An optimized dosing regimen of cimaglermin (neuregulin 1β3, glial growth factor 2) enhances molecular markers of neuroplasticity and functional recovery after permanent ischemic stroke in rats

摘要: Cimaglermin (neuregulin 1β3, glial growth factor 2) is a neuregulin family member in clinical development for chronic heart failure. Previously, permanent middle cerebral artery occlusion (pMCAO) rat stroke model, systemic cimaglermin treatment initiated up to 7 days after ischemia onset promoted recovery without reduced lesion volume. Presented here extend the evidence are two studies that use model evaluate effects of dose level and frequency 24 hr pMCAO. Forelimb- hindlimb-placing scores (proprioceptive behavioral tests), body-swing symmetry, infarct volume were compared between groups (n = 12/group). Possible mechanisms underlying cimaglermin-mediated neurologic examined through axonal synapse formation histological markers. was evaluated over wider range (0.02, 0.1, or 1.0 mg/kg) than doses previously shown be effective but used same dosing regimen (2 weeks daily intravenous administration, then 1 week treatment). The dose-frequency study dose-ranging study's most (1.0 mg/kg) compare daily, once per week, twice 3 (then Dose- frequency-dependent functional improvements observed with significantly increased growth-associated protein 43 expression both hemispheres (particularly somatosensory motor cortices) also synaptophysin expression. These data indicate enhances stroke. Immunohistochemical changes consistent sprouting not acute neuroprotection. represents potential candidate ischemic treatment.