Mapping Changes of Whole Brain Blood Flow in Rats with Myocardial Ischemia/Reperfusion Injury Assessed by Positron Emission Tomography.

18F-labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) is the most sensitive tool for studying brain metabolism in vivo. We investigated the image patterns of 18F-FDG PET during reperfusion injury and correlated changes of whole brain blood flow utilizing a rat myocardial ischemia/reperfusion injury (MIRI) model. The results assessed by echocardiography indicated resultant cardiac dysfunction after ischemia-reperfusion in the rat heart. It was found that the average standardized uptake value (SUVaverage) of the whole brain was significantly decreased in model rats, and the glucose uptake of different brain regions including accumbens core/shell (Acb), left caudate putamen (LCPu), hippocampus (HIP), left hypothalamus (LHYP), olfactory (OLF), superior colliculus (SC), right midbrain (RMID), ventral tegmental area (VTA), inferior colliculus (IC) and left thalamus whole (LTHA) was significantly decreased in MIRI rats whereas no significant difference was found in the SUVaverage of amygdala (AMY), right CPu, RHYP, right HYP, left MID, right THA, pons and medulla oblongata (MO). These 18F-FDG PET data provide a reliable identification method for brain metabolic changes in rats with MIRI.

Quantitative proteomics reveal the alterations in the spinal cord after myocardial ischemia­reperfusion injury in rats.

There is now substantial evidence that myocardial ischemia­reperfusion (IR) injury affects the spinal cord and brain, and that interactions may exist between these two systems. In the present study, the spinal cord proteomes were systematically analyzed after myocardial IR injury, in an attempt to identify the proteins involved in the processes. The myocardial IR injury rat model was first established by cross clamping the left anterior descending coronary artery for 30­min ischemia, followed by reperfusion for 2 h, which resulted in a significant histopathological and functional myocardial injury. Then using the stable isotope dimethyl labeling quantitative proteomics strategy, a total of 2,362 shared proteins with a good distribution and correlation were successfully quantified. Among these proteins, 33 were identified which were upregulated and 57 were downregulated in the spinal cord after myocardial IR injury, which were involved in various biological processes, molecular function and cellular components. Based on these proteins, the spinal cord protein interaction network regulated by IR injury, including apoptosis, microtubule dynamics, stress­activated signaling and cellular metabolism was established. These heart­spinal cord interactions help explain the apparent randomness of cardiac events and provide new insights into future novel therapies to prevent myocardial I/R injury.

Identification of lncRNA and mRNA expression profiles in rat spinal cords at various time­points following cardiac ischemia/reperfusion.

The identification of the expression patterns of long non­coding RNAs (lncRNAs) and mRNAs in the spinal cord under normal and cardiac ischemia/reperfusion (I/R) conditions is essential for understanding the genetic mechanisms underlying the pathogenesis of cardiac I/R injury. The present study used high­throughput RNA sequencing to investigate differential gene and lncRNA expression patterns in the spinal cords of rats during I/R­induced cardiac injury. Male Sprague Dawley rats were assigned to the following groups: i) Control; ii) 2 h (2 h post­reperfusion); and iii)v0.5 h (0.5 h post­reperfusion). Further mRNA/lncRNA microarray analysis revealed that the expression profiles of lncRNA and mRNA in the spinal cords differed markedly between the control and 2 h groups, and in total 7,980 differentially expressed (>2­fold) lncRNAs (234 upregulated, 7,746 downregulated) and 3,428 mRNAs (767 upregulated, 2,661 downregulated) were identified. Reverse transcription­quantitative polymerase chain reaction analysis was performed to determine the expression patterns of several lncRNAs. The results indicated that the expression levels of lncRNA NONRATT025386 were significantly upregulated in the 2 and 0.5 h groups when compared with those in the control group, whereas the expression levels of NONRATT016113, NONRATT018298 and NONRATT018300 were elevated in the 2 h group compared with those in the control group; however, there was no statistically significant difference between the 0.5 h and control groups. Furthermore, the expression of lncRNA NONRATT002188 was significantly downregulated in the 0.5 and 2 h groups when compared with the control group. The present study determined the expression pattern of lncRNAs and mRNAs in rat spinal cords during cardiac I/R. It was suggested that lncRNAs and mRNAs from spinal cords may be novel therapeutic targets for the treatment of I/R­induced cardiac injury.

Alterations in amino acid levels and metabolite ratio of spinal cord in rat with myocardial ischemia-reperfusion injury by proton magnetic resonance spectroscopy.

OBJECTIVES: The mechanism behind spinal metabolites and myocardial ischemia-reperfusion (IR) injury is not well understood. Proton magnetic resonance spectroscopic analysis of spinal cord extracts provides a quick evaluation of the specific metabolic activity in rats with myocardial IR injury. We investigated the relationship between the IR-related variables and the changes in spinal metabolites. METHODS: Proton magnetic resonance spectroscopy (1H-MRS) was used to assess the spinal metabolites of adult rats with and without myocardial IR injury (n = 6 per group). Myocardial IR injury was reproduced using intermittent occlusion of the left anterior descending coronary artery. We studied the relationship between the metabolite ratio measurement and IR-related variables. All rats underwent 1H-MRS, with the ratio of interest placed in different spinal cord segments to measure levels of twelve metabolites including N-acetylaspartate (NAA), taurine (Tau), glutamate (Glu), gamma amino acid butyric acid (GABA), creatine (Cr), and myoinositol (MI), etc. Results: Rats with myocardial IR injury had higher concentration of Tau in the upper thoracic spinal cord (P < 0.05), and lower concentration of Gly and Glu in the cervical segment of the spinal cord (P < 0.05), when compared to the Control group. The ratios of glutamate/taurine (Glu/Tau), Glu/(GABA + Tau) and Glu/Total were significantly different between the IR group and the Control group in the upper thoracic spinal cord (P < 0.05). So were the ratios of Glu/(GABA + Tau) in the cervical segment (P < 0.05), and Glu/Tau and Glu/(GABA + Tau) in the lower thoracic spinal cord (P < 0.05). CONCLUSIONS: These findings suggest that myocardial IR injury may be related to spinal biochemical alterations. It is speculated that these observed changes in the levels of spinal metabolites may be involved in the pathogenesis and regulation of myocardial IR injury.

Pressure pain assessment may predict the outcome of spinal cord stimulation for refractory epilepsy.

It was well-documented that epilepsy and pain arise from an excitation-inhibition imbalance within neuronal networks. A previous meta-analysis of data from clinical trials showed an association between anticonvulsants and specific pain types, e.g. multiple sclerosis pain. Multiple multicentre randomized controlled trials have shown that antiepileptic drugs have a prominent role in the treatment of several types of pain, e.g. neuropathic pain. Many anticonvulsants have been introduced to better manage acute postoperative pain, with improvements in analgesic efficacy and safety. These data suggested that there existed the similar mechanisms of certain forms of epilepsy and pain, and the therapeutic mechanism of spinal cord stimulation for certain forms of epilepsy and pain may be involved in the melanocortinergic signaling, and the change in cerebral glucose metabolism. We hypothesized that pressure pain assessment may predict the outcome of spinal cord stimulation in refractory epilepsy.