123 I-Iomazenil Single Photon Emission Computed Tomography Visualizes Recovery of Neuronal Integrity by Bone Marrow Stromal Cell Therapy in Rat Infarct Brain

Abstract

This study was aimed to assess whether (123)I-iomazenil (IMZ) single photon emission computed tomography can serially monitor the effects of bone marrow stromal cell (BMSC) transplantation on neuronal integrity in infarct brain of rats. The BMSCs were harvested from green fluorescent protein-transgenic rats and were cultured. The rats were subjected to permanent middle cerebral artery occlusion. Their motor function was serially quantified throughout the experiments. The BMSCs or vehicle was stereotactically transplanted into the ipsilateral striatum at 7 days after the insult. Using small-animal single photon emission computed tomography/computed tomography apparatus, the (123)I-IMZ uptake was serially measured at 6 and 35 days after the insult. Finally, fluorescence immunohistochemistry was performed to evaluate the distribution of engrafted cells and their phenotypes. The distribution of (123)I-IMZ was markedly decreased in the ipsilateral neocortex at 6 days postischemia. The vehicle-transplanted animals did not show a significant change at 35 days postischemia. However, BMSC transplantation significantly improved the distribution of (123)I-IMZ in the peri-infarct neocortex as well as motor function. The engrafted BMSCs were densely distributed around cerebral infarct, and some of them expressed neuronal nuclear antigen and γ-aminobutyric acid type-A receptor. The present findings strongly suggest that the BMSCs may enhance functional recovery by improving the neuronal integrity in the peri-infarct area, when directly transplanted into the infarct brain at clinically relevant timing. (123)I-IMZ single photon emission computed tomography may be a promising modality to scientifically prove the beneficial effects of BMSC transplantation on the host brain in clinical situation.