Brain vessels in the rats exposed to primary and repeated tail-suspension. Minimization of structural changes after repeated exposure

The aim of study was histological examination of brain vessels in the rats exposed to repeated tail-suspension (TS). The rats were subjected to 30-day TS, then readapted to horizontal position for 30 days and again exposed to 14-day TS simultaneously with the rats which were underwent to 14-day TS for the first time. 30-day TS induced in brain vessels the adaptive changes hindering the excessive blood inflow to brain--spasm and hypertrophy of muscle-elastic valves in extra- and intracerebral arteries and also the destructive changes--loss of vascular tone in extra- and intracerebral arteries, plethora in extra- and intracerebral veins, intracerebral venules and capillaries, conglutination of erythrocytes in capillaries, plasmatization of veins and capillaries and edema of brain tissue pointing out in total the increase in blood inflow to the brain and difficulty of blood outflow. After 30-day readaptation of TS-rats to horizontal position only adaptive changes in extracerebral arteries and intracerebral capillaries (cell proliferation) and edema of brain tissue were revealed. After repeated, 14-day TS in spite of new redistribution of blood to the head, in contrast to the vessel alterations after primary 14-day TS, the adaptive and destructive changes in brain vessels were lack, excluding only moderate plethora of intracerebral veins, cell proliferation in capillaries and weak signs of edema.     

Pancreatic cell responses to primary and repeated 2 G influence

The pancreas of the rats exposed to primary and repeated prolonged hypergravity was studied by means of cytological methods. The rats were rotated on centrifuge at 2 G for 19 days and then after 30-day adaptation to 1 G were repeatedly exposed to 2 G for 5 days simultaneously with the rats first subjected to 5-day 2 G. After 5-day and 19-day hypergravity in pancreatic beta-cells the signs of decrease in insulin production were found. Adaptation of rats to 1 G for 30 days restored this process. Repeated 2 G for 5 days induced in beta-cells the changes of structure and hormonal product content indicating the pronounced increase in insulin synthesis and secretion. Response of alpha-cells to repeated 5-day 2 G was in parallel with beta-cell reactions.     

Chronic lithium administration attenuates up-regulated brain arachidonic acid metabolism in a rat model of neuroinflammation

Neuroinflammation, caused by a 6-day intracerebroventricular infusion of lipopolysaccharide (LPS) in rats, is associated with the up-regulation of brain arachidonic acid (AA) metabolism markers. Because chronic LiCl down-regulates markers of brain AA metabolism, we hypothesized that it would attenuate increments of these markers in LPS-infused rats. Incorporation coefficients k* of AA from plasma into brain, and other brain AA metabolic markers, were measured in rats that had been fed a LiCl or control diet for 6 weeks, and subjected in the last 6 days on the diet to intracerebroventricular infusion of artificial CSF or of LPS. In rats on the control diet, LPS compared with CSF infusion increased k* significantly in 28 regions, whereas the LiCl diet prevented k* increments in 18 of these regions. LiCl in CSF infused rats increased k* in 14 regions, largely belonging to auditory and visual systems. Brain cytoplasmic phospholipase A(2) activity, and prostaglandin E(2) and thromboxane B(2) concentrations, were increased significantly by LPS infusion in rats fed the control but not the LiCl diet. Chronic LiCl administration attenuates LPS-induced up-regulation of a number of brain AA metabolism markers. To the extent that this up-regulation has neuropathological consequences, lithium might be considered for treating human brain diseases accompanied by neuroinflammation.     

Morphometric and Ultrastructural Characteristics of the Mitochondrial System of Cardiomyocytes in the Rat Left Ventricle under Conditions of Hypergravity

For the first time, electron-microscopic morphometric analysis of the mitochondrial system in cardiomyocytes of the left ventricle was performed in rats exposed to hypergravity (2 g). After five days of exposure, the number of long mitochondria sharply increased in the interfibrillar zone of cardiomyocytes. The numbers of intermitochondrial junctions (IMJs) were increased in all zones of mitochondria localization. The ultrastructure and numerical density of mitochondria remained within the normal limits. The same picture was revealed on day 19 (the end of exposure), but the numbers of IMJs in the perinuclear and subsarcolemmal pericapillary zones were lower than on day 5. One months after the end of 19-day exposure at 2 g, the test parameters of the mitochondrial system did not return to the norm. Apparently, this is why repeated exposure to hypergravity (2 g for five days after 30-day rest) failed to evoke a similar response from the mitochondrial system of cardiomyocytes.     

