric Research Summer Medical Student Program. This work was supported by NS 33997. DMF was supported by National Institutes of Health 33997.
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Koo, E., Sheldon, R., Lee, B. et al. Effects of therapeutic hypothermia on white matter injury from murine neonatal hypoxia–ischemia. Pediatr Res 82, 518–526 (2017). https://doi.org/10.1038/pr.2017.75
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DOI: https://doi.org/10.1038/pr.2017.75
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