Background:
Hypoxic-ischemic encephalopathy (HIE) is a major cause of pediatric and
adult mortality and morbidity. Unfortunately, to date, no effective treatment has been identified. In
the striatum, neuronal injury is analogous to the cellular mechanism of necrosis observed during NMethyl-
D-Aspartate (NMDA) excitotoxicity. Adenosine acts as a neuromodulator in the central nervous
system, the role of which relies mostly on controlling excitatory glutamatergic synapses.
Objective:
To examine the effect of pretreatment of SCH58261, an adenosine 2A (A2A) receptor
antagonist and modulator of NMDA receptor function, following hypoxic-ischemia (HI) on sodium-
potassium ATPase (Na+, K+-ATPase) activity and oxidative stress.
Methods:
Piglets (4-7 days old) were subjected to 30 min hypoxia and 7 min of airway occlusion
producing asphyxic cardiac arrest. Groups were divided into four categories: HI samples were divided
into HI-vehicle group (n = 5) and HI-A2A group (n = 5). Sham controls were divided into
Sham vehicle (n = 5) and Sham A2A (n = 5) groups. Vehicle groups were pretreated with 0.9% saline,
whereas A2A animals were pretreated with SCH58261 10 min prior to intervention. Striatum
samples were collected 3 h post-arrest. Sodium-potassium ATPase (Na+, K+-ATPase) activity,
malondialdehyde (MDA) + 4-hydroxyalkenals (4-HDA) and glutathione (GSH) levels were compared.
Results:
Pretreatment with SCH58261 significantly attenuated the decrease in Na+, K+-ATPase, decreased
MDA+4-HDA levels and increased GSH in the HI-A2A group when compared to HIvehicle.
Conclusion:
A2A receptor activation may contribute to neuronal injury in newborn striatum after
HI in association with decreased Na+, K+-ATPase activity and increased oxidative stress.
Developmental Changes in Erythrocyte Sodium-Potassium-ATPase (Na,K-ATPase) Subunit Isoform Abundance, ATPase Activity, and Cation-Pump Function in Neonates
