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At least 739 records · Page 41Linked to original sources
PubMed2005

Endotoxin exposure alters brain and liver effects of fumonisin B1 in BALB/c mice: implication of blood brain barrier.

Fumonisin B(1) (FB(1)), a mycotoxin produced by Fusarium verticillioides, causes equine leukoencephalomalacia and hepatotoxicity. We studied the modulation of FB(1) toxicity in brain and liver of female BALB/c mice after endotoxin administration to compromise the blood-brain barrier (BBB) integrity. Mice were injected intraperitoneally with saline or 3 mg/kg of lipopolysaccharide (LPS) followed 2 h later by either a single or three daily subcutaneous doses of 2.25 mg/kg of FB(1). After 4h of a single FB(1) injection the inhibition of sphingolipid biosynthesis occurred in liver. Circulating alanine aminotransferase increased by LPS alone at this time. In brain LPS triggered inflammation increasing the expression of tumor necrosis factor (TNF) alpha, interferon (IFN) gamma, interleukin (IL)-1beta, IL-6, and IL-12; no effect of FB(1) was observed. In liver LPS+FB(1) attenuated the expression TNFalpha and IFNgamma compared to LPS alone. One day after the 3-day FB(1) treatment the biosynthesis of sphingolipids was markedly reduced in brain and liver and it was further inhibited when LPS was given before FB(1). FB(1) induced hepatotoxicity, as measured by circulating liver enzymes, was reduced after the combined treatment with LPS+FB(1) compared to FB(1) alone. FB(1) decreased the LPS-induced brain expression of IFNgamma and IL-1beta, whereas the expression of IL-6 and IL-12 was augmented. In liver FB(1) also reduced the expression of IL-1beta and IFNgamma compared to LPS alone. Results indicated that endotoxemia concurrent with FB(1) intoxication facilitated the permeability of fumonisin in brain indicated by increased accumulation of sphinganine and endotoxin modified the effects of FB(1) in both brain and liver.

Animals↗
PubMed2007

Effect of prophylactic hyperbaric oxygen treatment for radiation-induced brain injury after stereotactic radiosurgery of brain metastases.

PURPOSE: The purpose of the present study was to evaluate the prophylactic effect of hyperbaric oxygen (HBO) therapy for radiation-induced brain injury in patients with brain metastasis treated with stereotactic radiosurgery (SRS). METHODS AND MATERIALS: The data of 78 patients presenting with 101 brain metastases treated with SRS between October 1994 and September 2003 were retrospectively analyzed. A total of 32 patients with 47 brain metastases were treated with prophylactic HBO (HBO group), which included all 21 patients who underwent subsequent or prior radiotherapy and 11 patients with common predictors of longer survival, such as inactive extracranial tumors and younger age. The other 46 patients with 54 brain metastases did not undergo HBO (non-HBO group). The radiation-induced brain injuries were divided into two categories, white matter injury (WMI) and radiation necrosis (RN), on the basis of imaging findings. RESULTS: The radiation-induced brain injury occurred in 5 lesions (11%) in the HBO group (2 WMIs and 3 RNs) and in 11 (20%) in the non-HBO group (9 WMIs and 2 RNs). The WMI was less frequent for the HBO group than for the non-HBO group (p = 0.05), although multivariate analysis by logistic regression showed that WMI was not significantly correlated with HBO (p = 0.07). The 1-year actuarial probability of WMI was significantly better for the HBO group (2%) than for the non-HBO group (36%) (p < 0.05). CONCLUSIONS: The present study showed a potential value of prophylactic HBO for the radiation-induced WMIs, which justifies further evaluation to confirm its definite benefit.

Adult↗
PubMed2000

Functional brain imaging as a looking-glass into the degraded brain: reviewing evidence from Alzheimer disease in relation to normal aging.

