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Sample records for irradiated rat brain

  1. Cognitive dysfunction and histological findings in adult rats one year after whole brain irradiation.

    PubMed

    Akiyama, K; Tanaka, R; Sato, M; Takeda, N

    2001-12-01

    Cognitive dysfunction and histological changes in the brain were investigated following irradiation in 20 Fischer 344 rats aged 6 months treated with whole brain irradiation (WBR) (25 Gy/single dose), and compared with the same number of sham-irradiated rats as controls. Performance of the Morris water maze task and the passive avoidance task were examined one year after WBR. Finally, histological and immunohistochemical examinations using antibodies to myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and neurofilament (NF) were performed of the rat brains. The irradiated rats continued to gain weight 7 months after WBR whereas the control rats stopped gaining weight. Cognitive functions in both the water maze task and the passive avoidance task were lower in the irradiated rats than in the control rats. Brain damage consisting of demyelination only or with necrosis was found mainly in the body of the corpus callosum and the parietal white matter near the corpus callosum in the irradiated rats. Immunohistochemical examination of the brains without necrosis found MBP-positive fibers were markedly decreased in the affected areas by irradiation; NF-positive fibers were moderately decreased and irregularly dispersed in various shapes in the affected areas; and GFAP-positive fibers were increased, with gliosis in those areas. These findings are similar to those in clinically accelerated brain aging in conditions such as Alzheimer's disease, Binswanger's disease, and multiple sclerosis.

  2. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour

    PubMed Central

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-01

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects. We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model. Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males. PMID:26678032

  3. SU-E-T-492: Implementing a Method for Brain Irradiation in Rats Utilizing a Commercially Available Radiosurgery Irradiator

    SciTech Connect

    Cates, J; Drzymala, R

    2014-06-01

    Purpose: The purpose of the study was to implement a method for accurate rat brain irradiation using the Gamma Knife Perfexion unit. The system needed to be repeatable, efficient, and dosimetrically and spatially accurate. Methods: A platform (“rat holder”) was made such that it is attachable to the Leskell Gamma Knife G Frame. The rat holder utilizes two ear bars contacting bony anatomy and a front tooth bar to secure the rat. The rat holder fits inside of the Leskell localizer box, which utilizes fiducial markers to register with the GammaPlan planning system. This method allows for accurate, repeatable setup.A cylindrical phantom was made so that film can be placed axially in the phantom. We then acquired CT image sets of the rat holder and localizer box with both a rat and the phantom. Three treatment plans were created: a plan on the rat CT dataset, a phantom plan with the same prescription dose as the rat plan, and a phantom plan with the same delivery time as the rat plan. Results: Film analysis from the phantom showed that our setup is spatially accurate and repeatable. It is also dosimetrically accurate, with an difference between predicted and measured dose of 2.9%. Film analysis with prescription dose equal between rat and phantom plans showed a difference of 3.8%, showing that our phantom is a good representation of the rat for dosimetry purposes, allowing for +/- 3mm diameter variation. Film analysis with treatment time equal showed an error of 2.6%, which means we can deliver a prescription dose within 3% accuracy. Conclusion: Our method for irradiation of rat brain has been shown to be repeatable, efficient, and accurate, both dosimetrically and spatially. We can treat a large number of rats efficiently while delivering prescription doses within 3% at millimeter level accuracy.

  4. Fetal hypothalamic transplants into brain irradiated rats: Graft morphometry and host behavioral responses

    SciTech Connect

    Pearlman, S.H.; Rubin, P.; White, H.C.; Wiegand, S.J.; Gash, D.M. )

    1990-08-01

    This study was designed to test the hypothesis that neural implants can ameliorate or prevent some of the long-term changes associated with CNS irradiation. Using a rat model, the initial study focused on establishing motor, regulatory, and morphological changes associated with brain radiation treatments. Secondly, fetal hypothalamic tissue grafts were placed into the third ventricle of rats which had been previously irradiated. Adult male Long Evans rats received one of three radiation doses (15, 22.5, 30 Gy) or no radiation. Three days after irradiation, 7 animals in each dose group received an embryonic day 17 hypothalamic graft into the third ventricle while the remaining 8-9 animals in each group received injections of vehicle solution (sham). Few changes were observed in the 15 and 22.5 Gy animals, however rats in the 30 Gy treatment group showed stereotypic and ambulatory behavioral hyperactivity 32 weeks after irradiation. Regulatory changes in the high dose group included decreased growth rate and decreased urine osmolalities, but these measures were extremely variable among animals. Morphological results demonstrated that 30 Gy irradiated animals showed extensive necrosis primarily in the fimbria, which extended into the internal capsule, optic nerve, hippocampus, and thalamus. Hemorrhages were found in the hippocampus, thalamus, and fimbria. Defects in the blood-brain barrier also were evident by entry of intravascularly injected horseradish peroxidase into the parenchyma of the brain. Animals in the 30 Gy grafted group showed fewer behavioral changes and less brain damage than their sham grafted counterparts. Specifically, activity measures were comparable to normal levels, and a dilute urine was not found in the 30 Gy implanted rats. Morphological changes support these behavioral results since only two 30 Gy implanted rats showed necrosis.

  5. Effects of single-dose and fractionated cranial irradiation on rat brain accumulation of methotrexate

    SciTech Connect

    Kamen, B.A.; Moulder, J.E.; Kun, L.E.; Ring, B.J.; Adams, S.M.; Fish, B.L.; Holcenberg, J.S.

    1984-11-01

    The effects of single-dose and fractionated whole-brain irradiation on brain methotrexate (MTX) has been studied in a rat model. The amount of MTX present in the brain 24 hr after a single i.p. dose (100 mg/kg) was the same whether animals were sham irradiated or given a single dose of 2000 rads 6 or 48 hr prior to the drug (6.9, 8.3, and 6.8 pmol MTX/g, wet weight, respectively). Animals sham irradiated or given 2000 rads in 10 fractions over 11 days and treated with an average dose of 1.2 mg MTX/kg i.p. twice a week for 24 weeks did not differ significantly in their brain MTX concentration (7.9 and 8.3 pmol MTX/g, wet weight, respectively). Chronically MTX-treated animals became folate deficient whether they were irradiated or not (450 and 670 pmol folate/g, wet weight, brain in MTX-treated and control animals). Thus, MTX accumulates in the brain with acute or chronic administration, and this accumulation is not altered by this amount of brain irradiation.

  6. Cerebrovascular and metabolic effects on the rat brain of focal Nd:YAG laser irradiation

    SciTech Connect

    Kiessling, M.; Herchenhan, E.; Eggert, H.R. )

    1990-12-01

    To investigate the effects of focal neodymium:yttrium-aluminum-garnet (Nd:YAG) laser irradiation (lambda = 1060 nm) on regional cerebral blood flow, cerebral protein synthesis, and blood-brain barrier permeability, the parietal brain surface of 44 rats was irradiated with a focused laser beam at a constant output energy of 30 J. Survival times ranged from 5 minutes to 48 hours. Laser irradiation immediately caused well-defined cortical coagulation necrosis. Within 5 minutes after unilateral irradiation, 14C-iodoantipyrine autoradiographs demonstrated severely reduced blood flow to the irradiation site and perilesional neocortex, but a distinct reactive hyperemia in all other areas of the forebrain. Apart from a persistent ischemic focus in the vicinity of the cortical coagulation necrosis, blood flow alterations in remote areas of the brain subsided within 3 hours after irradiation. Autoradiographic assessment of 3H-tyrosine incorporation into brain proteins revealed rapid onset and prolonged duration of protein synthesis inhibition in perifocal morphologically intact cortical and subcortical structures. Impairment of amino acid incorporation proved to be completely reversible within 48 hours. Immunoautoradiographic visualization of extravasated plasma proteins using 3H-labeled rabbit anti-rat immunoglobulins-showed that, up to 1 hour after irradiation, immunoreactive proteins were confined to the neocortex at the irradiation site. At 4 hours, vasogenic edema was present in the vicinity of the irradiation site and the subcortical white matter, and, at later stages (16 to 36 hours), also extended into the contralateral hemisphere. Although this was followed by a gradual decrease in labeling intensity, resolution of edema was still not complete after 48 hours.

  7. Low dose X-irradiation mitigates diazepam induced depression in rat brain.

    PubMed

    Kaur, Amandeep; Singla, Neha; Dhawan, D K

    2016-10-01

    Depression is considered as one of the most prevalent health ailments. Various anti-depressant drugs have been used to provide succour to this ailment, but with little success and rather have resulted in many side effects. On the other hand, low dose of ionizing radiations are reported to exhibit many beneficial effects on human body by stimulating various biological processes. The present study was conducted to investigate the beneficial effects of low doses of X-rays, if any, during diazepam induced depression in rats. Female Sprague Dawley rats were segregated into four different groups viz: Normal control, Diazepam treated, X-irradiated and Diazepam + X-irradiated. Depression model was created in rats by subjecting them to diazepam treatment at a dosage of 2 mg/kg b.wt./day for 3 weeks. The skulls of animals belonging to X-irradiated and Diazepam + X-irradiated rats were X-irradiated with a single fraction of 0.5 Gy, given twice a day for 3 days, thereby delivered dose of 3 Gy. Diazepam treated animals showed significant alterations in the neurobehavior and neuro-histoarchitecture, which were improved after X-irradiation. Further, diazepam exposure significantly decreased the levels of neurotransmitters and acetylcholinesterase activity, but increased the monoamine oxidase activity in brain. Interestingly, X-rays exposure to diazepam treated rats increased the levels of neurotransmitters, acetylcholinesterase activity and decreased the monoamine oxidase activity. Further, depressed rats also showed increased oxidative stress with altered antioxidant parameters, which were normalized on X-rays exposure. The present study, suggests that low dose of ionizing radiations, shall prove to be an effective intervention and a novel therapy in controlling depression and possibly other brain related disorders.

  8. Low dose X-irradiation mitigates diazepam induced depression in rat brain.

    PubMed

    Kaur, Amandeep; Singla, Neha; Dhawan, D K

    2016-10-01

    Depression is considered as one of the most prevalent health ailments. Various anti-depressant drugs have been used to provide succour to this ailment, but with little success and rather have resulted in many side effects. On the other hand, low dose of ionizing radiations are reported to exhibit many beneficial effects on human body by stimulating various biological processes. The present study was conducted to investigate the beneficial effects of low doses of X-rays, if any, during diazepam induced depression in rats. Female Sprague Dawley rats were segregated into four different groups viz: Normal control, Diazepam treated, X-irradiated and Diazepam + X-irradiated. Depression model was created in rats by subjecting them to diazepam treatment at a dosage of 2 mg/kg b.wt./day for 3 weeks. The skulls of animals belonging to X-irradiated and Diazepam + X-irradiated rats were X-irradiated with a single fraction of 0.5 Gy, given twice a day for 3 days, thereby delivered dose of 3 Gy. Diazepam treated animals showed significant alterations in the neurobehavior and neuro-histoarchitecture, which were improved after X-irradiation. Further, diazepam exposure significantly decreased the levels of neurotransmitters and acetylcholinesterase activity, but increased the monoamine oxidase activity in brain. Interestingly, X-rays exposure to diazepam treated rats increased the levels of neurotransmitters, acetylcholinesterase activity and decreased the monoamine oxidase activity. Further, depressed rats also showed increased oxidative stress with altered antioxidant parameters, which were normalized on X-rays exposure. The present study, suggests that low dose of ionizing radiations, shall prove to be an effective intervention and a novel therapy in controlling depression and possibly other brain related disorders. PMID:27316553

  9. Gamma Knife irradiation method based on dosimetric controls to target small areas in rat brains

    SciTech Connect

    Constanzo, Julie; Paquette, Benoit; Charest, Gabriel; Masson-Côté, Laurence; Guillot, Mathieu

    2015-05-15

    Purpose: Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The purpose of this work is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Methods: Euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomography (CT), to estimate positioning variations relative to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates obtained from CT images, different regions of the brain were delimited and a treatment plan was generated. A single isocenter treatment plan delivering ≥100 Gy in 100% of the target volume was produced by Leksell GammaPlan using the 4 mm diameter collimator of sectors 4, 5, 7, and 8 of the Gamma Knife unit. Impact of positioning deviations of the rat brain on dose deposition was simulated by GammaPlan and validated with dosimetric measurements. Results: The authors’ results showed that 90% of the target volume received 100 ± 8 Gy and the maximum of deposited dose was 125 ± 0.7 Gy, which corresponds to an excellent relative standard deviation of 0.6%. This dose deposition calculated with GammaPlan was validated with dosimetric films resulting in a dose-profile agreement within 5%, both in X- and Z-axes. Conclusions: The authors’ results demonstrate the feasibility of standardizing the irradiation procedure of a small volume in the rat brain using a Gamma Knife.

