Adrenomedullin reduces ischemic brain injury after transient middle cerebral artery occlusion in rats.

BACKGROUND

The effect of adrenomedullin, a vasodilatory peptide on transient middle cerebral artery (MCA) occlusion was investigated in rats.

METHODS

Transient MCA occlusion for 2 hours was made by using the intra-arterial suture method, followed by reperfusion.

FINDINGS: An intravenous infusion of adrenomedullin (1 microg/kg/min) from one hour before ischemia to one hour after ischemia significantly reduced the infarct size and improved neurological deficits (p<0.05), without affecting systemic blood pressure or other physiological parameters. The infarct size was reduced with adrenomedullin by 25.4+/-12.7%, 31.3+/-5.8%, 31.6+/-6.1% respectively at the coronal level 6, 8 and 10 mm posterior from the frontal pole. Adrenomedullin also significantly inhibited the increase in myeloperoxidase (MPO) activity in the MCA area of the ischemic hemisphere after 22-hour reperfusion (control: 0.205+/-0.054 unit/g wet tissue, adrenomedullin group: 0.047+/-0.009 unit/g wet tissue, p<0.0001).

INTERPRETATION: These data suggest that adrenomedullin reduces acute ischemic brain injury and one of is neuroprotective mechanisms may be derived from inhibition of the infiltration of neutrophils into the ischemic tissue.