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Adenosine Receptor Modulation of Hypoxic-ischemic Injury in Striatum of Newborn Piglets

[ Vol. 17 , Issue. 4 ]

Author(s):

Santiago Ortega-Gutierrez, Brandy Jones, Alan Mendez-Ruiz, Pankhil Shah and Michel T. Torbey*   Pages 510 - 517 ( 8 )

Abstract:


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.

Keywords:

Hypoxic-ischemic encephalopathy, adenosine receptor, Na, K ATPase, striatal injury, piglet model, lipid peroxidation, hypoxic-ischemic cardiac arrest model.

Affiliation:

Department of Neurology , University of Iowa Hospitals and Clinics, Iowa City, IA 52242, Department of Neurology, Medical College of Wisconsin, Wauwatosa, WI 53226, Department of Neurology , University of Iowa Hospitals and Clinics, Iowa City, IA 52242, Department of Neurology, Medical College of Wisconsin, Wauwatosa, WI 53226, Department of Neurology, University of New Mexico, Albuquerque, NM 87131



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