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 271 records · Page 15Linked to original sources
PubMed1984

Cerebrovascular permeability and delivery of gentamicin to normal brain and experimental brain abscess in rats.

Antibiotics vary widely in their ability to penetrate the blood-brain barrier. In studies of 70 rats, the permeability of the normal blood-brain barrier to gentamicin was shown to be poor. In experimental brain abscesses, during the cerebritic stage of development, the penetration of intravenous antibiotics was increased compared to normal brain but was very inconsistent. Antibiotic delivery to brain abscess was not significantly altered with the administration of high-dose steroids, but the macrophage and glial response was markedly decreased with high-dose steroid therapy. Reversible osmotic blood-brain barrier modification with mannitol increased the delivery of gentamicin both to brain abscess and to the surrounding brain. It also resulted in more consistent tissue drug levels. The clinical implications of these studies suggest that, because of the inconsistent delivery of gentamicin to brain abscess, the therapeutic efficacy of medical management alone may be quite variable. This mode of therapy could possibly increase the efficacy of medical management of brain abscesses, especially in patients with multiple or surgically inaccessible brain abscesses.

Animals↗
PubMed1999

Brain free magnesium concentration is predictive of motor outcome following traumatic axonal brain injury in rats.

A number of studies have supported a role for brain free magnesium as an important secondary injury factor in the development of neurologic deficits following traumatic brain injury. Despite this, few studies have characterised free magnesium changes in diffuse models of brain injury relevant to clinical trauma, and none have critically examined the association between brain free magnesium concentration and degree of neurologic deficit following graded trauma. In the present study, a combination of nuclear magnetic resonance spectroscopy and rotarod motor function tests were used to characterise the relationship between brain free magnesium concentration and neurologic motor function following graded traumatic axonal brain injury in rats. Induction of moderate or severe impact-acceleration induced traumatic brain injury resulted in a profound decline (p < 0.01) in brain free magnesium concentration that persisted for a minimum of 4 days post-trauma in both injury groups. Posttraumatic rotarod deficits assessed on a daily basis after injury were linearly correlated with brain free magnesium concentration measured in the same animals immediately after the motor tests were performed (r = 0.87; p < 0.001). These results suggest that brain free magnesium declines following graded diffuse axonal brain injury and that the concentration of the ion after trauma may be a prognostic indicator of motor outcome following.

Animals↗
PubMed2000

AIT-082, a cognitive enhancer, is transported into brain by a nonsaturable influx mechanism and out of brain by a saturable efflux mechanism.

A fundamental feature of any drug designed to treat a disease of the central nervous system is the ability to cross the blood-brain barrier. Passage across the blood-brain barrier of AIT-082, a cognitive enhancer, was investigated in mice. [(14)C]AIT-082 crossed the blood-brain barrier in young male Swiss-Webster mice with a mean influx constant (K(i)) of 0.6 +/- 0.2 microl g(-1) min(-1). Furthermore, [(14)C]AIT-082 was transported into brain of both young and old male C57BL/6 mice with a K(i) of 0.35 +/- 0.06 and 0.33 +/- 0.02 microl g(-1) min(-1), respectively. There was no significant effect of age or strain on the movement of [(14)C]AIT-082 across the blood-brain barrier in mice. When 110- or 650-fold excess unlabeled AIT-082 was included in the injection solution, the K(i) was not significantly changed in either Swiss-Webster or C57BL/6 mice. This indicated that [(14)C]AIT-082 crossed the blood-brain barrier by a nonsaturable mechanism. The passage of AIT-082 into brain extracellular fluid was confirmed with capillary depletion and microdialysis. The efflux of [(14)C]AIT-082 from brain also was examined. After i.c.v. injection, [(14)C]AIT-082 levels in brain decreased over time with a t(1/2) of 20.0 +/- 1.0 min. Excess unlabeled AIT-082 (600-fold) increased the t(1/2) to 35.5 +/- 3.6 min. Together, these data indicate that AIT-082 moves into brain via a nonsaturable mechanism and is actively transported out of brain.

Age Factors↗
PubMed2002

Effects of repeated brain ischemia induced by rapid lower body negative pressure on brain water and Na+,K+-ATPase activity in rats.