  10. Electroacupuncture Prevents Cognitive Impairments by Regulating the Early Changes after Brain Irradiation in Rats

    PubMed Central

    Fan, Xing-Wen; Chen, Fu; Chen, Yan; Chen, Guan-Hao; Liu, Huan-Huan; Guan, Shi-Kuo; Deng, Yun; Liu, Yong; Zhang, Sheng-Jian; Peng, Wei-Jun; Jiang, Guo-Liang; Wu, Kai-Liang

    2015-01-01

    Cognitive impairments severely affect the quality of life of patients who undergo brain irradiation, and there are no effective preventive strategies. In this study, we examined the therapeutic potential of electroacupuncture (EA) administered immediately after brain irradiation in rats. We detected changes in cognitive function, neurogenesis, and synaptic density at different time points after irradiation, but found that EA could protect the blood-brain barrier (BBB), inhibit neuroinflammatory cytokine expression, upregulate angiogenic cytokine expression, and modulate the levels of neurotransmitter receptors and neuropeptides in the early phase. Moreover, EA protected spatial memory and recognition in the delayed phase. At the cellular/molecular level, the preventative effect of EA on cognitive dysfunction was not dependent on hippocampal neurogenesis; rather, it was related to synaptophysin expression. Our results suggest that EA applied immediately after brain irradiation can prevent cognitive impairments by protecting against the early changes induced by irradiation and may be a novel approach for preventing or ameliorating cognitive impairments in patients with brain tumors who require radiotherapy. PMID:25830357

  11. Effects of nerve growth factor on X-irradiated reaggregation cultures of rat brain cells.

    PubMed

    Dimberg, Y; Aspberg, A; Tottmar, O

    1993-12-01

    The effects of exogenously added nerve growth factor (NGF) on reaggregation cultures of foetal rat brain cells after X-irradiation with 2 Gy were studied. Irradiation caused decreased protein and DNA levels, which was not prevented by NGF. The activities of the cholinergic marker enzymes choline acetyl transferase and acetylcholine esterase were increased in irradiated cultures. However, no difference in the activities of these enzymes was found between irradiated and unirradiated NGF-treated cultures. Irradiation did not affect the activity of the marker enzyme for oligodendrocytes (2',3'-cyclic nucleotide 3'-phosphodiesterase), but caused an increase in the astrocyte marker (glutamine synthetase) activity. This effect on astrocytes was prevented by NGF. PMID:7903341

  12. Modulation of gamma-irradiation and carbon tetrachloride induced oxidative stress in the brain of female rats by flaxseed oil.

    PubMed

    Ismail, Amel F M; Salem, Asmaa A M; Eassawy, Mamdouh M T

    2016-08-01

    The activity of flaxseed oil (FSO) on gamma-irradiation (7Gy) and/or carbon tetrachloride (CCl4) induced acute neurotoxicity in rats' brain was investigated. The results revealed a significant decrease (p<0.05) in superoxide dismutase (SOD), catalase (CAT), glutathione-peroxidase (GSH-Px) activities, reduced glutathione (GSH) and manganese (Mn) contents. Further, a significant elevation (p<0.05) in malondialdehyde, nitric oxide (NO), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1-beta (IL-1β), Interleukin-6 (IL-6), transforming growth factor-beta-1 (TGF-β1), iron (Fe), calcium (Ca), copper (Cu) and magnesium (Mg) levels were observed. Furthermore, the relative ratio of xanthine oxidase (XO) and inducible nitric-oxide synthase (iNOS) gene expression levels were elevated in the brain tissues of γ-irradiated and CCl4 intoxicated animals. Those effects were augmented due to the effect of CCl4-induced toxicity in γ-irradiated rats. The treatment of FSO displayed significant amendment of the studied parameters in the brain tissues of γ-irradiated and CCl4 intoxicated animals. FSO has a neuroprotective effect against CCl4-induced brain injury in gamma-irradiated rats. This effect is interrelated to the ability of FSO to scavenges the free radicals, enhances the antioxidant enzymes activity, increases GSH contents, down-regulates the inflammatory responses, ameliorates the iron, calcium, copper, magnesium, manganese levels and inhibiting the gene expression level of XO and iNOS in the brain tissues of intoxicated animals. In conclusion, this study demonstrated that the potent antioxidant and anti-inflammatory activities of FSO have the ability to improve the antioxidant status, suppress the inflammatory responses, and regulate the trace elements in the brain tissues of γ-irradiated, CCl4, and their combined effect in intoxicated animals. Consequently, FSO exhibited neuroprotective activity on γ-irradiated, CCl4, and their combined effect induced brain injury in

  13. Modulation of gamma-irradiation and carbon tetrachloride induced oxidative stress in the brain of female rats by flaxseed oil.

    PubMed

    Ismail, Amel F M; Salem, Asmaa A M; Eassawy, Mamdouh M T

    2016-08-01

    The activity of flaxseed oil (FSO) on gamma-irradiation (7Gy) and/or carbon tetrachloride (CCl4) induced acute neurotoxicity in rats' brain was investigated. The results revealed a significant decrease (p<0.05) in superoxide dismutase (SOD), catalase (CAT), glutathione-peroxidase (GSH-Px) activities, reduced glutathione (GSH) and manganese (Mn) contents. Further, a significant elevation (p<0.05) in malondialdehyde, nitric oxide (NO), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1-beta (IL-1β), Interleukin-6 (IL-6), transforming growth factor-beta-1 (TGF-β1), iron (Fe), calcium (Ca), copper (Cu) and magnesium (Mg) levels were observed. Furthermore, the relative ratio of xanthine oxidase (XO) and inducible nitric-oxide synthase (iNOS) gene expression levels were elevated in the brain tissues of γ-irradiated and CCl4 intoxicated animals. Those effects were augmented due to the effect of CCl4-induced toxicity in γ-irradiated rats. The treatment of FSO displayed significant amendment of the studied parameters in the brain tissues of γ-irradiated and CCl4 intoxicated animals. FSO has a neuroprotective effect against CCl4-induced brain injury in gamma-irradiated rats. This effect is interrelated to the ability of FSO to scavenges the free radicals, enhances the antioxidant enzymes activity, increases GSH contents, down-regulates the inflammatory responses, ameliorates the iron, calcium, copper, magnesium, manganese levels and inhibiting the gene expression level of XO and iNOS in the brain tissues of intoxicated animals. In conclusion, this study demonstrated that the potent antioxidant and anti-inflammatory activities of FSO have the ability to improve the antioxidant status, suppress the inflammatory responses, and regulate the trace elements in the brain tissues of γ-irradiated, CCl4, and their combined effect in intoxicated animals. Consequently, FSO exhibited neuroprotective activity on γ-irradiated, CCl4, and their combined effect induced brain injury in

  14. Effect of Alpha-Particle Irradiation on Brain Glycogen in the Rat

    NASA Technical Reports Server (NTRS)

    Wolfe, L. S.; Klatzo, Igor; Miquel, Jaime; Tobias, Cornelius; Haymaker, Webb

    1962-01-01

    The studies of Klatzo, Miquel, Tobias and Haymaker (1961) have shown that one of the earliest and most sensitive indications of the effects of alpha-particle irradiation on rat bran is the appearance of glycogen granules mainly in the neuroglia of the exposed area of the brain. Periodic acid-Schiff (PAS) positive, alpha-amylase soluble granules were demonstrated within 12 hr after irradiation, preceding by approximately 36 hr the first microscopically detectable vascular permeability disturbances, as shown by the fluorescein labeled serum protein technique. These studies suggested that the injurious effects of alpha-particle energy were on cellular elements primarily, according to the physical properties and distribution of the radiation in the tissue, and that the vascular permeability disturbances played a secondary role in pathogenesis. The purpose of this study was to correlate the histochemical observations on glycogen with a quantitative assessment of the glycogen in the irradiated brain tissue. It is felt that such a study may contribute to the understanding of radiation injury at the molecular level. A practical aspect of this problem is that the information on biological radiation effects due to accelerated particles from the cyclotron source, is employed in this study, is applicable to radiation from cosmic particles both in free space and entrapped in the Van Allen belts.

  15. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    PubMed

    Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

    2012-01-01

    Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and

  16. Microwave irradiation decreases ATP, increases free [Mg2+], and alters in vivo intracellular reactions in rat brain

    PubMed Central

    Srivastava, Shireesh; Kashiwaya, Yoshihiro; Chen, Xuesong; Geiger, Jonathan D.; Pawlosky, Robert; Veech, Richard L.

    2012-01-01

    Rapid inactivation of metabolism is essential for accurately determining the concentrations of metabolic intermediates in the in vivo state. We compared a broad spectrum of energetic intermediate metabolites and neurotransmitters in brains obtained by microwave irradiation to those obtained by freeze blowing, the most rapid method of extracting and freezing rat brain. The concentrations of many intermediates, cytosolic free NAD(P)+/NAD(P)H ratios, as well as neurotransmitters were not affected by the microwave procedure. However, the brain concentrations of ATP were about 30% lower, whereas those of ADP, AMP, and GDP were higher in the microwave-irradiated compared with the freeze-blown brains. In addition, the hydrolysis of approximately 1 μmol/g of ATP, a major in vivo Mg2+-binding site, was related to approximately five-fold increase in free [Mg2+] (0.53 ± 0.07 mM in freeze blown vs. 2.91 mM ± 0.48 mM in microwaved brains), as determined from the ratio [citrate]/[isocitrate]. Consequently, many intracellular properties, such as the phosphorylation potential and the ΔG’ of ATP hydrolysis were significantly altered in microwaved tissue. The determinations of some glycolytic and TCA cycle metabolites, the phosphorylation potential, and the ΔG’ of ATP hydrolysis do not represent the in vivo state when using microwave-fixed brain tissue. PMID:23013291

  17. Control of anoxic depolarization in rat brain by near-infrared laser irradiation and its monitoring by intrinsic optical signal imaging

    NASA Astrophysics Data System (ADS)

    Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Ashida, Hiroshi

    2012-03-01

    In brain anoxia or ischemia, spreading depolarization is a key event that deterimines brain tissue survival. After onset of anoxia/ischemia, impairment of energy metabolism causes anoxic/ischemic depolarization (AD), which considerably consumes energy, leading to acute neuronal death in the brain. Our previous intrinsic-optical-signal imaging for the rat brains showed that about 2 min after starting hypoxia, AD-related light-scattering waves were focally generated in the bilateral outermost regions in the cortex and spread toward the midline, indicating that AD can be monitored by lightscattering signal. The behaviors of the scattering waves were found to be correlated with the survival of the rats. In the present study, we used the scattering signal-based monitoring method for AD and examined whether near-infrared laser irradiation can control AD in the rat brains. The left hemisphere was irradiated with 808-nm laser transcranially at 7.5 mW/cm2 before (30 min) and during hypoxia. The onset time of the scattering wave (AD) was significantly delayed in the irradiated hemisphere when compared with that in the non-irradiated hemisphere (3.4 s, n=8). The area of AD spreading in the irradiated hemisphere was significantly smaller than that in the non-irradiated hemisphere (27-90% reduction at 10-50 s after AD onset). These results suggest that near-infrared light can delay and reduce anoxic depolarization in the brain, which is probably due to increase in the cerebral ATP by near-infrared laser irradiation.

  18. Effects of naltrexone in postnatal rats on the recovery of disturbed brain and lymphatic tissues after X-irradiation or ethylnitrosourea treatment in utero

    SciTech Connect

    Schmahl, W.G.; Plendl, J.; Reinoehl-Kompa, S.

    1987-01-01

    The role of endogenous opioid systems in preweaning development after intrauterine exposure to X-irradiation or ethylnitrosourea (ENU) was explored in rats using naltrexone, a potent antagonist of beta-endorphin. After daily s.c. injections of 50 mg/kg naltrexone only the prenatally untreated controls had body weights increased by 11% from control level on day 28 (weaning). In the X-irradiated as well as the ENU-treated pups no significant effects of naltrexone on body weight gain were observed. However, brain weight increased in all animals under the influence of naltrexone, irrespective of prenatal treatment or the severity of brain lesions: 9.5% above control values in untreated offspring and 14% after X-irradiation (1 Gy) on gestation day 14. The brain weight of ENU-treated rats (50 mg/kg on gest. day 14) was 13% higher after postnatal naltrexone application than that of their postnatally untreated counterparts. ENU (80 mg/kg) effects on the brain when given on gestation day 18 were ameliorated to 9.2% by naltrexone in the weaning period. Naltrexone significantly increased the thymus weight in controls. Prenatally treated animals also showed an increased thymus weight at weaning, presumably due to compensatory growth. In these cases naltrexone revealed a suppressive effect on the thymus, whereas spleen weight was apparently not influenced by naltrexone treatment. These results provide compelling evidence that endogenous opioid systems play a crucial role not only in normal development, but also in reparative growth events of the brain after prenatal injuries. The thymus, predominantly containing T-lymphocytes, seems to represent another sensitive system which is regulated under the influence of opioids.

  19. Local brain heavy ion irradiation induced Immunosuppression

    NASA Astrophysics Data System (ADS)

    Lei, Runhong; Deng, Yulin; Huiyang Zhu, Bitlife.; Zhao, Tuo; Wang, Hailong; Yu, Yingqi; Ma, Hong; Wang, Xiao; Zhuang, Fengyuan; Qing, Hong

    Purpose: To investigate the long term effect of acute local brain heavy ion irradiation on the peripheral immune system in rat model. Methodology: Only the brain of adult male Wistar rats were radiated by heavy ions at the dose of 15 Gy. One, two and three months after irradiation, thymus and spleen were analyzed by four ways. Tunel assay was performed to evaluate the percentage of apoptotic cells in thymus and spleen, level of Inflammatory cytokines (IL-2, IL-6, SSAO, and TNF-α) was detected by ELISA assay, the differentiation of thymus T lymphocyte subsets were measured by flow cytometry and the relative expression levels of genes related to thymus immune cell development were measured by using quantitative real-time PCR. Results: Thymus and spleen showed significant atrophy from one month to three months after irradiation. A high level of apoptosis in thymus and spleen were obtained and the latter was more vulnerable, also, high level of inflammatory cytokines were found. Genes (c-kit, Rag1, Rag2 and Sca1) related to thymus lymphocytes’ development were down-regulated. Conclusion: Local area radiation in the rat brain would cause the immunosuppression, especially, the losing of cell-mediated immune functions. In this model, radiation caused inflammation and then induced apoptosis of cells in the immune organs, which contributed to immunosuppression.

