Search PubMed⌕ Search

Biomedical subjects

T Brannan

Publications and source records attributed to T Brannan.

31 records · Page 2Linked to original sources
PubMed1992

Catechol-O-methyltransferase inhibition increases striatal L-dopa and dopamine: an in vivo study in rats.

We administered Ro 40-7592, an inhibitor of the enzyme catechol-O-methyltransferase (COMT) that crosses the blood-brain barrier, to rats and monitored extracellular catecholamine levels in the corpus striatum before and after the intraperitoneal administration of a bolus of l-dopa. Acute administration of Ro 40-7592 increased basal levels of l-dopa and dihydroxyphenylacetic acid (DOPAC) and decreased basal homovanillic acid (HVA) levels, but did not affect basal dopamine levels. In rats treated with Ro 40-7592, l-dopa administration produced a greater increase in striatal levels of l-dopa, dopamine, and DOPAC than it did in controls, while HVA formation was attenuated. We conclude that inhibition of COMT activity promotes central dopamine synthesis and release following administration of pharmacologic doses of l-dopa.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Effect of yohimbine on brain monoamines: an in vivo study.

Following the administration of yohimbine, an alpha 2-adrenoreceptor antagonist, the levels of norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA) increased significantly in the lateral ventricular fluid of rats. These increases were abolished when animals were pretreated with alpha-methyl-para-tyrosine or reserpine. Dopamine (DA) was not detected in ventricular fluid either before or after yohimbine administration. Yohimbine administration did, however, increase intracellular DA levels in the corpus striatum. These findings indicate that yohimbine promotes NE and DA release in the brain and suggest that it also modifies the activity of the serotonin system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Effect of dietary protein on striatal dopamine formation following L-dopa administration: an in vivo study.

We varied the diet of rats and monitored extracellular levels of dopamine in the striatum. Following L-dopa administration, the increase in striatal dopamine levels was attenuated by 78% in rats that had consumed a high protein diet as opposed to a low protein diet. Similarly, the increase in striatal dopamine levels was attenuated by 61% in rats that had just eaten a protein-containing meal as compared to fasting animals. These findings demonstrate that dietary protein strongly affects brain dopamine formation from exogenous L-dopa.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Effect of long-term L-dopa administration on striatal extracellular dopamine release.

When L-dopa was administered acutely to rats, the increase in the extracellular level of dopamine in the corpus striatum was attenuated by 43% in animals that had received L-dopa daily for 60 days as compared with animals receiving placebo. These findings indicate that chronic treatment with L-dopa impairs striatal dopamine formation or release.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Ischemia in the dorsal hippocampus is associated with acute extracellular release of dopamine and norepinephrine.

The cerebral dialysis technique was employed to monitor extracellular concentrations of dopamine (DA), norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the dorsal hippocampus of gerbils before and after cerebral ischemia induced by carotid artery occlusion. Extracellular concentrations of DA and NE in the dorsal hippocampus increased from baseline levels of less than 35 fmol/collection interval to 180 and 200 fmol/collection, respectively, within 36 minutes following carotid artery ligation (n = 8 animals). Extracellular concentrations of the DA metabolites, DOPAC and HVA, did not change significantly following carotid artery ligation. These data demonstrate that ischemia in the dorsal hippocampus is associated with a mared release of DA and NE. This release may contribute to the selective vulnerability of the dorsal hippocampus to neuronal damage during ischemia.

Animals↗
PubMed1990

Pentobarbital inhibits extracellular release of dopamine in the ischemic striatum.

We examined whether pentobarbital (PB) inhibited the acute extracellular release of dopamine that occurs in the striatum following the onset of ischemic injury in the gerbil model of stroke. The cerebral dialysis technique was employed to monitor striatal extracellular dopamine concentrations before and after carotid artery occlusion while perfusing either a control solution of artificial cerebrospinal fluid (CSF) or a 1 mM solution of pentobarbital in CSF (PB/CSF). During perfusion with CSF, extracellular dopamine increased from a baseline concentration of 0.40 +/- 0.09 (SEM) pmoles/10 minute collection interval to 30.0 +/- 9.0 pmoles/10 minutes after carotid artery occlusion. In contrast, during perfusion with PB/CSF, dopamine levels increased from a baseline of 1.37 +/- 0.3 pmoles/10 minutes to 8.30 +/- 2.6 pmoles/10 minutes; this increase was significantly less than the increase in controls. In animals with established ischemia, repeatedly alternating the perfusion fluid between CSF and PB/CSF demonstrated that dopamine concentrations were significantly increased with CSF alone and decreased with PB/CSF. These findings demonstrate that pentobarbital perfusion either before or following the onset of ischemia inhibits extracellular release of dopamine in the striatum. Inhibition of neurotransmitter release may, in part, be responsible for the protective effect of pentobarbital in ischemic brain injury.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Striatal L-dopa metabolism studied in vivo in rats with nigrostriatal lesions.

