Bone Marrow Stromal Cell Transplantation Enhances Recovery of Local Glucose Metabolism After Cerebral Infarction in Rats: A Serial ¹⁸F-FDG PET Study

Abstract

This study aimed to assess whether 18 F-FDG PET could serially monitor the beneficial effects of bone marrow stromal cells (BMSC) on cerebral glucose metabolism when transplanted into the infarct brain of rats. Methods: The BMSC from green fluorescent protein transgenic rats or vehicle was stereotactically transplanted into the ipsilateral striatum at 7 d after permanent middle cerebral artery occlusion of rats. Local glucose metabolism was semiquantitatively measured at 6 and 35 d after ischemia using 18 F-FDG PET. Motor function was serially evaluated throughout the experiments. At 35 d after ischemia, immunohistochemistry was performed to evaluate the phenotype of BMSC and their effects on the expression of brain-type glucose transporters. Results: BMSC transplantation not only enhanced functional recovery but also promoted the recovery of glucose utilization in the periinfarct area when stereotactically transplanted at 1 wk after ischemia. The engrafted cells were widely distributed, and most expressed a neuron-specific protein, NeuN. BMSC transplantation also prevented the pathologic upregulation of glucose transporters in the periinfarct neocortex. Conclusion: The present findings strongly suggest that the BMSC may enhance functional recovery by promoting the recovery of local glucose metabolism in the periinfarct area when directly transplanted into the infarct brain at clinically relevant timing. The BMSC also inhibit the pathologic upregulation of brain-isoform glucose transporters type 1 and 3. 18 F-FDG PET may be a valuable modality to scientifically prove the beneficial effects of BMSC transplantation on the host brain in clinical situations.

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

“…The BMSCs were isolated from male 8-week-old transgenic rats expressing enhanced green fluorescence protein (GFP; Japan SLC, Inc, Hamamatsu, Japan) and were cultured as previously reported. 4,5,7,10 The cells were passed 3 times.…”

“…Permanent middle cerebral artery (MCA) occlusion was induced as described previously. 4,5,7,10 Briefly, the rats were anesthetized, and the bilateral common carotid arteries were exposed. Then, temporal craniotomy was performed, using a small dental drill.…”

“…1,2 Recent animal studies have demonstrated that the BMSCs significantly enhance functional recovery after ischemic stroke, when directly transplanted into the brain at clinically relevant timing. [3][4][5][6][7] Several clinical trials have also indicated that BMSC transplantation is at least feasible for patients with CNS disorders. 8 As pointed out by several investigators, however, there are several concerns to be resolved before clinical application of BMSC transplantation for CNS disorders.…”

Bone marrow stromal cells as a therapeutic treatment for ischemic stroke

“…(IBZ) 24 h/3 days Enhanced endogenous neurogenesis; increased MMP9 activation, [13,22] stimulating neurons to modulate cerebral blood fl ow Transient MCAO (2 h)/ i.c. (striatum) 24 h/7 days Inhibited pathologic upregulation of brain-isoform glucose transporters [9,23] Permanent MCAO types 1 and 3, and promoted recovery of local glucose metabolism in peri-infarct area Permanent MCAO i.c. (lateral ventricle) 24 h BMSCs survived, adhered to ventricular wall, and clearly reduced [18] behavioral functional defi cits Cortical ischemia i.c.…”

Advanced Molecular Imaging for Exploring Classic Conditioning and Extinction

“…Although exposure-based therapy (i.e., conceptually based on fear extinction) has been widely used in the treatment of PTSD (2), its underlying mechanism remains unclear. Recently, 18 F-FDG PET has been increasingly applied to the characterization of brain regional metabolic activation, and methods of whole-brain imaging analysis such as statistical parametric mapping have been applied more extensively to determine the relationship of measured behavior with brain metabolic changes in humans and rodents (5)(6)(7)(8).…”