  20. Washout rate in rat brain irradiated by a 11C beam after acetazolamide loading using a small single-ring OpenPET prototype

    NASA Astrophysics Data System (ADS)

    Hirano, Yoshiyuki; Takuwa, Hiroyuki; Yoshida, Eiji; Nishikido, Fumihiko; Nakajima, Yasunori; Wakizaka, Hidekatsu; Yamaya, Taiga

    2016-03-01

    In dose verification techniques of particle therapies based on in-beam positron emission tomography (PET), the causes of washout of positron emitters by physiological effects should be clarified to correct washout for accurate verification. As well, the quantitative washout rate has a potential usefulness as a diagnostic index which should be explored. Therefore, we measured washout rates of rat brain after vasodilator acetazolamide loading to investigate the possible effects of blood flow on washout. Six rat brains were irradiated by a radioisotope 11C beam and time activity curves on the whole brains were obtained with a small single-ring OpenPET prototype. Then, washout rates were calculated with the Mizuno model, where two washout rates (k 2m and k 2s ) were assumed, and a two-compartment model including efflux from tissue to blood (k 2) and influx (k 3) and efflux (k 4) between the two tissue compartments. Before the irradiations, we used laser-Doppler flowmetry to confirm that acetazolamide increased cerebral blood flow (CBF) of a rat. We compared means of k 2m , k 2s and k 2, k 3 and k 4 without acetazolamide loading (Rest) and with acetazolamide loading (ACZ). For all k values, ACZ values were lower than Rest values. In other words, though CBF increased, washout rates were decreased. This may be attributed to the implanted 11C reacting to form 11CO2. Because acetazolamide increased the concentration of CO2 in brain, suppressed diffusion of 11CO2 and decomposition of 11CO2 into ions were prevented.

  1. Effects of chronic postnatal opioid receptor blockade by naltrexone upon proliferation capacity in the prenatally x-irradiated brain of the rat

    SciTech Connect

    Schmahl, W.; Miaskowski, U. )

    1991-01-01

    We recently reported that in rats prenatally x-irradiated on gestation day 14 with 1 Gy, postnatal chronic application of the opioid antagonist naltrexone (Nx) led to a remarkable growth spurt of the microencephalic brain. In the present study we present histological and autoradiographic results found in the subependymal layer (SEL) of the forebrain lateral ventricles. Nx led to an intermittent augmentation of the mitotic index of the x-irradiated brains within a postnatal observation period of 24 weeks. The most conspicuous finding was transient hyperplasia of the SEL at 4-6 weeks of age which occurred in close proximity to an intact ependymal lining. Districts of the lateral ventricles which were denuded from ependyme and where the rest of the ependymal layer (EL) was dislocated peripherally showed upon Nx treatment a long-lasting SEL hyperplasia with a tendency towards dysplasia. These results revealed that repair proliferation of embryotoxic x-irradiation is normally under strong control by the opioid system. If that system, which exerts a suppressing effect upon glial growth, is blocked by Nx, prominent hyperplastic reactions occur which may be useful for repairing the lesion pattern.

  2. Interstitial irradiation of brain tumors: a review

    SciTech Connect

    Bernstein, M.; Gutin, P.H.

    1981-12-01

    As an adjuvant to surgery, radiation therapy has consistently proven to be the most successful form of treatment for primary and secondary malignant brain tumors and possibly for inoperable benign tumors. Because the risk of radiation necrosis of normal brain limits the amount of radiation that can be given by external beam therapy at conventional dose rates, interstitial radiation of brain tumors is a logical alternative treatment approach. We discuss the radiobiological advantages of low dose rate irradiation and intratumoral placement of sources that make interstitial irradiation an attractive treatment for brain tumors and review the history of clinical brachytherapy for intracranial neoplasia.

  3. Brain tumors in irradiated monkeys.

    NASA Technical Reports Server (NTRS)

    Haymaker, W.; Miquel, J.; Rubinstein, L. J.

    1972-01-01

    A study was made of 32 monkeys which survived one to seven years after total body exposure to protons or to high-energy X rays. Among these 32 monkeys there were 21 which survived two years or longer after exposure to 200 to 800 rad. Glioblastoma multiforme developed in 3 of the 10 monkeys surviving three to five years after receiving 600 or 800 rad 55-MeV protons. Thus, the incidence of tumor development in the present series was far higher than the incidence of spontaneously developing brain tumors in monkeys cited in the literature. This suggests that the tumors in the present series may have been radiation-induced.

  4. Brain astrocytomas: biopsy, then irradiation.

    PubMed

    Lunsford, L D; Somaza, S; Kondziolka, D; Flickinger, J C

    1995-01-01

    terms of glial tumor management. These goals include prolonged and higher-quality survival, reduced surgical and postoperative morbidity, and the development of new surgical, chemotherapeutic, and molecular tools that will allow us to improve clinical outcomes. Needless and senseless arguing over cytoreductive surgery versus biopsy, radiation versus no radiation, or any of these procedures versus observation alone trivialize the issues that face us and our patients: astrocytomas of the brain are neither indolent nor benign. The vast majority of our patients with astrocytomas are dead within 5 years, and almost all within 10. Our papers, our meetings, our approach should encourage us to pursue new basic science and clinical strategies to fight glial neoplasms. Surgery alone cures no patient with a glioma. Radiation therapy cures relatively few, and chemotherapy cures none. New ideas and new approaches are needed to improve the plight of our patients.

  5. Damage and repair of irradiated mammalian brain

    SciTech Connect

    Frankel, K.; Lo, E.; Phillips, M.; Fabrikant, J.; Brennan, K.; Valk, P.; Poljak, A.; Delapaz, R.; Woodruff, K.; Stanford Univ., CA . Medical Center; Brookside Hospital, San Pablo, CA )

    1989-07-01

    We have demonstrated that focal charged particle irradiation of the rabbit brain can create well-defined lesions which are observable by nuclear magnetic resonance imaging (NMR) and positron emission tomography (PET) imaging techniques. These are similar, in terms of location and characteristic NMR and PET features, to those that occur in the brain of about 10% of clinical research human subjects, who have been treated for intracranial vascular malformations with stereotactic radiosurgery. These lesions have been described radiologically as vasogenic edema of the deep white matter,'' and the injury is of variable intensity and temporal duration, can recede or progress to serious neurologic sequelae, and persist for a considerable period of time, frequently 18 mon to 3 yr. 8 refs., 6 figs.

  6. Head and neck tumors after energetic proton irradiation in rats

    NASA Astrophysics Data System (ADS)

    Wood, D.; Cox, A.; Hardy, K.; Salmon, Y.; Trotter, R.

    1994-10-01

    This is a two-year progress report on a life span dose-response study of brain tumor risk at moderate to high doses of energetic protons. It was initiated because a joint NASA/USAF life span study of rhesus monkeys that were irradiated with 55-MeV protons (average surface dose, 3.5 Gy) indicated that the incidence of brain tumors per unit surface absorbed dose was over 19 times that of the human tinea capitis patients whose heads were exposed to 100 kv x-rays. Examination of those rats that died in the two-year interval after irradiation of the head revealed a linear dose-response for total head and neck tumor incidence in the dose range of 0-8.5 Gy. The exposed rats had a greater incidence of pituitary chromophobe adenomas, epithelial and mesothelial cell tumors than the unexposed controls but the excessive occurrence of malignant gliomas that was observed in the monkeys was absent in the rats. The estimated dose required to double the number of all types of head and neck tumors was 5.2 Gy. The highest dose, 18 Gy, resulted in high mortality due to obstructive squamous metaplasia at less than 50 weeks, prompting a new study of the relative bological effectiveness of high energy protons in producing this lesion.

  7. Hypothalamic dysfunction following whole-brain irradiation

    SciTech Connect

    Mechanick, J.I.; Hochberg, F.H.; LaRocque, A.

    1986-10-01

    The authors describe 15 cases with evidence of hypothalamic dysfunction 2 to 9 years following megavoltage whole-brain x-irradiation for primary glial neoplasm. The patients received 4000 to 5000 rads in 180- to 200-rad fractions. Dysfunction occurred in the absence of computerized tomography-delineated radiation necrosis or hypothalamic invasion by tumor, and antedated the onset of dementia. Fourteen patients displayed symptoms reflecting disturbances of personality, libido, thirst, appetite, or sleep. Hyperprolactinemia (with prolactin levels up to 70 ng/ml) was present in all of the nine patients so tested. Of seven patients tested with thyrotropin-releasing hormone, one demonstrated an abnormal pituitary gland response consistent with a hypothalamic disorder. Seven patients developed cognitive abnormalities. Computerized tomography scans performed a median of 4 years after tumor diagnosis revealed no hypothalamic tumor or diminished density of the hypothalamus. Cortical atrophy was present in 50% of cases and third ventricular dilatation in 58%. Hypothalamic dysfunction, heralded by endocrine, behavioral, and cognitive impairment, represents a common, subtle form of radiation damage.

  8. Profound and Sexually Dimorphic Effects of Clinically-Relevant Low Dose Scatter Irradiation on the Brain and Behavior

    PubMed Central

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Yaroslav; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kolb, Bryan; Kovalchuk, Olga

    2016-01-01

    Irradiated cells can signal damage and distress to both close and distant neighbors that have not been directly exposed to the radiation (naïve bystanders). While studies have shown that such bystander effects occur in the shielded brain of animals upon body irradiation, their mechanism remains unexplored. Observed effects may be caused by some blood-borne factors; however they may also be explained, at least in part, by very small direct doses received by the brain that result from scatter or leakage. In order to establish the roles of low doses of scatter irradiation in the brain response, we developed a new model for scatter irradiation analysis whereby one rat was irradiated directly at the liver and the second rat was placed adjacent to the first and received a scatter dose to its body and brain. This work focuses specifically on the response of the latter rat brain to the low scatter irradiation dose. Here, we provide the first experimental evidence that very low, clinically relevant doses of scatter irradiation alter gene expression, induce changes in dendritic morphology, and lead to behavioral deficits in exposed animals. The results showed that exposure to radiation doses as low as 0.115 cGy caused changes in gene expression and reduced spine density, dendritic complexity, and dendritic length in the prefrontal cortex tissues of females, but not males. In the hippocampus, radiation altered neuroanatomical organization in males, but not in females. Moreover, low dose radiation caused behavioral deficits in the exposed animals. This is the first study to show that low dose scatter irradiation influences the brain and behavior in a sex-specific way. PMID:27375442

  9. The Effect of Photoluminescence of Bioceramic Irradiation on Middle Cerebral Arterial Occlusion in Rats.

    PubMed

    Zhang, Lei; Chan, Paul; Liu, Zhong-Min; Hwang, Ling-Ling; Lin, Kuo-Chi; Chan, Wing P; Leung, Ting-Kai; Choy, Cheuk Sing

    2016-01-01

    The purpose of this study is to determine the possible effect of photoluminescence of bioceramic (PLB) on ischemic cerebral infarction (stroke), by using an animal model of transient middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were used to induce MCAO to block the origin of the left MCAO; three months later, the positive chronic stroke rats were selected by running tunnel maze; the MCAO rats with significant chronic stroke and neurological defects were used for treadmill experiments with varying speed settings to test their capability for restoration after muscular fatigue under conditions of with and without PLB irradiation. As a result, PLB irradiation could improve exercise completion rate and average running speed during slow and fast treadmill settings. After PLB irradiation, the selected MCAO rats successfully completed all the second-round treadmill exercises at the maximum speed setting, and they had better restoration from muscular fatigue. An in vitro cell study on astrocytes of rats by bioceramic irradiation further demonstrated increased intracellular nitric oxide. To explain these results, we suggest that cortical brain stimulation of microcirculation and enhancement of peripheral muscular activity are the main causes of the improved exercise performance in MCAO rats by PLB. PMID:27375765

  10. The Effect of Photoluminescence of Bioceramic Irradiation on Middle Cerebral Arterial Occlusion in Rats.

    PubMed

    Zhang, Lei; Chan, Paul; Liu, Zhong-Min; Hwang, Ling-Ling; Lin, Kuo-Chi; Chan, Wing P; Leung, Ting-Kai; Choy, Cheuk Sing

    2016-01-01

    The purpose of this study is to determine the possible effect of photoluminescence of bioceramic (PLB) on ischemic cerebral infarction (stroke), by using an animal model of transient middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were used to induce MCAO to block the origin of the left MCAO; three months later, the positive chronic stroke rats were selected by running tunnel maze; the MCAO rats with significant chronic stroke and neurological defects were used for treadmill experiments with varying speed settings to test their capability for restoration after muscular fatigue under conditions of with and without PLB irradiation. As a result, PLB irradiation could improve exercise completion rate and average running speed during slow and fast treadmill settings. After PLB irradiation, the selected MCAO rats successfully completed all the second-round treadmill exercises at the maximum speed setting, and they had better restoration from muscular fatigue. An in vitro cell study on astrocytes of rats by bioceramic irradiation further demonstrated increased intracellular nitric oxide. To explain these results, we suggest that cortical brain stimulation of microcirculation and enhancement of peripheral muscular activity are the main causes of the improved exercise performance in MCAO rats by PLB.