BACKGROUND: It has been demonstrated that during +Gz exposure cerebral blood flow is significantly reduced resulting in brain ischemia. Animal centrifuge models are commonly used to investigate the mechanisms of +Gz-induced loss of consciousness (G-LOC) and their pathophysiological effects on the brain. These dynamic models are limited because we currently are unable to obtain accurate measures of membrane ion flux or single cell electrophysiological responses from animals under centrifugation. HYPOTHESIS: The aim of the present study was to develop a non-centrifuge animal model of short-term, repeatable and complete brain ischemia using a rodent lower body negative pressure (LBNP), and to investigate the effects of repeated complete brain ischemia induced by LBNP on brain Na+,K+-ATPase activity, Na+, K+ and water contents in rats. METHODS: Eight anesthetized rats were exposed randomly to LBNP of -2.67 kPa, -4.00 kPa, and -5.33 kPa, respectively, at the rate of -0.67 kPa x s(-1). The pressure rapidly returned to control level when EEG became isoelectric (flat). The mean arterial BP (MAP), EEG and ECG were recorded. Twenty-one rats were divided randomly into control, single LBNP exposure, and three LBNP exposures groups (n = 7 in each group). Brain samples were analyzed for Na+,K+-ATPase activity, Na+, K+ and water contents 1 h after single and three 2-min LBNP exposures (-4.00 kPa at a rate of 0.67 kPa x s(-1)), respectively. RESULTS: MAP decreased rapidly during LBNP exposure. The mean time to isoelectric EEG was 41.33 +/- 11.48, 30.67 +/- 3.88 and 25.67 +/- 3.45 s during -2.67, -4.00 and -5.33 kPa LBNP, respectively. Heart rate (HR) significantly decreased when EEG became isoelectric. MAP, HR and EEG rapidly returned after releasing LBNP. The brain Na+,K-ATPase activity decreased significantly after single LBNP exposure and decreased further after three LBNP exposures. The brain K+, Na+ and water contents increased significantly after three LBNP exposures. CONCLUSIONS: A rat model of short-term, repeatable brain ischemia was developed using rapid LBNP. Three -4.00 kPa LBNP exposures (2 min each) cause a significant reduction in brain Na+,K+-ATPase activity and brain edema in rats.

Adenosine Triphosphatases↗
PubMed1999

[Relationship between brain edema induced by freezing injury and concentration of Evan blues and cytosolic free calcium in brain tissues].

The authors studied the changes of Evan blues(EB) of brain tissues and concentration of cytosolic free calcium ([Ca2+]i), and relationship between them and water content of brain tissues following freezing brain edema in rats, to elucidate mechanism and type of brain edema induced by freezing injury. The results indicated that there were close positive relationship between water content and EB of brain tissues, and between [Ca2+]i and water content. We found that not only cytotoxic brain edema(intracellular edema) occurred but also occurred vasogenic brain edema(extracellular edema) followed by blood brain barrier breakdown after brain edema. Freezing brain edema is mixed brain edema.

Animals↗
PubMed1992

Therapeutic modulation of brain temperature: relevance to ischemic brain injury.

Hypothermia was first applied therapeutically as a local anesthetic and later was used to achieve organ protection during procedures necessitating circulatory interruption. Profound whole-body hypothermia, typically carried out in conjunction with extracorporeal bypass, has long been employed during cardiac and neurosurgical operative procedures. More recently, studies in small-animal experimental models of cerebral ischemia have provided persuasive evidence that even small decreases in brain temperature confer striking protection against ischemic neuronal injury. By contrast, small elevations of brain temperature during ischemia accelerate and extend pathologic changes in the brain and promote early disruption of the blood-brain barrier. Hypothermia retards the rate of high-energy phosphate depletion during ischemia and promotes postischemic metabolic recovery. More importantly, mild intraischemic hypothermia markedly attenuates the release of glutamate into the brain's extracellular space and significantly diminishes the release of dopamine. Similarly, the inhibition of calcium-calmodulin-dependent protein kinase II triggered by normothermic ischemia is prevented by hypothermia, as is the ischemia-induced translocation and inhibition of the key regulatory enzyme protein kinase C. Hypothermia also appears to facilitate the resynthesis of ubiquitin following ischemia. Studies of potential clinical importance have shown that moderate hypothermia is capable of attenuating ischemic damage even if instituted early in the postischemic period. In the setting of focal cerebral ischemia, moderate brain hypothermia reduces the infarct size (particularly in the setting of reversible middle cerebral artery occlusion); conversely, hyperthermia markedly increases the infarct volume. These studies underscore the importance of monitoring and regulating the brain temperature during experimental studies of cerebral ischemia to insure a consistent pathologic outcome and to avoid the false attribution of "pharmacoprotection" to drugs that reduce the body temperature. The measurement of brain temperature is now practicable in neurosurgical patients requiring invasive monitoring, and human studies have shown that cortical and cerebroventricular temperatures may exceed systemic temperatures. Mild to moderate decreases in brain temperature are neuroprotective in cerebral ischemia, while mild elevations of brain temperature are markedly deleterious in the setting of ischemia or injury. It is anticipated that controlled clinical trials of therapeutic brain temperature modulation will be undertaken over the next several years.

