Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “brain”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,099 records · Page 61Linked to original sources
PubMed1985

Monitoring the effect of a tryptophan load on brain indole metabolism in freely moving rats by simultaneous cerebrospinal fluid sampling and brain dialysis.

Rats were given L-tryptophan, 50 mg/kg i.p., and its concentration in the CNS was monitored in individual freely moving animals using repeated sampling of cisternal CSF and concurrent striatal dialysis. The 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid (5-HIAA) was also measured. Results were compared with changes of central tryptophan and 5-HIAA concentrations in brains of rats killed at various times after administration of L-tryptophan, 50 mg/kg i.p. Tryptophan changes in CSF were proportionate to those in whole brain and followed essentially identical time courses. Results for the striatal dialysate and whole striatum also paralleled each other. Similarly, results for 5-HIAA showed proportionality between CSF and brain and between dialysate and striatum. The data obtained were used to determine pharmacokinetic data for individual rats, i.e., areas under curves for both tryptophan and 5-HIAA and half-lives for the decline of tryptophan. Kinetic parameters varied considerably from rat to rat. However, mean half-lives for tryptophan in CSF, brain, dialysate, and striatum were all comparable. Results in general show the value of repeated CSF sampling and intracerebral dialysis for concurrent monitoring of changes of indole metabolism in the whole brain and a specific brain region, respectively. The methods should be suitable for the continuous monitoring of changes of central transmitter metabolism in parallel with observation of behavior following environmental or dietary changes or drug administration. They also should be of use in the investigation of drug kinetics in the CNS.

Animals↗
PubMed1987

Equilibration of halothane with brain tissue in vitro: comparison to brain concentrations during anesthesia.

A method was devised for reproducing anesthetic concentrations of halothane in slice and membrane preparations of rat brain in vitro. Rats were anesthetized with varying concentrations of halothane, responsiveness was tested, and brain halothane content was determined by heptane extraction and gas chromatography. The inspired concentration of halothane at which half of all animals were unresponsive was 1.05%. At 1.25% halothane, all animals were unresponsive and brain halothane was determined to be 41 +/- 1.3 nmol/mg lipid. No significant differences in halothane concentration between whole brain and a variety of brain regions were detected. To obtain similar concentrations in vitro, membranes or slices of cerebral cortex were incubated in Krebs-Ringer bicarbonate buffer (KRB) that had been preequilibrated with anesthetic. Halothane equilibrated rapidly with the buffer and the tissues. The partition coefficient between gas and KRB was found to be 0.78, and between brain slices and KRB approximately 12. Slightly lower gas concentrations were necessary in vitro than in vivo to obtain the same tissue levels of anesthetic. Using this method, it was shown that there was no effect of anesthetic concentrations of halothane on the uptake of [3H]norepinephrine or [3H]choline into slices of rat cerebral cortex.

Anesthesia↗
PubMed1993

Kynurenine pathway enzymes in brain: responses to ischemic brain injury versus systemic immune activation.

Accumulation of L-kynurenine and quinolinic acid (QUIN) in the brain occurs after either ischemic brain injury or after systemic administration of pokeweed mitogen. Although conversion of L-[13C6]tryptophan to [13C6]-QUIN has not been demonstrated in brain either from normal gerbils or from gerbils given pokeweed mitogen, direct conversion in brain tissue does occur 4 days after transient cerebral ischemia. Increased activities of enzymes distal to indoleamine-2,3-dioxygenase may determine whether L-kynurenine is converted to QUIN. One day after 10 min of cerebral ischemia, the activities of kynureninase and 3-hydroxy-3,4-dioxygenase were increased in the hippocampus, but local QUIN levels and the activities of the indoleamine-2,3-dioxygenase and kynurenine-3-hydroxylase were unchanged. By days 2 and 4 after ischemia, however, the activities of all these enzymes in the hippocampus as well as QUIN levels were significantly increased. Kynurenine aminotransferase activity in the hippocampus was unchanged on days 1 and 2 after ischemia but was decreased on day 4, at a time when local kynurenic acid levels were unchanged. A putative precursor of QUIN, [13C6]anthranilic acid, was not converted to [13C6]QUIN in the hippocampus of either normal or 4-day post-ischemic gerbils. Gerbil macrophages stimulated by endotoxin in vitro converted L-[13C6]tryptophan to [13C6]QUIN. Kinetic analysis of kynurenine-3-hydroxylase activity in the cerebral cortex of postischemic gerbils showed that Vmax increased, without changes in Km. Systemic administration of pokeweed mitogen increased indoleamine-2,3-dioxygenase and kynureninase activities in the brain without significant changes in kynurenine-3-hydroxylase or 3-hydroxyanthranilate-3,4-dioxygenase activities. Increases in kynurenine-3-hydroxylase activity, in conjunction with induction of indoleamine-2,3-dioxygenase, kynureninase, and 3-hydroxyanthranilate-3,4-dioxygenase in macrophage infiltrates at the site of brain injury, may explain the ability of postischemic hippocampus to convert L-[13C6]tryptophan to [13C6]QUIN.

