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PubMed2001

Blood-brain barrier disturbances and morphological changes in rat brain after photochemically induced focal ischaemia.

The disturbances in cerebral circulation lead to focal brain ischaemia and brain infarcts. The pathogenesis of brain ischaemia has been a subject of numerous experimental studies employing different models and focusing on the anatomy of collateral circulation. The aim of this study was the evaluation of our own model of focatcerebral damage caused by a photodynamic reaction, and determination of its utility as a model of brain necrosis and blood-brain barrier damage in the rat. Wistar rats were used for the experiments. The animals were anaesthetised with 3% chloral hydrate (325 mg/kg) and injected intravenously with 40 mg/kg of 3% solution of rose bengal. After removal of the periostium the brain was irradiated through the skull for 30 min with a 250 W halogen, air-cooled light source. The material for morphologic studies was sampled 24 h, 4 days and 7 days after irradiation. The brains were fixed by perfusion, embedded in paraffin, and stained with haematoxilin-eosin (HE), acid vanadium fuchsin, cresyl violet, and GFAP. The results document the usefulness of this method for studying focal brain ischaemia in rats. The observed morphological changes and disturbances in blood-brain barrier provided information about the dynamics of the formation of gliosis, the formation of necrotic foci, and the quality and extent of brain damage in the surrounding tissue.

Anesthetics, Intravenous↗
PubMed1984

[Auditory evoked brain-stem responses (ABRs) in brain dead status].

Auditory evoked brain-stem responses (ABRs) were recorded in 19 out of 52 brain dead cases in Department of Emergency Medicine, University of Tokyo Hospital from May, 1981 to January, 1984. The causes of brain death were severe head injury (9 cases), cerebro-vascular disease (7 cases), anoxia (2 cases), hydrocephalus (1 case). Eleven cases of them fulfilled the clinical criteria which included absence of cortical and brain-stem functions excluding severe hypothermia and depressant drug intoxication. The remainders who were subjected to barbiturate therapy were diagnosed as brain death for non-filling phenomenon in cerebral angiography. Results were as follows; Fourteen cases (74%) had no identifiable ABR waves. One case (5%) had only 1st wave. Three cases (16%) had 1st and 2nd waves. One case (5%) had 1st, 2nd, and 3rd waves. In spite of definition of clinical brain death, 5 cases had at least 1st wave, and therefore these datum suggested that ABR might have less clinical utility in diagnosis of brain death. Each case did not necessarily demonstrate the total extinction of ABRs, as was shown in (2) to (4) mentioned above. The clinical status which met the criteria of brain death might therefore possibly imply any conditions in which brain death was impending gradually to result in the total brain death of cerebrum through medulla oblongata. Under these circumstances, how barbiturate might produce ABRs abnormality remained unsolved, though it has been said not to produce ABRs abnormality. Among 8 cases under barbiturate therapy, there were 5 cases with no identifiable waves and 3 cases with 1st and 2 nd waves.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

[Dynamic observation of brainstem auditory evoked potential and pathological changes of the brain after closed brain injuries in rats].

OBJECTIVE: To investigate the dynamic experiences of pathological changes in brain and the injured role of brainstem auditory evoked potential (BAEP) after closed Mild Traumatic Brain Injury (MTBI) in rat. METHODS: A closed diffuse brain injury model was successfully produced in rat by hit the parietal bone with a spring-droved steel stick. The auditory brainstem response evoked by click at 50Hz stimulating frequency were recorded at pre-trauma, 15 min and 1, 3, 6, 12 h and 1, 2, 4, 7, 10, 14, 21 d after brain injury. The pathological changes of brain were observed under light microscope and the brain edema was detected by wet weight/dry weight rations. RESULTS: The I-V, III-V of BAEP wave inter peak latency (IPL) in MTBI group increased immediately in 15 minutes after injury. The III, V wave peak latency (PL) and I-V, III-V wave IPL became longer than the pre-trauma level in 6, 12 h post-injury (P<0.05). The III, V wave PL and I - III, I - V, III - V wave IPL became longer than the pre-trauma level in 1, 2 d after injury (P < 0.001), the BAEP retuned to normal level in 14 d after brain injury. At 15 minutes after injury, the water content in brain increased and met its peak in 1 d, decreased gradually in 4 d, then decreased slowly and returned to normal level in 10 d after injury. CONCLUSION: The regular changes of BAEP could be an objective tool for evaluating hearing dysfunction after closed mild diffuse traumatic brain injury.

