Details

Autor(en) / Beteiligte

• Atef, Reham M.
• Agha, Azza M.
• Abdel-Rhaman, Abdel-Rahman A.
• Nassar, Noha N.

Titel

The Ying and Yang of Adenosine A1 and A2A Receptors on ERK1/2 Activation in a Rat Model of Global Cerebral Ischemia Reperfusion Injury

Ist Teil von

• Molecular neurobiology, 2018-02, Vol.55 (2), p.1284-1298

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Adenosine impacts cerebral ischemia reperfusion (IR) through the inhibitory A 1 and the excitatory A 2 receptors. The present study aimed at investigating the contrasting role of pERK1/2 in mediating adenosine A 1 R (protective) versus A 2A R (deleterious) effects in IR. Male Wistar rats subjected to bilateral carotid occlusion (45 min) followed by reperfusion (24 h) exhibited increased pERK1/2 activity, downstream from DAG pathway, along with increases in hippocampal glutamate, c-Fos, NF-κB, TNF-α, iNOS, TBARS, cytochrome c, caspase-3, BDNF, Nrf2, and IL-10 contents. Further, hippocampal microglial reactivity, glial TNF-α, and BDNF expression were observed. Although unilateral intrahippocampal injection of either the A 1 R agonist CHA or the A 2A R agonist CGS21680 increased pERK1/2, only CHA mitigated histopathological and behavioral deficits along with reducing glutamate, microglial activation, c-Fos, TNF-α, iNOS, TBARS, cytochrome c and caspase-3 and elevating Nrf2 and IL-10 levels in IR rats. These results yield insight into the double-faceted nature of pERK1/2 in mediating protective and deleterious effects of A 1 R and A 2A R signaling, respectively, against IR injury.