2-fluoro-2-deoxyglucose-6-phosphate and Brain-Ischemia

Targeted energy metabolism balance contributes to neural survival during ischemic stroke. Herein, we tested the hypothesis that electro‑acupuncture (EA) can enhance cerebral glucose metabolism assessed by 18F‑fluorodeoxyglucose/positron emission tomography (18F‑FDG/PET) imaging to prevent propagation of tissue damage and improve neurological outcome in rats subjected to ischemia and reperfusion injury. Rats underwent middle cerebral artery occlusion (MCAO) and received EA treatment at the LI11 and ST36 acupoints or non‑acupoint treatment once a day for 7 days. After EA treatment, a significant reduction in the infarct volume was determined by T2‑weighted imaging, accompanied by the functional recovery in CatWalk and Rota-rod performance. Moreover, EA promoted higher glucose metabolism in the caudate putamen (CPu), motor cortex (MCTX), somatosensory cortex (SCTX) regions as assessed by animal 18F‑FDG/PET imaging, suggesting that three‑brain regional neural activity was enhanced by EA. In addition, the AMP‑activated protein kinase α (AMPKα) in the CPu, MCTX and SCTX regions was phosphorylated at threonine 172 (Thr172) after ischemic injury; however, phosphorylation of AMPK was further increased by EA. These results indicate that EA could promote AMPKα phosphorylation of the CPu, MCTX and SCTX regions to enhance neural activity and motor functional recovery after ischemic stroke.

Topics: AMP-Activated Protein Kinases; Animals; Brain; Brain Ischemia; Electroacupuncture; Glucose; Glucose-6-Phosphate; Male; Phosphorylation; Positron-Emission Tomography; Rats; Rats, Sprague-Dawley; Stroke

At present, the goal of stroke research is the identification of a potential recoverable tissue surrounding the ischemic core, suggested as ischemic penumbra, with the aim of applying a treatment that attenuates the growth of this area. Our purpose was to determine whether a combination of imaging techniques, including (18)F-FDG PET and MRI could identify the penumbra area. Longitudinal studies of (18)F-FDG PET and MRI were performed in rats 3 h, 24 h and 48 h after the onset of ischemia. A transient and a permanent model of focal cerebral ischemia were performed. Regions of interest were located, covering the ischemic core, the border that progresses to infarction (recruited tissue), and the border that recovers (recoverable tissue) with early reperfusion. Analyses show that permanent ischemia produces severe damage, whereas the transient ischemia model does not produce clear damage in ADC maps at the earliest time studied. The only significant differences between values for recoverable tissue, (18)F-FDG (84±2%), ADC (108±5%) and PWI (70±8%), and recruited tissue, (18)F-FDG (77±3%), ADC (109±4%) and PWI (77±4%), are shown in (18)F-FDG ratios. We also show that recoverable tissue values are different from those in non-infarcted tissue. The combination of (18)F-FDG PET, ADC and PWI MRI is useful for identification of ischemic penumbra, with (18)F-FDG PET being the most sensitive approach to its study at early times after stroke, when a clear DWI deficit is not observed.

Topics: Animals; Brain Ischemia; Brain Mapping; Glucose-6-Phosphate; Magnetic Resonance Imaging; Male; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Rats, Inbred F344

The biophysical mechanism(s) underlying diffusion-weighted MRI contrast following brain injury remains to be elucidated. Although it is generally accepted that water apparent diffusion coefficient (ADC) decreases after brain injury, it is unknown whether this is associated with a decrease in intracellular or extracellular water displacement, or both. To address this question, 2-[19F]luoro-2-deoxyglucose-6-phosphate (2FDG-6P) was employed as a compartment-specific marker in normal and globally ischemic rat brain. Through judicious choice of routes of administration, 2FDG-6P was confined to the intra- or extracellular space. There was no statistical difference between intra- and extracellular 2FDG-6P ADCs in normal or in globally ischemic brain (P > 0.16), suggesting that water ADCs in both compartments are similar. However, ischemia did result in a 40% ADC decrease in both compartments (P < 0.001). Assuming that 2FDG-6P reflects water motion, this study shows that water ADC decreases in both spaces after ischemia, with the reduction of intracellular water motion being the primary source of diffusion-weighted contrast.

Topics: Animals; Biomarkers; Brain; Brain Ischemia; Cells, Cultured; Diffusion; Disease Models, Animal; Extracellular Space; Fluorine; Glucose-6-Phosphate; Intracellular Fluid; Magnetic Resonance Spectroscopy; Male; Mice; Neuroglia; Neurons; Phantoms, Imaging; Rats; Rats, Sprague-Dawley; Reference Values; Sensitivity and Specificity