Animals↗
PubMed2002

Abnormal regional cerebral blood flow found by technetium-99m ethyl cysteinate dimer brain single photon emission computed tomography in systemic lupus erythematosus patients with normal brain MRI findings.

In this study, technetium-(99m) ethyl cysteinate dimer ((99m)Tc ECD) brain single photon emission computed tomography (SPECT) was used to detect regional cerebral blood flow (rCBF) of the brain in SLE patients with normal brain magnetic resonance imaging (MRI) findings. Twenty female SLE patients were enrolled in this study, divided into two groups. Group 1 consisted of 10 patients with neuropsychiatric manifestations. Group 2 consisted of 10 patients without neuropsychiatric manifestations. All patients had normal brain MRI findings. Another 10 SLE patients with abnormal MRI findings were included as group 3 for comparison. Meanwhile, 10 healthy female volunteers also underwent brain MRI and (99m)Tc ECD brain SPECT for comparison. The scans revealed hypoperfusion lesions in 9/20 (45%) SLE patients, including 7/10 (70%) cases in group 1 and 2/10 (20%) cases in group 2. In contrast, all 10 patients (100%) in group 3 had abnormal (99m)Tc ECD brain SPECT findings. The parietal lobes were the most commonly involved areas. We conclude that (99m)Tc ECD brain SPECT is more sensitive for detecting rCBF changes than is brain MRI in detecting the brain anatomic changes, and may have a diagnostic value in lupus cerebral involvement. However, (99m)Tc ECD brain SPECT may not be indicated for SLE patients with normal MRI and mild neuropsychiatric symptoms/signs, such headaches and dizziness.

Adult↗
PubMedDate not supplied

Age-related changes in barrier function in mouse brain I. Accelerated age-related increase of brain transfer of serum albumin in accelerated senescence prone SAM-P/8 mice with deficits in learning and memory.

The time course of brain accumulation of radiolabelled human serum albumin ((125)I-HSA) injected intravenously and the transfer of (125)I-HSA from blood to brain were evaluated in DDD mice using a double isotope technique. The brain accumulation of (125)I-HSA at 3 and 9 h but not at 24 h postinjection and the brain transfer rates were significantly higher in 22-month-old DDD mice than in 4-month-old ones. The brain transfer rates of (125)I-HSA were measured also in senescence accelerated prone mice (SAM-P/8) with age-related deficits in learning and memory, and in senescence accelerated resistant mice (SAM-R/I) without these deficits. The brain transfer rates were significantly higher in 13-month-old SAM-P/8 and 22-month-old SAM-R/1 than in 3-month-old mice of the same strains, respectively. The mean brain transfer rates in five regions observed in 22-month-old DDD mice, 22-month-old SAM-R/1 and 13-month-old SAM-P/8 increased by 31%, 41% and 51% compared with corresponding values in 3- or 4-month-old mice of the same strains. DDD mice and SAM-R/1 mice with normal characteristics of aging showed similar age-related significant changes in brain transfer rates. Age-related increase in the brain transfer rate was manifested at the youngest age in SAM-P/8 among the three strains examined. These findings show that the transfer of human serum albumin into the mouse brain increases with aging and suggest that the barrier function in the mouse brain against macromolecules changes with aging.

Journal Article↗
PubMed2000

Brain-derived neurotrophic factor and tyrosine kinase receptor TrkB in rat brain are significantly altered after haloperidol and risperidone administration.