We have used cerebral dialysis to monitor striatal metabolism of exogenously administered L-dopa (L-dihydroxyphenylalanine) in rats with unilateral lesions of the substantia nigra. The concentration of extracellular dopamine (DA) increased in both striata following L-dopa administration but the increase was markedly attenuated in the lesioned striatum. The formation of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the major DA metabolites, was also reduced in the lesioned striata following L-dopa administration; however, the reduction was not as great as was that of DA formation. A significant metabolism of exogenous L-dopa to 3-O-methyldopa occurred in both striata. L-dopa administration transiently increased extracellular levels of 5-hydroxyindoleacetic acid (5 HIAA) in both the lesioned and intact striata. These results suggest that the striatum with a reduction in DA nerve terminals is deficient both in the capacity to synthesize DA and in the storage mechanisms necessary to protect the newly synthesized DA from oxidative metabolism.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Intracerebral dialysis monitoring of striatal dopamine release and metabolism in response to L-dopa.

We have used intracerebral dialysis to monitor the striatal extracellular fluid (ECF) in rats with unilateral lesions of the nigrostriatal dopamine (DA) pathway. Dialysis samples were collected before and after L-dihydroxy-phenylalanine (L-DOPA) administration both in the presence and absence of carbidopa, an extracerebral DOPA decarboxylase (DDC) inhibitor. The baseline ECF levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were always higher in the intact than in the lesioned striata. In the normal striata, dopamine (DA) concentrations increased following L-DOPA administration. Pretreatment with carbidopa prolonged the duration of the DA increase. In the lesioned striata, DA levels increased following L-DOPA administration only in animals pretreated with carbidopa. Following L-DOPA administration, striatal HVA and DOPAC levels increased considerably more in animals not pretreated with carbidopa than they did in pretreated animals. This increase was particularly marked in the lesioned striata and leads us to conclude that extracerebrally produced HVA and DOPAC can enter the brain extracellular space.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Treatment of orthostatic hypotension due to autonomic failure with a peripheral alpha-adrenergic agonist (midodrine).

The therapeutic efficacy of midodrine, an alpha-adrenergic agonist that does not cross the blood-brain barrier, was investigated in a double-blind crossover trial in seven patients with orthostatic hypotension due to autonomic failure. We identified two groups of patients: those in whom upright mean arterial pressure significantly increased (group I, n = 3) and those in whom upright mean arterial pressure decreased (group II, n = 4) during midodrine treatment. Body weight changed in a parallel manner with upright blood pressure, increasing in patients of group I and decreasing in patients of group II (p less than 0.05). Autonomic cardiovascular reflexes were significantly more impaired in patients of group II than in patients of group I. We conclude that midodrine is effective in the treatment of orthostatic hypotension only in those patients with significant preservation of autonomic reflexes. Conversely, in patients with markedly impaired baroreceptor mechanisms, treatment with midodrine may produce extracellular fluid volume depletion and exacerbate orthostatic hypotension.

Adrenergic alpha-Agonists↗
PubMed1980

Subarachnoid hemorrhage secondary to spinal arteriovenous malformation and aneurysm. Report of a case and review of the literature.

A patient with recurrent subarachnoid hemorrhage was seen initially with intermittent signs and symptoms of intracranial and spinal cord dysfunction. Myelography and spinal angiography revealed an arteriovenous malformation (AVM) and aneurysm of the spinal cord. Extensive investigation failed to reveal any intracranial lesion. The relationship of subarachnoid hemorrhage at a spinal level to the development of remote neurological abnormalities is discussed, and previous reports of aneurysms associated with spinal AVM are reviewed.

Adult↗
PubMedDate not supplied

Direct evidence of acute, massive striatal dopamine release in gerbils with unilateral strokes.

Dopamine release into the extracellular space was measured with in vivo electrochemical detection in the ipsilateral and contralateral striata in Mongolian gerbils that suffered a stroke after acute unilateral carotid artery ligations. A sevenfold increase in the dopamine signal occurred within 15 minutes of carotid ligation in the ischemic side, while the unlesioned side had no significant change. Increased extracellular levels of dopamine persisted throughout the 3-hour recording period. Pretreatment with alpha-methyl-p-tyrosine 6 hours prior to recording significantly attenuated the signal increase. This study is the first direct demonstration of the marked, continuous dopamine release that occurs during acute cerebral ischemia.

Animals↗