Research on the real-time relationship between brain activity and mental performance is intense. However, relatively few studies have been devoted to patients with different diseases or lesions. Such studies may cast light on certain aspects of brain activity, such as plasticity. This review summarizes studies on Alzheimer's disease (AD) patients where the techniques to map brain activity in relation to mental performance have been utilized. Research findings suggest, that there is a spectrum of changes in AD patients that is distinct from that seen in healthy aging. These changes include: (i) loss of activated regions, (ii) reduced activation possibly due to brain degeneration typical of AD, (iii) the emergence of newly activated regions in order to compensate for minor brain deterioration (e.g., an enlargement of activated regions sometimes manifested as an increased bilaterality or a hemispheric shift of activation, and dedifferentiation), (iv) decreased level of activation, and (v) no change at all, which may occur in easy tasks or tasks that do not involve regions exposed to brain atrophy. In conclusion, the pattern of activation in AD depends on interactions between the clinical stage of patients, and the pattern of brain degeneration, as well as the task difficulty and specific networks necessary for solving the task.

Aged↗
PubMed1998

Affinity-purification and characterization of caveolins from the brain: differential expression of caveolin-1, -2, and -3 in brain endothelial and astroglial cell types.

Caveolins 1, 2 and 3 are the principal protein components of caveolae organelles. It has been proposed that caveolae play a vital role in a number of essential cellular functions including signal transduction, lipid metabolism, cellular growth control and apoptotic cell death. Thus, a major focus of caveolae-related research has been the identification of novel caveolins, caveolae-associated proteins and caveolin-interacting proteins. However, virtually nothing is known about the expression of caveolins in brain tissue. Here, we report the purification and characterization of caveolins from brain tissue under non-denaturing conditions. As a final step in the purification, we employed immuno-affinity chromatography using rabbit polyclonal anti-caveolin IgG and specific elution at alkaline pH. The final purified brain caveolin fractions contained three bands with molecular masses of 52 kDa, 24 kDa and 22 kDa as visualized by silver staining. Sequencing by ion trap mass spectrometry directly identified the major 24-kDa component of this hetero-oligomeric complex as caveolin 1. Further immunocyto- and histochemical analyses demonstrated that caveolin 1 was primarily expressed in brain endothelial cells. Caveolins 2 and 3 were also detected in purified caveolin fractions and brain cells. The cellular distribution of caveolin 2 was similar to that of caveolin 1. In striking contrast, caveolin 3 was predominantly expressed in brain astroglial cells. This finding was surprising as our previous studies have suggested that the expression of caveolin 3 is confined to striated (cardiac and skeletal) and smooth muscle cells. Electron-microscopic analysis revealed that astrocytes possess numerous caveolar invaginations of the plasma membrane. Our results provide the first biochemical and histochemical evidence that caveolins 1, 2 and 3 are expressed in brain endothelial and astroglial cells.

Amino Acid Sequence↗
PubMed1999

Induction of blood-brain barrier properties in immortalized bovine brain endothelial cells by astrocytic factors.

The blood-brain barrier (B-BB) protects the free passage of substances into the brain and maintains the homeostasis of the central nervous system. It is commonly accepted that astrocytes surrounding brain endothelial cells influence the B-BB formation and the exhibition of B-BB function of capillaries. To begin the in vitro study on the B-BB, it is essential to obtain a homogenous and sufficient supply of brain endothelial cells as well as astrocytes. We thus immortalized the bovine brain endothelial cell (BBEC) by transfection of the SV40 large T antigen and obtained a single clone, t-BBEC-117, which retained the brain endothelial cell phenotype. Astrocyte in co-culture was found to tighten the intercellular contacts of the immortal cells resulting in a reduced L-glucose permeability, and its conditioned medium (CM) augmented a B-BB phenotype, alkaline phosphatase (ALP) activity. Among known astrocytic factors, only fibroblast growth factor-basic (bFGF) could mimic the actions of astrocytes as measured by L-glucose permeability and ALP activity. Moreover, anti-bFGF antibody canceled 90% of ALP activation by astrocyte CM. Basic FGF, however, failed to induce other B-BB phenotypes such as the expressions of multidrug resistance (mdr) and glucose transporter (GLUT-1) genes. These data suggest that bFGF is one of the most plausible astrocytic factors to induce the B-BB properties of immortal brain endothelial cells together with some unknown factors in the astrocyte CM.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Effect of ionizing radiation on the human brain: white matter and gray matter T1 in pediatric brain tumor patients treated with conformal radiation therapy.

