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Biomedical subjects

D E Redmond

Publications and source records attributed to D E Redmond.

At least 73 records · Page 4Linked to original sources
PubMed1987

Intracerebral grafting and culture of cryopreserved primate dopamine neurons.

Dopamine neurons from the ventral midbrain and olfactory bulb of fetal and postnatal African green monkeys were frozen, stored in liquid nitrogen for intervals of 4-28 days, thawed, and tested for viability and growth following intracerebral transplantation into 3 adult monkeys. Well developed tyrosine hydroxylase positive neurons from all donors were seen in intracerebral transplants at 7-50 days after grafting. Freeze-stored neurons also were tested at various intervals by Trypan blue dye exclusion and development in tissue culture. More than 99% of the cryopreserved cells from both pre- and postnatal donors were viable by dye exclusion, and fetal tissue developed neuronal morphology in culture. This evidence further supports the fact that primate neurons survive intracerebral transplantation, even after cryopreservation and storage. The ability to store, transport and verify the transmitter phenotype of neurons offered by this approach is pertinent to possible therapeutic applications.

Animals↗
PubMed1987

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on catecholamines and metabolites in primate brain and CSF.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration is able to produce nigrostriatal damage and motor disabilities in primates similar to those seen in Parkinson's disease. Two months after MPTP treatment in African Green monkeys, significant depletions of dopamine (DA) and/or homovanillic acid (HVA) were found in the dorsal ventral tegmental area, and septum, but not in the ventral part of the ventral tegmental area or nucleus accumbens. However, DA losses were greater at all examined sites in the striatum. In putamen and caudate nucleus the decreases in DA and HVA appeared more marked dorsolaterally than ventromedially. After MPTP treatment the ratio HVA/DA was elevated in the septum and all striatal regions; in the striatum the increases in ratio were greater in the dorsolateral than in the ventromedial samples. NE concentration was not significantly altered by MPTP in the mesolimbic system. In control animals the HVA concentration and the ratio HVA/DA were higher in the putamen than in the caudate nucleus. A longitudinal study showed that CSF HVA and 3-methoxy-4-hydroxyphenylglycol were reduced by MPTP and remained below baseline level for 12 months after MPTP treatment. This biochemical study indicates that in the monkey MPTP is able to induce selective damage within both the nigrostriatal and mesolimbic DA systems.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Differential responsiveness to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in sub-regions of the primate substantia nigra and striatum.

After treatment with the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), there was a severe loss of dopamine (DA) at all examined sites in the striatum, both in those monkeys which remained asymptomatic (77-99%) and in one monkey which developed severe parkinsonian disability (94-99%). However, the asymptomatic animals had normal DA concentration in the substantia nigra (SN); yet in the symptomatic animal DA was largely depleted in the central (86%) and medial (94%), but not lateral (8%) regions of the SN. The HVA/DA ratio was raised in the striatum of all MPTP-treated animals. In the SN though, this ratio was elevated only in the symptomatic animal, in the central and medial, but not lateral regions. The contralateral half of these brains were examined for DA histofluorescence. The SN of asymptomatic animals had a slight increase in lipofuscin fluorescence within dopaminergic neurons and a small reduction in the number of dopaminergic cells, while fluorescent intensity of individual neurons was unchanged. The SN of the symptomatic animal displayed a sharp decline in the number of DA neurons along with an increase in autofluorescent pigment granules; these changes were most pronounced in the central and medial regions of the SN. These data suggest that after MPTP the terminals of the nigrostriatal pathway are affected before the cell bodies. In the one symptomatic animal emergence of parkinsonian disability corresponded with a marked loss of DA neurons and DA concentration in the central and medial regions of the SN. In the control monkeys a gradient in the concentration of amines and metabolites was observed within the SN; the lateral region contained the highest and the medial region the lowest concentration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Homovanillic acid concentrations in brain, CSF and plasma as indicators of central dopamine function in primates.

