Biomedical subjects

C C Duncan

Publications and source records attributed to C C Duncan.

102 records · Page 6Linked to original sources

PubMedDate not supplied

Neurotensin modulates K(+)-stimulated dopamine release from the caudate-putamen but not the nucleus accumbens of mice with differential sensitivity to ethanol.

Slices of caudate-putamen (CP) and nucleus accumbens (NA) prepared from Long-Sleep (LS) and Short-Sleep (SS) mice were used to determine the effects of neurotensin (NT) and ethanol on K(+)-stimulated 3H-dopamine (3H-DA) release and to test the hypothesis that ethanol acts, in part, via NT receptor-mediated processes. Slices prepared from either LS or SS CP or NA did not differ in submaximal (25 mM) K(+)-stimulated 3H-DA release but 60 mM K+ induced significantly greater 3H-DA release from LS CP slices compared with SS CP slices. NT had no effect on unstimulated 3H-DA overflow but enhanced 25 mM K(+)-stimulated 3H-DA release from slices of the CP of both lines of mice. Augmentation of DA release by NT from caudate slices was concentration dependent and tetrodotoxin (TTX) insensitive, implicating a role of presynaptic neurotensin receptors located on nigrostriatal DA neurones. In contrast, NT did not enhance K(+)-stimulated 3H-DA release from NA slices from either line of mice. The absence of an NT effect in NA slices was not due to a rapid desensitization of NT receptors but the data were consistent with the absence of presynaptic NT receptors on dopaminergic terminals in the NA. Between-line differences were observed in the effect of ethanol on NT enhancement of 25 mM K(+)-stimulated 3H-DA release from CP slices. Ethanol (100 mM) applied concomitantly with NT blocked the NT enhancement of 3H-DA release from CP slices of LS but not SS mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Neurodevelopmental assessment of very low birth weight neonates: effect of germinal matrix and intraventricular hemorrhage.

During a recent 36-month interval, all neonates of less than or equal to 1250 gram birth weight who were admitted to our Newborn Special Care Unit and survived the first 36 postnatal hours underwent either computed tomography or echoencephalography or both for the assessment of neonatal germinal matrix hemorrhage and intraventricular hemorrhage. Seventy of the 164 long-term surviving infants experienced neonatal germinal matrix and/or intraventricular hemorrhage (GMH/IVH Group), whereas 94 infants had studies that were negative (Non-hemorrhage Group). Serial neurodevelopmental assessments were performed on 142 (87%) of the 164 long-term surviving infants; these assessments included the Bayley Scales of Infant Development at 3, 6, 12, and 18 months (corrected age) and the Stanford-Binet and Peabody Picture Vocabulary examinations at 30 months (corrected age). At 30 months (corrected age), the incidence of major neurologic abnormalities was extremely low in both the GMH/IVH and the Non-hemorrhage groups. In addition, although there were few survivors of the more severe grades of intraventricular hemorrhage, we could detect no difference between the developmental scores of the GMH/IVH and the Non-hemorrhage Group infants.

Brain Damage, Chronic↗

PubMedDate not supplied

Bacterial meningitis as an etiology of perinatal cerebral infarction.

Despite significant improvement in mortality rate, survivors of neonatal bacterial meningitis experience a significant incidence of neurodevelopmental sequelae. Neuropathologic studies have demonstrated vasculitis, arachnoiditis, and ventriculitis with secondary edema and encephalomalacia. Areas of cerebral infarction, most commonly thought to be venous in origin, have been reported as well. We performed cranial computed tomographic scans on all eight neonates with bacterial meningitis admitted to our Newborn Special Care Unit within the past 36 months and demonstrated abnormalities in seven. Six of these infants were found to have large areas of infarction related primarily to major arterial vascular distributions. We suggest computed tomographic studies for all neonates with bacterial meningitis and subsequent scans at 4-6 months of age in those with abnormal neonatal scans in order to plan better for early intervention services.

Bacterial Infections↗

PubMedDate not supplied

Beagle puppy model of perinatal asphyxia: alterations in cerebral blood flow and metabolism.