Action of anorexigenic peptide injected into the brain: Dissociation of effect on body weight and feeding in the rat

Previous reports on the effect of anorexigenic peptide (AXP) administered systemically in the rodent are inconsistent in terms of the effect of the tri-peptide on food intake and body weight. The purpose of this study was to examine the effect of AXP infused into the brain on these measures. In post-pubescent female rats of the Sprague-Dawley strain, guide cannulae were permanently implanted in the lateral cerebral ventricle for repeated intracerebroventricular (ICV) infusion. Postoperatively, measures of food and water intake and body weight were obtained every day at the same time. After a 7-day base-line period, AXP was infused bilaterally in a total volume of 15 μl and in a dose of either 0.25 μg (n=7) or 1.25 μg (n=5), with artificial CSF vehicle serving as the control solution (n=6). ICV infusions were given once daily for 20 consecutive days, after which the same intake and body weight measures were recorded for another 7-day period. The rats given 0.25 μg AXP showed a significant suppression in weight gain with the overall slope of the growth curve being 0.358. In contrast, the growth slope of the rats given the 1.25 μg dose of AXP was 0.621, whereas those given the CSF was 0.823. Although the trends of intake of food tended to follow the curves of the rats' body weight, the difference between g/kg food intake of rats during ICV infusions of either dose of AXP was not significantly different from that of the CSF controls. Water intake also was unaffected by either dose of AXP. These results demonstrate that this tri-peptide derived from urine of patients afflicted with anorexia nervosa exerts a direct effect on the brain. Since the 0.25 μg dose of AXP infused acutely ICV caused a sustained hyperthermia, its mechanism of action is apparently a metabolic one; that is, the interruption in the gain in body weight of the rat is independent of the amount of food it ingests.     

Facilitation of hypothalamic-pituitary-adrenal responses to novel stress following repeated social stress using the resident/intruder paradigm

Our goal in these studies was to characterize some specific aspects of hypothalamic-pituitary-adrenal (HPA) activity in rats exposed to repeated social stress. We used a modification of the resident/intruder paradigm in which male intruder rats were subjected to defeat and then separated from the resident by an enclosure for a total of 30 min on Day 1. On Days 2-7, intruder rats were exposed to different resident rats every day through a wire mesh enclosure for 30 min in order to minimize injurious physical contact between the two rats. The intruder rats gained significantly less weight than controls over the 7-day period of stress though basal corticosterone levels and adrenal and thymus weights were not significantly different between the two groups. On Day 8, repeatedly stressed rats exhibited facilitation of HPA responses to novel restraint compared to controls but no differences in negative feedback sensitivity to dexamethasone (0.05 or 0.2 mg/kg) were observed. Thus, the HPA axis of socially stressed rats remains responsive to a stimulus that has never been encountered. Using this type of repeated presentation to an aggressive resident allows us to examine the neuroendocrine and behavioral consequences, and their underlying neural mechanisms, of exposure to a stressor that is social in nature and naturalistic for rodents.     

新生期触觉刺激和母婴分离对雌性大鼠成年后的焦虑和情绪记忆的影响

采用split-litter法对仔鼠进行分组和处理,共5组NTS组(未经实验人员抓握和标记),PND2—9TS组和PND10—17TS组(分别在仔鼠出生后的2—9天、10—17天,每天短暂抓握和标记仔鼠),PND2—9MS组和PND10—17MS组(分别在仔鼠出生后的2—9天、10—17天,除了按TS组相同方式抓握并在不同部位标记外,每天把仔鼠与母鼠分离1h)。待雌鼠成年后,进行明/暗箱测试和一次性被动回避反应测试。结果发现与NTS组相比,PND2—9TS组和PND10—17TS组的雌鼠在明/暗箱测试中停留于明室的累计时间明显较长,在被动回避作业中的重测试潜伏期也明显较长,表明新生期的触觉刺激经历减少雌性大鼠成年后在新异环境中的焦虑,并改善情绪记忆。与相应TS组相比,MS处理组的所有行为指标都无显著性差异,说明短时间母婴分离对雌鼠成年后的焦虑和情绪记忆无明显影响。结果提示,新生期的触觉刺激和母婴分离经历对仔鼠神经系统的发育产生不同的长期效应。     

The neonatal glucocorticoid treatment-produced long-term changes of the pituitary-adrenal function and brain corticosteroid receptors in rats.

