scholarly journals NOC/oFQ contributes to age-dependent impairment of NMDA-induced cerebrovasodilation after brain injury

2000 ◽  
Vol 279 (5) ◽  
pp. H2188-H2195 ◽  
Author(s):  
William M. Armstead
Keyword(s):  
Cerebrospinal Fluid ◽  
Amino Acid ◽  
Brain Injury ◽  
Excitatory Amino Acid ◽  
Age Groups ◽  
Orphanin Fq ◽  
Pial Artery ◽  
Age Related ◽  
Age Dependent

This study characterized the effects of fluid percussion brain injury (FPI) on N-methyl-d-aspartate (NMDA)-induced vasodilation and determined the role of nociceptin/orphanin FQ (NOC/oFQ) in such changes as a function of age and time postinsult. FPI elevated cerebrospinal fluid (CSF) NOC/oFQ from 70 ± 3 to 444 ± 56 pg/ml (≈10−10 M) within 1 h and to 1,931 ± 112 pg/ml within 8 h, whereas values returned to control levels within 168 h in the newborn pig. In contrast, FPI elevated CSF NOC/oFQ from 77 ± 4 to 202 ± 16 pg/ml within 1 h and values returned to control levels within 8 h in the juvenile pig. Topical NOC/oFQ (10−10 M) had no effect on pial artery diameter but attenuated NMDA (10−8, 10−6M)-induced dilation (9 ± 1 and 16 ± 1 vs. 5 ± 1 and 10 ± 1%) in both age groups. In the newborn, NMDA-induced pial artery dilation was reversed to vasoconstriction within 1 h post-FPI and responses remained impaired for 72 h, but such vasoconstriction was attenuated by pretreatment with [F/G]NOC/oFQ(1–13)-NH2 (10−6 M, 1 mg/kg iv), an NOC/oFQ antagonist (9 ± 1 and 16 ± 1 vs. −7 ± 1 and −12 ± 1 vs −2 ± 1 and −3 ± 1% for control, FPI, and FPI pretreated with the NOC/oFQ antagonist). In contrast, in the juvenile, NMDA-induced vasodilation was only attenuated within 1 h post-FPI and returned to control within 8 h. Such dilation was also partially restored by the NOC/oFQ antagonist. These data indicate that NOC/oFQ contributes to impaired NMDA pial artery dilation after FPI. These data suggest that the greater NOC/oFQ release in the newborn versus the juvenile may contribute to age-related differences in FPI effects on excitatory amino acid-induced pial dilation.

Excitatory amino acids in cerebrospinal fluid following traumatic brain injury in humans

1993 ◽  
Vol 79 (3) ◽  
pp. 369-372 ◽  
Author(s):  
Andrew J. Baker ◽  
Richard J. Moulton ◽  
Vernon H. MacMillan ◽  
Peter M. Shedden
Keyword(s):  
Amino Acids ◽  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Amino Acid ◽  
Brain Injury ◽  
Excitatory Amino Acids ◽  
Excitatory Amino Acid ◽  
Neuronal Damage ◽  
Control Group ◽  
Injured Patients

✓ Evidence from models of traumatic brain injury implicates excitotoxicity as an integral process in the ultimate neuronal damage that follows. Concentrations of the excitatory amino acid glutamate were serially measured in the cerebrospinal fluid (CSF) of patients with traumatic brain injuries and in control patients for comparison. The purpose of the study was to determine whether glutamate concentrations were significantly elevated following traumatic brain injury and, if so, whether they were elevated in a time frame that would allow the use of antagonist therapy. Cerebrospinal fluid was sampled fresh from ventricular drains every 12 hours and analyzed using high-performance liquid chromatography for the excitatory amino acids. The peak concentrations of glutamate in the CSF of the 12 brain-injured patients ranged from 14 to 474 µM and were significantly higher than those in the three control patients, 4.9 to 17 µM (Mann-Whitney U-test, p < 0.02). Glutamate concentrations in five of the eight patients who were still being sampled on Day 3 were beyond the control group range. The implication of this study is that severely head-injured patients are exposed to high concentrations of a neurotoxic amino acid for days following injury and thus may benefit from antagonist intervention.

scholarly journals Factors affecting excitatory amino acid release following severe human head injury

1998 ◽  
Vol 5 (2) ◽  
pp. E1
Author(s):  
Ross Bullock ◽  
Alois Zauner ◽  
John J. Woodward ◽  
John Myseros ◽  
Sung C. Choi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Brain Injury ◽  
Head Injury ◽  
Excitatory Amino Acid ◽  
Neuronal Damage ◽  
Cell Swelling ◽  
Microdialysis Probe ◽  
Glutamate Antagonists

