phosphorus-radioisotopes and Brain-Ischemia

The study aims to characterize age-associated changes in skeletal muscle bioenergetics by evaluating the response to ischemia-reperfusion in the skeletal muscle of the Goto-Kakizaki (GK) rats, a rat model of non-obese type 2 diabetes (T2D). (31)P magnetic resonance spectroscopy (MRS) and blood oxygen level-dependent (BOLD) MRI was performed on the hindlimb of young (12 weeks) and adult (20 weeks) GK and Wistar (control) rats. (31)P-MRS and BOLD-MRI data were acquired continuously during an ischemia and reperfusion protocol to quantify changes in phosphate metabolites and muscle oxygenation. The time constant of phosphocreatine recovery, an index of mitochondrial oxidative capacity, was not statistically different between GK rats (60.8 ± 13.9 sec in young group, 83.7 ± 13.0 sec in adult group) and their age-matched controls (62.4 ± 11.6 sec in young group, 77.5 ± 7.1 sec in adult group). During ischemia, baseline-normalized BOLD-MRI signal was significantly lower in GK rats than in their age-matched controls. These results suggest that insulin resistance leads to alterations in tissue metabolism without impaired mitochondrial oxidative capacity in GK rats.

Topics: Animals; Brain Ischemia; Diabetes Mellitus, Type 2; Disease Models, Animal; Hydrogen-Ion Concentration; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Mitochondria; Muscle, Skeletal; Phosphocreatine; Phosphorus Radioisotopes; Rats; Reperfusion Injury

Northern blot analysis was performed to investigate the long-term changes in mRNA expression of protein kinase C (PKC) in the gerbil brain following transient cerebral ischemia. We have previously demonstrated an increase in mRNA levels of certain Ca(2+)-independent forms of PKC in early recirculation periods i.e., 6 h and 24 h postischemia (PI). But, since neuronal death in susceptible regions usually occurs 2-3 days following ischemia, this study examined the mRNA levels of PKC after prolonged periods of reperfusion following ischemia. The mRNA expression was also examined at an early recirculation period, i.e., 1 h, to determine how early the alterations begin to occur. Global forebrain ischemia was produced in gerbils by 10 min of bilateral carotid artery occlusion. RNA was prepared from forebrains of nonischemic controls and PI animals following 1 h, 3 d, and 7 d of recirculation (n = 3 to 4 in each group) and hybridized with synthetic oligonucleotide probes for PKC, delta, epsilon, and zeta based on cDNA sequences in rat and labelled with 32P. The autoradiographs were recorded and quantified by a sensitive system, Phosphor Imager, followed by conventional x-ray film exposure. The mRNA levels of all 3 PKC isozymes examined were found to be elevated as early as 1 h recirculation following ischemia. The increases in mRNA levels of both delta PKC following 6 h and 24 h of recirculation as well as that of zeta PKC following 24 h of recirculation, as reported earlier, return to control levels by 3 d PI and remain at that level 7 d PI.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blotting, Northern; Brain; Brain Ischemia; Cell Death; Gerbillinae; Male; Neurons; Oligonucleotide Probes; Phosphorus Radioisotopes; Protein Kinase C; Reperfusion; RNA, Messenger

The striatum is vulnerable to hypoxic-ischemic injury during development. In a rodent model of perinatal hypoxia-ischemia, it has been shown that striatal neurons are not uniformly vulnerable. Cholinergic neurons and NADPH-diaphorase-positive neurons are relatively spared. However, it is unknown what classes of striatal neurons are relatively sensitive. One of the major classes of striatal neurons uses enkephalin as a neurotransmitter. We have studied the effect of early hypoxic-ischemic injury on this class of neurons using a quantitative solution hybridization assay for preproenkephalin mRNA in conjunction with in situ hybridization. Hypoxia-ischemia results in an early (up to 24 h) decrease in striatal preproenkephalin mRNA, which is shown by in situ hybridization to occur mainly in the dorsal portion of the striatum. By 14 days, whole striatal preproenkephalin mRNA and total enkephalin-containing peptide levels are normal. However, at 14 days, in situ hybridization reveals that regions of complete preproenkephalin mRNA-positive neuron loss remain in the dorsal region. Normal whole striatal levels are due to an up-regulation of preproenkephalin mRNA expression in the ventrolateral region of the injured striatum. Given the important role that the enkephalin-containing striatal efferent projection plays in regulating motor function, its relative loss may be important in the chronic disturbances of motor control observed in brain injury due to developmental hypoxic-ischemic injury.

Topics: Aging; Animals; Autoradiography; Brain Ischemia; Corpus Striatum; Enkephalins; Female; Hypoxia, Brain; In Situ Hybridization; NADPH Dehydrogenase; Neurons; Phosphorus Radioisotopes; Protein Precursors; Rats; Rats, Sprague-Dawley; RNA, Messenger; Suppression, Genetic

Topics: Adenosine Triphosphate; Animals; Brain; Brain Ischemia; Energy Metabolism; Magnetic Resonance Spectroscopy; NAD; Phosphocreatine; Phosphorus Radioisotopes; Rats

The peculiarities of brain energy metabolism were studied in male rats before and during cerebral ischemia of various severity elicited by bilateral common carotid arteries ligation. A multidimensional analysis was applied. In the rats which died after the ischemia, the NAD + NADH+/phosphocreatine (PCr) ratio and ATP content before ligation were higher than those in the surviving group. Also the strength of relationships between parameters of NMR spectra in each correlation matrix were 10 times higher and the variability of elements in each matrix was significantly lower in victims than those in the surviving group. The development of severe ischemia and the animals death were accompanied by an increase in the inorganic phosphate content, decrease in pH and stepwise disappearing of PCr and ATP. In animals surviving the same brain ischemia model, the changes in 31P spectra parameters pointed to some increase in the ratio of NAD + NADH+ only to ATP + ADP but not to PCr, and to an increase in summarized strength of correlation between 31P spectra parameters with the variability of elements decreased within each correlation matrix. Detection of these changes can be helpful in the diagnosis of mild ischemia without neurological deficit which already needs preventive therapy against more severe ischemia.

Topics: Animals; Brain; Brain Ischemia; Energy Metabolism; Magnetic Resonance Spectroscopy; Male; Phosphorus Radioisotopes; Rats; Severity of Illness Index

A high rate of 32P turnover in polyphosphoinositides (up to 80% of the total radioactivity) was found in synaptosomes of normal and ischemic rat brain. Corticotropin (ACTH) increases the rate of 32P turnover in polyphosphoinositides of normal synaptosomes and decreases it in ischemic synaptosomes. Depolarization (high KCl concentration in the incubation medium) activates polyphosphoinositide metabolism in normal (by 50%) and ischemic (by 30%) synaptosomes. The combined influence of depolarization and ACTH results in the additive effect. Thus, a stimulating effect of ACTH on phosphoinositide metabolism disturbed in ischemia was recovered during depolarization of ischemic synaptosomes.

Topics: Adrenocorticotropic Hormone; Animals; Brain; Brain Ischemia; Male; Phosphates; Phosphatidylinositols; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains; Stimulation, Chemical; Synaptosomes

Topics: Adenosine Triphosphate; Animals; Brain; Brain Ischemia; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Phosphocreatine; Phosphorus Radioisotopes; Rabbits