Two distinct periods of sensitivity to elevated glucocorticoid hormone levels during postnatal development of the pituitary-adrenal axis were studied. Wistar rats were injected subcutaneously (s.c.) with cortisol (1 mg/kg) on postnatal days 1-5 or 14-18. The steroid treatment during the first postnatal week resulted in a decrease of the morning basal and stress-induced plasma corticosterone levels in 30 day-old male rats, as well as in rats that were injected with cortisol on the third postnatal week. Stress-induced corticosterone levels in 90-day old cortisol-treated rats were determined in blood samples drawn from the tail vein before the restraint stress, immediately after the 20-min long stress, then 60 and 180 min afterwards. Only the rats treated with cortisol during the third week showed a prolonged stress-induced corticosterone secretion, with the highest corticosterone level in 180 min after the restraint stress. The early neonatal cortisol treatment had no effect on (3)H-corticosterone binding in all studied brain areas of the 90-day old rats. The rats treated with cortisol at the 14-17th postnatal days showed a significantly lower (3)H-corticosterone binding in the frontal cortex, hippocampus, and hypothalamus. These findings suggest that the third week of life in rats is more sensitive to elevated levels of corticosterone than the first one. The high level of glucocorticoids at this period has long-term effects on the efficiency of the negative feedback mechanisms provided by hypothalamus-pituitary-adrenal axis.     

Adaptive Responses of Secretory Cardiomyocytes of the Right Atrium during Simulation of Microgravity Effects by Long-Term and Repeated Antiorthostatic Tail Suspension of Rats

Reactive changes in right atrial cardiomyocytes during antiorthostatic tail suspension of rats, which is commonly used to simulate effects of microgravity, have been studied by electron microscopy and morphometry. A 14-day tail suspension proved to increase contractile and secretory activities of cardiomyocytes. At the same time, signs of depleted activity are observed in some cells. Prolongation of the experiment to 30 days leads to development of adaptive compensatory responses and increases their secretory capacity. A 30-day rest in the normal orthostatic position does not completely restores the structure and functioning of cardiomyocytes and leads to accumulation of internal secretion in them. A repeated 14-day tail suspension to a certain extent facilitates cardiomyocyte adaptation to altered conditions as compared to a single exposure; apparently, secretion release decreases, while its production is activated.     

BDNF Level in the Rat Prefrontal Cortex Increases Following Chronic but Not Acute Treatment with Duloxetine, a Dual Acting Inhibitor of Noradrenaline and Serotonin Re-uptake

Aims Brain-Derived Neurotrophic Factor (BDNF) has a central role in neuronal survival, differentiation, and plasticity. The brain level of BDNF is changed by several mood stabilizers and antidepressant drugs acting on neurotransmitters such as noradrenaline and serotonin. We investigated the effects of acute and chronic treatment with Duloxetine, a new drug blocking the re-uptake of serotonin and noradrenaline (SNRI), on BDNF level in the prefrontal cortex, cerebrospinal fluid, plasma, and serum. Methods Wistar male rats were treated with acute (single treatment) and chronic oral administration (14 days) of different concentrations of Duloxetine (10, 30, and 100 mg/kg/day). At the end of the treatment periods, samples of blood, CSF and the prefrontal cortex were collected. BDNF levels were measured by ELISA. Levels of mature and precursor form of BDNF were measured by Western blot analysis. Results Animals treated with the Duloxetine at all concentrations and examined after 1 and 24 h (single treatment) did not reveal a significant change in the total BDNF level. In animals treated for 14 days with Duloxetine at 30 and 100 mg/kg, the total BDNF level increased significantly in the prefrontal cortex and CSF, but not in the plasma and serum. Using a specific antibody and Western blot we showed that the mature, but not the precursor, form of BDNF was significantly increased in the prefrontal cortex of rats treated for 14 days with Duloxetine at 30 mg/kg/day. Conclusions Our results show a major finding that repeated, but not single, Duloxetine treatment increases the level of BDNF in the prefrontal cortex. Claudio Mannari and Nicola Origlia are contributed equally to this work.     

Alterations in Cerebrospinal Fluid Proteins in a Presymptomatic Primary Glioma Model

Background

Understanding the early relationship between brain tumor cells and their environment could lead to more sensitive biomarkers and new therapeutic strategies. We have been using a rodent model of neurocarcinogenesis in which all animals develop brain tumors by six months of age to establish two early landmarks in glioma development: the appearance of a nestin⁺ cell at thirty days of age and the appearance of cellular hyperplasia between 60 and 120 days of age. We now report an assessment of the CSF proteome to determine the changes in protein composition that occur during this period.