Recent animal studies demonstrate that excitatory amino acids (EAAs) play a major role in neuronal damage after brain trauma and ischemia. However, the role of EAAs in patients who have suffered severe head injury is not understood. Excess quantities of glutamate in the extracellular space may lead to uncontrolled shifts of sodium, potassium, and calcium, disrupting ionic homeostasis, which may lead to severe cell swelling and cell death. The authors evaluated the role of EEAs in human traumatic brain injury. In 80 consecutive severely head injured patients, a microdialysis probe was placed into the gray matter along with a ventriculostomy catheter or an intracranial pressure (ICP) monitor for 4 days. Levels of EAAs and structural amino acids were analyzed using high-performance liquid chromatography. Multifactorial analysis of the amino acid pattern was performed and its correlations with clinical parameters and outcome were tested. The levels of EAAs were increased up to 50 times normal in 30% of the patients and were significantly correlated to levels of structural amino acids both in each patient and across the whole group (p < 0.01). Secondary ischemic brain injury and focal contusions were most strongly associated with high EAA levels (27 ± 22 μmol/L). Sustained high ICP and poor outcome were significantly correlated to high levels of EAAs (glutamate > 20 μmol/L; p < 0.01). The release of EAAs is closely linked to the release of structural amino acids and may thus reflect nonspecific development of membrane micropores, rather than presynaptic neuronal vesicular exocytosis. The magnitude of EAA release in patients with focal contusions and ischemic events may be sufficient to exacerbate neuronal damage, and these patients may be the best candidates for treatment with glutamate antagonists in the future.

Role of Excitatory Amino Acid-Mediated Ionic Fluxes in Traumatic Brain Injury

1995 ◽  
Vol 5 (4) ◽  
pp. 427-435 ◽  
Author(s):  
Yoichi Katayama ◽  
Takeshi Maeda ◽  
Morimichi Koshinaga ◽  
Tatsuro Kawamata ◽  
Takashi Tsubokawa
Keyword(s):  
Traumatic Brain Injury ◽  
Amino Acid ◽  
Brain Injury ◽  
Excitatory Amino Acid ◽  
Ionic Fluxes

Different ATP-catabolism in reperfused adult and newborn rat hearts

1988 ◽  
Vol 254 (6) ◽  
pp. H1091-H1098
Author(s):  
P. W. Achterberg ◽  
A. S. Nieukoop ◽  
B. Schoutsen ◽  
J. W. de Jong
Keyword(s):  
Oxidase Activity ◽  
Age Groups ◽  
Similar Degree ◽  
Ischemia And Reperfusion ◽  
Xanthine Oxidoreductase ◽  
Newborn Rat ◽  
Age Related ◽  
Rat Hearts ◽  
Age Dependent ◽  
Atp Breakdown

Age-dependent differences in the effects of ischemia and reperfusion on ATP breakdown were studied in perfused adult and newborn (10 days old) rat hearts. No-flow ischemia (15 min at 37, 30, or 23 degrees C) was applied and reperfusion (20 min at 37 degrees C) was studied after ischemia at 23 or 37 degrees C. Hypothermia during ischemia protected both age groups to a similar degree against ATP decline, which was linear with temperature. Reperfusion after normothermic ischemia resulted in higher ATP levels in newborn hearts with less release of ATP catabolites (purines). We found no age-related differences in lactate release but large differences in purine release. During normoxia, adult hearts released mainly urate (80% of total) and inosine (7%), but newborns released hypoxanthine (64%) and inosine (15%). Early during reperfusion adult hearts released inosine (58%) and adenosine (18%), but newborns released inosine (53%) and hypoxanthine (38%). These data suggested a lower activity of the potentially deleterious enzyme xanthine oxidoreductase in newborn hearts, which was confirmed by enzymatic assay. ATP-catabolite release during reperfusion was less in newborn than adult hearts, and this coincided with lower xanthine oxidase activity.

Concrete and Formal Operational thought Processes in Young Adulthood and Old Age

1976 ◽  
Vol 7 (3) ◽  
pp. 237-245 ◽  
Author(s):  
Vivian Clayton ◽  
Willis F. Overton
Keyword(s):  
Old Age ◽  
Living Arrangements ◽  
Fluid Intelligence ◽  
Age Groups ◽  
Thought Processes ◽  
Crystallized Intelligence ◽  
Age Related ◽  
Concrete Operational ◽  
Fluid And Crystallized Intelligence

A study was conducted to examine the role of concrete and formal operations in a young and old population. In addition, the present study explored the relation between operational thought and Cattell's concept of fluid and crystallized intelligence, as well as the role of differential living arrangements in maintaining operational thought. Eighty females from three age groups (18–20 years, 60–70 years and 70–80 years of age) were tested on a series of Piagetian tasks and indices of fluid and crystallized intelligence. The findings supported the notion that age-related performance differences occur in the area of formal operational thought prior to the time they occur in concrete operational thought. Except for the young sample, the operational tasks were found to be unrelated to fluid intelligence at the age levels represented in this study. Living independently as opposed to living in an old age home did not appear to be a significant factor in maintaining operational thought. Discussion focused on the necessity of identifying those factors which influence the developmental course of formal operational thought across the life span.

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