  11. The Effect of Photoluminescence of Bioceramic Irradiation on Middle Cerebral Arterial Occlusion in Rats

    PubMed Central

    Zhang, Lei; Chan, Paul; Liu, Zhong-Min; Hwang, Ling-Ling; Lin, Kuo-Chi; Chan, Wing P.; Leung, Ting-Kai; Choy, Cheuk Sing

    2016-01-01

    The purpose of this study is to determine the possible effect of photoluminescence of bioceramic (PLB) on ischemic cerebral infarction (stroke), by using an animal model of transient middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were used to induce MCAO to block the origin of the left MCAO; three months later, the positive chronic stroke rats were selected by running tunnel maze; the MCAO rats with significant chronic stroke and neurological defects were used for treadmill experiments with varying speed settings to test their capability for restoration after muscular fatigue under conditions of with and without PLB irradiation. As a result, PLB irradiation could improve exercise completion rate and average running speed during slow and fast treadmill settings. After PLB irradiation, the selected MCAO rats successfully completed all the second-round treadmill exercises at the maximum speed setting, and they had better restoration from muscular fatigue. An in vitro cell study on astrocytes of rats by bioceramic irradiation further demonstrated increased intracellular nitric oxide. To explain these results, we suggest that cortical brain stimulation of microcirculation and enhancement of peripheral muscular activity are the main causes of the improved exercise performance in MCAO rats by PLB. PMID:27375765

  12. Hippocampal Neuron Number Is Unchanged 1 Year After Fractionated Whole-Brain Irradiation at Middle Age

    SciTech Connect

    Shi Lei Molina, Doris P.; Robbins, Michael E.; Wheeler, Kenneth T.; Brunso-Bechtold, Judy K.

    2008-06-01

    Purpose: To determine whether hippocampal neurons are lost 12 months after middle-aged rats received a fractionated course of whole-brain irradiation (WBI) that is expected to be biologically equivalent to the regimens used clinically in the treatment of brain tumors. Methods and Materials: Twelve-month-old Fischer 344 X Brown Norway male rats were divided into WBI and control (CON) groups (n = 6 per group). Anesthetized WBI rats received 45 Gy of {sup 137}Cs {gamma} rays delivered as 9 5-Gy fractions twice per week for 4.5 weeks. Control rats were anesthetized but not irradiated. Twelve months after WBI completion, all rats were anesthetized and perfused with paraformaldehyde, and hippocampal sections were immunostained with the neuron-specific antibody NeuN. Using unbiased stereology, total neuron number and the volume of the neuronal and neuropil layers were determined in the dentate gyrus, CA3, and CA1 subregions of hippocampus. Results: No differences in tissue integrity or neuron distribution were observed between the WBI and CON groups. Moreover, quantitative analysis demonstrated that neither total neuron number nor the volume of neuronal or neuropil layers differed between the two groups for any subregion. Conclusions: Impairment on a hippocampal-dependent learning and memory test occurs 1 year after fractionated WBI at middle age. The same WBI regimen, however, does not lead to a loss of neurons or a reduction in the volume of hippocampus.

  13. Aspartame and the rat brain monoaminergic system.

    PubMed

    Perego, C; De Simoni, M G; Fodritto, F; Raimondi, L; Diomede, L; Salmona, M; Algeri, S; Garattini, S

    1988-12-01

    A high dose of aspartame (APM) was administered to rats to study possible effects on brain monoaminergic systems. APM and its metabolite phenylalanine (Phe) were given orally at doses of 1000 and 500 mg/kg, respectively. Significant increases were seen in brain Phe and tyrosine (Tyr) levels. Two different approaches were used to study monoaminergic systems: whole tissue measurements by HPLC-ED and in vivo voltammetry in freely moving rats. Dopamine, serotonin and their metabolites were taken as indexes of neuronal activity. In spite of the high dose used, no modification was found in monoamines or their metabolites in striatum, hippocampus and nucleus accumbens.

  14. Interaction of ethanol and microwaves on the blood-brain barrier of rats

    SciTech Connect

    Neilly, J.P.; Lin, J.C.

    1986-01-01

    The combined effects of ethanol and microwaves on the permeation of Evans blue dye through the mammalian blood-brain barrier was studied in male Wistar rats. Anesthetized rats were infused through a cannula in the left femoral vein with 0.1, 0.3, 0.5 or 0.7 grams of absolute ethanol per kilogram of body mass. A control group was given 0.7 g/kg of isotonic saline. The left hemisphere of the brain was irradiated by 3.15-GHz microwave energy at 3.0 W/cm2 rms for 15 min. The rat's rectal temperature was maintained at 37.0 degrees C. Immediately after irradiation, 2% Evans blue dye in saline (2.0 ml/kg body mass) was injected through the cannula. The results show that as the quantity of alcohol was increased, the degree of staining was decreased or eliminated. The temperature of the irradiated area of the brain increased for the first 4 to 5 minutes of irradiation and then stabilized for the remainder of the irradiation period. The steady-state temperature was highest in animals receiving saline or the smallest dose of alcohol. As the quantity of alcohol was increased, the steady-state temperature was reduced. These results indicate that ethanol inhibits microwave-induced permeation of the blood-brain barrier through reduced heating of the brain.

  15. Effects of Irradiation on Brain Vasculature Using an In Situ Tumor Model

    SciTech Connect

    Zawaski, Janice A.; Gaber, M. Waleed; Sabek, Omaima M.; Wilson, Christy M.; Duntsch, Christopher D.; Merchant, Thomas E.

    2012-03-01

    Purpose: Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials: Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood-brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results: The presence of tumor alone increases permeability but has little effect on leukocyte-endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions: We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation.

  16. Physiologic consequences of local heart irradiation in rats

    SciTech Connect

    Geist, B.J.; Lauk, S.; Bornhausen, M.; Trott, K.R. )

    1990-05-01

    Noninvasive methods have been used to study the long-term cardiovascular and pulmonary functional changes at rest and after exercise in adult rats following local heart irradiation with single x-ray doses of 15, 17.5 or 20 Gy, and in non-irradiated control animals. Rats that had undergone a chronic exercise program were compared with untrained cohorts. The earliest dysfunction detected was an increased respiratory rate (f) at 10 weeks after irradiation in the highest dose group. In contrast, both telemetric heart-rate (HR) and rhythm and indirect systolic blood pressure measurements performed at rest only revealed changes starting at 43 weeks after irradiation with 20 Gy, up to which point the rats showed no clinical signs of heart failure. However, the number of minutes required for the recovery of the HR to pre-exercise levels following the implementation of a standardized exercise challenge was elevated in untrained rats compared with their trained cohorts at 18 weeks after irradiation with 20 Gy. Increases in recovery times were required in the two lowest dose groups, starting at 26 weeks after irradiation. It was concluded that the reserve capacity of the cardiopulmonary system masks functional decrements at rest for many months following local heart irradiation, necessitating the use of techniques which reveal reductions in reserve capacities. Further, the influence of local irradiation to the heart and lungs deserves closer scrutiny due to mutual interactions.

  17. Genetic influence on brain catecholamines: high brain norepinephrine in salt-sensitive rats

    SciTech Connect

    Iwai, J; Friedman, R; Tassinari, L

    1980-01-01

    Rats genetically sensitive to salt-induced hypertension evinced higher levels of plasma norepinephrine and epinephrine than rats genetically resistant to hypertension. The hypertension-sensitive rats showed higher hypothalamic norepinephrine and lower epinephrine than resistant rats. In response to a high salt diet, brain stem norepinephrine increased in sensitive rats while resistant rats exhibited a decrease on the same diet.

  18. Laser scattering by transcranial rat brain illumination

    NASA Astrophysics Data System (ADS)

    Sousa, Marcelo V. P.; Prates, Renato; Kato, Ilka T.; Sabino, Caetano P.; Suzuki, Luis C.; Ribeiro, Martha S.; Yoshimura, Elisabeth M.

    2012-06-01

    Due to the great number of applications of Low-Level-Laser-Therapy (LLLT) in Central Nervous System (CNS), the study of light penetration through skull and distribution in the brain becomes extremely important. The aim is to analyze the possibility of precise illumination of deep regions of the rat brain, measure the penetration and distribution of red (λ = 660 nm) and Near Infra-Red (NIR) (λ = 808 nm) diode laser light and compare optical properties of brain structures. The head of the animal (Rattus Novergicus) was epilated and divided by a sagittal cut, 2.3 mm away from mid plane. This section of rat's head was illuminated with red and NIR lasers in points above three anatomical structures: hippocampus, cerebellum and frontal cortex. A high resolution camera, perpendicularly positioned, was used to obtain images of the brain structures. Profiles of scattered intensities in the laser direction were obtained from the images. There is a peak in the scattered light profile corresponding to the skin layer. The bone layer gives rise to a valley in the profile indicating low scattering coefficient, or frontal scattering. Another peak in the region related to the brain is an indication of high scattering coefficient (μs) for this tissue. This work corroborates the use of transcranial LLLT in studies with rats which are subjected to models of CNS diseases. The outcomes of this study point to the possibility of transcranial LLLT in humans for a large number of diseases.

  19. Prenatal irradiation: a major concern for the developing brain.

    PubMed

    Kimler, B F

    1998-04-01

    Irradiation of the mammalian foetus produces a broad spectrum of congenital abnormalities, growth retardations, developmental delays, and functional deficits, depending upon the dose and the specific gestational phase of irradiation. The developing brain is particularly susceptible to production of deleterious effects, with decreased brain size, behavioural alterations, and mental retardation having been documented. Supplementing the limited human data, rodent models have been extensively used to investigate the specific processes by which relatively low doses, with correspondingly minor cellular damage to the developing neocortex, can produce dramatic postnatal consequences in brain structure and function. The effects of a variety of physical (dose, linear energy transfer, dose rate, fractionation) and biological (species, strain, gestational age, time course post-irradiation) parameters have been examined in an attempt to provide much needed information on such critical aspects as dose response, threshold doses for effect, and extrapolation to human risk estimates. Various acute cellular responses (e.g. appearance of pyknotic cells and macrophages) observed in the developing neocortex 0-24 h after in utero irradiation can be associated with postnatal effects. Moreover, it is possible to correlate thinning of specific layers of the cerebral cortex with specific behavioural aberrations, allowing prediction of brain structural changes from functional alterations, and vice versa. Thus, it is possible to speculate as to the mechanisms and targets for extremely sensitive, radiation-induced cellular damage in the developing foetal brain, that will interfere with the orderly and precisely programmed development of the mammalian brain, leading finally to postnatal expression as delays in growth and development, perturbations in behaviour, and alterations in brain structure. PMID:9587081

  20. Biotransformation of norcocaine to norcocaine nitroxide by rat brain microsomes.

    PubMed

    Kloss, M W; Rosen, G M; Rauckman, E J

    1984-01-01

    In the mid 1970's, norcocaine was identified as a metabolite of cocaine in rat brain tissue. We extend these studies by demonstrating that rat brain FAD-containing monooxygenase metabolizes norcocaine to N-hydroxynorcocaine. This hydroxylamine is then further oxidized to the nitroxyl free radical norcocaine nitroxide by rat brain cytochrome P-450. Brain microsomal reduction of norcocaine nitroxide leads to the generation of superoxide. Finally, incubation of rat brain microsomes with either N-hydroxynorcocaine or norcocaine nitroxide leads to significant lipid peroxidation as monitored by spin-trapping techniques.

  1. EVALUATION OF PERFLUOROOCTANE SULFONATE (PFOS) IN THE RAT BRAIN

    EPA Science Inventory

    This study examined whether there is a differential distribution of PFOS within the brain, and compares adult rats with neonatal rats at an age when formation of the blood-brain barrier is not yet complete (postnatal day 7). Male and female Sprague-Dawley rats (60-70 day old, 4/...

  2. Secretin: specific binding to rat brain membranes

    SciTech Connect

    Fremeau, R.T. Jr.; Jensen, R.T.; Charlton, C.G.; Miller, R.L.; O'Donohue, T.L.; Moody, T.W.

    1983-08-01

    The binding of (/sup 125/I)secretin to rat brain membranes was investigated. Radiolabeled secretin bound with high affinity (KD . 0.2 nM) to a single class of noninteracting sites. Binding was specific, saturable, and reversible. Regional distribution studies indicated that the specific binding was greatest in the cerebellum, intermediate in the cortex, thalamus, striatum, hippocampus, and hypothalamus, and lowest in the midbrain and medulla/pons. Pharmacological studies indicated that only secretin, but not other peptides, inhibits binding of (/sup 125/I)secretin with high affinity. Also, certain guanine nucleotides inhibited high affinity binding. These data indicate that rat brain membranes possess high affinity binding sites specific for secretin and that with the use of (/sup 125/I) secretin the kinetics, stoichiometry, specificity, and distribution of secretin receptors can be directly investigated.

  3. Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction.

    PubMed

    Xu, Yali; Cui, Hai; Zhu, Qiong; Hua, Xing; Xia, Hongmei; Tan, Kaibin; Gao, Yunhua; Zhao, Jing; Liu, Zheng

    2016-01-01

    Objective. Blood-brain barrier (BBB) is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p < 0.01). Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4 ± 1, grade 2) while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery. PMID:27579317

  4. Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction

    PubMed Central

    Cui, Hai; Zhu, Qiong; Hua, Xing; Xia, Hongmei; Tan, Kaibin; Gao, Yunhua; Zhao, Jing

    2016-01-01

    Objective. Blood-brain barrier (BBB) is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p < 0.01). Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4 ± 1, grade 2) while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery. PMID:27579317

  5. Reductions in calcium uptake induced in rat brain synaptosomes by ionizing radiation

    SciTech Connect

    Kandasamy, S.B.; Howerton, T.C.; Hunt, W.A. )

    1991-02-01

    Gamma irradiation (60Co) reduced KCl-stimulated voltage-dependent 45Ca2+ uptake in whole-brain, cortical, and striatal synaptosomes. The time course (3, 10, 30, and 60 s) of calcium uptake by irradiated (3 Gy) and nonirradiated synaptosomes, as well as the effect of KCl (15-65 mM), was measured in whole-brain synaptosomes. The fastest and highest rate of depolarization-dependent calcium uptake occurred at 3 s with 65 mM KCl. Irradiation reduced calcium uptake at all incubation times and KCl concentrations. Bay K 8644 enhancement of KCl-stimulated calcium influx was also reduced by radiation exposure. Nimodipine binding to dihydropyridine (DHP) L-type calcium channel receptors was not altered following radiation exposure. These results demonstrate an inhibitory effect of ionizing radiation on the voltage-sensitive calcium channels in rat brain synaptosomes that are not mediated by DHP receptors.