OBJECTIVE: To test a hypothesis that fractionated radiation therapy (RT) to less than 60 Gy is associated with a dose-related change in the spin-lattice relaxation time (T1) of normal brain tissue, and that such changes are detectable by quantitative MRI (qMRI). METHODS: Each of 21 patients received a qMRI examination before treatment, and at several time points during and after RT. A map of brain T1 was calculated and segmented into white matter and gray matter at each time point. The RT isodose contours were then superimposed upon the T1 map, and changes in brain tissue T1 were analyzed as a function of radiation dose and time following treatment. We used a mixed-model analysis to analyze the longitudinal trend in brain T1 from the start of RT to 1 year later. Predictive factors evaluated included patient age and clinical variables, such as RT dose, time since treatment, and the use of an imaging contrast agent. RESULTS: In white matter (WM), a dose level of greater than 20 Gy was associated with a dose-dependent decrease in T1 over time, which became significant about 3 months following treatment. In gray matter (GM), there was no significant change in T1 over time, as a function of RT doses < 60 Gy. However, GM in close proximity to the tumor had an inherently lower T1 before therapy. Neither use of a contrast agent nor a combination of chemotherapy plus steroids had a significant effect on brain T1. CONCLUSION: Results suggest that T1 mapping may be sensitive to radiation-related changes in human brain tissue T1. WM T1 appears to be unaffected by RT at doses less than approximately 20 Gy; GM T1 does not change at doses less than 60 Gy. However, tumor appears to have an effect upon adjacent GM, even before treatment. Conformal RT may offer a substantial benefit to the patient, by minimizing the volume of normal brain exposed to greater than 20 Gy.

Adolescent↗
PubMed2000

Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05.

PURPOSE: To determine the maximum tolerated dose of single fraction radiosurgery in patients with recurrent previously irradiated primary brain tumors and brain metastases. METHODS AND MATERIALS: Adults with cerebral or cerebellar solitary non-brainstem tumors </= 40 mm in maximum diameter were eligible. Initial radiosurgical doses were 18 Gy for tumors </= 20 mm, 15 Gy for those 21-30 mm, and 12 Gy for those 31-40 mm in maximum diameter. Dose was prescribed to the 50-90% isodose line. Doses were escalated in 3 Gy increments providing the incidence of irreversible grade 3 (severe) or any grade 4 (life threatening) or grade 5 (fatal) Radiation Therapy Oncology Group (RTOG) central nervous system (CNS) toxicity (unacceptable CNS toxicity) was < 20% within 3 months of radiosurgery. Chronic CNS toxicity was also assessed. RESULTS: Between 1990-1994, 156 analyzable patients were entered, 36% of whom had recurrent primary brain tumors (median prior dose 60 Gy) and 64% recurrent brain metastases (median prior dose 30 Gy). The maximum tolerated doses were 24 Gy, 18 Gy, and 15 Gy for tumors </= 20 mm, 21-30 mm, and 31-40 mm in maximum diameter, respectively. However, for tumors < 20 mm, investigators' reluctance to escalate to 27 Gy, rather than excessive toxicity, determined the maximum tolerated dose. In a multivariate analysis, maximum tumor diameter was one variable associated with a significantly increased risk of grade 3, 4, or 5 neurotoxicity. Tumors 21-40 mm were 7.3 to 16 times more likely to develop grade 3-5 neurotoxicity compared to tumors < 20 mm. Other variables significantly associated with grade 3-5 neurotoxicity were tumor dose and Karnofsky Performance Status. The actuarial incidence of radionecrosis was 5%, 8%, 9%, and 11% at 6, 12, 18, and 24 months following radiosurgery, respectively. Forty-eight percent of patients developed tumor progression within the radiosurgical target volume. A multivariate analysis revealed two variables that were significantly associated with an increased risk of local progression, i.e. progression in the radiosurgical target volume. Patients with primary brain tumors (versus brain metastases) had a 2.85 greater risk of local progression. Those treated on a linear accelerator (versus the Gamma Knife) had a 2.84 greater risk of local progression. Of note, 61 % of Gamma Knife treated patients had recurrent primary brain tumors compared to 30% of patients treated with a linear accelerator. CONCLUSIONS: The maximum tolerated doses of single fraction radiosurgery were defined for this population of patients as 24 Gy, 18 Gy, and 15 Gy for tumors </= 20 mm, 21-30 mm, and 31-40 mm in maximum diameter. Unacceptable CNS toxicity was more likely in patients with larger tumors, whereas local tumor control was most dependent on the type of recurrent tumor and the treatment unit.