The antipsychotics haloperidol and risperidone are widely used in the therapy of schizophrenia. The former drug mainly acts on the dopamine (DA) D(2) receptor whereas risperidone binds to both DA and serotonin (5HT) receptors, particularly in the neurons of striatal and limbic structures. Recent evidence suggests that neurotrophins might also be involved in antipsychotic action in the central nervous system (CNS). We have previously reported that haloperidol and risperidone significantly affect brain nerve growth factor (NGF) level suggesting that these drugs influence the turnover of endogenous growth factors. Brain-derived neurotrophic factor (BDNF) supports survival and differentiation of developing and mature brain DA neurons. We hypothesized that treatments with haloperidol or risperidone will affect synthesis/release of brain BDNF and tested this hypothesis by measuring BDNF and TrkB in rat brain regions after a 29-day-treatment with haloperidol or risperidone added to chow. Drug treatments had no effects on weight of brain regions. Chronic administration of these drugs, however, altered BDNF synthesis or release and expression of TrkB-immunoreactivity within the brain. Both haloperidol and risperidone significantly decreased BDNF concentrations in frontal cortex, occipital cortex and hippocampus and decreased or increased TrkB receptors in selected brain structures. Because BDNF can act on a variety of CNS neurons, it is reasonable to hypothesize that alteration of brain level of this neurotrophin could constitute one of the mechanisms of action of antipsychotic drugs. These observations also support the possibility that neurotrophic factors play a role in altered brain function in schizophrenic disorders.

Animals↗
PubMed2006

Loss of shear stress induces leukocyte-mediated cytokine release and blood-brain barrier failure in dynamic in vitro blood-brain barrier model.

Brain ischemia is associated with an acute release of pro-inflammatory cytokines, notably TNF-alpha and IL-6 and failure of the blood-brain barrier. Shear stress, hypoxia-hypoglycemia, and blood leukocytes play a significant role in blood-brain barrier failure during transient or permanent ischemia. However, these mechanisms have not been studied as independent variables for in vitro ischemia. The present study, using a dynamic in vitro blood-brain barrier model, showed that flow cessation/reperfusion under normoxia-normoglycemia or hypoxia-hypoglycemia without blood leukocytes in the luminal perfusate had a modest, transient effect on cytokine release and blood-brain barrier permeability. By contrast, exposure to normoxic-normoglycemic flow cessation/reperfusion with blood leukocytes in the luminal perfusate led to a significant increase in TNF-alpha and IL-6, accompanied by biphasic blood-brain barrier opening. Enhanced permeability was partially prevented with an anti-TNF-alpha antibody. In leukocyte-free cartridges, the same levels of IL-6 had no effect, while TNF-alpha caused a moderate increase in blood-brain barrier permeability, suggesting that blood leukocytes are the prerequisite for cytokine release and blood-brain barrier failure during reduction or cessation of flow. These cells induce release of TNF-alpha early after ischemia/reperfusion; TNF-alpha triggers release of IL-6, since blockade of TNF-alpha prevents IL-6 release, whereas blockade of IL-6 induces TNF-alpha release. Pre-treatment of blood leukocytes with the cyclooxygenase (COX) inhibitor, ibuprofen, inhibited cytokine release and completely preserved blood-brain barrier permeability during the reperfusion period. In conclusion, loss of flow (flow cessation/reperfusion) independent of hypoxia-hypoglycemia plays a significant role in blood-brain barrier failure by stimulating leukocyte-mediated inflammatory mechanisms.

Animals↗
PubMed2002

Multi-chemical networking profile of the living human brain: potential relevance to molecular studies of cognition and behavior in normal and diseased brain.

Anatomical, electrophysiological and functional neuroimaging studies show that the human brain is a complex network, where cortico-cortical and thalamo-cortical connections are organized in a specific pattern giving rise to brain function. In our recent studies we found that chemical connectivity between brain regions might be changed in different conditions (e.g. aging, chronic pain, cognitive interference). The elucidation of properties of the human brain multi-chemical networking profile is the subject of this study. In vivo proton magnetic resonance spectroscopy was used to determine relative concentrations of multiple chemicals (N-Acetyl aspartate, choline, glutamate, glutamine, GABA, inositol, glucose, and lactate in relation to creatine/phosphocreatine complex) in 6 brain regions: thalamus, and cingulate, insula, sensorimotor, orbital frontal, and dorsolateral prefrontal cortices. The properties of the brain multi-chemical networking profile within and across the studied regions were examined using correlation analysis. Strong positive correlations were seen between chemicals within brain regions. Negative correlations were primarily seen across brain regions. The cortical connectivity for both neurotransmitters (GABA and glutamate) was stronger than for the other chemicals, and was stronger than for the same neurotransmitters in the thalamus. Factor analysis indicated that the natural clustering of regional chemical concentrations is by brain region and not by chemicals. These findings support the idea for the existence of a specific pattern of multi-chemical networking profile in the brain where the major excitatory and inhibitory neurotransmitters in neocortex perform a regulatory function.

