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Updated: Jun 23, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Delayed P2X4R expression after hypoxia-ischemia is associated with microglia in the immature rat brain
Julie A Wixey1, Hanna E Reinebrant, Michelle L Carty
1Perinatal Research, Clinical Neuroscience, University of Queensland Centre for Clinical Research, Herston, Queensland 4029, Australia.
Abstract:
In a preterm hypoxia-ischemia model in the post-natal day 3 rat, we characterized how the expression of purine ionotropic P2X(4) receptors change in the brain post-insult. After hypoxia-ischemia, P2X(4) receptor expression increased significantly and was associated with a late increase in ionised calcium binding adapter molecule-1 protein expression indicative of microglia cell activation. Minocycline, a potent inhibitor of microglia, attenuated the hypoxia-ischemia-induced increase in P2X(4) receptor expression. We postulate that P2X(4) receptor-positive microglia may represent a population of secondary injury-induced activated microglia. Future studies will determine whether this population contributes to the progression of injury in the immature brain.
Insights
Hypoxia-ischemia in immature rat brains increases P2X(4) receptors and activates microglia. Minocycline treatment reduced these effects, suggesting P2X(4) receptors on microglia contribute to secondary brain injury.
Area of Science:
- Neuroscience
- Neuroinflammation
- Developmental Neuroscience
Background:
- Hypoxia-ischemia (HI) is a major cause of brain injury in preterm infants.
- Microglia activation plays a critical role in neuroinflammation and secondary brain injury.
- Purinergic signaling, particularly through P2X receptors, is implicated in neuroinflammatory processes.
Purpose of the Study:
- To investigate the changes in P2X(4) receptor expression in the immature brain following hypoxia-ischemia.
- To determine the role of microglia in the regulation of P2X(4) receptor expression post-HI.
- To explore the potential contribution of P2X(4) receptor-expressing microglia to secondary injury.
Main Methods:
- Utilized a preterm hypoxia-ischemia (HI) model in post-natal day 3 rats.
- Quantified P2X(4) receptor expression using immunohistochemistry.
- Assessed microglia activation via ionized calcium-binding adapter molecule-1 (Iba1) protein expression.
- Administered minocycline, a known microglia inhibitor, to evaluate its effect on P2X(4) expression.
Main Results:
- Hypoxia-ischemia significantly increased P2X(4) receptor expression in the immature rat brain.
- Increased P2X(4) receptor expression was temporally associated with elevated Iba1 protein, indicating microglia activation.
- Minocycline treatment attenuated the HI-induced upregulation of P2X(4) receptors.
- P2X(4) receptor expression was localized to activated microglia.
Conclusions:
- P2X(4) receptor expression is upregulated in the immature brain following hypoxia-ischemia.
- Activated microglia are likely responsible for the increased P2X(4) receptor expression post-HI.
- P2X(4) receptor-positive microglia may represent a population contributing to secondary brain injury progression.
- Targeting P2X(4) receptors or microglia could be a therapeutic strategy for preterm brain injury.