  6. Neurosarcoidosis associated with hypersomnolence treated with corticosteroids and brain irradiation

    SciTech Connect

    Rubinstein, I.; Gray, T.A.; Moldofsky, H.; Hoffstein, V.

    1988-07-01

    Narcoleptic features developed in a young man with CNS sarcoidosis. This was associated with a structural lesion in the hypothalamus as demonstrated on CT scans of the head. The diagnosis of narcolepsy was established by compatible clinical history and the Multiple Sleep Latency Test. Treatment with high-dose corticosteroids was ineffective, but when the low-dose, whole-brain irradiation was added, complete resolution of the narcoleptic features ensued.

  7. Efficacy of Intracerebral Delivery of Carboplatin in Combination With Photon Irradiation for Treatment of F98 Glioma-Bearing Rats

    SciTech Connect

    Rousseau, Julia; Barth, Rolf F.; Moeschberger, Melvin L.; Elleaume, Helene

    2009-02-01

    Purpose: To evaluate the efficacy of prolonged intracerebral (i.c.) administration of carboplatin by means of ALZET osmotic pumps, in combination with radiotherapy for the treatment of intracranial F98 glioma in rats. Methods and Materials: Seven days after stereotactic implantation of F98 glioma cells into the brains of Fischer rats, carboplatin was administrated i.c. by means of ALZET pumps over 6 days. Rats were treated at the European Synchrotron Radiation Facility with a single 15-Gy X-ray dose, either given alone or 24 h after administration of carboplatin. Results: Untreated rats had a mean survival time (MST) {+-} SE of 23 {+-} 1 days, compared with 44 {+-} 3 days for X-irradiated animals and 69 {+-} 20 days for rats that received carboplatin alone, with 3 of 13 of these surviving >195 days. Rats that received carboplatin followed by X-irradiation had a MST of >142 {+-} 21 days and a median survival time of >195 days, with 6 of 11 rats (55%) still alive at the end of the study. The corresponding percentage increases in lifespan, based on median survival times, were 25%, 85%, and 713%, respectively, for carboplatin alone, radiotherapy alone, or the combination. Conclusions: Our data demonstrate that i.c. infusion of carboplatin by means of ALZET pumps in combination with X-irradiation is highly effective for the treatment of the F98 glioma. They provide strong support for the approach of concomitantly administering chemo- and radiotherapy for the treatment of brain tumors.

  8. Cranial irradiation modulates hypothalamic-pituitary-adrenal axis activity and corticosteroid receptor expression in the hippocampus of juvenile rat.

    PubMed

    Velickovic, Natasa; Djordjevic, Ana; Drakulic, Dunja; Stanojevic, Ivana; Secerov, Bojana; Horvat, Anica

    2009-01-01

    Glucocorticoids, essential for normal hypothalamic-pituitary-adrenal (HPA) axis activity, exert their action on the hippocampus through two types of corticosteroid receptors: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Recent studies report that exposure of juvenile rats to cranial irradiation adversely affects HPA axis stability leading to its activation along with radiation- induced inflammation. This study was aimed to examine the acute effects of radiation on HPA axis activity and hippocampal corticosteroid receptor expression in 18-day-old rats. Since immobilization was part of irradiation procedure, both irradiated and sham-irradiated animals were exposed to this unavoidable stress. Our results demonstrate that the irradiated rats exhibited different pattern of corticosteroid receptor expression and hormone levels compared to respective controls. These differences included upregulation of GR protein in the hippocampus with a concomitant elevation of GR mRNA and an increase in circulating level of corticosterone. In addition, the expression of MR, both at the level of protein and gene expression, was not altered. Taken together, this study demonstrates that cranial irradiation in juvenile rats leads to enhanced HPA axis activity and increased relative GR/MR ratio in hippocampus. The present paper intends to show that neuroendocrine response of normal brain tissue to localized irradiation comprise both activation of HPA axis and altered corticosteroid receptor balance, probably as consequence of innate immune activation.

  9. Long-term cognitive effects of human stem cell transplantation in the irradiated brain

    PubMed Central

    Acharya, Munjal M.; Martirosian, Vahan; Christie, Lori-Ann; Limoli, Charles L.

    2016-01-01

    Purpose Radiotherapy remains a primary treatment modality for the majority of central nervous system tumors, but frequently leads to debilitating cognitive dysfunction. Given the absence of satisfactory solutions to this serious problem, we have used human stem cell therapies to ameliorate radiation-induced cognitive impairment. Here, past studies have been extended to determine whether engrafted cells provide even longer-term benefits to cognition. Materials and methods Athymic nude rats were cranially irradiated (10 Gy) and subjected to intrahippocampal transplantation surgery 2 days later. Human embryonic stem cells (hESC) or human neural stem cells (hNSC) were transplanted, and animals were subjected to cognitive testing on a novel place recognition task 8 months later. Results Grafting of hNSC was found to provide long lasting cognitive benefits over an 8-month post-irradiation interval. At this protracted time, hNSC grafting improved behavioral performance on a novel place recognition task compared to irradiated animals not receiving stem cells. Engrafted hESC previously shown to be beneficial following a similar task, 1 and 4 months after irradiation, were not found to provide cognitive benefits at 8 months. Conclusions Our findings suggest that hNSC transplantation promotes the long-term recovery of the irradiated brain, where intrahippocampal stem cell grafting helps to preserve cognitive function. PMID:24882389

  10. Ethanol effects on rat brain phosphoinositide metabolism

    SciTech Connect

    Huang, H.M.

    1987-01-01

    An increase in acidic phospholipids in brain plasma and synaptic plasma membranes upon chronic ethanol administration was observed. Chronic ethanol administration resulted in an increase in {sup 32}P{sub i} incorporation into the acidic phospholipids in synaptosomes. Postdecapitative ischemic treatment resulted rapid degradation of poly-PI in rat brain. However, there was a rapid appearance of IP{sub 2} in ethanol group which indicated a more rapid turnover of IP{sub 3} in the ethanol-treated rats. Carbachol stimulated accumulation of labeled inositol phosphates in brain slices and synaptosomes. Carbachol-stimulated release of IP and IP{sub 2} was calcium dependent and was inhibited by EGTA and atropine. Adenosine triphosphates and 1 mM further enhanced carbachol-induced formation of IP and IP{sub 2}, but showed an increase and a decrease in IP{sub 3} at 1 mM and 0.01 mM, respectively. Guanosine triphosphate at 0.1 mM did not change in labeled IP, but there was a significant increase in labeled IP{sub 2} and decrease in IP{sub 3}. Mn and CMP greatly enhanced incorporation of ({sup 3}H)-inositol into PI, but not into poly-PI labeling in brain synaptosomes. Incubation of brain synaptosomes resulted in a Ca{sup 2+}, time-dependent release of labeled IP. However, the pool of PI labeled through this pathway is not susceptible to carbachol stimulation. When saponin permeabilized synaptosomal preparations were incubated with ({sup 3}H)-inositol-PI or ({sup 14}C)-arachidonoyl-PI, ATP enhanced the formation of labeled IP and DG.

  11. Hydro-proteolytic activity in rat's pancreas after irradiation.

    PubMed

    Koćmierska-Grodzka, D; Radwan, J

    1975-07-01

    Investigations were carried out on the problem of hydrolytic ability of rat's pancreas 24 h after whole body irradiation with the single dose of 800 R and after fractionated irradiation (5 x 150 R). Besides kallikrein, enzymes of intracellular digestion (B-glucuronidase, acid phosphatase, cathepsin) and enzymes of intraluminal digestion (amylase, lipase) were chosed for examination. It was stated, that single irradiation evokes rather moderate changes in the activity of examined enzymes causing increase of catheptic and lipolytic activity and decrease in amylase activity accompanied by sharp increase of kallikrein activity in the tissue. Mechanical obstruction of biliopancreatic duct renders trend to decrease of enzymatic activity in almost all enzymes of irradiated group. After fractionated irradiation the general increase of hydroproteolytic activity (with one exception of pancreatic amylase) was stated. PMID:241136

  12. Studies of aluminum in rat brain

    SciTech Connect

    Lipman, J.J.; Brill, A.B.; Som, P.; Jones, K.W.; Colowick, S.; Cholewa, M.

    1985-01-01

    The effects of high aluminum concentrations in rat brains were studied using /sup 14/C autoradiography to measure the uptake of /sup 14/C 2-deoxy-D-glucose (/sup 14/C-2DG) and microbeam proton-induced x-ray emission (microPIXE) with a 20-..mu..m resolution to measure concentrations of magnesium, aluminum, potassium, and calcium. The aluminum was introduced intracisternally in the form of aluminum tartrate (Al-T) while control animals were given sodium tartrate (Na-T). The /sup 14/C was administered intravenously. The animals receiving Al-T developed seizure disorders and had pathological changes that included cerebral cortical atrophy. The results showed that there was a decreased uptake of /sup 14/C-2DG in cortical regions in which increased aluminum levels were measured, i.e., there is a correlation between the aluminum in the rat brain and decreased brain glucose metabolism. A minimum detection limit of about 16 ppM (mass fraction) or 3 x 10/sup 9/ Al atoms was obtained for Al under the conditions employed. 14 refs., 4 figs., 1 tab.

  13. Dichloroacetate increases glucose use and decreases lactate in developing rat brain

    SciTech Connect

    Miller, A.L.; Hatch, J.P.; Prihoda, T.J. )

    1990-12-01

    Dichloroacetate (DCA) activates pyruvate dehydrogenase (PDH) by inhibiting PDH kinase. Neutralized DCA (100 mg/kg) or saline was intravenously administered to 20 to 25-day-old rats (50-75g). Fifteen minutes later a mixture of {sup 6-14}C glucose and {sup 3}H fluorodeoxyglucose (FDG) was administered intravenously and the animals were sacrificed by microwave irradiation (2450 MHz, 8.0 kW, 0.6-0.8 sec) after 2 or 5 min. Brain regional rates of glucose use and metabolite levels were determined. DCA-treated rats had increased rates of glucose use in all regions studied (cortex, thalamus, striatum, and brain stem), with an average increase of 41%. Lactate levels were lower in all regions, by an average of 35%. There were no significant changes in levels of ATP, creatine phosphate, or glycogen in any brain region. Blood levels of lactate did not differ significantly between the DCA- and the saline-treated groups. Blood glucose levels were higher in the DCA group. In rats sacrificed by freeze-blowing, DCA treatment caused lower brain levels of both lactate and pyruvate. These results cannot be explained by any systemic effect of DCA. Rather, it appears that in the immature rat, DCA treatment results in activation of brain PDH, increased metabolism of brain pyruvate and lactate, and a resulting increase in brain glycolytic rate.

  14. Radioimmunoassay of met-enkephalin in microdissected areas of paraformaldehyde-fixed rat brain

    SciTech Connect

    Correa, F.M.A.; Saavedra, J.M.

    1984-02-27

    The effects were studied of various sample preparation procedures on rat brain met-enkephalin content, measured by radioimmunoassay. Whole brain met-enkephalin content of rats killed by decapitation followed by immediate tissue freezing was similar to that of rats killed by microwave irradiation and to those of rats anesthetized with pentobarbital or halothane before killing, whether previously perfused with paraformaldehyde or not. In contrast, a decrease (up to 80%) in met-enkephalin concentrations was observed when brain samples were frozen and thawed to mimic the procedure utilized in the ''punch'' technique for analysis of discrete brain nuclei. This decrease was totally prevented by paraformaldehyde perfusion of the brain prior to sacrifice. Brain perfusion did not alter the amount of immunoassayable met-enkephalin extracted from tissue or its profile after Sephadex chromatography. Paraformaldehyde perfusion results in better morphological tissue preservation and facilitates the ''punch'' dissecting technique. Paraformaldehyde perfusion may be the procedure of choice for the measurement of neuropeptides in specific brain nuclei dissected by the ''punch'' technique.

  15. Protein purification and cloning of diacylglycerol lipase from rat brain.

    PubMed

    Aso, Chizu; Araki, Mari; Ohshima, Noriyasu; Tatei, Kazuaki; Hirano, Tohko; Obinata, Hideru; Kishi, Mikiko; Kishimoto, Koji; Konishi, Akimitsu; Goto, Fumio; Sugimoto, Hiroyuki; Izumi, Takashi

    2016-06-01

    Diacylglycerol (DG) lipase, which hydrolyses 1-stearoyl-2-arachidonyl-sn-glycerol to produce an endocannabinoid, 2-arachidonoylglycerol, was purified from the soluble fraction of rat brain lysates. DG lipase was purified about 1,200-fold by a sequential column chromatographic procedure. Among proteins identified by mass spectrometry analysis in the partially purified DG lipase sample, only DDHD domain containing two (DDHD2), which was formerly regarded as a phospholipase A1, exhibited significant DG lipase activity. Rat DDHD2 expressed in Chinese hamster ovary cells showed similar enzymatic properties to partially purified DG lipase from rat brain. The source of DG lipase activity in rat brain was immunoprecipitated using anti-DDHD2 antibody. Thus, we concluded that the DG lipase activity in the soluble fraction of rat brain is derived from DDHD2. DDHD2 is distributed widely in the rat brain. Immunohistochemical analysis revealed that DDHD2 is expressed in hippocampal neurons, but not in glia.