Adult↗
PubMed1988

Actions of the brain-penetrating H2-antagonist zolantidine on histamine dynamics and metabolism in rat brain.

The effects of zolantidine, the first brain-penetrating H2-receptor antagonist, on the brain levels of histamine (HA) and the HA metabolite tele-methylhistamine (t-MH), the activity of histamine methyltransferase (HMT) and the brain HA turnover rates were investigated in rats. Zolantidine dimaleate (0.1 to 100 mg/kg, s.c.) had no effect on whole brain levels of HA or t-MH and no effect on brain HMT activity, when measured 30 min after administration. Furthermore, brain t-MH levels in pargyline-treated animals were unaffected by zolantidine (0.1 to 25 mg/kg), indicating the absence of an effect on brain HA turnover. In vitro, zolantidine was a potent competitive inhibitor of both brain and kidney HMT, with Ki values of 2.3 and 2.7 microM respectively. These results show that, despite the ability of zolantidine to inhibit HMT in vitro, large doses of this drug did not alter brain HA methylation or turnover in vivo, and they imply that blockade of post-synaptic H2-receptors does not change brain HA dynamics.

Animals↗
PubMed1988

Synthesis and localization of plasma proteins in the developing human brain. Integrity of the fetal blood-brain barrier to endogenous proteins of hepatic origin.

The distribution and possible origins of plasma proteins in the human embryonic and fetal brain at different stages of development have been investigated by a combination of isolation and translation of mRNAs and immunocytochemistry using specific antisera. As many as 23 plasma-like proteins have been identified using immunocytochemical methods at the light microscopical level. The presence of mRNAs for 13 of the immunocytochemically positive plasma proteins was demonstrated by in vitro and in ovo translation followed by crossed immunoelectrophoresis and autoradiography; this indicates in situ synthesis of these proteins (e.g., alpha-fetoprotein, alpha 1-antitrypsin, GC-globulin, alpha 2-macroglobulin, pseudocholinesterase, and transferrin) in some brain regions. The regional distribution of some proteins and the absence of some mRNAs suggest that the presence of certain plasma proteins in developing brain may be accounted for by uptake from csf or via nerve processes extending beyond the blood-brain barrier. In several cases, specific proteins appear to be associated with defined cell types, e.g., alpha-fetoprotein, GC-globulin, and ceruloplasmin with neurons, alpha 2-macroglobulin with endothelial cells, and ferritin with glial cells. Some proteins were associated with two or three cell types, e.g., alpha 1-antitrypsin with neurons and glia, and transferrin and alpha 2HS-glycoprotein with neurons, glia, and endothelial cells. Comparison of the expression of mRNAs from fetal brain and liver injected into Xenopus oocytes showed that a few proteins (transferrin and ceruloplasmin) were secreted when liver mRNA was injected, but not when brain mRNA was injected. This suggests that there may be an important difference in the structure and/or processing of these proteins in the brain which may reflect a function different from that associated with them when they originate from the liver. Staining was generally intracellular rather than extracellular; plasma proteins were not associated with the areas immediately around blood vessels although there was a strong immunoprecipitation for each protein within the lumen of cerebral blood vessels. These immunocytochemical findings together with the identification of mRNAs for a large number of plasma proteins in immature brain are discussed in relation to animal experimental work which suggests that the blood-brain barrier to protein is present even at very early stages of brain development.

Blood Proteins↗
PubMed1984

Specific gravity increases and brain water content decreases during short epileptiform seizures in discrete rabbit brain areas.