Adult↗
PubMedDate not supplied

The role of the blood-brain barrier transporter PTS-1 in regulating concentrations of methionine enkephalin in blood and brain.

Previous studies have suggested that peptide transport system (PTS)-1, a saturable efflux system from brain to blood, regulates the concentration in the brain of methionine enkephalin (Met-Enk), an opiate peptide related to the drinking of ethanol in mice. We determined the relationship of PTS-1 to concentrations of immunoreactive Met-Enk in plasma and whole brain in eight randomly selected strains of mice. An active PTS-1 system could be demonstrated in five of the eight strains. In those five strains, faster efflux rates due to PTS-1 correlated with higher concentrations of Met-Enk in brain and plasma. These concentrations of Met-Enk in brain and plasma were positively correlated in the five strains in which PTS-1 was demonstrable and were inversely correlated in the three strains in which PTS-1 was not demonstrable. The results are consistent with previous observations indicating that the chronic level of brain Met-Enk can set the level of activity of PTS-1 and that, once set, PTS-1 can play a major role in determining the concentrations of Met-Enk in brain and blood.

Animals↗
PubMed2000

Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption.

Mice with a genetic disruption (knockout) of the multiple drug resistance (Mdr1a) gene were used to examine the effect of the absence of the drug-transporting P-glycoprotein at the blood-brain barrier on the uptake of amitriptyline (AMI) and fluoxetine (FLU) and their metabolites into the brain. One hour after intraperitoneal injection of AMI or FLU, knockout (-/-) and wild-type (+/+) mice were sacrificed and drug concentrations of brain, kidney, liver, testis, and plasma were measured. The plasma concentrations of the AMI metabolites and the brain:spleen ratios of AMI, nortriptyline (NOR), 10-OH-AMI and 10-OH-NOR were significantly higher in the -/- mice, demonstrating that AMI and its metabolites are substrates of the P-glycoprotein and that mdr1a activity at the level of the blood-brain barrier reduces the penetration of these substances into the brain. In contrast, tissue distributions of FLU and its metabolites among the various tissues tested were indistinguishable between groups. The herein reported differences in brain penetration of antidepressant drugs depending on the presence of the mdr1a gene may offer an explanation for differences in the treatment response at a given plasma concentration. Moreover, individual differences in mdr1 gene activity may account for variable response patterns at different episodes and development of therapy resistance.

ATP Binding Cassette Transporter, Subfamily B↗
PubMedDate not supplied

Epidermal growth factor radiopharmaceuticals: 111In chelation, conjugation to a blood-brain barrier delivery vector via a biotin-polyethylene linker, pharmacokinetics, and in vivo imaging of experimental brain tumors.

Epidermal growth factor (EGF) is a potential peptide radiopharmaceutical for detection of brain tumors, because many human gliomas overexpress the EGF receptor (EGFR). The transport of EGF to the brain, however, is restricted by the blood-brain barrier (BBB). The purpose of the present study was to develop a vector-mediated brain delivery system for radiolabeled EGF. Human EGF was monobiotinylated with NHS-PEG3400-biotin, where NHS is N-hydroxysuccinimide and PEG3400 is poly(ethylene glycol) of 3400 Da molecular mass. EGF-PEG3400-biotin was radiolabeled with either 125I or 111In through the metal chelator, diethylenetriaminepentaacetic acid (DTPA). The radiolabeled EGF was then conjugated to a BBB delivery vector comprised of a complex of the OX26 monoclonal antibody (MAb) to the rat transferrin receptor, which was coupled to streptavidin (SA). Following intravenous injection in rats, the 125I conjugate was rapidly degraded in vivo, while the 111In conjugate was metabolically stable. The brain delivery of [111In]DTPA-EGF-PEG3400-biotin was enabled by conjugation with OX26/SA and was optimized by co-injection of unlabeled EGF to saturate EGF receptors in the liver. The specific binding of the [111In]DTPA-EGF-PEG3400-biotin conjugated to OX26/SA to the EGF receptor was confirmed in C6 rat glioma cells, which had been transfected with a gene encoding for the human EGF receptor under the regulation of a dexamethasone-inducible promoter. In vivo studies of C6-EGFR experimental tumors in Fischer 344 rats demonstrated successful brain imaging only when the peptide radiopharmaceutical was conjugated to the BBB delivery system, although the C6-EGFR tumors did not express EGFR in vivo. In conclusion, these studies describe the molecular formulation of a peptide radiopharmaceutical that can be used for imaging brain tumors behind the BBB.

