Dexmedetomidine post-treatment induces neuroprotection via activation of extracellular signal-regulated kinase in rats with subarachnoid haemorrhage.

Abstract

Dexmedetomidine, a sedative agent, provides neuroprotection when administered during or before brain ischaemia. This study was designed to determine whether dexmedetomidine post-treatment induces neuroprotection against subarachnoid haemorrhage (SAH) and the mechanisms for this effect. Subarachnoid haemorrhage was induced by endovascular perforation to the junction of the right middle and anterior cerebral arteries in adult rats. Dexmedetomidine was applied immediately or 2 h after onset of SAH. Neurological outcome was evaluated 2 days after SAH. Right frontal cortex area 1 was harvested 24 h after SAH for western blotting. Subarachnoid haemorrhage reduced neurological scores and increased brain oedema and blood-brain barrier permeability. These effects were attenuated by dexmedetomidine post-treatment. Neuroprotection by dexmedetomidine was abolished by PD98095, an inhibitor of extracellular signal-regulated kinase (ERK) activation. Phospho-ERK, the activated form of ERK, was increased by dexmedetomidine; this activation was inhibited by PD98095. Dexmedetomidine post-treatment provides neuroprotection against SAH. This effect appears to be mediated by ERK.