Abstract
Objective: To study the effect of whole body cooling and/or xenon treatment on molecular changes induced by transient hypoxic-ischemia (HI) in the developing brain.
Methods: Experiments were performed under UK Home Office licence in accordance with UK guidelines. Newborn Large-White piglets were anesthetized and subjected to controlled transient HI. Piglets remained anesthetized and randomised to: (i) no treatment (ii) whole body cooling to a rectal temperature of 33.5 ±0.5 °C after HI; (iii) xenon or (iv) cooling + xenon treatment. (v) naïve group subjected only to anaesthesia. Piglets were subjected to intensive care and monitoring. After euthenasia brains were perfused with 4% formalin and processed for in situ hybridization and immunohistochemistry. To characterize possible effects HI and treatments on the transcriptional activity of key neuronal and glial genes, we used in situ hybridization with probes designed to detect mRNA encoding HSP70, MAP2 and GFAP.
Results: HI caused GFAP mRNA levels to increase in cortex cerebri, but not in striatum. None of the treatments could counter act the increase in cortex. HSP70 mRNA was increased by HI in cortex and striatum. Treatments enhanced cortical increases, while slightly counteracting striatal. MAP2 mRNA decreased in cortex by HI. Protective effects were noted by both xenon and hypothermia, although not additive. Striatal levels were lower then cortical, although the general pattern was similar to cortex. Understanding of the molecular mechanisms of hypothermic and other neuroprotective agents will assist in determining optimal combination(s) of neuroprotective agents for protection of the challenged newborn brain.
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Olson, L., Faulkner, S., Lundströmer, K. et al. 198 Molecular Changes After Whole Body Cooling on Piglets with Induced Transient Hypoxic-Ischemia in the Developing Brain. Pediatr Res 68 (Suppl 1), 103 (2010). https://doi.org/10.1203/00006450-201011001-00198
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DOI: https://doi.org/10.1203/00006450-201011001-00198