Cerebrolysin is a
peptide preparation mimicking the action of
neurotrophic factors and has beneficial effects on
neurodegenerative diseases and
stroke. The present study investigated the effect of
Cerebrolysin on neurogenesis in a rat model of embolic
middle cerebral artery occlusion (MCAo). Treatment with
Cerebrolysin at doses of 2.5 and 5 ml/kg significantly increased the number of
bromodeoxyuridine-positive (
BrdU(+)) subventricular zone (SVZ) neural progenitor cells and doublecortin (DCX) immunoreactivity (migrating neuroblasts) in the ipsilateral SVZ and striatal ischemic boundary 28 days after
stroke when the treatment was initiated 24 hr after
stroke. The treatment also reduced TUNEL(+) cells by ∼50% in the ischemic boundary. However, treatment with
Cerebrolysin at a dose of 2.5 ml/kg initiated at 24 and 48 hr did not significantly reduce
infarct volume but substantially improved neurological outcomes measured by an array of behavioral tests 21 and 28 days after
stroke. Incubation of SVZ neural progenitor cells from ischemic rats with
Cerebrolysin dose dependently augmented
BrdU(+) cells and increased the number of Tuj1(+) cells (a marker of immature neurons). Blockage of the PI3K/Akt pathway abolished
Cerebrolysin-increased
BrdU(+) cells. Moreover,
Cerebrolysin treatment promoted neural progenitor cell migration. Collectively, these data indicate that
Cerebrolysin treatment when initiated 24 and 48 hr after
stroke enhances neurogenesis in the ischemic brain and improves functional outcome and that
Cerebrolysin-augmented proliferation, differentiation, and migration of adult SVZ neural progenitor cells contribute to
Cerebrolysin-induced neurogenesis, which may be related to improvement of neurological outcome. The PI3K/Akt pathway mediates
Cerebrolysin-induced progenitor cell proliferation.