Body Temperature↗
PubMed1992

Differential permeability of the blood-brain barrier in experimental brain metastases produced by human neoplasms implanted into nude mice.

This study clarified whether and when the blood-brain barrier in experimental brain metastases is impaired by using hydrosoluble sodium fluorescein (MW 376) as a blood-brain barrier function indicator. Cells from eight human tumor lines (four melanomas, two breast carcinomas, one colon carcinoma, and one renal carcinoma) were inoculated into the internal carotid artery of nude mice. Brain metastases at different stages of development were sampled and the permeability of the blood-brain barrier around the metastases determined. Histologic examination showed two patterns of tumor growth. In the first, tumor cells formed isolated, well-defined nodules in the parenchyma of the brain. In lesions smaller than 0.2 mm2, the blood-brain barrier was intact. In the second, small diffuse nests of tumor cells were distributed throughout the brain parenchyma. The blood-brain barrier was intact until the small tumor cell colonies coalesced to form large tumor masses. These results suggest that the permeability of the blood-brain barrier varies among different experimental brain metastases and that its function is related to the growth pattern and size of the lesions.

Animals↗
PubMed1988

Delivery of human interferon-alpha to brain by transient osmotic blood-brain barrier modification in the rat.

Pharmacokinetic parameters of human lymphoblastoid interferon (IFN-alpha) delivery to normal rat brain were examined. IFN-alpha concentrations in brain parenchyma could only be detected 120 min after its intravascular administration, and were 0.003% per gram of the administered dose. The mean cerebrovascular permeability-surface area (permeability x surface area) product to IFN, 120 min after infusion, was 0.35 x 10(-6) sec-1, which is not significantly different from zero. Neither i.v. nor intracarotid IFN-alpha administration significantly affected delivery to brain. Intrathecal administration of IFN-alpha, via the cisterna magna, resulted in undetectable concentrations in brain tissue and plasma at 30 and 60 min. However, osmotic blood-brain barrier opening significantly increased IFN-alpha delivery to brain after its carotid administration. A maximum concentration of 0.18% per gram of the total administered dose was achieved at 120 min, and the cerebrovascular permeability-surface area was increased to 30.8 x 10(-6) sec-1. Intracerebral IFN-alpha concentrations did not decline significantly during the 240 min study. Osmotic blood-brain barrier opening increased the area under the brain concentration vs. time curve, measured between 30 and 240 min, from 0.012 x 10(6) U.min/g, in controls, to 1.24 x 10(6) U.min/g, at least 100-fold. This study indicates that osmotic blood-brain barrier opening significantly increases the delivery of IFN-alpha into brain, and that delivered remains within the brain for many hours.

Animals↗
PubMed1996

Brain efflux index as a novel method of analyzing efflux transport at the blood-brain barrier.

