Phosphate Energy Metabolism During Domoic Acid-Induced Seizures

The effect of domoic acid-induced seizure activity on energy metabolism and on brain pH in mice was studied by continuous EEC recording and in vivo 31 P nuclear magnetic resonance (NMR) spectroscopy. Mice were divided into ventilated (n = 6) and nonventilated (n = 7) groups. Baseline EEG was 0.1-mV amplitude with frequence of >30-Hz and of 4–5 Hz. After intraperitoneal (i.p.) administration of domoic acid (6 mg/kg), electro graphic spikes appeared at increasing frequency, pro gressing to high-amplitude (0.1-0.8 mV) continuous sei zure activity (status epilepticus). In ventilated mice, the [ 31 P]NMR spectra showed that high-energy phosphate levels and tissue pH did not change after domoic acid administration or during the intervals of spiking or status epilepticus. Nonventilated mice showed periods of EEG suppression accompanied by decreases in the levels of high-energy phosphate metabolites and in pH, corresponding to episodic respiratory suppression during the spiking interval. In all animals, status epilepticus was fol lowed by a marked decrease in EEG amplitude that pro gressed rapidly to isoelectric silence. [ 31 P]NMR spectra obtained after this were indicative of total energy failure and tissue acidosis. In a separate group of ventilated mice (n = 4), domoic acid-induced status epilepticus was ac companied initially by an increase in mean arterial blood pressure (MAP) that slowly returned to baseline level. Isoelectric silence was accompanied by a decrease in MAP to 75 ± 8 mm Hg. These experiments suggest that domoic acid-induced seizures are not accompanied by an increase in substrate demand that exceeds supply.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65953/1/j.1528-1157.1993.tb02124.x.pd

The effect of methionine on the uptake, distribution, and binding of the convulsant methionine sulfoximine in the rat

The effect of methionine on the uptake, distribution, and binding of the convulsant methionine sulfoximine (MSO) in 7 rat brain regions, the spinal cord, the liver, and the kidney was investigated. The administration of methionine decreased the uptake of MSO in all brain regions. The uptake of MSO by and its distribution in the nervous tissue was uniform and failed to result in any preferential accumulation of the drug. Methionine decreased the amount of MSO bound to cerebral structures and to the spinal cord. MSO bound to the spinal cord was less susceptible to release by Triton X-100 than was brain-bound MSO.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45398/1/11064_2004_Article_BF00965631.pd

In situ biospectroscopic investigation of rapid ischemic and postmortem induced biochemical alterations in the rat brain

© 2014 American Chemical Society. Rapid advances in imaging technologies have pushed novel spectroscopic modalities such as Fourier transform infrared spectroscopy (FTIR) and X-ray absorption spectroscopy (XAS) at the sulfur K-edge to the forefront of direct in situ investigation of brain biochemistry. However, few studies have examined the extent to which sample preparation artifacts confound results. Previous investigations using traditional analyses, such as tissue dissection, homogenization, and biochemical assay, conducted extensive research to identify biochemical alterations that occur ex vivo during sample preparation. In particular, altered metabolism and oxidative stress may be caused by animal death. These processes were a concern for studies using biochemical assays, and protocols were developed to minimize their occurrence. In this investigation, a similar approach was taken to identify the biochemical alterations that are detectable by two in situ spectroscopic methods (FTIR, XAS) that occur as a consequence of ischemic conditions created during humane animal killing. FTIR and XAS are well suited to study markers of altered metabolism such as lactate and creatine (FTIR) and markers of oxidative stress such as aggregated proteins (FTIR) and altered thiol redox (XAS). The results are in accordance with previous investigations using biochemical assays and demonstrate that the time between animal death and tissue dissection results in ischemic conditions that alter brain metabolism and initiate oxidative stress. Therefore, future in situ biospectroscopic investigations utilizing FTIR and XAS must take into consideration that brain tissue dissected from a healthy animal does not truly reflect the in vivo condition, but rather reflects a state of mild ischemia. If studies require the levels of metabolites (lactate, creatine) and markers of oxidative stress (thiol redox) to be preserved as close as possible to the in vivo condition, then rapid freezing of brain tissue via decapitation into liquid nitrogen, followed by chiseling the brain out at dry ice temperatures is required

Technical and Comparative Aspects of Brain Glycogen Metabolism.

It has been known for over 50 years that brain has significant glycogen stores, but the physiological function of this energy reserve remains uncertain. This uncertainty stems in part from several technical challenges inherent in the study of brain glycogen metabolism, and may also stem from some conceptual limitations. Factors presenting technical challenges include low glycogen content in brain, non-homogenous labeling of glycogen by radiotracers, rapid glycogenolysis during postmortem tissue handling, and effects of the stress response on brain glycogen turnover. Here, we briefly review aspects of glycogen structure and metabolism that bear on these technical challenges, and discuss ways these can be overcome. We also highlight physiological aspects of glycogen metabolism that limit the conditions under which glycogen metabolism can be useful or advantageous over glucose metabolism. Comparisons with glycogen metabolism in skeletal muscle provide an additional perspective on potential functions of glycogen in brain

Cerebral metabolic changes in profound, insulin-induced hypoglycemia, and in the recovery period following glucose administration

Severe hypoglycemia was induced by insulin in lightly anaesthetized (70°o N2O) and artificially ventilated rats. Brain tissue was frozen in situ after spontaneous EEG potentials had disappeared for 5. 10. 15 or 30 min and cerebral cortex concentrations of labile organic phosphates, glycolytic metabolites, ammonia and amino acids were determined. In other experiments, recovery was induced by glucose injection at the end of the period of EEG silence. All animals with an isoelectric EEG showed extensive deterioration of the cerebral energy state. and gross perturbation of amino acid concentrations. The latter included a 4-fold rise in aspartate concentration and reductions in glutamate and glutamine concentrations to 20 and 5oo of control levels respectively. There was an associated rise in ammonia concentration to about 3μmol-g-1. Administration of glucose brought about extensive recovery of cerebral energy metabolism. For example, after an isoelectric period of 30 min tissue concentrations of phosphocreatine returned to or above normal, the accumulation of ADP and AMP was reversed, there was extensive resynthesis of glycogen and glutamine and full normalisation of tissue concentrations of pyruvate. α-ketoglutarate. GABA and ammonia. However, even after 3 h of recovery there was a reduction in the ATP concentration and thereby in adenine nucleotide pool, moderate elevations of lactate content and the lactate pyruvate ratio, and less than complete restoration of the amino acid pool. It is concluded that some cells may have been irreversibly damaged by the hypoglycemia