In a large number (91) of vervet monkeys, correlation coefficients were determined between homovanillic acid (HVA) concentrations in four brain areas. Significant correlations existed between dorsal frontal cortex and orbital frontal cortex and between putamen and caudate nucleus. However, no significant correlations existed between either cortical area and the basal ganglia areas. Correlations were tested between CSF and plasma HVA and between these fluids and brain regions. The only significant relationship found was between CSF and dorsal frontal cortex, after possible treatment effects were statistically removed. The assumption that primate CSF HVA concentration necessarily reflects basal ganglia HVA concentration is questioned and furthermore, the results suggest that HVA from cortex contributes significantly to that in cisternal CSF. Raw plasma HVA measurements (even when uninfluenced by diet or anesthetic) appear to be of limited value in gauging central dopamine metabolism and turnover.

Animals↗
PubMed1986

Preferential vulnerability of A8 dopamine neurons in the primate to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Immunohistochemical examination of the midbrain of vervet monkeys treated with MPTP revealed a marked loss of dopaminergic neurons in the lateral, but not medial, region of the A8 dopamine (DA) cell group. In the same animals, the number of DA neurons in the substantia nigra was only slightly decreased. Biochemical assessment revealed a marked (greater than 85%) depletion of DA in the striatum. However, in the DA cell body regions significant decreases in DA and homovanillic acid were observed only in the lateral A8 region, and not in the medial A8 region or substantia nigra. These data suggest that those A8 DA neurons which project to the striatum are preferentially vulnerable to MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Fetal neuronal grafts in monkeys given methylphenyltetrahydropyridine.

Fetal substantia nigra cells of two different gestational ages were successfully transplanted into the brains of three methylphenyltetrahydropyridine-treated monkeys with severe parkinsonian motor and behavioural deficits. Functional improvement continued for 10 weeks after cell grafts into the striata of two monkeys with substantial numbers of tyrosine-hydroxylase-positive fetal neurons at necropsy. Behavioural improvement was correlated with increases in cerebrospinal fluid (CSF) homovanillic acid (HVA) concentrations after the transplants. A control monkey with inappropriately placed transplanted cells of an earlier gestational age remained severely parkinsonian and died during a similar period. CSF HVA fell slightly in this monkey from the low level seen before the transplants. Fetal dopamine neurons of two different gestational ages appear to survive transplantation in primates and have biochemical and functional effects.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Carbon dioxide sensitivity in panic anxiety. Ventilatory and anxiogenic response to carbon dioxide in healthy subjects and patients with panic anxiety before and after alprazolam treatment.

One hypothesis that could account for the anxiogenic response to breathing air supplemented with carbon dioxide seen in panic anxiety patients is that panic patients might have abnormally high central medullary chemoreceptor sensitivity. Chemoreceptor sensitivity was assessed by using a rebreathing technique to measure the ventilatory response to CO2 in 14 medication-free patients with agoraphobia and panic attacks and 23 healthy subjects. Ventilatory response to CO2 was similar in patients and controls (mean +/- SEM, 1.58 +/- 0.16 vs 1.58 +/- 0.14 L/min/mm Hg), suggesting that abnormal chemoreceptor sensitivity does not explain the behavioral sensitivity of panic patients to CO2. Anxiety ratings increased markedly during rebreathing both in patients and controls; anxiety increases were significantly greater in patients than in healthy subjects matched for age, sex, and rebreathing duration. Alprazolam treatment in eight patients markedly attenuated anxiety increases during rebreathing. Differences in anxiogenic sensitivity to CO2 between patients and controls may be due to differences in the regulation of noradrenergic or other neuronal systems.

Adult↗
PubMed1986

Cerebrospinal fluid amine metabolites. Relationships with behavioral measurements in depressed, manic, and healthy control subjects.