A brain efflux index method has been developed to characterize an efflux transport system for substrates from the cerebrum to the circulating blood across the blood-brain barrier. The brain efflux index value is defined as the relative amount of test drug effluxed from cerebrum compared with that of a reference compound, [14C]carboxylinulin, which has limited blood-brain barrier permeability. Microinjection of 0.2, 0.5 or 1.0 microliter into the parietal cortex area 2 region was found to be an appropriate procedure for obtaining a high recovery and for restricting the test drug and reference compound to the ipsilateral cerebrum. No significant increase in influx clearance of [14C]carboxylinulin into the brain was observed for the ipsilateral cerebrum after the sham microinjection compared with the contralateral cerebrum, which demonstrated that only limited physical damage is caused. Microinjection of [3H]H2O into the cerebrum devoid of cerebral blood flow yielded no elimination from the brain. Analysis based on a pharmacokinetic model demonstrated that the elimination of a highly permeable compound [3H]H2O from the brain was governed by cerebral blood flow. The apparent elimination rate constant (Kel) of [3H]3-O-methyl-D-glucose from the brain was determined as 0.129 +/- 0.014 (min-1) and was reduced significantly by a preinjection of excess cold 3-O-methyl-D-glucose and phloridzin, whereas no significant elimination was observed for L[3H]glucose. The efflux clearance of 3-O-methyl-D-glucose was calculated from the Kel value and the compound's distribution volume, the value being close to that of the influx clearance. These results demonstrate that the brain efflux index method is a useful technique for analyzing an efflux process from the brain across the blood-brain barrier involving a carrier-mediated transport system.

Animals↗
PubMed1979

Diet-induced changes in plasma amino acid pattern: effects on the brain uptake of large neutral amino acids, and on brain serotonin synthesis.

Tryptophan is transported into brain by a competitive carrier system it shares with such other large neutral amino acids as tyrosine, phenylalanine, leucine, isoleucine, and valine. Physiologic variations in the plasma neutral amino acid pattern (either as a change in plasma tryptophan, or in the plasma concentration of one or more of its competitors) directly alter this competitive process, and thereby modify the uptake of tryptophan into brain. Such variations in tryptophan uptake influence brain tryptophan levels, and thus serotonin synthesis. Food intake, by influencing directly the plasma levels of large neutral amino acids, ca- therefore predictably modify brain trypotphan uptake and serotonin synthesis. The effect of food intake on the competitive uptake of tryptophan into brain, and on brain tryptophan levels, has recently been shown not to be limited to this amino acid, but also holds for other large neutral amino acids, and for certain large neutral amino acid drugs (e.g., methyldopa). Hence, following a meal, the brain concentration of any large neutral amino acid appears to depend on how the food modifies the plasma level of that amino acid relative to the plasma concentrations of its competitors. The binding of tryptophan to albumin in blood has also been suggested to influence brain tryptophan uptake. However, this notion has not been sustained by the results of nutritional studies, in which meal-induced changes in brain tryptophan levels were readily shown not to be predicted by the alterations in the size of the serum free tryptophan pool. Taken together, these data affirm the importance of competitive transport in determining brain tryptophan uptake and levels, but question whether serum albumin binding and the size of the free tryptophan pool function physiologically to modulate brain tryptophan concentrations.

Animals↗
PubMed1997

Aluminum citrate is transported from brain into blood via the monocarboxylic acid transporter located at the blood-brain barrier.

Aluminum citrate transport across the blood-brain barrier was assessed in rats by in vivo microdialysis. Microdialysis probes were implanted in the jugular vein as well as the left and right frontal cortex. It was demonstrated previously (Allen et al., 1995), in this study, that the steady-state aluminum citrate brain-to-blood-ratio (BBr) is less than 1, suggesting the presence of a process other than diffusion. The addition of 2,4-dinitrophenol (10 microM) to the dialysate perfusing a microdialysis probe in the brain increased the steady-state aluminum citrate brain-to-blood-ratio to a value (1.14) not significantly different from 1, suggesting the presence of an active transporter that is blocked by the metabolic inhibitor. The addition of valproic and pyruvic acid, as putative and known substrates for the monocarboxylic acid transporter, respectively, to brain dialysate (10 and 100 mM) had different outcomes. Valproic acid was ineffective at either concentration, whereas pyruvic acid (100 mM) significantly increased the aluminum citrate brain-to-blood-ratio from 0.19 to 0.31. Pyruvic acid (1 M in the dialysate) increased the aluminum citrate brain-to-blood-ratio to a value not different from unity, suggesting competition between aluminum citrate and pyruvic acid for transport. The only energy-dependent, pyruvic acid-inhibitable transporter is the monocarboxylic acid transporter. Theoretical, pharmacokinetic modeling suggests that the transporter producing an aluminum citrate brain-to-blood-ratio less than 1 is predominantly located at the blood-brain barrier, rather than at neuronal or glial cell membranes. We propose that the monocarboxylic acid transporter at the blood-brain barrier maintains a steady-state aluminum citrate brain-to-blood-ratio much less than 1.

