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Limited penetration of neuroprotective drug citicoline into the central nervous system (CNS) by systemic administration led to poor efficiency. A novel method of stereotactic drug delivery was explored to make citicoline bypass the blood brain barrier (BBB) and take effect by direct contact with ischemic neurons. A permanent middle cerebral artery occlusion (pMCAO) model of rats was prepared. To get the optimal conditions for citicoline administration by the novel stereotactic delivery pathway, magnetic resonance imaging (MRI) tracer method was used, and a dose-dependent effect was given. Examinations of MRI, behavior evaluation, infarct volume assessment and histological staining were performed to evaluate the outcome. This MRI-guided stereotactic delivery of citicoline resulted in a notable reduction (>80%) in infarct size and a delayed ischemic injury in cortex 12 hours after onset of acute ischemia when …