Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic changes in neonatal hydrocephalus that lead to permanent brain injury are not clearly defined, nor is the extent to which these changes can be prevented by a cerebrospinal fluid shunt. To clarify these processes, cerebral glucose utilization was examined using [14C]2-deoxyglucose autoradiography in 1-month-old kittens, kaolin-induced hydrocephalic littermates, and hydrocephalic kittens in which a ventriculoperitoneal shunt had been inserted 10 days after kaolin injection. The hydrocephalic kittens showed thinning of the cerebral mantle and an anterior-to-posterior gradient of enlargement of the ventricular system, with a ventricle:brain ratio of 24% for the frontal and 35% for the occipital horns compared with control (< 0.5%) and shunted (< 5%) animals. White matter in hydrocephalic animals was edematous. Myelination was delayed in the periventricular region and in the cores of the cerebral gyri. Glucose utilization in hydrocephalic and shunted animals was unchanged from control animals in all gray-matter regions examined. However, in hydrocephalic animals, the frontal white matter exhibited a significant increase in glucose utilization (25 mumol.100 gm-1.min-1) in the cores of gyri compared with normal surrounding white-matter values (14.8 mumol.100 gm-1.min-1). Very low values (mean 4 mumol.100 gm-1.min-1) were found in areas corresponding to severe white-matter edema, and these areas were surrounded by a halo of increased activity (24 mumol.100 gm-1.min-1). In contrast, cytochrome oxidase activity in white matter was homogeneous. Shunting resulted in restoration of the cerebral mantle thickness, a return to normal levels of glucose utilization in the white matter, and an improvement in myelination. It is suggested that the areas of increased glucose utilization seen in the white matter represent anaerobic glycolysis which, if untreated, progresses to infarction. The pattern of this increased glucose utilization matches that of expected myelination and, during this period of high energy demand, white matter may be susceptible to the hypoperfusion associated with hydrocephalus.
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PMID:Anaerobic glycolysis preceding white-matter destruction in experimental neonatal hydrocephalus. 811 62

The metabolic changes that occur in the neonatal brain as a result of hydrocephalus, and the response to ventriculoperitoneal shunting, vary with the maturational stage of the brain. In this study, local glucose utilization (LCMRglu) and oxidative metabolic capacity were estimated using 2-deoxyglucose autoradiography and cytochrome oxidase histochemistry, respectively. Hydrocephalus was induced in rabbit pups via intracisternal kaolin injections at 4-6 days of age. Shunting occurred at 19-26 days of age and the animals were sacrificed at ages ranging from 33 to 331 days. In normal animals there was a high glucose demand early in life which showed a decrease at about 60 days of age. In rabbits sacrificed prior to 60 days of age the controls showed the highest LCMRglu with significant decreases in both the hydrocephalic and shunted animals. After 60 days of age the shunted animals had higher LCMRglu than both the hydrocephalic and control subjects. Oxidative metabolic capacity peaked before 50 days of age in normal animals. At the youngest age, both the hydrocephalic and shunted animals showed higher cytochrome oxidase density rates than the control rabbits. In the older group, the hydrocephalic animals remained high while the shunted animals approximated the control densities. Neither the changes seen in the LCMRglu nor the oxidative metabolic capacity were correlated with changes in cell packing density or increased intracranial pressure. These data suggest that when the brain is compromised by hydrocephalus, there is an initial compensatory increase in oxidative metabolic capacity. The development of the glycolytic pathway appears to be retarded by hydrocephalus, but with shunting and the passage of time, the LCMRglu rebounds to levels above that of controls.
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PMID:Metabolic responses of the neonatal rabbit brain to hydrocephalus and shunting. 884 Oct 78

Rational intervention in infants with posthemorrhagic hydrocephalus (PHH) would be facilitated greatly by bedside measure of impaired cerebral perfusion, as there is substantial evidence that impaired perfusion and oxidative metabolism contribute to irreversible brain injury in hydrocephalus. Near-infrared spectroscopy (NIRS) measures changes in the cerebral concentration of oxygenated and deoxygenated hemoglobin and oxidized cytochrome oxidase at the bedside of infants continuously and noninvasively. The total hemoglobin and the hemoglobin difference signal are derived from the sum and difference, respectively, of oxygenated and deoxygenated hemoglobin. Changes in total hemoglobin reflect changes in cerebral blood volume; our previous work has shown that changes in hemoglobin difference signal reflect changes in cerebral blood flow. We hypothesized that cerebrospinal fluid (CSF) removal in infants with PHH would result in significant increases in cerebral perfusion, cerebral blood volume, and oxidative metabolism, as measured by NIRS. Continuous NIRS recordings were performed during CSF removal on 16 infants with PHH. There was a statistically significant increase in oxygenated hemoglobin (p < 0.001), total hemoglobin (p = 0.001), and hemoglobin difference signal (p = 0.006), but not oxidized cytochrome oxidase, accompanying CSF removal. There was no significant correlation between either the volume of CSF removed (in milliliters per kilogram body weight) or the opening pressure and the change in any of the measured or calculated NIRS signals. These findings demonstrate the pronounced effect of CSF removal on cerebral perfusion in infants with PHH. NIRS may be a useful technique to detect impending cerebral ischemia in such infants and thereby provide a means to guide the rational management of PHH.
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PMID:CSF removal in infantile posthemorrhagic hydrocephalus results in significant improvement in cerebral hemodynamics. 1473 52

Hydrocephalus induces interstitial brain edema, which causes neurological deficits, even if the intracranial pressure is maintained within the normal range, and the cerebral blood flow (CBF) does not decline to an ischemic level. The precise mechanisms underlying such edema-induced neuronal dysfunction remain unclear. In the present study, in an attempt to elucidate the metabolic derangements in brain tissue with interstitial edema, we evaluated the changes in CBF and oxidative/glucose metabolism using a rat model of kaolin-induced hydrocephalus. Hydrocephalus was produced in male Wistar rats by intrathecal injection of 0.1 ml aluminum silicate suspension (200 mg/ml) via the cisterna magna. CBF was determined by 14[C]-iodoantipyrine autoradiography. Oxidative metabolism was evaluated by cytochrome oxidase (CYO) histochemistry, and glucose metabolism by hexokinase (HK) histochemistry. CBF declined with the development of hydrocephalus, but did not reach an ischemic level. The CYO activity was diffusely depressed in both the cortex and hippocampus. The HK activity was preserved at the early stage of hydrocephalus. At the advanced stage, the HK activity was reduced in the hippocampal CA3 region first, and diffusely thereafter. In conclusion, interstitial brain edema impairs oxidative metabolism even at the early stage of hydrocephalus, and shifts the metabolism to anaerobic glycolysis despite a preserved CBF. Impairment of glucose metabolism was first observed in the CA3 region, suggesting that the CA3 is metabolically vulnerable, and CA3 dysfunction may contribute to the memory deficits seen in hydrocephalus.
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PMID:Metabolic derangements in interstitial brain edema with preserved blood flow: selective vulnerability of the hippocampal CA3 region in rat hydrocephalus. 1475 3