2,4-Dinitrophenol↗
PubMed2002

Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases: results and implications.

PURPOSE: A single-institution experience using primary stereotactic radiosurgery (SRS) alone in the management of newly diagnosed brain metastases was analyzed to identify the risk of symptomatic brain tumor recurrence (BTR) and neurologic deficit associated with such a treatment strategy. METHODS AND MATERIALS: Thirty-six patients were treated for newly diagnosed single/multiple brain metastases using SRS alone followed by planned observation. SRS minimum tumor dose ranged from 8 to 25 Gy (median: 20 Gy). Factors evaluated in analysis of treatment outcome included number of metastases, site of metastasis, primary tumor site, histology, extent of intracranial and extracranial disease, and interval to diagnosis of brain metastasis. RESULTS: Median and 1-year survival for the entire group was 9 months and 36%, respectively. BTR anywhere in the brain occurred in 47% (17/36) of patients. Forty-seven percent of BTR (8/17) recurred at the site of original metastasis; 35% (6/17) recurred at both original [corrected] and distant sites in the brain, and 18% (3/17) recurred at distant only [corrected] brain sites. Seventy-one percent (12/17) of the patients were symptomatic at the time of recurrence, and 59% (10/17) had an associated neurologic deficit. Multivariate analysis found that only the extent of disease was a predictor of BTR. Patients who had disease limited to the brain only had a BTR rate of 80% (8/10) vs. 35% (9/26) who had disease involving the brain, primary site, and/or other extracranial metastatic sites (p = 0.03). CONCLUSIONS: Use of primary SRS alone in this setting is associated with an increasingly significant risk of BTR with increasing survival time. In addition, the majority of such recurrences are symptomatic and associated with a neurologic deficit, a finding not analyzed in recently reported experiences withholding whole brain radiation therapy as part of the primary treatment of brain metastasis.

Adult↗
PubMed1999

Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases.

PURPOSE: Multiple brain metastases are a common health problem, frequently diagnosed in patients with cancer. The prognosis, even after treatment with whole brain radiation therapy (WBRT), is poor with average expected survivals less than 6 months. Retrospective series of stereotactic radiosurgery have shown local control and survival benefits in case series of patients with solitary brain metastases. We hypothesized that radiosurgery plus WBRT would provide improved local brain tumor control over WBRT alone in patients with two to four brain metastases. METHODS: Patients with two to four brain metastases (all < or =25 mm diameter and known primary tumor type) were randomized to initial brain tumor management with WBRT alone (30 Gy in 12 fractions) or WBRT plus radiosurgery. Extent of extracranial cancer, tumor diameters on MRI scan, and functional status were recorded before and after initial care. RESULTS: The study was stopped at an interim evaluation at 60% accrual. Twenty-seven patients were randomized (14 to WBRT alone and 13 to WBRT plus radiosurgery). The groups were well matched to age, sex, tumor type, number of tumors, and extent of extracranial disease. The rate of local failure at 1 year was 100% after WBRT alone but only 8% in patients who had boost radiosurgery. The median time to local failure was 6 months after WBRT alone (95% confidence interval [CI], 3.5-8.5) in comparison to 36 months (95% CI, 15.6-57) after WBRT plus radiosurgery (p = 0.0005). The median time to any brain failure was improved in the radiosurgery group (p = 0.002). Tumor control did not depend on histology (p = 0.85), number of initial brain metastases (p = 0.25), or extent of extracranial disease (p = 0.26). Patients who received WBRT alone lived a median of 7.5 months, while those who received WBRT plus radiosurgery lived 11 months (p = 0.22). Survival did not depend on histology or number of tumors, but was related to extent of extracranial disease (p = 0.02). There was no neurologic or systemic morbidity related to stereotactic radiosurgery. CONCLUSIONS: Combined WBRT and radiosurgery for patients with two to four brain metastases significantly improves control of brain disease. WBRT alone does not provide lasting and effective care for most patients.

