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 compared with the systematic delivery. The improved neuroprotective efficiency was realized by a full distribution of
citicoline in most of middle cerebral artery (MCA) territory and an adequate
drug reaction in the involved areas of the brain. Brain lesions of treated rats by stereotactic delivery of
citicoline were well predicted in the lateral ventricle and thalamus due to a limited
drug deposition by MRI tracer method. Our study realized an improved neuroprotective efficiency of
citicoline by stereotactic delivery, and an optimal
therapeutic effect of this administration pathway can be achieved under MRI guidance.