Materials and Methods

Nestin⁺ cell clusters and microtumors were assessed in 63 ethylnitrosourea-exposed rats on 30, 60, and 90 days of age. CSF was obtained from the cisterna magna from 101 exposed and control rats at 30, 60, and 90 days and then analyzed using mass spectrometry. Differentially expressed peaks were isolated and identified.

Results

Nestin⁺ cells were noted in all ethylnitrosourea-exposed rats assessed pathologically. Small microtumors were noted in 0%, 18%, and 67% of 30-, 60-, and 90-day old rats, respectively (p<0.05, Chi square). False Discovery Rate analysis of peak intensities showed that the number of true discoveries with p<0.05 increased markedly with increasing age. Isolation and identification of highly differentially detected proteins at 90 days of age revealed increases in albumin and a fragment of α1 macroglobulin and alterations in glutathionylated transthyretin.

Conclusions

The presence of increased albumin, fragments of cerebrospinal fluid proteins, and glutathione breakdown in temporal association with the development of cellular hyperplasia, suggests that, similar to many other systemic cancers, inflammation and oxidative stress is playing an important early role in the host’s response to brain tumor development and may be involved in affecting the early growth of brain tumor.     

Content of N-acetyl-L-asparate, N-acetyl-L-glutamate and N-acetyl-L-aspartyl-L-glutamate in the brain of mammals at increased oxygen tension

The contents of N-acetyl-l-asparate and N-acetyl-l-glutamate, N-acetyl-l-aspartyl-l-glutamate were studied in the brain of rats of six age groups: newborns and on the 1st, 7th, 14th, and 30th day after birth. The amount of N-acetyl-l-asparate, N-acetyl-l-glutamate and peptide in the rat brain for 30 days of the postanal life is 8, 3.5 and 14.3 times as high, respectively. Under hyperoxic the amount of peptide, N-acetyl-l-asparate and N-acetyl-l-glutamate in the brain of rats of all the examined groups decreases especially in 14-, 21- and 30-day animals.     

Repeated immobilization stress increases total cytosolic glucocorticoid receptor in rat liver

Glucocorticoids are well-known mediators of stress-related endocrine, autonomic, and behavioral responses in mammals and human beings. However, our understanding of the mechanisms of glucocorticoid action in response to stress remains elusive. Therefore, in the present study, an effort has been made to systematically examine glucocorticoid action during acute (2 h) and repeated (2 h daily for 7, 15, and 30 days) immobilization stress in male Sprague-Dawley rats. Prolonged 30-day stress resulted in reduced total body weight gain. There was a dramatic 3- to 4-fold increase in plasma corticosterone levels after single acute stress paradigm, which remained augmented 2- to 3-fold higher than basal control levels during the repeated 30-day immobilization conditions. There was good relationship between increased plasma corticosterone levels and elevation of tyrosine aminotransferase activity in the liver during 30 days of stress. Because repeated immobilization stress animals showed increased levels of both plasma corticosterone and tyrosine aminotransferase activity, the regulation of cytosolic glucocorticoid receptor (GR) in rat liver, a major target tissue for glucocorticoid, was carried out during repeated stress by using GR binding assay, exchange assay, and Western blotting techniques. Exposure of animals to acute and repeated stress resulted in decreased free cytosolic GR. Interestingly, the bound cytosolic GR increased remarkably in liver during prolonged stress of 7-30 days. Overall, results obtained by using both binding assays and Western blotting for the first time showed that repeated stress animals had higher levels of total hepatic cytosolic GR as compared to control animals. These novel results suggest that repeated stress influences the hypothalamic-pituitary-adrenal axis in rats by elevating both the level of plasma corticosterone and total hepatic cytosolic GR.     

Sodium balance, arterial pressure, and the role of the subfornical organ during chronic changes in dietary salt