Adult↗
PubMed1984

Effects of aspartame and glucose administration on brain and plasma levels of large neutral amino acids and brain 5-hydroxyindoles.

Administration of the artificial sweetener aspartame (L-aspartylphenylalanylmethyl ester; 200 mg/kg) by gavage to rats caused large increments in brain and plasma levels of phenylalanine and its product tyrosine. Glucose administration (3 g/kg, by gavage, a dose sufficient to cause insulin-mediated reductions in plasma levels of the large neutral amino acids leucine, isoleucine, and valine) also elevated brain phenylalanine and tyrosine, and enhanced the increments caused by the aspartame, nearly doubling the rise in brain phenylalanine. Each animal's brain phenylalanine or tyrosine levels were highly correlated (r = 0.97 and 0.99, respectively) with its plasma phenylalanine or tyrosine ratios, affirming that aspartame's effects on the brain amino acids result from the changes it produces in plasma composition. As described previously, glucose consumption increased brain tryptophan levels, and consequently, brain levels of the 5-hydroxyindoles serotonin and 5-hydroxyindoleacetic acid. Aspartame alone had no effect on these compounds but completely blocked the changes in 5-hydroxyindoles caused by glucose. Each animal's brain level of tryptophan (r = 0.89) and 5-hydroxyindoles (r = 0.74) was also significantly correlated with its plasma tryptophan ratio, affirming that the effects of glucose or aspartame on these brain constituents also result from the changes they produce in plasma composition. The aspartame-glucose combination also reduced brain levels of leucine, isoleucine, and valine to a significantly greater extent than aspartame or glucose alone. These observations indicate that high aspartame doses can generate major neurochemical changes in rats, especially when consumed along with carbohydrate-containing foods. However, they should not in any way be interpreted as demonstrating that aspartame significantly affects the human brain.

Amino Acids↗
PubMed2000

Cocaine and cocaethylene binding to normal human brain and Alzheimer disease brain.

The binding of cocaine and cocaethylene to homogenates of both normal whole brain and whole brain with Alzheimer disease patients (Alzheimer brain) was investigated in vitro using equilibrium dialysis of the unlabelled drugs at 4 degrees C. Two binders of cocaine were characterized in normal brain (binder 1: Ka, 5.73 x 10(3) L/mol; Bo, 7.44 x 10(-5) mol/L) (binder 2: Ka, 1.54 x 10(3) L/mol; Bo, 2.50 x 10(-4) mol/L) and in Alzheimer brain (binder 1: Ka, 3.08 x 10(2) L/mol; Bo, 6.66 x 10(-4) mol/L) (binder 2: Ka, 8.74 x 10(1) L/mol; Bo, 4.30 x 10(-3) mol/L). For cocaethylene three binders were noted in normal brain (binder 1: Ka, 3.23 x 10(3) L/mol; Bo, 1.22 x 10(-4) mol/L) (binder 2: Ka, 3.10 x 10(3) L/mol; Bo, 2.01 x 10(-4) mol/L) (binder 3: Ka, 1.63 x 10(3) L/mol; Bo, 3.59 x 10(-4) mol/L) and two binders in Alzheimer brain (binder 1: Ka, 5.18 x 10(3) L/mol; Bo, 3.06 x 10(-5) mol/L) (binder 2: Ka, 3.36 x 10(3) L/mol; Bo, 7.75 x 10(-5) mol/L). The binding of cocaine to normal brain was much stronger than to Alzheimer brain (ten- to 100-fold), whereas the binding of cocaethylene was similar in normal and Alzheimer brain. Cocaine and cocaethylene binding to human brain was compared with cocaine and cocaethylene binding to other human tissues previously studied by this laboratory.

Aged↗
PubMed1981

Identification with a monoclonal antibody of a phylogenetically conserved brain-specific determinant on a 130,000 molecular weight glycoprotein of human brain.

