ro-16-0154 and Brain-Infarction

[123I]iomazenil (IMZ) is a specific radioligand for the central benzodiazepine (BZ) receptor that may be useful as a marker of cortical neuron loss after cerebral ischemia using single photon emission computed tomography (SPECT). This study used statistical imaging analysis for IMZ-SPECT to investigate the relationship between higher brain dysfunction and cortical neuron loss in the medial frontal lobes, to establish a confirmatory diagnosis of higher brain dysfunction in patients with adult moyamoya disease. IMZ-SPECT was estimated by three-dimensional stereotactic surface projections (3D-SSP). Cortical neuron loss was analyzed using the stereotactic extraction estimation (SEE) method (level 3: gyrus level) for 3D-SSP Z-score maps (Z-score >2). Extent of pixels with significant reduction of BZ receptor density within the target gyri (i.e. bilateral medial frontal gyri [MFGs] and anterior cingulate gyri [ACGs]) was calculated. In 6 patients with higher brain dysfunction, significant cortical neuron loss was observed in the bilateral MFGs in 4 patients, unilateral MFG in 1 patient, and bilateral ACGs in 2 patients. In 12 patients without higher brain dysfunction, no significant cortical neuron loss was observed in the bilateral MFGs or ACGs, and mild loss was observed in the bilateral MFGs in 2 patients, unilateral MFG in 4 patients, and unilateral ACG in 2 patients. Long-standing mild hemodynamic ischemia in the anterior circulation of patients with adult moyamoya disease could lead to incomplete brain infarction within the medial frontal lobes. Statistical imaging analysis using 3D-SSP and SEE methods for IMZ-SPECT could demonstrate significant cortical neuron loss in the bilateral frontal medial cortices involving MFG and/or ACG which correlate with higher brain dysfunction in patients with adult moyamoya disease.

Topics: Adult; Brain Infarction; Cerebral Cortex; Data Interpretation, Statistical; Female; Flumazenil; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Male; Middle Aged; Moyamoya Disease; Pilot Projects; Tomography, Emission-Computed, Single-Photon

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.

Topics: Animals; Bone Marrow Cells; Bone Marrow Transplantation; Brain Infarction; Flumazenil; Iodine Radioisotopes; Male; Neocortex; Neurons; Radiography; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Recovery of Function; Stromal Cells; Time Factors; Tomography, Emission-Computed, Single-Photon; Transplantation, Homologous