In rabbits subjected to bicuculline (BC)- or pentylenetetrazole (PTZ)-seizures of 3 or 20 min duration or to adrenaline-induced hypertension, specific gravity (SG) was measured bilaterally in 15 regional brain areas in order to detect possible associations between the regionally limited blood-brain barrier openings due to these insults (see Nitsch and Klatzo 1983) and the presence of brain edema. In controls, a large variation between regional SG levels became evident: between 1.0467 in cerebellum and 1.0417 in preoptic area. A seizure duration of only 3 min was not sufficient to change SG significantly. After 20 min of seizures independent from the inducing agent, SG increased in all brain areas. The degree of increase seemed to be unrelated to presence or absence of a blood-brain barrier opening. In an attempt to avoid the influence of blood impregnation on the SG value, blood was replaced by saline before measurement. In controls, saline perfusion decreased SG only in the two areas with the highest original levels, thus documenting the partial dependency of the regional SG on the hematisation of the tissue. After 20 min of PTZ-induced seizures, SG in saline-perfused rabbits increased, but no longer significantly in all brain areas. This suggests that a part of the seizure-induced SG increase can be attributed to the hyperemia of the brain during the convulsions. On the other hand, an increase in flow volume due to hypertension did not change SG with the exception of the septum, preoptic area and hypothalamus. The direct measurement of water content with the classical wet/dry method in 4 gross brain areas showed that early seizure periods are in fact associated with a dehydration of the brain. This phenomenon could be explained by a glucose- and lactate-induced rise in blood osmolarity which in turn might cause a dehydration of the brain tissue.

Animals↗
PubMed1993

Blood-brain barrier permeability and the brain extracellular space in acute cerebral inflammation.

The diffusion properties of the brain cortical extracellular space have never been examined in models of inflammation, even though inflammation can cause increased blood-brain barrier permeability. Uptake of intravascular 125I-labelled albumin and the diffusion of the tetramethylammonium ion within the brain extracellular space was measured in an experimental brain abscess to determine the effect of acute inflammation upon blood-brain barrier permeability and diffusion properties of the cortical extracellular space. The blood-brain transfer constant for albumin was increased in the abscess region, indicating that an increase in blood-brain barrier permeability occurred in animals inoculated with a weakly pathogenic strain of Staphylococcus aureus. The volume fraction of the extracellular space, as measured by the diffusion of tetramethylammonium ion, ranged from 0.19 to 0.23 in bacteria inoculated subjects and from 0.21 to 0.22 in controls. The tortuosity of the extracellular space ranged from 1.40 to 1.42 in bacteria inoculated subjects and was 1.39 in controls. These results showed that the volume fraction and tortuosity of the cortical extracellular space were not affected by inflammation even though vascular permeability was increased. This result was supported by the finding that brain water content, measured in the same animals, was increased to a non-significant extent in the bacteria inoculated subjects. These findings lead to the conclusion that acute inflammation induced by a weak pathogen can cause increased blood-brain barrier permeability without a significant change in the diffusion properties of the brain cortical space.

Animals↗
PubMed2006

Inhibition of the Na+ -K+ -2Cl- -cotransporter in choroid plexus attenuates traumatic brain injury-induced brain edema and neuronal damage.

The present study was aimed to elucidate the possible role of Na+ -K+ -2Cl- -cotransporter (NKCC1) on traumatic brain injury-induced brain edema, cerebral contusion and neuronal death by using traumatic brain injury animal model. Contusion volume was verified by 2,3,5,-triphenyltetrazolium chloride monohydrate staining. NKCC1 mRNA expression was detected by RT-PCR and the protein expression of NKCC1 was measured by Western blot. We found that the expression of NKCC1 RNA and protein were up-regulated in choroid plexus apical membrane from 2 h after traumatic brain injury, peaked at 8 h, and lasted for 24 h. Rats in the experimental group displayed severe brain edema (water content: 81.45 +/- 0.32% compared with 78.38 +/- 0.62% of sham group) and contusion volume significantly increased 8 h after traumatic brain injury (864.14 +/- 28.07 mm3). Administration of the NKCC1 inhibitor bumetanide (15 mg/kg, I.V.) significantly attenuated the contusion volume (464.03 +/- 23.62 mm3) and brain edema (water content: 79.12 +/- 0.28%) after traumatic brain injury. Our study demonstrates that NKCC1 contributes to traumatic brain injury-induced brain edema and neuronal damage.

Animals↗
PubMed2006

Increased brain uptake and brain to blood efflux transport of 14C-GABA in spontaneously hypertensive rats.