Human brain glycoproteins depleted of Thy-1 antigen were used to immunise Balb/c mice for monoclonal antibody production. The F3-87-8 antibody described in this paper interacts with a determinant present in large amounts on all human brain subregions studied (cerebral cortical grey matter, white matter, caudate, thalamus, dentate nucleus, putamen, cerebellar cortex) but absent from all other tissues examined (liver, heart, kidney, spleen, thymus, lymph node, erythrocyte, adrenal gland, and peripheral nerve). The determinant is conserved in mammalian evolution, as the brains of the rat and dog have amounts equal to that found in human brain. Balb/c mouse brain has approximately one-third as much antigen activity as these other mammalian brains, whereas brains of the frog and chicken have no detectable antigenic activity. Developmental studies showed that 16-week human foetal brain and neonatal dog brain had little or no antigen activity, indicating a dramatic increase in the amount of the determinant with brain maturation. Biochemical studies showed that the F3-87-8-bearing molecule was a major sialoglycoprotein of human brain with an apparent molecular weight of 130,000. It was shown by immunofluorescence to be particularly localised in what appeared to be fibre tracts in the thalamus and basal ganglia, and in the dentate nucleus, although all regions including grey matter were stained.

Animals↗
PubMed1985

Effects of conditioned running on plasma, liver and brain tryptophan and on brain 5-hydroxytryptamine metabolism of the rat.

An investigation was made into the effects of conditioned running (1 h and 2 h at 20 m min-1), which accelerates lipolysis, on the concentrations of tryptophan (Trp) in plasma, liver and brain and on 5-hydroxytrptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in brain. Running caused time-dependent increases in plasma free Trp and brain Trp of the rat, leading to increased brain 5-HT turnover as revealed by higher amounts of its metabolite, 5-HIAA. The ratio of brain Trp to plasma free Trp was decreased after 2 h of running. Liver Trp content rose only after 3 h of running, while liver unesterified fatty acid (UFA) concentrations remained unmodified. A comparison between food deprivation and running (both of which promote lipolysis) was performed. Running for 2 h affected to the same extent plasma Trp disposition when compared with 24 h food deprivation. Nevertheless, the ratio of brain Trp to plasma free Trp was decreased in the food-deprived rats, when compared to the runners. Nicotinic acid, which inhibits fat catabolism, completely abolished the plasma UFA increase induced by 1 h of running. The drug did not affect plasma free Trp, brain Trp, 5-HT or 5-HIAA but enhanced plasma total Trp level. Naloxone, an opiate antagonist, which decreased running-induced lipolysis, did not alter plasma Trp disposition. Desipramine, an antidepressant compound, affected only peripheral Trp concentrations of the runners. Plasma free and total Trp concentrations were increased in desipramine-treated runners, compared with saline-treated runners. In addition, desipramine increased the ratio of brain Trp to plasma free Trp of the runners. Brain 5-HT and 5-HIAA were increased in both desipramine-treated controls and runners. 9 The results suggest that running, which like food deprivatiQn accelerates lipolysis, increases brain Trp content and then 5-HT turnover. Comparison of these two physiological situations suggests that effectiveness of brain Trp entry is much more altered by fasting.

Animals↗
PubMed2002

Abnormal regional cerebral blood flow on 99mTc ECD brain SPECT in patients with primary Sjögren's syndrome and normal findings on brain magnetic resonance imaging.

OBJECTIVE: Technetium-99m ethyl cysteinate dimer (99mTc ECD) single photon emission computed tomography (SPECT) of the brain was used to detect abnormal regional cerebral blood flow (rCBF) in patients with primary Sjögren's syndrome (pSS) and normal findings on brain magnetic resonance imaging (MRI). METHODS: (99m)Tc ECD brain SPECT was performed to detect brain lesions showing hypoperfusion in 32 female patients with pSS and definite neuropsychiatric symptoms or signs. Seventeen female patients with pSS without neuropsychiatric symptoms and signs were included as a control group for comparison. All of the 49 patients with pSS had normal findings on brain MRI. RESULTS: 99mTc ECD brain SPECT showed brain regions with hypoperfusion in 18 (56.3%) of the 32 patients, and parietal lobes were the most common areas with such lesions. By contrast, 99mTc ECD brain SPECT showed brain regions with hypoperfusion in only three (17.6%) of the 17 patients with pSS without neuropsychiatric symptoms or signs. CONCLUSION: This study suggests that 99mTc ECD SPECT is a sensitive tool for detecting regions of hypoperfusion in the brains of patients with pSS and neuropsychiatric symptoms or signs and normal findings on brain MRI. However, a review of the literature showed that the (99m)Tc ECD SPECT findings in patients with pSS were non-specific.

Adult↗