The subfornical organ (SFO), one of the brain circumventricular organs, is known to mediate some of the central effects of angiotensin II related to sodium and water homeostasis. Because angiotensin II levels are altered with changes in chronic dietary salt intake, we reasoned that the actions of angiotensin II at the SFO might be involved in the regulation of arterial pressure during long-term alterations in dietary salt. The present study was designed to test the hypothesis that long-term control of arterial pressure during chronic changes in dietary salt intake requires an intact SFO. Male Sprague-Dawley rats were randomly selected for electrolytic lesion (SFOx, n = 8) or sham (n = 9) operation of the SFO. After a 1-wk recovery period, rats were instrumented with radio-telemetric blood pressure transducers for continuous 24-h measurement of mean arterial pressure (MAP) and heart rate (HR) and then were placed individually in metabolic cages. After another 1 wk of recovery, the rats were subjected to a 49-day protocol as follows: 1) a 7-day control period (1.0% NaCl diet), 2) 14 days of high-salt (4.0% NaCl) diet, 3) 7 days of normal-salt (1.0% NaCl) diet, 4) 14 days of low-salt (0.1% NaCl) diet, and 5) 7 days of recovery (1.0% NaCl diet). There were no significant differences in MAP or HR between SFOx and sham-operated rats throughout the protocol. These results do not support the hypothesis that the SFO is necessary for regulation of arterial pressure during chronic changes in dietary salt. However, SFOx rats demonstrated significantly less cumulative sodium balance than sham-operated rats on days 2-6 of the high-salt diet period. These data suggest that the SFO is important in the regulation of sodium homeostasis during chronic changes in salt intake.     

Expression of the immediate-early gene cFos in brain of the rats exposed to repeated 2 G influence

Early gene c-Fos expression was studied by means of c-Fos protein immunostaining in brain locus coeruleus (LC) of the rats exposed to primary and repeated hypergravity. One-hour 2 G influence on rats induced in LC cells expression of c-Fos protein, pointing out early gene c-Fos expression and synaptic activation of LC neurons. After repeated 1-hour 2 G, postponed for 35 days after primary 30-day 2 G influence, expression of c-Fos protein in LC neurons was not found. This fact is considered as a sign of memorizing of primary hypergravity influence.     

Concurrent Determination of Brain Dopamine and 5-Hydroxytryptamine Turnovers in Individual Freely Moving Rats Using Repeated Sampling of Cerebrospinal Fluid

5-Hydroxytryptamine (5-HT) turnover and dopamine (DA) turnover values were obtained in individual conscious rats by measuring the rates of accumulation of 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in cisternal CSF samples taken from each rat at 0, 30, and 60 min after probenecid (200 mg/kg i.p.) administration. In a separate experiment, 5-HT and DA turnover values were determined in CSF, striatum, and rest of brain of groups of rats killed 0, 30, or 60 min after probenecid. Whole brain turnover values were calculated from striatal and rest of brain values. Mean turnover values using CSF were comparable with both procedures. DA turnover values were greater when based on total (i.e., free + conjugated) DA metabolites than when based on free metabolites. After partial inhibition of monoamine synthesis with the decarboxylase inhibitor DL-alpha- monofluoromethyl -DOPA ( MFMD , 100 mg/kg p.o.) DA and 5-HT turnover values were comparably reduced in whole brain, rest of brain, and CSF but more markedly reduced in the striatum. Mean DA and 5-HT turnover values obtained using CSF were similar with probenecid doses over the range 150-250 mg/kg i.p. but were variable when repeatedly determined in the same rats after administration of 200 mg/kg probenecid. Results in general show that the CSF procedure may be used to determine concurrently both 5-HT and DA turnover (when estimated from the sum of total but not free metabolites) and that it provides a good index of whole brain turnover of these transmitters in the conscious individual rat.     

Influence of alternating extremely low frequency ELF magnetic field on structure and function of pancreas in rats.

The aim of this study was to estimate the influence on ultrastructure and function of endocrine and excretoric part of pancreas in rats of extremely low frequency alternating magnetic fields with parameters used in therapy in humans. The animals from the two experimental groups were exposed to a rectangular magnetic field waveform at a frequency of 10 Hz and induction of 1.8-3.8 mT--(group P) or a sinusoidal magnetic field at a frequency of 40 Hz and induction of 1.3-2.7 mT--(group S), respectively. The control rats were subjected to sham exposure. The cycle of 1, 3, 6, 9, and 14 daily exposure sessions lasting 30 min was made in all groups. Some of rats after finishing the cycle of 14 exposures were left in the same conditions except for the magnetic field for 3 or 10 days. In both groups of rats exposed to magnetic field, a distinct tendency to decrease glucose concentration, compared to control group, was observed during the exposure cycle. Serum glucose became normal after the end of exposure sessions. The concentrations of insulin in both groups of rats exposed to magnetic field were significantly higher, compared to the controls, during the exposure cycle. After the end of exposure cycle the concentration of insulin in group S became normal. In contrast, in group P the concentration of insulin decreased significantly on the last day of exposure, with a subsequent increase in the following days. The activity of alpha-amylase and lipase in the serum of experimental and control rats was not affected. In both groups of exposed rats, reversible changes of ultrastructure of the pancreatic islets, including expansion of the Golgi apparatus, extension of rough endoplasmatic reticulum, mitochondrial swelling, expansion of beta-granules and increase in number of empty vesicles in beta cells, occurred during the exposure. In acinar cells of exposed animals, a slight extension of rough endoplasmatic reticulum and mitochondrial swelling as transitory changes were observed. The structural and functional changes in pancreas are probably adaptative ones.     