Animals↗
PubMed2002

Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer's disease brain and damage the blood-brain barrier.

BACKGROUND: Monocyte/macrophages are known to infiltrate the brain of patients with HIV-1 encephalitis (HIVE). In Alzheimer's disease brain, the origin of activated microglia has not been determined. MATERIALS AND METHODS: We employed the antigen retrieval technique, immunocytochemistry, immunofluorescense, and confocal microscopy to identify macrophages and microglia in relation to amyloid-beta plaques and the blood-brain barrier in autopsy brain tissues from patients with Alzheimer's disease (AD) and HIVE. RESULTS: In both conditions, cyclooxygenase-2 positive macrophages and, to a lesser degree, T and B cells infiltrate brain perivascular spaces and neuropil. The macrophages are distinguishable from ramified microglia, and decorate the vessels at the sites of apparent of endothelial tight junction protein ZO-1 disruption. The macrophages also infiltrate amyloid-beta plaques, display intracellular amyloid-beta and are surrounded by amyloid-beta-free lacunae. Furthermore, the macrophages partially encircle the walls of amyloid-beta-containing vessels in amyloid angiopathy, and exhibit intracellular amyloid-beta but not paracellular lacunae. Significantly larger zones of fibrinogen leakage surround the microvessels in HIVE brain tissues compared with AD tissues (P = 0.034), and AD tissues have significantly greater leakage than control tissues (P = 0.0339). The AD group differs from a normal control age-matched group with respect to both the area occupied by CD68 (P = 0.03) and cyclooxygenase-2 immunoreactive cells (P = 0.004). CONCLUSION: In both HIVE and AD, blood-borne activated monocyte/macrophages and lymphocytes appear to migrate through a disrupted blood-brain barrier. The lacunae around macrophages in amyloid-beta plaques but not in vessel walls are consistent with the ability of macrophages to phagocytize and clear amyloid-beta deposits in vitro.

AIDS Dementia Complex↗
PubMed2002

Brain glucose levels are elevated in chronically hyperglycemic diabetic rats: no evidence for protective adaptation by the blood brain barrier.

Recent evidence suggests that brain function may be impaired by prolonged elevations of blood glucose, such as those that occur in poorly controlled diabetes. However, little is known about the effects of such hyperglycemia on brain metabolic substrate levels. Using microdialysis in awake, freely moving rats, we directly measured brain extracellular fluid (ECF) glucose, lactate, and beta-hydroxybutyrate (betaOHB) levels in the inferior colliculus in chronically hyperglycemic BB/wor diabetic rats and in control (Sprague-Dawley) rats during euglycemia and acute hyperglycemia. The ECF:plasma glucose ratio (0.27 to 0.34) was remarkably similar in animals from all 3 groups, resulting in proportional elevations of brain ECF glucose in the hyperglycemic groups. Moreover, brain ECF levels of lactate and beta-OHB were increased in diabetic (DM) rats as compared with controls. Our results suggest that no significant protective adaptation of the blood brain barrier (BBB) transfer of glucose occurs in chronic hyperglycemia. Hence, brain tissue may be chronically exposed to markedly elevated levels of glucose and other metabolic fuels during poorly controlled diabetes, and therefore it may be subject to the same long-term adverse effects of hyperglycemia seen in peripheral tissues.