  16. Morphological changes in cultures of hippocampus following prenatal irradiation in the rat

    SciTech Connect

    Hamdorf, G.; Shahar, A.; Cervos-Navarro, J.; Scheffler, A.; Sparenberg, A.; Skoberla, A. )

    1990-07-01

    The effect of prenatal irradiation was studied in organotypic cultures of hippocampus, prepared from newborn rats that had been exposed to whole-body irradiation of 1 Gy from a {sup 60}Co-source at day 13 of pregnancy. Light and electron microscopic observations showed remarkable damage to neuronal mitochondria accompanied by extensive swelling, vacuolation of the Golgi complex, and formation of multilamellar bodies and vesicles of the lysosomal type. In contrast to neuronal alterations, no delay in synaptogenesis or onset of myelination was observed based upon the absence of significant morphological changes in synapses and myelin sheaths. Using this tissue culture model it could be confirmed that prenatal exposure to irradiation, even at low doses, induces specific morphological changes in the brain.

  17. Selective ablation of rat brain tumors by boron neutron capture therapy

    SciTech Connect

    Coderre, J.; Joel, D. ); Rubin, P.; Freedman, A.; Hansen, J.; Wooding, T.S. Jr.; Gash, D. )

    1994-03-30

    Damage to the surrounding normal brain tissue limits the amount of radiation that can be delivered to intracranial tumors. Boron neutron capture therapy (BNCT) is a binary treatment that allows selective tumor irradiation. This study evaluates the damage imparted to the normal brain during BNCT or x-irradiation. The brains of rats with implanted 9L gliosarcomas were examined 1 year after tumor-curative doses of either 250 kV X-rays or BNCT. Histopathologic techniques included hematoxylin and eosin staining, horseradish peroxidase perfusion, and electron microscopy. Longterm X-ray survivors showed extensive cortical atrophy, loss of neurons, and widespread leakage of the blood-brain barrier (BBB), particularly around the tumor scar. In contrast, the brains and the BBB of longterm BNCT survivors appeared relatively normal under both light- and electron-microscopic examination. Intact blood vessels were observed running directly through the avascular, collagenous tumor scar. The selective therapeutic effect of BNCT is evident in comparison to x-irradiation. Both groups of animals showed no evidence of residual tumor at 1 year. However, with x-irradiation there is no therapeutic ratio and tumor eradication severely injuries the remaining brain parenchyma. These observations indicate a substantial therapeutic gain for BNCT. 50 refs., 8 figs., 1 tab.

  18. Induction of acute phase gene expression by brain irradiation

    SciTech Connect

    Hong, Ji-Hong |; Sun, Ji-Rong; Withers, H.R.

    1995-10-15

    To investigate the in vivo acute phase molecular response of the brain to ionizing radiation, C3Hf/Sed/Kam mice were given midbrain or whole-body irradiation. Cerebral expression of interleukins (IL-1{alpha}, IL-1{beta}, IL-2, IL-3, IL-4, IL-5, IL-6), interferon (IFN-{gamma}), tumor necrosis factors (TNF-{alpha} and TNF-{beta}), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthetase (iNOS), von Willebrand factor (vWF), {alpha}1-antichymotrypsin (EB22/5.3), and glial fibrillary acidic protein (GFAP) was measured at various times after various radiation doses by ribonuclease (RNase) protection assay. The effects of dexamethasone or pentoxifylline treatment of mice on radiation-induced gene expression were also examined. Levels of TNF-{alpha}, IL-1{beta}, ICAM-1, EB22/5.3, and to a lesser extent IL-1{alpha} and GFAP, messenger RNA were increased in the brain after irradiation, whether the dose was delivered to the whole body or only to the midbrain. Responses were radiation dose dependent, but were not found below 7 Gy; the exception being ICAM-1, which was increased by doses as low as 2 Gy. Most responses were rapid, peaking within 4-8 h, but antichymotrypsin and GFAP responses were delayed and still elevated at 24 h, by which time the others had subsided. Pretreatment of mice with dexamethasone or pentoxifylline suppressed radiation-induced gene expression, either partially or completely. Dexamethasone was more inhibitory than pentoxifylline at the doses chosen. The initial response of the brain to irradiation involves expression of inflammatory gene products, which are probably responsible for clinically observed early symptoms of brain radiotherapy. This mechanism explains the beneficial effects of the clinical use of steroids in such circumstances. 64 refs., 4 figs.

  19. Gastroprotective effect of kefir on ulcer induced in irradiated rats.

    PubMed

    Fahmy, Hanan A; Ismail, Amel F M

    2015-03-01

    The current study was designed to investigate the protective effect of kefir milk on ethanol-induced gastric ulcers in γ-irradiated rats. The results of the present study revealed that treatment with γ-irradiation and/or ethanol showed a significant increase in ulcers number, total acidity, peptic, H(+)K(+)ATPase, MMP-2 and MMP-9 activities and MDA level, which were accompanied by a significant decrease in the mucus content, the stomach GSH level, the GSH-Px activity and DNA damage. Pre-treatment with kefir milk exert significant improvement in all the tested parameters. Kefir milk exerts comparable effect to that of the antiulcer drug ranitidine. In conclusion, the present study revealed that oral administration of kefir milk prevents ethanol-induced gastric ulcer in γ-irradiated rats that could attribute to its antioxidant, anti-apoptotic and radio-protective activities. PMID:25728227

  20. Gastroprotective effect of kefir on ulcer induced in irradiated rats.

    PubMed

    Fahmy, Hanan A; Ismail, Amel F M

    2015-03-01

    The current study was designed to investigate the protective effect of kefir milk on ethanol-induced gastric ulcers in γ-irradiated rats. The results of the present study revealed that treatment with γ-irradiation and/or ethanol showed a significant increase in ulcers number, total acidity, peptic, H(+)K(+)ATPase, MMP-2 and MMP-9 activities and MDA level, which were accompanied by a significant decrease in the mucus content, the stomach GSH level, the GSH-Px activity and DNA damage. Pre-treatment with kefir milk exert significant improvement in all the tested parameters. Kefir milk exerts comparable effect to that of the antiulcer drug ranitidine. In conclusion, the present study revealed that oral administration of kefir milk prevents ethanol-induced gastric ulcer in γ-irradiated rats that could attribute to its antioxidant, anti-apoptotic and radio-protective activities.

  1. Radiation effects of boron neutron capture therapy on brain, skin, and eye of rats

    SciTech Connect

    Matalka, K.Z.; Barth, R.F.; Bailey, M.Q.; Wilkie, D.A.; Koestner, A. ); Hopewell, J.W. )

    1994-03-30

    The present study was carried out to evaluate the radiation effects of boron neutron capture therapy (BNCT) on the brain, skin, and eyes of nude rats following systemic administration of boronophenylalanine (BPA) and neutron irradiation to the head. A solution containing 120 mg of [sup 10]B-enriched-L-BPA complexed with fructose was administered IP to nude rats. Boron concentrations were [approximately] 8.4, 9.4, 10.0, and 11.0 [mu]g/g in the brain, blood, skin, and eyes, respectively, at 6 h when the animals were irradiated at the Brookhaven Medical Research Reactor to cause tumor regression in nude rats carrying intracerebral implants of the human melanoma cell line MRA 27. Mild to moderate increases in loose fibrous tissue were observed in the choroid plexus at estimated physical doses to the brain and blood that ranged from 4.3-7.1 Gy and 4.6-7.7 Gy, respectively, and these appeared to be dose and time dependent. Other changes in the choroid plexus included occasional infiltrates of macrophages and polymorphonuclear leukocytes and vacuolation of epithelial cells. Dose-dependent moist desquamation of the skin was observed in all rats, but this had healed by 28 days following irradiation. Cataracts and keratitis developed in the eyes of most animals, and these were dose dependent. The minimal histopathological changes seen in the brain at doses that were sufficient to eradicate intracerebral melanoma indicates that BNCT has the potential to cure a tumor-bearing host without producing the normal brain injury usually associated with conventional external beam radiation therapy. Studies in canines, which currently are in progress, should further define the dose-effect relationships of BNCT on critical neuroanatomic structures within the brain. 42 refs., 4 figs., 3 tabs.

  2. The neuroprotective effects of intravascular low level laser irradiation on cerebral ischemia rats

    NASA Astrophysics Data System (ADS)

    Qiu, Yongming; Lu, Zhaofeng; Wang, Zhongguang; Jiang, Jiyao

    2005-07-01

    The effects of intravascular low level laser irradiation of He-Ne on rat MCAo-induced cerebral injury were studied. The results showed that control rats (subjected to MCAo injury without laser treatment) at 7d exhibited striatal and cortical brain infarction in the right hemisphere from approximately 3 to 11mm from the front pole. the total infarct volume in this group was 34.5+/-8.1mm3. For experimental rats (with laser management), the total infarct volume was 29.0+/-9.0mm3. P was gained less than 0.05. The neurological score of control group was 4.7+/-0.6 and it was 5.2+/-1.0 in experimental group, comparison by statistical analysis showed P less than 0.05. The cerebral pathological damages in the control group were more severe than in experimental group. We concluded that the intravascular low level laser irradiation has no remarked complication and is helpful to reduce ischemic damage. There is clinically potential for the application of intravascular He-Ne low level laser irradiation in ischemia stroke.

  3. Propofol Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats.

    PubMed

    Shi, Song-sheng; Zhang, Hua-bin; Wang, Chun-hua; Yang, Wei-zhong; Liang, Ri-sheng; Chen, Ye; Tu, Xian-kun

    2015-12-01

    Our previous studies demonstrated that propofol protects rat brain against focal cerebral ischemia. However, whether propofol attenuates early brain injury after subarachnoid hemorrhage in rats remains unknown until now. The present study was performed to evaluate the effect of propofol on early brain injury after subarachnoid hemorrhage in rats and further explore the potential mechanisms. Sprague-Dawley rats underwent subarachnoid hemorrhage (SAH) by endovascular perforation then received treatment with propofol (10 or 50 mg/kg) or vehicle after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evans blue extravasation, the myeloperoxidase activity, and malondialdehyde (MDA) content were measured 24 h after SAH. Expression of nuclear factor erythroid-related factor 2 (Nrf2), nuclear factor-kappa B (NF-κB) p65, and aquaporin 4 (AQP4) expression in rat brain were detected by Western blot. Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) were determined by reverse transcription-polymerase chain reaction (RT-PCR). Expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were assessed by ELISA. Neurological scores, brain water content, Evans blue extravasation, the myeloperoxidase activity, and MDA content were significantly reduced by propofol. Furthermore, expression of Nrf2 in rat brain was upregulated by propofol, and expression of NF-κB p65, AQP4, COX-2, MMP-9, TNF-α, and IL-1β in rat brain were attenuated by propofol. Our results demonstrated that propofol improves neurological scores, reduces brain edema, blood-brain barrier (BBB) permeability, inflammatory reaction, and lipid peroxidation in rats of SAH. Propofol exerts neuroprotection against SAH-induced early brain injury, which might be associated with the inhibition of inflammation and lipid peroxidation. PMID:26342279

  4. Propofol Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats.

    PubMed

    Shi, Song-sheng; Zhang, Hua-bin; Wang, Chun-hua; Yang, Wei-zhong; Liang, Ri-sheng; Chen, Ye; Tu, Xian-kun

    2015-12-01

    Our previous studies demonstrated that propofol protects rat brain against focal cerebral ischemia. However, whether propofol attenuates early brain injury after subarachnoid hemorrhage in rats remains unknown until now. The present study was performed to evaluate the effect of propofol on early brain injury after subarachnoid hemorrhage in rats and further explore the potential mechanisms. Sprague-Dawley rats underwent subarachnoid hemorrhage (SAH) by endovascular perforation then received treatment with propofol (10 or 50 mg/kg) or vehicle after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evans blue extravasation, the myeloperoxidase activity, and malondialdehyde (MDA) content were measured 24 h after SAH. Expression of nuclear factor erythroid-related factor 2 (Nrf2), nuclear factor-kappa B (NF-κB) p65, and aquaporin 4 (AQP4) expression in rat brain were detected by Western blot. Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) were determined by reverse transcription-polymerase chain reaction (RT-PCR). Expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were assessed by ELISA. Neurological scores, brain water content, Evans blue extravasation, the myeloperoxidase activity, and MDA content were significantly reduced by propofol. Furthermore, expression of Nrf2 in rat brain was upregulated by propofol, and expression of NF-κB p65, AQP4, COX-2, MMP-9, TNF-α, and IL-1β in rat brain were attenuated by propofol. Our results demonstrated that propofol improves neurological scores, reduces brain edema, blood-brain barrier (BBB) permeability, inflammatory reaction, and lipid peroxidation in rats of SAH. Propofol exerts neuroprotection against SAH-induced early brain injury, which might be associated with the inhibition of inflammation and lipid peroxidation.

  5. Incidence of brain tumors in rats fed aspartame.

    PubMed

    Ishii, H

    1981-03-01

    The brain tumorigenicity of aspartame (APM) and of its diketopiperazine (DKP) was studied in 860 SCL Wistar rats. APM at dietary levels of 1 g/kg, 2 gK/, 4 g/kg or APM + DKP (3:1) 4 g/kg was fed for 104 weeks. One atypical astrocytoma was found in a control rat and 2 astrocytomas, 2 oligodendrogliomas and 1 ependymoma were scattered among the 4 test groups. There was no significant difference in the incidence of brain tumors between control and test groups. It is concluded that neither AMP nor DKP caused brain tumors in rats in this study.

  6. Apparent target size of rat brain benzodiazepine receptor, acetylcholinesterase, and pyruvate kinase is highly influenced by experimental conditions

    SciTech Connect

    Nielsen, M.; Braestrup, C.