3-Hydroxyanthranilate 3,4-Dioxygenase↗
PubMed1999

Early and late posttraumatic seizures in traumatic brain injury rehabilitation patients: brain injury factors causing late seizures and influence of seizures on long-term outcome.

PURPOSE: To demonstrate risk factors involved in the origin of late posttraumatic seizures (LPTSs) in civilian traumatic brain injury (TBI) rehabilitation patients and the occurrence of LPTSs in this population, as well as the time of the first late seizures, and influence of these seizures on functional and occupational long-term outcome. METHODS: A consecutive sample of 490 patients (age range, 0.8-71 years) with TBI, and with postinjury problems in their education and employment, were followed up for > or =5 years from the time of injury in a rehabilitation and reemployment program. The study was carried out at the outpatient neurologic clinic of the Kauniala Hospital, which specializes in brain injuries in Finland and works in close cooperation with the Department of Clinical Neurosciences at the Helsinki University Central Hospital. Main outcome measures were functional outcome, as measured on the Glasgow Outcome Scale (GOS), and the capacity for employment at the end of follow-up. Outcomes were studied separately among patients with late seizures and for the nonseizure group. RESULTS: Children age 7 years or younger at time of injury more often had early posttraumatic seizures (EPTSs), than did adolescents or adults. The time elapsed between brain injury and the first late seizure also was longer in older age groups. EPTSs and depressed skull fracture had a statistically significant relation to the origin of LPTSs. Permanent posttraumatic neurologic deficit, linear skull fracture, and permanent local brain lesion documented on a computed tomography (CT) scan appeared clinically important as risk factors. Late seizures did worsen the functional outcome but had no significant influence on reemployment at the end of follow-up. CONCLUSIONS: Young children are more prone to early seizures, and adolescents and adults, to late seizures. The main risk factors for LPTSs are early seizures and depressed skull fracture. Severity of brain injury, as measured by a low GCS score, prolonged unconsciousness, and posttraumatic amnesia (PTA) without local brain lesion, should not be considered risk factor for LPTSs. Thorough follow-up of patients with TBI with seizures and adequate antiepileptic therapy may help attain rehabilitation goals and reemployment.

Adolescent↗
PubMed2005

Injections of blood, thrombin, and plasminogen more severely damage neonatal mouse brain than mature mouse brain.

The mechanism of brain cell injury associated with intracerebral hemorrhage may be in part related to proteolytic enzymes in blood, some of which are also functional in the developing brain. We hypothesized that there would be an age-dependent brain response following intracerebral injection of blood, thrombin, and plasminogen. Mice at 3 ages (neonatal, 10-day-old, and young adult) received autologous blood (15, 25, and 50 microl respectively), thrombin (3, 5, and 10 units respectively), plasminogen (0.03, 0.05, and 0.1 units respectively) (the doses expected in same volume blood), or saline injection into lateral striatum. Forty-eight hours later they were perfusion fixed. Hematoxylin and eosin, lectin histochemistry, Fluoro-Jade, and TUNEL staining were used to quantify changes related to the hemorrhagic lesion. Damage volume, dying neurons, neutrophils, and microglial reaction were significantly greater following injections of blood, plasminogen, and thrombin compared to saline in all three ages of mice. Plasminogen and thrombin associated brain damage was greatest in neonatal mice and, in that group unlike the other 2, greater than the damage caused by whole blood. These results suggest that the neonatal brain is relatively more sensitive to proteolytic plasma enzymes than the mature brain.

Age Factors↗
PubMed1971

Electroshock effects on brain protein synthesis: relation to brain seizures and retrograde amnesia.

