Recent studies using
middle cerebral artery occlusion in the rat have suggested a role of
neuropeptide Y in ischemic pathophysiology. In this study, we investigated the effects of an i.c.v. injection of a
neuropeptide Y-Y2 receptor agonist,
neuropeptide Y 3-36, a Y1 receptor agonist, [Leu(31),Pro(34)]-
neuropeptide Y, or a Y1 receptor antagonist,
BIBP3226, on
infarct volume and hemodynamic parameters following
middle cerebral artery occlusion. Adult male Sprague-Dawley rats were subjected to transient
middle cerebral artery occlusion for 2 h. A single i.c.v. injection of
neuropeptide Y 3-36 (15 microg/kg), [Leu(31),Pro(34)]-
neuropeptide Y (30 microg/kg), or
BIBP3226 (5, 15, or 45 microg/kg) was given at 30 min of
ischemia. Blood pressure, heart rate, and regional cerebral perfusion were monitored during
ischemia and reperfusion. The rats were decapitated after 70 h of reperfusion, and their brains were cut into 2-mm-thick coronal slices before reaction with a 2%
solution of
2,3,5-triphenyltetrazolium chloride to reveal the
infarct. When compared with an
infarct volume of 17.4+/-4.4% of the ipsilateral hemisphere following injection of
neuropeptide Y 3-36, administration of the Y1 receptor analogs significantly modified the
infarct volume (ordinary one-way analysis of variance (ANOVA), P<0.0001). [Leu(31),Pro(34)]-
neuropeptide Y increased the
infarct volume to 32.0+/-4.1% (Student-Newman-Keuls post-test, P<0.01), whereas
BIBP3226 at 15 microg/kg decreased the
infarct volume to 6.5+/-1.0% (post-test P<0.05). Although there was no major difference in the hemodynamic parameters among the groups, injection of [Leu(31),Pro(34)]-
neuropeptide Y tended to further reduce cerebral perfusion during
ischemia, while injection of
BIBP3226 at 15 microg/kg appeared to have the opposite effect. In addition to
glutamate,
calcium ion and
nitric oxide, activation of the
neuropeptide Y-Y1 receptors may mediate cerebral damage during focal
ischemia. Conversely, inhibiting the Y1 receptors may protect the brain against ischemic injury. Further studies are warranted to confirm the neuroprotective potential of
neuropeptide Y-Y1 receptor inhibition.