    1988-08-25

    Radiation inactivation is a method to determine the apparent target size of molecules. In this report we examined whether radiation inactivation of various enzymes and brain receptors is influenced by the preparation of samples preceding irradiation. The apparent target sizes of endogenous acetylcholinesterase and pyruvate kinase from rat brain and from rabbit muscle and benzodiazepine receptor from rat brain were investigated in some detail. In addition the target sizes of alcohol dehydrogenase (from yeast and horse liver), beta-galactosidase (from Escherichia coli), lactate dehydrogenase (endogenous from rat brain), and 5-HT2 receptors, acetylcholine muscarine receptors, and (/sup 35/S) butyl bicyclophosphorothionate tertiary binding sites from rat brain were determined. The results show that apparent target sizes are highly influenced by the procedure applied for sample preparation before irradiation. The data indicate that irradiation of frozen whole tissue as opposed to lyophilized tissue or frozen tissue homogenates will estimate the smallest and most relevant functional target size of a receptor or an enzyme.

  7. Creatine kinase reaction rates in rat brain during chronic ischemia.

    PubMed

    Mlynárik, V; Kasparová, S; Liptaj, T; Dobrota, D; Horecký, J; Belan, V

    1998-12-01

    Creatine kinase reaction rates were measured by magnetisation transfer technique in the brain of healthy adult and aged rats and in the rats with mild or severe chronic cerebral ischemia. These measurements indicated that the rate constant of the creatine kinase reaction is significantly reduced in the case of chronic brain ischemia in aged rats. In contrast, occlusion of both carotid arteries in adult rats produced a slight increase in the reaction rate 4 weeks after occlusion. At the same time, corresponding conventional phosphorus magnetic resonance spectra showed negligible changes in signal intensities. PMID:10050942

  8. Congenital hydrocephalus following X-irradiation of pregnant rats on an early gestational day

    SciTech Connect

    Takeuchi, I.K.; Takeuchi, Y.K.

    1986-03-01

    When pregnant rats were X-irradiated at a dose of 100 R on gestational day 9.5, a considerable number of postnatally-viable hydrocephalic offspring resulted, all of which were accompanied with bilateral micro- or anophthalmia. Histological studies revealed that the cerebral aqueduct of the congenital hydrocephalic brain was severely stenosed, and the subcommissural organ was reduced in size and displaced at some distance from the anterior end of the cerebral aqueduct. From embryological studies, it was considered that the maldevelopment of the subcommissural organ in the X-irradiated fetus might cause a reduction in the amount of its secretions which function as a cushion preventing complete closure of the cerebral aqueduct during fetal life, resulting in stenosis of the cerebral aqueduct.

  9. 26Al uptake and accumulation in the rat brain

    NASA Astrophysics Data System (ADS)

    Yumoto, S.; Nagai, H.; Imamura, M.; Matsuzaki, H.; Hayashi, K.; Masuda, A.; Kumazawa, H.; Ohashi, H.; Kobayashi, K.

    1997-03-01

    To investigate the cause of Alzheimer's disease (senile dementia), 26Al incorporation in the rat brain was studied by accelerator mass spectrometry (AMS). When 26Al was injected into healthy rats, a considerable amount of 26Al entered the brain (cerebrum) through the blood-brain barrier 5 days after a single injection, and the brain 26Al level remained almost constant from 5 to 270 days. On the other hand, the level of 26Al in the blood decreased remarkably 75 days after injection. Approximately 89% of the 26Al taken in by the brain cell nuclei bound to chromatin. This study supports the theory that Alzheimer's disease is caused by irreversible accumulation of aluminium (Al) in the brain, and brain cell nuclei.

  10. Brain damage following prophylactic cranial irradiation in lung cancer survivors.

    PubMed

    Simó, Marta; Vaquero, Lucía; Ripollés, Pablo; Jové, Josep; Fuentes, Rafael; Cardenal, Felipe; Rodríguez-Fornells, Antoni; Bruna, Jordi

    2016-03-01

    Long-term toxic effects of prophylactic cranial irradiation (PCI) on cognition in small cell lung cancer (SCLC) patients have not yet been well-established. The aim of our study was to examine the cognitive toxic effects together with brain structural changes in a group of long-term SCLC survivors treated with PCI. Eleven SCLC patients, who underwent PCI ≥ 2 years before, were compared with an age and education matched healthy control group. Both groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging. Voxel-based morphometry and Tract-based Spatial Statistics were used to study gray matter density (GMD) and white matter (WM) microstructural changes. Cognitive deterioration was correlated with GMD and Fractional Anisotropy (FA). Finally, we carried out a single-subject analysis in order to evaluate individual structural brain changes. Nearly half of the SCLC met criteria for cognitive impairment, all exhibiting a global worsening of cognitive functioning. Patients showed significant decreases of GMD in basal ganglia bilaterally (putamen and caudate), bilateral thalamus and right insula, together with WM microstructural changes of the entire corpus callosum. Cognitive deterioration scores correlated positively with mean FA values in the corpus callosum. Single-subject analysis revealed that GMD and WM changes were consistently observed in nearly all patients. This study showed neuropsychological deficits together with brain-specific structural differences in long-term SCLC survivors. Our results suggest that PCI therapy, possibly together with platinum-based chemotherapy, was associated to permanent long-term cognitive and structural brain effects in a SCLC population.

  11. Effects of Xylopia aethiopica (Annonaceae) fruit methanol extract on gamma-radiation-induced oxidative stress in brain of adult male Wistar rats.

    PubMed

    Adaramoye, O A; Popoola, Bosede O; Farombi, E O

    2010-09-01

    Xylopia aethiopica (XA) (Annonaceae) possesses great nutritional and medicinal values. This study was designed to investigate the effects of XA fruit methanol extract on oxidative stress in brain of rats exposed to whole body gamma-radiation (5 Gy). Vitamin C (VC) served as standard antioxidant. Forty-four rats were divided into 4 groups of 11 rats each. One group served as control, two different groups were treated with XA and VC (250 mg/kg), 6 weeks before and 8 weeks after irradiation, and fourth group was only irradiated. Rats were sacrificed 1 and 8 weeks after irradiation. The antioxidant status, viz. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and glutathione (GSH) were estimated. Results indicate a significant increase (p < 0.05) in levels of brain LPO after irradiation. LPO increased by 90% and 151%, after 1 and 8 weeks of irradiation, respectively. Irradiation caused significant (p < 0.05) decreases in levels of GSH and GST by 61% and 43% after 1 week and, 75% and 73%, respectively, after 8 weeks of exposure. CAT and SOD levels were decreased by 62% and 68%, respectively, after 8 weeks of irradiation. Treatment with XA and VC ameliorated the radiation-induced decreases in antioxidant status of the animals. These suggest that XA could have beneficial effect by inhibiting oxidative damage in brain of exposed rats.

  12. Effect of whole brain radiation on local cerebral glucose utilization in the rat

    SciTech Connect

    d'Avella, D.; Cicciarello, R.; Albiero, F.; Mesiti, M.; Gagliardi, M.E.; Russi, E.; d'Aquino, A.; Princi, P.; d'Aquino, S. )

    1991-04-01

    We assessed, by means of the ({sup 14}C)-2-deoxy-D-glucose autoradiography method, the effect of whole-brain x-radiation on local cerebral glucose utilization in the rat brain. Animals were exposed to conventional fractionation (200 +/- 4 cGy/day, 5 days/week; total dose, 4000 cGy). Metabolic experiments were made 2 to 3 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased after irradiation. Statistically significant decreases in metabolic activity were observed in 13 of 27 brain regions studied. In general, the brain areas with the highest basal metabolic rates showed the greatest percentage of decrease in glucose utilization. The concept that radiation suppresses glucose utilization before any morphological change takes place in the cell structures was the basis of this study. Metabolic alterations after irradiation may explain the syndrome of early delayed deterioration observed in humans after whole-brain radiotherapy. These studies have applications to observations made with the ({sup 18}F)-fluorodeoxyglucose method in conjunction with positron emission tomographic scans in patients receiving radiation therapy for intracranial malignancies. The data reported here also have potential clinical implications for the evaluation of a risk/benefit ratio for radiotherapy in patients with benign neurosurgical diseases or children undergoing prophylactic treatment of the central nervous system.

  13. Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

    SciTech Connect

    Schindler, Matthew K. Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

    2008-03-01

    Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals.

  14. Busulfan Conditioning Enhances Engraftment of Hematopoietic Donor-derived Cells in the Brain Compared With Irradiation

    PubMed Central

    Wilkinson, Fiona L; Sergijenko, Ana; Langford-Smith, Kia J; Malinowska, Marcela; Wynn, Rob F; Bigger, Brian W

    2013-01-01

    Hematopoietic stem cell gene therapy for neurological disorders relies on transmigration of donor-derived monocytes to the brain, where they can engraft as microglia and deliver therapeutic proteins. Many mouse studies use whole-body irradiation to investigate brain transmigration pathways, but chemotherapy is generally used clinically. The current evidence for transmigration to the brain after chemotherapy is conflicting. We compared hematopoietic donor cell brain engraftment after bone marrow (BM) transplants in busulfan- or irradiation-conditioned mice. Significantly more donor-derived microglial cells engrafted posttransplant in busulfan-conditioned brain compared with the irradiated, in both the short and long term. Although total Iba-1+ microglial content was increased in irradiated brain in the short term, it was similar between groups over long-term engraftment. MCP-1, a key regulator of monocyte transmigration, showed long-term elevation in busulfan-conditioned brain, whereas irradiated brains showed long-term elevation of the proinflammatory chemokine interleukin 1α (IL-1α), with increased in situ proliferation of resident microglia, and significant increases in the relative number of amoeboid activated microglia in the brain. This has implications for the choice of conditioning regimen to promote hematopoietic cell brain engraftment and the relevance of irradiation in mouse models of transplantation. PMID:23423338

  15. Microwave irradiation increases recovery of neuropeptides from brain tissues

    SciTech Connect

    Theodorsson, E.; Stenfors, C.; Mathe, A.A. )

    1990-11-01

    The effect of focused high energy microwave treatment (MW) on brain concentrations and molecular forms of substance P, neurokinin A, neuropeptide Y, neurotensin, galanin and calcitonin gene-related peptide was investigated. Groups of rats were treated as follows: (1) MW, storage for 60 min at 22 degrees C, (2) Decapitation, storage for 60 min at 22 degrees C, (3) Decapitation, storage for 60 min at 22 degrees C, MW treatment, (4) MW, decapitation, storage for 2 min at 22 degrees C and 5. Decapitation, storage for 2 min at 22 degrees C. Peptide concentrations were in all instances highest in the MW sacrificed groups. MW increased the concentration of intact peptides by rapid inhibition of peptidase activity and increase in peptide solubility/extractability.

  16. Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

    SciTech Connect

    Lee, Won Hee; Warrington, Junie P.; Sonntag, William E.; Lee, Yong Woo

    2012-04-01

    Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy {gamma}-rays or a fractionated dose of 40 Gy {gamma}-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

  17. Actin purification from a gel of rat brain extracts.

    PubMed

    Levilliers, N; Peron-Renner, M; Coffe, G; Pudles, J

    1984-01-01

    Actin, 99% pure, has been recovered from rat brain with a high yield (greater than 15 mg/100 g brain). We have shown that: 1. a low ionic strength extract from rat brain tissue is capable of giving rise to a gel; 2. actin is the main gel component and its proportion is one order of magnitude higher than in the original extract; 3. actin can be isolated from this extract by a three-step procedure involving gelation, dissociation of the gel in 0.6 M KCl, followed by one or two depolymerization-polymerization cycles. PMID:6529588

  18. [Influence of transcranial electromagnetic brain stimulation on development of conditioned reflex in rats].

    PubMed

    Samoilov, V O; Shadrin, E B; Filippova, E B; Katsnelson, Ya; Backhoff, H; Eventov, M

    2015-01-01

    The influence of transcranial electromagnetic stimulation on the development of an active avoidance reflex with painful reinforcement in laboratory rats is investigated. It is shown, that an exposure of the rats' brain to electromagnetic radiation in the millimeter range ((λ = 5,6 and 7,1 mm), modulated as a series of low-frequency pulses, leads to a suppression of the development of the conditioned avoidance reflex occurred in 50% of cases. In other 25% of cases irradiation leads to inhibition of reflex development. Transcranial electromagnetic stimulation after intraperitoneal injection of the blocking agent of serotonergic receptors (kitryl) has no influence on reflex development. Electromagnetic brain stimulation does not influence reflex retention in the case when it has been acquired. Based on the data obtained it is assumed that transcranial electromagnetic stimulation promotes the development of serotonin, exerting an inhibiting effect on the formation of temporal bindings of the studied conditioned reflex.

  19. Computed tomography analysis of the canine brain: effects of hemibrain x irradiation

    SciTech Connect

    Fike, J.R.; Cann, C.E.; Davis, R.L.; Borcich, J.K.; Phillips, T.L.; Russell, L.B.

    1984-08-01

    Radiation damage induced by megavoltage X irradiation in normal brain tissue can manifest as one of several pathologic processes depending upon the time of brain examination after irradiation. Serial quantitative computed tomography (QCT) analyses were used to study the development of radiation damage in the normal canine brain. Tissue density, volume of low density areas, magnitude and volume of contrast uptake, and ventricular volume were measured following hemibrain irradiation and were correlated with histopathology. Low density areas correlated with edema, demyelination, axonal swelling, and necrosis and appeared 3-4 months after irradiation. Large regions of contrast enhancement appeared 5-6 months after irradiation. Results from this study demonstrated that the pathologic changes induced in the dog brain after single doses of X rays were similar to the changes observed in nonhuman primates and man after exposure to radiation.

  20. Effects of photoradiation therapy on normal rat brain

    SciTech Connect

    Cheng, M.K.; McKean, J.; Boisvert, D.; Tulip, J.; Mielke, B.W.