The effects of electroshock on brain seizure activity and brain protein synthesis were studied in male mice. A significant but short-lasting inhibition of brain protein synthesis and an increase in the amount of free leucine were produced by electroshock at intensities above the brain seizure threshold. Electroshock at intensities below the brain seizure threshold did not affect brain protein synthesis.

Amnesia↗
PubMed2000

Cloning the antibody response in humans with chronic inflammatory disease: immunopanning of subacute sclerosing panencephalitis (SSPE) brain sections with antibody phage libraries prepared from SSPE brain enriches for antibody recognizing measles virus antigens in situ.

In central nervous system (CNS) infectious and inflammatory diseases of known cause, oligoclonal bands represent antibody directed against the causative agent. To determine whether disease-relevant antibodies can be cloned from diseased brain, we prepared an antibody phage display library from the brain of a human with subacute sclerosing panencephalitis (SSPE), a chronic encephalitis caused by measles virus, and selected the library against SSPE brain sections. Antibodies that were retrieved reacted strongly with measles virus cell extracts by enzyme-linked immunosorbent assay and were specific for the measles virus nucleocapsid protein. These antibodies immunostained cells in different SSPE brains but not in control brain. Our data provide the first demonstration that diseased brain can be used to select in situ for antibodies directed against the causative agent of disease and point to the potential usefulness of this approach in identifying relevant antibodies in chronic CNS or systemic inflammatory diseases of unknown cause.

Antibodies, Viral↗
PubMed2004

Biological analysis of human immunodeficiency virus type 1 R5 envelopes amplified from brain and lymph node tissues of AIDS patients with neuropathology reveals two distinct tropism phenotypes and identifies envelopes in the brain that confer an enhanced tropism and fusigenicity for macrophages.

Complete envelope genes were amplified from autopsy brain tissue of five individuals who had died of AIDS and had neurological complications. Lymph node samples were included for two of the patients. Nineteen different envelope clones from the five patients had distinct V1V2 sequences. Thirteen of the envelopes were functional and conferred fusigenicity and infectivity for CD4(+) CCR5(+) cells. Infectivity and cell-cell fusion assays showed that most envelopes used both CCR5 and CCR3. One brain-derived envelope used a broad range of coreceptors, while three other brain envelopes from one individual were restricted to CCR5. However, there was no correlation between tissue of origin and coreceptor use. Envelopes showed two very distinct phenotypes depending on their capacity to infect macrophages and to exploit low levels of CD4 and/or CCR5 for infection. Envelopes that were highly fusigenic and tropic for macrophages were identified in brain tissue from four of the five patients. The enhanced macrophage tropism correlated with reduced sensitivity to inhibition by Q4120, a CD4-specific antibody, but not with sensitivity to the CCR5 inhibitor, TAK779. The highly macrophage-tropic envelopes were able to infect cells expressing low levels of CD4 and/or CCR5. Comparison with several well-characterized macrophage-tropic envelopes showed that the four identified patient envelopes were at the top limit of macrophage tropism. In contrast, all four lymph node-derived envelopes exhibited a non-macrophage-tropic phenotype and required high levels of CD4 for infection. Our data support the presence of envelopes that are highly fusigenic and tropic for macrophages in the brains of patients with neurological complications. These envelopes are able to infect cells that express low levels of CD4 and/or CCR5 and may have adapted for replication in brain macrophages and microglia, which are known to express limited amounts of CD4.

AIDS Dementia Complex↗
PubMed1977

Cerebrospinal fluid enzymes in acute brain injury. 1. Dynamics of changes in CSF enzyme activity after acute experimental brain injury.

Changes in CSF enzyme activity were studied after brain trauma for their prognostic value. Raised values of CPK and HBDH were demonstrated in the CSF of patients with severe brain injuries. Standardised cold lesions of the brain were induced in cats. The activities of the enzymes CPK, HBDH, LDH, GOT, GPT, and pseudocholinesterase were studied at half hour intervals in the cerebrospinal fluid and at hourly intervals in the serum. A statistically highly significant increase of all enzymes studied developed in the CSF. The greatest changes occurred within four hours of freezing. Large increases could occur in half an hour. Isoenzyme studies demonstrated that CPK and LDH were of cerebral origin. No consistently significant changes could be shown in the serum enzyme activity. It is concluded that after brain injuries, enzymes are released into the extracellular fluid of the brain and transported to the CSF. The limited value of a single enzyme estimation is emphasised. The results described seem to provide indirect evidence for transependymal flow of extracellular fluid in brain oedema.

