Hypoxic postconditioning reduces microglial activation, astrocyte and caspase activity, and inflammatory markers after hypoxia-ischemia in the neonatal rat brain.
BACKGROUND
Postconditioning (PostC) with mild hypoxia shortly after a neonatal hypoxic-ischemic (HI) brain injury can reduce brain damage, however, the mechanisms underlying this protection are not known. We hypothesize that hypoxic PostC reduces brain markers of glial activity, inflammation, and apoptosis following HI injury.


METHODS
Sprague Dawley rat pups were exposed to right common carotid artery occlusion and hypoxia (7% oxygen, 3 h) on postnatal day 7 and 24 h later, pups were exposed to hypoxic PostC (8% O2 for 1 h/day for 5 d) or kept at ambient conditions for the same duration. HI+N pups demonstrated ~10% loss in ipsilateral brain tissue which was rescued with HI+PostC. To investigate the cellular responses, markers of astrocytes, microglia, inflammation, and caspase 3 activity were examined using immunohistochemistry and enzyme-linked immunosorbent assay.


RESULTS
PostC reduced the area of astrocyte staining compared to HI+N. There was also a shift in microglial morphology toward a primed state in both PostC groups. Protein levels of interleukin-1β and caspase 3 were elevated in HI+N brains and reduced by PostC.


CONCLUSIONS
This is the first demonstration that PostC can reduce glial activity, inflammatory mediators, and cell death after a neonatal HI brain injury.
Department of Pharmacology, School of Medical Sciences, University of New South Wales, New South Wales, Australia.
Jonathan D
JD
Teo
Department of Pharmacology, School of Medical Sciences, University of New South Wales, New South Wales, Australia.
Margaret J
MJ
Morris
Department of Pharmacology, School of Medical Sciences, University of New South Wales, New South Wales, Australia.
Nicole M
NM
Jones
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D020925:Hypoxia-Ischemia, Brain / Q000628:therapy*; D007150:Immunohistochemistry; D007249:Inflammation / Q000517:prevention & control*; D057775:Ischemic Postconditioning / Q000379:methods*; D017628:Microglia / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D020169:Caspases