A One‐Dimensional (Proton and Phosphorus) and Two‐Dimensional (Proton) In Vivo NMR Spectroscopic Study of Reversible Global Cerebral Ischemia

Abstract

The suitability of two‐dimensional (2D) proton spectroscopy for monitoring, in vivo, the changes in levels of brain metabolites induced by cerebral ischemia was investigated in an experimental model of 30‐min reversible ischemia induced by four‐vessel occlusion in the rat. The resulting data were compared with those obtained by one‐dimensional (1D) proton and phosphorus spectroscopy. Phosphorus spectra obtained during ischemia showed significant drops in levels of phosphocreatine (−73%), β‐ATP (−60%), and intracellular pH (to 6.30) and an increase in inorganic phosphate level (905%). 1D and 2D proton spectra showed decreases in the N‐acetylaspartate/creatine‐phosphocreatine ratio that were not significantly different [−21% (1D) and −32% (2D)]. Similarly, the increases in lactate/creatine‐phosphocreatine ratio were not significantly different [2,546% (1D) and 3,020% (2D)]. 2D spectroscopy also indicated a decrease in aspartate (−66%) and an increase in the inositol‐choline derivative (+124%) pools during ischemia and an increase in alanine pool (+516%) during reperfusion. The glutamate‐glutamine pool and taurine content did not change significantly during ischemia but decreased during reperfusion. The glucose level transiently decreased (−67%) during ischemia and increased immediately after (+261%). The levels of all the metabolites investigated returned to control values within 175 min after ischemia. 2D spectroscopy seems to be a reliable method of monitoring the changes in levels of cerebral compounds known to be involved in ischemia.

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

“…Data are means SEM Diabetic T 2 total creatine 177 3 190 4 a T 2 choline 317 11 303 13 T 2 N-acetylaspartate 358 16 358 13 Data are means SEM and were analysed by two-tailed t test for independent samples. Diabetic rats at 8 months were compared with 8-month controls (significant differences between the groups are indicated: a p < 0.05) density and viability but can also be used as a dynamic marker of neuronal metabolic (dys)function and integrity [34]. This latter interpretation would be in line with our observation that NAA ratios in the brain of STZ-diabetic rats were reduced well before functional and structural abnormalities are known to occur in this model.…”

“…A relative decrease in cerebral NAA levels has now been reported in such disorders as stroke, Alzheimer's disease and multiple sclerosis and has been attributed to neuronal loss [21,20]. More recently reductions in cerebral NAA were, however, shown to be potentially reversible [34,35], indicating that NAA levels not only reflect neuronal Fig. 3.…”

Proton magnetic resonance spectroscopy and its diagnostically important metabolites in the brain

“…In these studies, the tCho peak was increased in the short term, but its signal decreased after several days of global ischemia as a result of lowered GPC concentration (Brulatout et al 1996). In humans, a decrease of the tCho peak was confirmed 5 months after ischemia (Barker et al 1994b).…”

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

“…Berthet et al, 2011;Lei et al, 2009;Tkáč et al, 2007). In addition, after transient ischemia and brain injury without neuronal death, NAA levels are able to recover (Brulatout et al, 1996;De Stefano et al, 1995), suggesting it as a marker of neuronal functionality rather than neuronal density.…”