Alanine Transaminase↗
PubMed1988

Brain tissue elastic behavior and experimental brain compression.

This study was designed to test the hypothesis that the progressive expansion of an extradural mass causes detectable changes in brain mechanical response properties, in particular the nonlinear elastic behavior, before any significant changes in intracranial cerebrospinal fluid pressure can be detected. In 10 chronically prepared and anesthetized dogs, incremental inflation (0.07 ml/s) of an extradural balloon caused 1) a progressive fall in the brain nonlinear elastic parameter (G0, mmHg/mm2), 2) nonsignificant changes in brain tissue elasticity (G0, mmHg/mm), 3) a disproportionate progressive rise in subpial tension, and 4) a progressive fall in local cerebral blood flow (H2 clearance), despite a modest decrease in cerebral perfusion pressure (extracranial). In previous brain compression experiments (Brain Res. 305: 141-143, 1984) we have shown that the compression site becomes compacted and stiffer (increased G0) and its nonlinear elastic parameter (G0) increases markedly. These earlier findings, coupled with the present observation of a loss in tissue nonlinearity distally to the compression site, are most likely the major mechanisms by which, with a rapidly expanding intracranial mass, tissue pressure gradients and brain displacement, including transtentorial herniation, develop.

Animals↗
PubMed1989

Effect of acute hyponatremia on rat brain pH and rat brain buffering.

Acute hyponatremia was induced in rats by subcutaneous pitressin and intraperitoneal injection of 17.5 ml of 2.5% dextrose three times over 2 days. Brain pH was measured by use of 31P-nuclear magnetic resonance (31P-NMR). Two-hour infusion of a 500 meq sodium solution raised plasma sodium concentration (PNa) from 124.6 to 147 meq/l. Brain pH rose 0.1 pH units in the absence of changes in phosphocreatine or ATP. By contrast, increasing PNa in normal rats from 141 to 158 meq/l did not affect brain pH. Brain buffering was examined by 58-min exposure to 20% CO2 followed by a 38-min recovery. Intrinsic brain buffering (Bi) in hyponatremic and normal rats following 15 min of CO2 was similar, 49.1 and 45.5, respectively. After the next 40 min of CO2 exposure Bi was unchanged in hyponatremic rats at 45.8 but increased in controls to 102.5. In recovery Bi was higher initially in controls and rose significantly only in the controls. These results are consistent with the hypothesis that acute hyponatremia impairs the function of the Na+-H+ exchanger in brain.

Animals↗
PubMed2005

The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients.

Imatinib mesylate (signal transduction inhibitor 571, Gleevec) is a potent and selective tyrosine kinase inhibitor, which was shown to effectively inhibit platelet-derived growth factor-induced glioblastoma cell growth preclinically. However, in patients, a limited penetration of imatinib into the brain has been reported. Imatinib is transported in vitro and in vivo by P-glycoprotein (P-gp; ABCB1), which thereby limits its distribution into the brain in mice. Previously, imatinib was shown to potently inhibit human breast cancer resistance protein (BCRP; ABCG2). Here, we show that imatinib is efficiently transported by mouse Bcrp1 in transfected Madin-Darby canine kidney strain II (MDCKII) monolayers. Furthermore, we show that the clearance of i.v. imatinib is significantly decreased 1.6-fold in Bcrp1 knockout mice compared with wild-type mice. At t = 2 hours, the brain penetration of i.v. imatinib was significantly 2.5-fold increased in Bcrp1 knockout mice compared with control mice. We tested the hypothesis that P-gp and BCRP inhibitors, such as elacridar and pantoprazole, improve the brain penetration of imatinib. Firstly, we showed in vitro that pantoprazole and elacridar inhibit the Bcrp1-mediated transport of imatinib in MDCKII-Bcrp1 cells. Secondly, we showed that co-administration of pantoprazole or elacridar significantly reduced the clearance of i.v. imatinib in wild-type mice by respectively 1.7-fold and 1.5-fold. Finally, in wild-type mice treated with pantoprazole or elacridar, the brain penetration of i.v. imatinib significantly increased 1.8-fold and 4.2-fold, respectively. Moreover, the brain penetration of p.o. imatinib increased 5.2-fold when pantoprazole was co-administered in wild-type mice. Our results suggest that co-administration of BCRP and P-gp inhibitors may improve delivery of imatinib to malignant gliomas.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Comparison of stereotactic brain biopsy to interventional magnetic-resonance-imaging-guided brain biopsy.