We studied 99 hospitalized depressed, 14 manic, and 61 healthy control subjects and evaluated relationships during a drug-free baseline period between behavioral measures (postulated to be associated with brain norepinephrine, dopamine, and serotonin function) and metabolites of these neurotransmitters sampled from lumbar cerebrospinal fluid (CSF): 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid, and 5-hydroxyindoleacetic acid. Depressed subjects with increased anxiety, agitation, somatization, and sleep disturbance were found to have significantly elevated concentrations of CSF MHPG; this relationship was not found in the healthy controls. A correlation between CSF MHPG level and an anxiety/agitation dimension measured in all subjects was statistically significant but explained a modest portion of the total variance. No consistent relationships were found between CSF MHPG and depression/retardation, hostility/interpersonal sensitivity, and global severity, nor did any of these measures correlate significantly with the levels of the other monoamine metabolites, although some trends were found. Other factors did not account for the relationships between CSF MHPG and some behavioral measures, including diagnostic subgroup, motor movement, age, sex, and premenopausal or postmenopausal status in women. Suggested relationships among drug treatment modality, eventual treatment outcome, behavioral and mood state at baseline, and these metabolite levels will require further analyses.

Bipolar Disorder↗
PubMed1986

Path analysis of psychopharmacological data: catecholamine breakdown in man.

This article applies path analysis to the problem of characterizing metabolic alterations in catecholamine systems when only static or single measures of precursor and products are available. In this article, simulated data from kinetic models of norepinephrine metabolism were examined using path analysis. The method of path analysis, which is based on correlations between compartments and not actual flow, correctly identified operative and nonoperative metabolic pathways in simulated models. In addition, actual data from normal subjects as to the 24-hour urinary values for norepinephrine, normetanephrine, vanillylmandelic acid, and 3-methoxy-4-hydroxyphenylglycol were analyzed using path analysis. It was found that metabolic routes that are known to be incomplete did not fit these data, whereas the known metabolic pathways for norepinephrine were correctly identified using path analysis. These results suggest that path analysis may provide a useful tool in identifying normal and abnormal catecholamine metabolic pathways in experimental situations where only single values of precursor and products are available.

Humans↗
PubMed1986

Survival and growth of fetal catecholamine neurons transplanted into primate brain.

Dopamine and norepinephrine neuroblasts of the ventral mesencephalon, hypothalamus, and dorsolateral pons were transplanted from fetal African green monkeys into multiple brain sites in adult (host) African green monkeys. Tissue was grafted from both early and late gestational age fetuses. Immunohistochemical analysis, with antibodies to tyrosine hydroxylase, a marker of catecholamine-containing neurons, showed large numbers of transplanted catecholamine neurons in host cerebral cortex, corpus striatum and lateral ventricles up to 69 days after transplantation. Serial reconstructions revealed extensive outgrowth of neuronal processes from large numbers of transplanted neurons as well as expansion of the size of transplanted (solid) grafts of fetal brain tissue in the host brain. Some grafts extended from the caudate nucleus into the adjacent lateral ventricles or from the cerebral cortex into the underlying corpus callosum and ventricle. There were dense networks of varicose fibers emanating from the tyrosine hydroxylase positive neurons within intraparenchymal and intraventricular grafts. The size and shape of transplanted neurons retained characteristics common to catecholaminergic neurons from the dissected regions of fetal brain. Thus, a variety of fetal, catecholamine-containing neurons survive transplantation to primate brain and produce extensive neuritic outgrowths. Moreover, rejection of transplanted tissue was not apparent. These findings provide essential information on nerve cell grafting in a species closely related to humans as a prerequisite in the consideration of neural transplants as therapeutic measures in neurological disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Phenylacetic acid production in dominant and non-dominant vervet monkeys.

Free and conjugated plasma phenylacetic acid concentrations were significantly higher in dominant male vervet monkeys than in non-dominant males living in stable social groups. These findings may be connected with an earlier observation that plasma from aggressive human psychopaths contains higher concentrations of phenylacetic acid than non-aggressive controls; whether they reflect an increased production of phenylethylamine is still unknown.

Animals↗