3-Hydroxybutyric Acid↗
PubMed1985

[Heterogenous immune reactivity in brain tumors: results of cellular immunity in relation to brain tissue antigens].

In brain tumors and other neurological diseases cell-mediated immune reactions to fetal brain tissue antigens (FBA), normal tissue antigen of adult brain (NTA) and tumor-associated antigens of different brain tumors (TAA) have been analysed. The detection of sensitized lymphocytes using the MEM-(macrophage-electrophoretic-mobility-) test revealed general tumor-related results applying the FBA, in some extent a cross reactivity and partly no kind of reaction. A phase-specific reactivity to normal brain antigens could not be found, only cases of multiple sclerosis produced restrictive results employing the NTA. By testing tumor-associated brain antigens different reaction types were seen: The common TAA caused a tumor-characteristic reaction; the histo-specific TAA predominantly presented a organotypic form of reaction, confined a histo-specific reaction pattern; in some cases there were found inadequate, non-corresponding reactions as well as unreactivity. With regard to different types of reaction the problems of heterogeneity of the brain tumors and the cellular immune response--i.e. a heterogeneity of 1. or 2. order--were discussed including further factors concerning several special conditions in the nervous system.

Antigens, Neoplasm↗
PubMed1990

Transcranial Doppler monitoring in severe brain damage: relationships between intracranial haemodynamics, brain dysfunction and outcome.

Transcranial Doppler (TCD) monitoring in the middle cerebral (MCA) and common carotid arteries (CCA) was studied in 105 comatose patients with severe brain damage. TCD-measured velocity waveforms in the MCA were evaluated in relation to loss of cerebral function as assessed by EEG and compressed spectral arrays, loss of brain stem function as measured by somatosensory and auditory evoked potentials, loss of all brain function and the clinical outcome. The velocity waveforms exhibited six patterns: continuous forward flow (FF); diastolic no flow (NF); diastolic reverse flow with (RF) or without (DRF) diastolic FF; brief systolic FF (SFF); and undetectable (U). In the 58 fatal cases, the appearance of RF/DRF or SFF in the MCA more often preceded loss of brain stem function than loss of cerebral function. A U pattern in the MCA, which was confirmed by loss of FF in the CCA, was correlated with loss of brain stem function. Only one of the 47 survivors showed DRF in the MCA. No patients in whom SFF or U was observed in the MCA survived. Therefore the presence of these patterns is reliably predictive of brain death. Intracranial diastolic reverse flow (DRF), however, indicates imminent loss of brain function and the need for prompt resuscitative measures.

Adolescent↗
PubMedDate not supplied

Brain reactive antibodies and the blood-brain barrier: observations in aging rodents and the effects of peripheral kainic acid.

This study was initiated to confirm the existence of brain-reactive autoantibodies and to determine if such antibodies have higher affinity for brain regions especially affected in Alzheimer's disease. Serum collected from 90, 300, and 600 day old mice was incubated against brain tissues from these same mice, followed by incubation with fluorescently tagged rabbit antimouse IgG. No antibodies were present in the youngest serum, but considerable antibodies were present at 300 and, especially, at 600 days. Such antibodies were present in the blood vessels, but not in the brains of older animals. These antibodies, applied exogenously, labeled cells equally in all three ages of brains including most cortical and many other neurons, indicating that they are not neurotransmitter specific. In a further study, kainic acid or saline was administered peripherally to 15-month old rats. Kainic acid damaged the blood brain barrier and allowed the CNS entry of brain-reactive antibodies, especially into the subregions of hippocampus most damaged in Alzheimer's.

Aging↗
PubMed2006

Autoradiographic analysis of mouse brain kinin B1 and B2 receptors after closed head trauma and ability of Anatibant mesylate to cross the blood-brain barrier.