Lesions within the brain are commonly sampled using stereotactic techniques. The advent of interventional magnetic resonance (MR) imaging now allows neurosurgeons to interactively investigate specific regions with exquisite visualization. We compared the safety and efficacy of this new surgical approach with stereotaxis. From February 1991 to June 1998, 134 stereotactic and 35 interventional MR-guided brain biopsies were performed. Stereotactic biopsies utilized preoperative scanning. Interactive scanning was used to confirm accurate positioning of the biopsy needle within the region of interest. Intraoperative pathologic examination of biopsy material was performed to verify the presence of diagnostic tissue in both biopsy groups. Intra- and postoperative MR imaging was obtained to exclude the presence of intraoperative hemorrhage. Recently, MR spectroscopic targeting has been utilized in 6 patients. In the stereotactic group, 129/134 (96%) biopsies were diagnostic. One patient had a transient hemiparesis after a brain stem biopsy and another suffered a fatal hemorrhage for a morbidity rate of 0.7% and a mortality rate of 0.7%. In reviewing 7,471 stereotactic biopsies, the morbidity was 3.5%, mortality 0.7% and diagnostic yield 91%. All 35 MR-guided brain biopsies were diagnostic (100%). MR spectroscopy was accurate in all cases in distinguishing recurrent tumor (5 cases) from radiation necrosis (1 case). One patient (3%) suffered a transient hemiparesis following a pontine biopsy and another patient (3%) developed a postoperative scalp cellulitis. No patient sustained a clinically or radiologically significant hemorrhage as determined by the immediate postbiopsy, intraoperative MR imaging. Interventional MR-guided brain biopsy is a safe and effective technique for evaluating lesions of the brain with morbidity and mortality rates comparable to those of stereotaxis. MR-guided biopsy appears to have a higher diagnostic yield than stereotaxis, which may reflect the ability to perform interactive, intraoperative scanning with that technique.

Biopsy↗
PubMedDate not supplied

Localization of interleukin-1 beta converting enzyme mRNA in rat brain vasculature: evidence that the genes encoding the interleukin-1 system are constitutively expressed in brain blood vessels. Pathophysiological implications.

Interleukin (IL)-1 beta-converting enzyme (ICE) cleaves the biologically inactive precursor form of IL-1 beta into mature, bioactive IL-1 beta. Because of the potent effects of IL-1 in blood vessels, we conducted an in situ hybridization study to determine whether ICE mRNA is constitutively expressed in adult rat brain vasculature. Using in situ hybridization histochemistry, we were able to demonstrate that mRNA in blood vessels scattered throughout the brain. In a second set experiments, we found that the genes encoding not only ICE, but also IL-1 alpha, IL-1 beta, IL-1 receptor antagonist (IL-1ra), and the IL-1 type I receptor are expressed in brain vasculature. To our knowledge this is the first report documenting the expression of the genes encoding all of the functional elements of the IL-1 system in the same tissue. Our findings have three pathophysiological implications. First, they indicate a possible site where peripheral IL-1 may act in the brain. The vascular IL-1 system stimulates the production of nitric oxide and prostanoids, which could act as mediators of the effects of peripheral IL-1 in the central nervous system. Additionally, vascular IL-1 is known to activate adhesion molecules; our data that the genes encoding the IL-1 system are expressed in brain vasculature further support the concept that IL-1 is implicated in the pathophysiology of atherosclerosis and stroke. Finally, in the context of previous studies documenting that IL-1ra inhibits the effects of IL-1 on endothelial cells, our findings of endogenous IL-1ra mRNA in brain vasculature indicate that IL-1ra might be an endogenous vascular protective agent.

Animals↗
PubMed2007

Applications of a blood-brain barrier technology platform to predict CNS penetration of various chemotherapeutic agents. 2. Cationic peptide vectors for brain delivery.

BACKGROUND: SynB family peptides conjugated to several drugs have been shown to increase the brain uptake and in vivo activities of these drugs via an adsorptive-mediated transcytosis mechanism. Based on both in vivo and in vitro experimental data, a cell uptake component has been added to our computational model of blood-brain barrier. METHODS: In situ brain perfusion, in vitro cell model and a computational cell uptake model have been used to discover brain-penetrating properties of SynB peptides and to screen libraries of new rationally designed peptide vectors suitable for brain drug delivery. RESULTS AND CONCLUSION: Starting from small peptide vectors that enhance the brain transport coefficient, the BBB platform has made it possible to design libraries of peptide vectors with enhanced transport properties.