The brain uptake and brain to blood efflux transport of (14)C-GABA were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats using 20 min bilateral in situ brain perfusion in rats anesthetized using urethane. The volume of distribution (Vd) of (14)C-GABA into cerebrospinal fluid (CSF) and brain regions (cortex, diencephalon, cerebellum, and brain stem) was significantly greater in SHR than in the corresponding regions in WKY rats (p<0.05). The estimated Vd value of (14)C-GABA in CSF of SHR was 3.4 fold greater than that in WKY. Also compared to WKY, the Vd of (14)C-GABA into cerebellum and cortex of SHR was 15.3 fold and 19.4 fold greater, respectively. Although the study of blood-brain barrier (BBB) integrity using (3)H-mannitol revealed increased paracellular permeability at the brain capillaries of SHR when compared to WKY rats, this was found to be only partially responsible for the increased (14)C-GABA uptake. The study of brain to blood efflux transport of (14)C-GABA (after loading of brain with (14)C-GABA by vascular perfusion) revealed that the half-time of elimination was significantly shorter in SHR (5.35+/-0.66 min) than in WKY rats (14.83+/-1.94 min), (p<0.001). HPLC analysis revealed that GABA concentrations in brain extracts and CSF of SHR were similar to those in WKY rats (p>0.05). The faster efflux in SHR might be, at least partially, responsible to compensate for increased uptake of this neurotransmitter and to preserve the protective function of BBB towards GABA. The protective function of the BCSFB towards GABA appears to be also preserved, since systemic infusion of GABA within a wide range of administered doses (0.004-5.00 mg/kg) produced an increase in GABA CSF concentration from around 0.5 microM to only 11 microM, and the obtained pattern of CSF GABA concentrations under these conditions did not differ between SHR and WKY rats, as revealed by HPLC.

Animals↗
PubMed2004

Manganese distribution across the blood-brain barrier. IV. Evidence for brain influx through store-operated calcium channels.

Manganese (Mn) is a required co-factor for many ubiquitous enzymes; however, chronic Mn overexposure can cause manganism, a parkinsonian-like syndrome. Previous studies showed Mn influx into brain is carrier-mediated, though the putative carrier(s) were not established. Studies conducted with cultured bovine brain microvascular endothelial cells (bBMECs), which comprise the blood-brain barrier, revealed (54)Mn (II) uptake positively correlated with pH, was temperature-dependent, and was sodium- and energy-independent. Brain (54)Mn uptake correlated inversely with calcium (Ca) concentration, but (45)Ca uptake was unaltered by high Mn concentration. Lanthanum (La), a non-selective inhibitor of several Ca channel types, as well as verapamil and amiloride, inhibitors of voltage-operated Ca channels, failed to inhibit Mn uptake into cells. Nickel (Ni), another non-selective inhibitor of several Ca channel types, inhibited Mn and Ca uptake into cells by 88 and 85%, respectively. Cyclopiazonic acid (CPA) and thapsigargin, which activate store-operated calcium channels (SOCCs), increased (54)Mn and (45)Ca uptake into cultured bBMECs. In situ brain perfusion studies were conducted in adult, male Sprague-Dawley rats to verify the cell culture results. Both nickel and verapamil produced a non-significant decrease in Mn and Ca influx. Lanthanum significantly increased Mn influx to 675 and 450% of control in parietal cortex and caudate, respectively, while producing no significant effect on Ca influx. Vanadate, which inhibits Ca-ATPase, inhibited Mn uptake into cultured blood-brain barrier cells, but not into perfused rat brain. Overall these results suggest that both Ca-dependent and Ca-independent mechanisms play a role in brain Mn influx. This work provides evidence that store-operated Ca channels, as well as another mechanism at the blood-brain barrier, likely play a role in carrier-mediated Mn influx into the brain.

Animals↗
PubMed2005

Correlation of factors predicting intraoperative brain shift with successful resection of malignant brain tumors using image-guided techniques.

BACKGROUND: Intraoperative brain shift may cause inaccuracy of stereotactic image guidance on the basis of preoperatively acquired imaging data. The purpose of our study was to determine whether factors predicting brain shift affect the success of image-guided resection of malignant brain tumors. METHODS: We retrospectively studied 54 patients who underwent image-guided resections of histopathologically confirmed malignant brain tumors (9 metastases, 45 high-grade gliomas). Precautions were taken during surgery to minimize brain shift, but intraoperative imaging was not performed. The following factors predictive of intraoperative brain shift were assessed: tumor size, periventricular location, patient age, prior surgery or radiation therapy, patient positioning, use of mannitol, and length of operative time. Postoperative magnetic resonance imaging was obtained in all cases within 48 hours of surgery to assess extent of resection. RESULTS: Perioperative mortality was 0% in our series; perioperative morbidity was 3 of 54 patients (5.5%); 1 patient required reoperation for a hematoma, and 2 had transient neurological deficits. Successful resection was accomplished in 93% of tumors less than 30 cm(3) compared with 63.6% of tumors greater than 30 cm(3) (P = .026, Fisher exact test). This difference was more pronounced for patients with malignant gliomas. However, other factors predictive of intraoperative brain shift were not associated with unsuccessful resection. CONCLUSIONS: Intraoperative brain shift does not significantly affect the likelihood of successful resection of malignant brain tumors smaller than 30 cm(3). Larger tumors are less likely to be successfully resected, although factors other than brain shift can contribute to unsuccessful resection.