The potent non-peptide B2 receptor (R) antagonist, Anatibant mesylate (Ms) (LF 16-0687 Ms), reduces brain edema and improves neurological function recovery in various focal and diffuse models of traumatic brain injury in rodents. In the present study, alteration of kinin B1 and B2R after closed head trauma (CHT) and in vivo binding properties of Anatibant Ms (3 mg/kg, s.c.) injected 30 min after CHT were studied in mice by autoradiography using the radioligands [125I]HPP-Hoe 140 (B2R), and [125I]HPP-des-Arg10-Hoe 140 (B1R). Whereas B1R is barely detected in most brain regions, B2R is extensively distributed, displaying the highest densities in the hindbrain. CHT was associated with a slight increase of B1R and a decrease of B2R (10-50%) in several brain regions. Anatibant Ms (Ki = 22 pM) displaced the B2R radioligand from its binding sites in several areas of the forebrain, basal ganglia and hindbrain. Displacement was achieved in 1 h and persisted at 4 h post-injection. The inhibition did not exceed 50% of the total specific binding in non-injured mice. After CHT, the displacement by Anatibant Ms was higher and almost complete in the cortex, caudate putamen, thalamus, hippocampus, medial geniculate nucleus, ventral tegmental area, and raphe. Evans blue extravasation in brain tissue at 4 h after CHT was abolished by Anatibant Ms. It appeared that Anatibant Ms penetrated into the brain in sufficient amounts, particularly after disruption of the blood-brain barrier, to account for its B2R-mediated neuro- and vascular protective effects. The diminished binding of B2R after CHT may reflect the occupancy or internalization of B2R following the endogenous production of bradykinin (BK).

Animals↗
PubMed2002

Development of brain damage as measured by brain impedance recordings, and changes in heart rate, and blood pressure induced by different stunning and killing methods.

Poultry are electrically stunned before slaughter to induce unconsciousness and to immobilize the chickens for easier killing. From a welfare point of view, electrical stunning should induce immediate and lasting unconsciousness in the chicken. As an alternative to electroencephalography, which measures brain electrical activity, this study used brain impedance recordings, which measure brain metabolic activity, to determine the onset and development of brain damage. Fifty-six chickens were surgically equipped with brain electrodes and a canula in the wing artery and were subjected to one of seven stunning and killing methods: whole body electrical stunning; head-only electrical stunning at 50, 100 or 150 V; or an i.v. injection with MgCl2. After 30 s, the chickens were exsanguinated. Brain impedance and blood pressure were measured. Extracellular volume was determined from the brain impedance data and heart rate from the blood pressure data. An immediate and progressive reduction in extracellular volume in all chickens was found only with whole body stunning at 150 V. This treatment also caused cardiac fibrillation or arrest in all chickens. With all other electrical stunning treatments, extracellular volume was immediately reduced in some but not all birds, and cardiac fibrillation or arrest was not often found. Ischemic conditions, caused by cessation of the circulation, stimulated this epileptic effect. A stunner setting of 150 V is therefore recommended to ensure immediate and lasting unconsciousness, which is a requirement for humane slaughter.

Animals↗
PubMed1991

Brain potentials associated with movement in traumatic brain injury.

Brain potentials may be used to assess the functional abnormalities that underlie impairments of movement. The purpose of this article is to illustrate the usefulness of examining these potentials. In addition to an overview of the topic, the article includes a report of a study demonstrating that there were differences between the brain potentials of five patients with traumatic brain injury and those of four healthy control subjects. All five patients were in the postacute phase of hemiplegia. Slow cortical potentials associated with simple goal-directed forearm and finger movements were recorded from frontal and parietal electrodes. Two seconds of movement-related electroencephalographic activity (movement-related potential) were recorded. The patients showed reduced brain potentials for movements associated with their paretic limb and, to a lesser extent, reduced brain potentials for movements associated with their nonparetic limb. The waveforms obtained from the patients were unusual, with uncharacteristic cross-cortical movement-related potential correlations associated with specific electrode configurations, as well as with specific movement conditions. Brain potentials associated with the fore-period interval of a simple reaction time paradigm were later recorded in two of the patients with traumatic brain injury and in a control subject to help determine the functional significance of the relative positivity apparent in their movement-related potential data. This preliminary study indicates that electroencephalographic potentials obtained during the preparation for and execution of movement can provide information regarding the basis for motor dysfunction.

Adolescent↗