Amino Acid Sequence↗
PubMed1988

Survival after brain injury. Cause of death, length of survival, and prognostic variables in a cohort of brain-injured people.

Injuries are the leading cause of death in the United States for those between 1 and 44 years of age and brain injuries are a major component of trauma. This report examines survival in a cohort of San Diego County, California, residents who incurred a brain injury in 1981. Cumulative risk of death over time, using the Cox Proportional Hazards Model, and predictors of death (determined by logistic regression) are used to evaluate survival. The results showed that about half of all brain-injured people who died, died in less than 2 h. Severe overall body damage and severe brain injury are the greatest causes of prehospital death. Even if they survived to the hospital, most people who die have brain injury as their underlying cause of death. Age as well as nature and severity of brain injury are the important predictors of in-hospital death. People who are discharged alive from the hospital have survival comparable to that of the population they came from. However, more die from trauma-related causes than would be expected.

Adolescent↗
PubMed1991

Comparative diffusion study of two nitrosoureas: carmustine and fotemustine in normal rat brain, human and rat brain biopsies.

In order to assess the apparent diffusion coefficient of two nitrosoureas (carmustine and fotemustine) in the brain, a model of planar diffusion was used in the rat brain and in rat and human brain biopsies. Drugs were deposed on the brain surface at a constant concentration for 30 min. At the end of the diffusion time, the concentration gradient was determined with microelectrodes using voltammetry at 5 different depths in the extracellular space of the gray matter (0-304 microns). Voltammetry with microelectrodes measured quantitatively intact drug in the brain extracellular space (CV 4% for the 2 drugs) in the range studied. The same procedure was used for human and rat brain biopsies which were held in a small cup. The apparent diffusion coefficients in living animals were 0.49 x 10(-6) cm2.s-1 for carmustine and 0.23 x 10(-6) cm2.s-1 for fotemustine; in human biopsies, they were 0.84 x 10(-6) cm2.s-1 for carmustine and 0.37 x 10(-6) cm2.s-1 for fotemustine. Significant differences in the apparent diffusion coefficients of the drugs were accounted for by the fact that the intracellular penetration of fotemustine was better than that of carmustine.

Adult↗
PubMed2002

Brain sodium channels mediate increases in brain "ouabain" and blood pressure in Dahl S rats.

Central infusions of benzamil prevent/reverse salt-induced hypertension in genetic models of salt-sensitive hypertension. Benzamil acts by blockade of ion--presumably sodium--channels. In the present study, we assessed in Dahl salt-sensitive (S) rats on high salt intake whether these channels mediate increases in brain "ouabain" and, thereby, hypertension. Intracerebroventricular (icv) infusions of a low (1.2 microg/kg per hour) or high (4.0 microg/kg per hour) dose of benzamil were given to Dahl S rats on high salt diet (1370 micromol Na+/g food) for 2 or 4 weeks. "Ouabain" content was measured using a specific enzyme-linked immunosorbent assay (ELISA). Systolic blood pressure (BP) in Dahl S rats on high salt for 4 weeks increased markedly (188+/-10 versus 128+/-4 mm Hg, n=8, P<0.05). Benzamil fully blocked this increase (131+/-7 mm Hg after the high dose of benzamil). Hypothalamic and pituitary "ouabain" increased significantly (22+/-7 versus 12+/-3 and 151+/-38 versus 69+/-6 ng/g tissue, respectively, P<0.05) in Dahl S rats on high salt versus regular salt diet for 2 weeks. Benzamil blocked these increases of brain "ouabain" to high salt intake. Similarly, high salt intake for 4 weeks increased hypothalamic (18+/-2 versus 13+/-1 ng/g tissue, P<0.05) and pituitary (183+/-30 versus 78+/-8 ng/g tissue, P<0.05) "ouabain." Benzamil also inhibited these increases of brain "ouabain." Both hypothalamic and pituitary "ouabain" showed significant positive correlations with BP. In contrast, high salt intake did not affect "ouabain" levels in the adrenal gland or plasma in Dahl S rats on high salt for either 2 or 4 weeks. These findings indicate that in Dahl S rats high salt intake only increases brain and not peripheral "ouabain" and that benzamil-blockable brain sodium channels mediate the increases in brain "ouabain" and the subsequent hypertension.

Adrenal Glands↗