Adult↗
PubMed2000

Brain-to-blood efflux transport of estrone-3-sulfate at the blood-brain barrier in rats.

Efflux transport of estrogens such as estrone-3-sulfate (E1S), and estrone (E1) across the blood-brain barrier (BBB) was evaluated using the Brain Efflux Index (BEI) method. The apparent BBB efflux rate constant (Keff) of [3H]E1S, and [3H]E1 was 6.63 x 10(-2) +/- 0.77 x 10(-2) min(-1), and 6.91 x 10(-2) +/- 1.23 x 10(-2) min(-1), respectively. The efflux transport of [3H]E1S from brain across the BBB was a saturable process with Michaelis constant (Km) of 96.0 +/- 34.4 microM and 93.4 +/- 22.0 microM estimated by two different methods. By determining [3H]E1S metabolites using high performance liquid chromatography (HPLC) after intracerebral injection, significant amounts of [3H]E1S were found in the jugular venous plasma, providing direct evidence that most of [3H]E1S is transported from brain across the BBB in intact form. To compare the apparent efflux clearance across the BBB of E1S with that of E1, the brain distribution volume of E1S and E1 was estimated using the brain slice uptake method. The apparent efflux clearance of [3H]E1S was determined to be 74.9 +/- 3.8 microl/(min x g brain) due to the distribution volume of 1.13 +/- 0.06 ml/g brain. By contrast, the apparent efflux clearance of E1 was more than 227 +/- 3 microl/(min x g brain), since the distribution volume of [3H]E1 at 60 min was 3.28 +/- 0.13 ml/g. The E1S efflux transport process was inhibited by more than 40% by coadministration of bile acids (taurocholate, and cholate), and organic anions (sulfobromophthalein, and probenecid), whereas other organic anions did not affect the E1S efflux transport. The [3H]E1S efflux was significantly reduced by 48.6% after preadministration of 5 mM dehydroepiandrosterone sulfate. These results suggest that E1S is transported from brain to the circulating blood across the BBB via a carrier-mediated efflux transport system.

Animals↗
PubMed1997

Induction of brain derived neurotrophic factor mRNA by seizures in neonatal and juvenile rat brain.

Seizures have been shown to regulate neurotrophin expression in adult mammalian brain. However, there has been some controversy as to whether seizures affect neurotrophin expression in very immature brain. In the present study, we have examined the effects of seizures induced by pilocarpine following lithium pretreatment or by kainic acid on the expression of brain derived neurotrophic factor (BDNF) mRNA in developing rat brain by in situ hybridization. In adult brain, lithium/pilocarpine treatment resulted in dramatic elevations of hybridization to BDNF cRNA in neocortical and limbic brain structures. In developing brain, lithium/pilocarpine induced elevations of BDNF mRNA in the hippocampus, piriform and entorhinal cortex as early as postnatal day 7 (P7). By P12, the pattern of enhanced expression was similar to that of the adult. Maximal elevations of hybridization were present 2 to 4 h following pilocarpine injection. Electrophysiological recording demonstrated that lithium/pilocarpine treatment resulted in electrographic seizures. Pretreatment with diazepam blocked the seizures as well as the elevation of BDNF mRNA. Kainic acid induced elevations of BDNF mRNA in the CA3 subfield of the hippocampal pyramidal cell layer, but not in other brain areas in pups as young as P7. These data indicate that seizures during the neonatal and early juvenile period of brain development induce elevated BDNF mRNA expression, and that different methods of seizure induction yield different patterns of elevations in hybridization. Furthermore, BDNF may be capable of playing a role in the development of seizure susceptibility in the immature brain.

Animals↗