Effects of microgravity on organ development of the neonatal rat.

We analyzed various organs in the same rats to study effects of gravitational condition on organ development of the neonatal rat in this study. Eight-day old and 14-day old Sprague-Dawley rats were flown for 16 days on the Space Shuttle Columbia (April 17-May 3, 1998). The organs were weighed and the ratio of the organ weight to the body weight (organ weight ratio; OBR) was calculated. Tissues were analyzed using anatomical, immunohistochemical and molecular biological technique. Six animals of the 8-day old group were reared on the ground for 30 more days after landing. The differences between flight and control rats in 8-day group were drastic. The lung, heart, kidney and adrenal glands in flight rats were significantly larger than that of control rats in OBR comparison. However, only the lung and kidney were still larger after 30 more days on ground. The kidney in flight rats performed pelvis expansion with down-regulation of aquaporin-2 expression confirmed by immunohistochemistry. The thymus, spleen, mesentery and pancreas were smaller in OBR. But the thymus in flight rats was heavier after 30 more days. The organs in flight rats which had no differences in OBR showed normal characteristics in histological analysis. We also found that the number of unmyelinated fibers of the aortic nerve in flight rats of 8-day group was smaller than that in control rats. In flight rats of the 14-day group, only the kidney was heavier and the ovary was lighter as compared to the controls. These results implied the second week of life was important for development during spaceflight. And the sensitivity and the critical period on neonatal development under microgravity might differ in each organ.     

Repeated inhalation exposure of rats to aerosols of 144CeO2. II. Effects on survival and lung, liver, and skeletal neoplasms.

Groups of 94-day-old F344/Crl rats were exposed repeatedly to aerosols of 144CeO2 to reestablish desired lung burdens of 1.9, 9.2, 46, or 230 kBq of 144Ce every 60 days for 1 year (seven exposures). Other 94-day-old rats were exposed once to achieve similar desired initial lung burdens of 144Ce. Older rats were exposed once to achieve desired initial lung burdens of 46 or 230 kBq when 500 days of age, the same age at which rats had the last of the repeated exposures. Control rats were either unexposed, sham-exposed once or repeatedly, or exposed once or repeatedly to stable CeO2. Approximately equal numbers of male and female rats were used. The median survival time and cumulative percentage survival curves were significantly decreased only in male and female rats exposed repeatedly to reestablish a 230-kBq lung burden and among the 94-day-old male rats exposed once to achieve a 230-kBq lung burden of 144Ce. The crude incidences of primary lung cancers (well described by a single Weibull distribution function), time to death with lung tumors, and risk of lung cancer per unit of beta-radiation dose to the lungs were correlated with the cumulative beta-radiation dose rather than the rate at which the dose was accumulated. A linear function, 70 (+/- 7.3) + -0.15 (+/- 0.056) x dose (+/- SD), adequately described the excess numbers of rats with lung cancers over a beta-radiation dose range to the lungs of 6.8 to 250 Gy for two groups of rats with the highest doses to the lungs after a single exposure and for two groups with the highest doses after repeated exposure.     

Experimental Brain Ischemia: Neuron-Specific Enolase Level in Cerebrospinal Fluid as an Index of Neuronal Damage

Levels of neuron-specific enolase (NSE) were measured in rat CSF following occlusion of the four major arteries to the brain for 10, 20, or 30 min. In the CSF of rats submitted to 30 min of total ischemia, an up to nine-fold increase of NSE level occurred within the first few hours and then slowly diminished. Significant levels were seen for as long as 8 days. Histological observations 3 days after ischemia showed neuronal loss as well as neuronal damage in several forebrain regions such as hippocampus, striatum, and thalamus. Ischemia was followed by transient decreases in exploration behavior and neurological states that were no longer visible 24 h later. After 10 or 20 min ischemia, NSE levels were increased to a lesser degree and fewer damaged neurons were observed. The positive correlation between duration of ischemia and amount of NSE release in CSF indicates that the measurement of NSE in the CSF is a sensitive and reliable index of neuronal lesions.