Perinatal asphyxia remains a major cause of neurodevelopmental handicap. The neuropathologic and clinical sequelae of perinatal asphyxia are likely attributable to alterations in cerebral blood flow (CBF) to the developing brain with uncoupling of CBF and metabolism. The newborn beagle puppy model was used to study the control of CBF in physiologic and pathologic conditions in the developing brain. Pups, 2-10 days of age, were randomized to asphyxial insult (i.e., ventilator lines clamped for 5 min) or no insult. In the first series, pups underwent radioactive microsphere determinations of CBF immediately prior to insult (t = 0), at the end of insult (t = 5), and after 60 min of observation (t = 65). In the second series, utilizing a 2.0 tesla superconducting magnet, pups underwent continuous serial in vivo 31P nuclear magnetic resonance spectral analysis of cerebral hemispheric metabolic state. Animals exposed to insult had significant alterations in PO2, PCO2, pH, and mean arterial pressure at the end of insult compared to control pups (all pups: p less than 0.001). Serial CBF data demonstrated decreases in flow in cortical gray and white matter regions during insult and return to baseline 1 hour later; brainstem structures were hyperemic during insult. Analysis of phosphorylated metabolites inorganic phosphorus (Pi), phosphocreatine (PCr), and ATP demonstrated that during insult both the PCr/Pi and ATP/Pi ratios were depressed but by 20-30 min following insult, these ratios of cerebral phosphorylated metabolites had almost returned to baseline values. These data demonstrate that even after a severe asphyxial episode which results in electrocerebral silence, CBF and metabolism may return to normal.

Acid-Base Equilibrium↗

PubMedDate not supplied

Beagle puppy model of perinatal asphyxia: blockade of excitatory neurotransmitters.

The N-methyl-D-aspartate receptor antagonist MK801 has been reported to prevent neuronal change in models of ischemia in adult animal systems. We studied the hypothesis that blockade of the N-methyl-D-aspartate receptor would prevent the depression of cerebral high-energy phosphates found in perinatal asphyxia without producing alterations in cerebral blood flow, and thus prevent neuropathologic damage. Newborn beagle puppies were anesthetized, tracheotomized, ventilated, and randomized to asphyxial insult (I = discontinuation of ventilatory support for 5 min) or no insult (NI) and drug treatment with MK801 (10 mg/kg intravenously) or an equal volume of saline (S). Puppies received MK801 or saline 15 min prior to I/NI. In S/I pups during insult, blood flow increased to brainstem structures but decreased elsewhere. MK801 had no effect on cerebral blood flow in either control or insulted puppies. 1H NMR studies demonstrated no effect of the MK801 on NI brains. Phosphocreatine levels were 1.7 +/- 0.1, 0.6 +/- 0.1, and 0.9 +/- 0.1 mmole/kg (mean: +/- S.D.) for the S/NI, S/I, and MK801/I pups, respectively. Cerebral lactate was 1.3 +/- 0.2, 3.0 +/- 0.7, and 2.0 +/- 0.4, respectively. The pH fell 0.8 units in the S/I puppies, compared to 0.4 units in the MK801/I puppies. We conclude that pretreatment with the N-methyl-D-aspartate receptor antagonist MK801 in part protects the developing brain against severe metabolic insult.

Animals↗

PubMedDate not supplied

Correlation of sedative effects with brain levels of barbiturates in LS and SS mice.

Long-sleep (LS) and short-sleep (SS) mice, genetically selected for their differential CNS sensitivity to ethanol, have also been shown to differ in their response to other sedative-hypnotics, including the barbiturates. We have applied a gas-chromatographic method of analysis of brain barbiturate concentrations following IP administration of either the water-soluble barbiturate diethylbarbital (DB) or the lipid-soluble barbiturate secobarbital (SB). Brain barbiturate levels were assessed at loss of righting response, and at regaining righting response (waking). In addition, latency to loss of righting response and duration of loss of righting response were measured following IP barbiturate administration. We have observed a differential sensitivity of LS and SS mice to the sedative effects of DB, with LS mice having greater sensitivity compared to SS. This differential sensitivity to DB, as measured by a lower concentration of DB which caused loss of righting in LS, was accompanied by an equal rate of water-soluble barbiturate brain distribution and elimination in the two lines. With the lipid-soluble barbiturate SB, LS and SS mice did not differ in brain SB concentration at loss of righting response or at waking. However, sleep time was much longer in SS mice than LS due to slower brain clearance of the barbiturate in SS. Therefore, duration of loss of righting (sleep time) did not adequately reflect central sensitivity to the lipid-soluble barbiturate. These data suggest the importance of quantifying brain concentrations at loss of righting reflex when assessing central sensitivity to sedative-hypnotic agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Perinatal cerebral insults: hemorrhage and ischemia.

The incidence of major neurodevelopmental handicaps in the survivors of newborn special care has remained essentially unchanged over the past decade despite the development of sophisticated perinatal care. Preterm infants with parenchymal involvement of intraventricular hemorrhage and neonates of all gestational ages with cerebral infarction are believed to be at higher risk for both neurologic and developmental abnormalities than infants without these problems. Both lesions are thought secondary to alterations in cerebral blood flow to the developing brain, and many infants demonstrate evidence for both hemorrhage and ischemic insult.

