Simple diffusion delivery via brain interstitial route for the treatment of cerebral ischemia

Delivering pharmacologic agents directly into the brain has been proposed as a means of bypassing the blood brain barrier. However, despite 16 years of research on a number of central nervous system disorders, an effective treatment using this strategy has only been observed in the brain tumor glioblastoma multiforme. Within this study we propose a novel system for delivering drugs into the brain named the simple diffusion (SDD) system. To validate this technique, rats were subjected to a single intracranial (at the caudate nucleus), or intraperitoneal injection, of the compound citicoline, followed two hours later by a permanent middle cerebral artery occlusion (pMCAO). Results showed that 12 h after pMCAO, with 0.0025 g kg(-1) citicoline, an infarct volume 1/6 the size of the intraperitoneal group was achieved with a dose 1/800 of that required for the intraperitoneal group. These results suggest that given the appropriate injection point, through SDD a pharmacologically effective concentration of citicoline can be administered.