Brain Ischemia↗

PubMedDate not supplied

Observations of the dynamics of ionic potassium-38 in brain.

Short time course potassium dynamics in brain were investigated in the cat. 38K (T1/2 = 7.6m) was prepared on the BNL 60" cyclotron by the 40Ar(p, 3n)38K reaction. Positron decay in brain was measured by the limited angle of view positron camera (LAPC). Radioactivity corrected for physical decay following intravenous bolus injection of 38K showed an initial peak followed by a washout phase with a subsequent monotonic increase. The slope of the washout phase was linearly related to PaCO2 and the subsequent monotonic increase paralleled the arterial concentration of the tracer. No significant changes in 38K radioactivity were determined following coma producing levels of phenobarbital or seizure producing doses of potassium penicillin as compared to control.

Animals↗

PubMedDate not supplied

Beagle pup model of perinatal asphyxia: nimodipine studies.

Calcium antagonists may be of significant benefit in the pharmacotherapy of cerebral ischemia, possibly by improving postischemic cerebral blood flow (CBF). This study evaluated the effects of the calcium antagonist nimodipine on CBF in a newborn beagle pup model of perinatal asphyxia lasting 5 minutes. Immediately after the asphyxial episode, nimodipine (2 micrograms/kg/min) or saline was infused for 10 minutes, following which [14C]iodoantipyrine determinations of CBF were performed. In noninsulted pups, nimodipine caused both significant decreases in CBF to cortical and deep gray structures as well as a decrease in mean arterial blood pressure (MABP) (p less than 0.05). In insulted pups, nimodipine similarly decreased MABP (p less than 0.001) and CBF to cortical and deep gray matter regions. Nimodipine appeared to have no effect on arterial blood gases and EEG tracings in either insulted or noninsulted pups. Although nimodipine may be shown to improve neurologic outcome in asphyxiated newborn infants, the limits of this study do not show the mechanism to be that of improving CBF.

Animals↗

PubMedDate not supplied

The relation of proton activation of brain to cerebral blood flow.

The interaction of brain with high energy protons produces positron emitting nuclides. The present study examines the response of the decay events to oxygen-15 induced by such activation in brain to alterations of cerebral blood flow as measured by a limited angle planar positron camera. Decay events correlate directly to the cerebral blood flow. The interaction of brain with high energy protons appears to offer an alternative means for the delivery of a freely diffusible tracer into brain.

Animals↗

PubMedDate not supplied

Cerebral blood flow determinations by positron emission tomography.

Multiple approaches are available to measure global and regional cerebral blood flow. The inert gas method of Kety-Schmidt provides the mathematical basis for essentially all of these methods with the exception of microspheres. The preferred method depends largely upon the type of information to be obtained. The preferred method depends largely upon the type of information to be obtained. The three essential problems in cerebral blood flow measurement are establishing reliable cerebral blood flow measurements in pathological processes, the relation of this flow to metabolism, and the clinical application of cerebral blood flow measurements in man for the investigation of a wide variety of significant disease processes including ischemia and intracranial hypertension.

Autoradiography↗

PubMedDate not supplied

Significant enhancement of carbon dioxide removal by a new prototype IVOX.

The intravenacaval blood gas exchanger (IVOX) developed by Cardiopulmonics, Inc. has been tested in animals and in human clinical trials for partial support of gas exchange (25-30%) to allow reduction in mechanical ventilatory support and barotrauma during acute respiratory failure. After recognizing the limitations of the device and limited clinical utility of removing only 25-30% of CO2 production, the authors have made design changes in the IVOX (prototypes IIA and IIB), including increased fiber number, decreased fiber length, decreased fiber diameter, and increased crimping. Nine ewes underwent placement of the IVOX prototypes in an ovine model of severe smoke inhalation injury. A modification of the original insertion technique was used to implant the prototypes. CO2 removal was directly measured from the outlet gas. O2 exchange was calculated from IVOX on/off measurements. Neither IVOX IIA nor IIB significantly changed hemodynamics when a fluid bolus (15 ml/kg) was infused before insertion. There were no significant differences between prototypes regarding thrombosis, emboli, or incidence of bleeding complications. Both prototypes significantly improved CO2 removal (60-80%) compared with that reported for an older IVOX model. The improved gas transfer by these prototypes would serve to decrease mechanical ventilatory requirements and barotrauma in the treatment of severe respiratory failure.

Animals↗