    1984-12-01

    Laser photoradiation of the brain via an optical fiber positioned 5 mm above a burr hole was performed after the injection of hematoporphyrin derivative (HpD) in 33 normal rats and 6 rats with an intracerebral glioma. Normal rats received HpD, 5 or 10 mg/kg of body weight, followed by laser exposure at various doses or were exposed to a fixed laser dose after the administration of HpD, 2.5 to 20 mg/kg. One control group received neither HpD nor laser energy, and another was exposed to laser energy only. The 6 rats bearing an intracranial 9L glioma were treated with HpD, 5 mg/kg, followed by laser exposure at various high doses. The temperature in the cortex or tumor was measured with a probe during laser exposure. The rats were killed 72 hours after photoradiation, and the extent of necrosis of cerebral tissue was measured microscopically. In the normal rats, the extent of brain damage correlated with increases in the dose of both the laser and the HpD. In all 6 glioma-bearing rats, the high laser doses produced some focal necrosis in the tumors but also damaged adjacent normal brain tissue. The authors conclude that damage to normal brain tissue may be a significant complication of high dose photoradiation therapy for intracranial tumors.

  1. Brain uptake of ketoprofen-lysine prodrug in rats.

    PubMed

    Gynther, Mikko; Jalkanen, Aaro; Lehtonen, Marko; Forsberg, Markus; Laine, Krista; Ropponen, Jarmo; Leppänen, Jukka; Knuuti, Johanna; Rautio, Jarkko

    2010-10-31

    The blood-brain barrier (BBB) controls the entry of xenobiotics into the brain. Often the development of central nervous system drugs needs to be terminated because of their poor brain uptake. We describe a way to achieve large neutral amino acid transporter (LAT1)-mediated drug transport into the rat brain. We conjugated ketoprofen to an amino acid l-lysine so that the prodrug could access LAT1. The LAT1-mediated brain uptake of the prodrug was demonstrated with in situ rat brain perfusion technique. The ability of the prodrug to deliver ketoprofen into the site of action, the brain intracellular fluid, was determined combining in vivo and in vitro experiments. A rapid brain uptake from blood and cell uptake was seen both in in situ and in vivo experiments. Therefore, our results show that a prodrug approach can achieve uptake of drugs via LAT1 into the brain intracellular fluid. The distribution of the prodrug in the brain parenchyma and the site of parent drug release in the brain were shown with in vivo and in vitro studies. In addition, our results show that although lysine or ketoprofen are not LAT1-substrates themselves, by combining these molecules, the formed prodrug has affinity for LAT1. PMID:20727958

  2. In vitro comparison of rat and chicken brain neurotoxic esterase

    SciTech Connect

    Novak, R.; Padilla, S.

    1986-04-01

    A systematic comparison was undertaken to characterize neurotoxic esterase (NTE) from rat and chicken brain in terms of inhibitor sensitivities, pH optima, and molecular weights. Paraoxon titration of phenyl valerate (PV)-hydrolyzing carboxylesterases showed that rat esterases were more sensitive than chicken to paraoxon inhibition at concentrations less than or equal to microM and superimposable with chicken esterases at concentrations of 2.5-1000 microM. Mipafox titration of the paraoxon-resistant esterases at a fixed paraoxon concentration of 100 microM (mipafox concentration: 0-1000 microM) resulted in a mipafox I50 of 7.3 microM for chicken brain NTE and 11.6 microM for rat brain NTE. NTE (i.e., paraoxon-resistant, mipafox-sensitive esterase activity) comprised 80% of chicken and 60% of rat brain paraoxon-resistant activity with the specific activity of chicken brain NTE approximately twice that of rat brain NTE. The pH maxima for NTE from both species was similar showing broad, slightly alkaline optima from pH 7.9 to 8.6. (/sup 3/H)Diisopropyl phosphorofluoridate (DFP)-labeled NTE from the brains of both species had an apparent mol wt of 160,000 measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis. In conclusion, NTE from both species was very similar, with the mipafox I50 for rat NTE within the range of reported values for chicken and human NTE, and the inhibitor parameters of the chicken NTE assay were applicable for the rat NTE assay.

  3. Wearable 3-D Photoacoustic Tomography for Functional Brain Imaging in Behaving Rats

    PubMed Central

    Tang, Jianbo; Coleman, Jason E.; Dai, Xianjin; Jiang, Huabei

    2016-01-01

    Understanding the relationship between brain function and behavior remains a major challenge in neuroscience. Photoacoustic tomography (PAT) is an emerging technique that allows for noninvasive in vivo brain imaging at micrometer-millisecond spatiotemporal resolution. In this article, a novel, miniaturized 3D wearable PAT (3D-wPAT) technique is described for brain imaging in behaving rats. 3D-wPAT has three layers of fully functional acoustic transducer arrays. Phantom imaging experiments revealed that the in-plane X-Y spatial resolutions were ~200 μm for each acoustic detection layer. The functional imaging capacity of 3D-wPAT was demonstrated by mapping the cerebral oxygen saturation via multi-wavelength irradiation in behaving hyperoxic rats. In addition, we demonstrated that 3D-wPAT could be used for monitoring sensory stimulus-evoked responses in behaving rats by measuring hemodynamic responses in the primary visual cortex during visual stimulation. Together, these results show the potential of 3D-wPAT for brain study in behaving rodents. PMID:27146026

  4. Brain glucose content in fetuses of ethanol-fed rats

    SciTech Connect

    Pullen, G.; Singh, S.P.; Snyder, A.K.; Hoffen, B.

    1986-03-01

    The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4 and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.

  5. Cranial irradiation induces bone marrow-derived microglia in adult mouse brain tissue.

    PubMed

    Okonogi, Noriyuki; Nakamura, Kazuhiro; Suzuki, Yoshiyuki; Suto, Nana; Suzue, Kazutomo; Kaminuma, Takuya; Nakano, Takashi; Hirai, Hirokazu

    2014-07-01

    Postnatal hematopoietic progenitor cells do not contribute to microglial homeostasis in adult mice under normal conditions. However, previous studies using whole-body irradiation and bone marrow (BM) transplantation models have shown that adult BM cells migrate into the brain tissue and differentiate into microglia (BM-derived microglia; BMDM). Here, we investigated whether cranial irradiation alone was sufficient to induce the generation of BMDM in the adult mouse brain. Transgenic mice that express green fluorescent protein (GFP) under the control of a murine stem cell virus (MSCV) promoter (MSCV-GFP mice) were used. MSCV-GFP mice express GFP in BM cells but not in the resident microglia in the brain. Therefore, these mice allowed us to detect BM-derived cells in the brain without BM reconstitution. MSCV-GFP mice, aged 8-12 weeks, received 13.0 Gy irradiation only to the cranium, and BM-derived cells in the brain were quantified at 3 and 8 weeks after irradiation. No BM-derived cells were detected in control non-irradiated MSCV-GFP mouse brains, but numerous GFP-labeled BM-derived cells were present in the brain stem, basal ganglia and cerebral cortex of the irradiated MSCV-GFP mice. These BM-derived cells were positive for Iba1, a marker for microglia, indicating that GFP-positive BM-derived cells were microglial in nature. The population of BMDM was significantly greater at 8 weeks post-irradiation than at 3 weeks post-irradiation in all brain regions examined. Our results clearly show that cranial irradiation alone is sufficient to induce the generation of BMDM in the adult mouse.

  6. Ulinastatin attenuates brain edema after traumatic brain injury in rats.

    PubMed

    Cui, Tao; Zhu, Gangyi

    2015-03-01

    Traumatic brain injury (TBI) remains the leading cause of injury-related death and disability. Brain edema, one of the most major complications of TBI, contributes to elevated intracranial pressure, and poor prognosis following TBI. The objective of this study was to evaluate whether Ulinastatin (UTI), a serine protease inhibitor, attenuates brain edema following TBI. Our results showed that treatment with UTI at a dose of 50,000 U/kg attenuated the brain edema, as assayed by water content 24 h after TBI induction. This attenuation was associated with a significant decrease of the expression level of aquaporin-4. In addition, we showed that UTI treatment also markedly inhibited the expression of pro-inflammatory cytokines including IL-1β and TNF-α as well as activity of NF-κB. Collectively, our findings suggested that UTI may be a promising strategy to treat brain edema following TBI.

  7. Hydrogen-rich water attenuates brain damage and inflammation after traumatic brain injury in rats.

    PubMed

    Tian, Runfa; Hou, Zonggang; Hao, Shuyu; Wu, Weichuan; Mao, Xiang; Tao, Xiaogang; Lu, Te; Liu, Baiyun

    2016-04-15

    Inflammation and oxidative stress are the two major causes of apoptosis after traumatic brain injury (TBI). Most previous studies of the neuroprotective effects of hydrogen-rich water on TBI primarily focused on antioxidant effects. The present study investigated whether hydrogen-rich water (HRW) could attenuate brain damage and inflammation after traumatic brain injury in rats. A TBI model was induced using a controlled cortical impact injury. HRW or distilled water was injected intraperitoneally daily following surgery. We measured survival rate, brain edema, blood-brain barrier (BBB) breakdown and neurological dysfunction in all animals. Changes in inflammatory cytokines, inflammatory cells and Cho/Cr metabolites in brain tissues were also detected. Our results demonstrated that TBI-challenged rats exhibited significant brain injuries that were characterized by decreased survival rate and increased BBB permeability, brain edema, and neurological dysfunction, while HRW treatment ameliorated the consequences of TBI. HRW treatment also decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β and HMGB1), inflammatory cell number (Iba1) and inflammatory metabolites (Cho) and increased the levels of an anti-inflammatory cytokine (IL-10) in the brain tissues of TBI-challenged rats. In conclusion, HRW could exert a neuroprotective effect against TBI and attenuate inflammation, which suggests HRW as an effective therapeutic strategy for TBI patients. PMID:26826009

  8. Brain perfusion in acute and chronic hyperglycemia in rats

    SciTech Connect

    Kikano, G.E.; LaManna, J.C.; Harik, S.I. )

    1989-08-01

    Recent studies show that acute and chronic hyperglycemia cause a diffuse decrease in regional cerebral blood flow and that chronic hyperglycemia decreases the brain L-glucose space. Since these changes can be caused by a decreased density of perfused brain capillaries, we used 30 adult male Wistar rats to study the effect of acute and chronic hyperglycemia on (1) the brain intravascular space using radioiodinated albumin, (2) the anatomic density of brain capillaries using alkaline phosphatase histochemistry, and (3) the fraction of brain capillaries that are perfused using the fluorescein isothiocyanate-dextran method. Our results indicate that acute and chronic hyperglycemia do not affect the brain intravascular space nor the anatomic density of brain capillaries. Also, there were no differences in capillary recruitment among normoglycemic, acutely hyperglycemic, and chronically hyperglycemic rats. These results suggest that the shrinkage of the brain L-glucose space in chronic hyperglycemia is more likely due to changes in the blood-brain barrier permeability to L-glucose.

  9. Hydrophilic solute transport across the rat blood-brain barrier

    SciTech Connect

    Lucchesi, K.J.

    1987-01-01

    Brain capillary permeability-surface area products (PS) of hydrophilic solutes ranging in size from 180 to 5,500 Daltons were measured in rats according to the method of Ohno, Pettigrew and Rapoport. The distribution volume of 70 KD dextran at 10 minutes after i.v. injection was also measured to determine the residual volume of blood in brain tissue at the time of sacrifice. Small test solutes were injected in pairs in order to elucidate whether their transfer into the brain proceeds by diffusion through water- or lipid-filled channels or by vesicular transport. This issue was examined in rats whose blood-brain barrier (BBB) was presumed to be intact (untreated) and in rats that received intracarotid infusions to open the BBB (isosmotic salt (ISS) and hyperosmolar arabinose). Ohno PS values of {sup 3}H-inulin and {sup 14}C-L-glucose in untreated rats were found to decrease as the labelling time was lengthened. This was evidence that a rapidly equilibrating compartment exists between blood and brain that renders the Ohno two-compartment model inadequate for computing true transfer rate constants. When the data were reanalyzed using a multi-compartment graphical analysis, solutes with different molecular radii were found to enter the brain at approximately equal rates. Furthermore, unidirectional transport is likely to be initiated by solute adsorption to a glycocalyx coat on the luminal surface of brain capillary endothelium. Apparently, more inulin than L-glucose was adsorbed, which may account for its slightly faster transfer across the BBB. After rats were treated with intracarotid infusions of ISS or hyperosmolar arabinose, solute PS values were significantly increased, but the ratio of PS for each of the solute pairs approached that of their free-diffusion coefficients.

  10. Cell and tissue kinetics of the subependymal layer in mouse brain following heavy charged particle irradiation

    SciTech Connect

    Manley, N.B.; Fabrikant, J.I.; Alpen, E.L.

    1988-12-01

    The following studies investigate the cellular response and cell population kinetics of the subependymal layer in the mouse brain exposed to heavy charged particle irradiation. Partial brain irradiation with helium and neon ions was confined to one cortex of the brain. Both the irradiated and the unirradiated contralateral cortex showed similar disturbances of the cell and tissue kinetics in the subependymal layers. The irradiated hemisphere exhibited histological damage, whereas the unirradiated side appeared normal histologically. This study concerns the cell population and cell cycle kinetics of the subependymal layer in the mouse brain, and the effects of charged particle irradiations on this cell population. Quantitative high resolution autoradiography was used to study the kinetic parameters in this cell layer. This study should help in understanding the effects of these high-energy heavy ions on normal mammalian brain tissue. The response of the mammalian brain exposure to charged particle ionizing radiation may be extremely variable. It varies from minimal physiological changes to overt tissue necrosis depending on a number of factors such as: the administered dose, dose-rate, the volume of the irradiated tissue, and the biological end-point being examined.

  11. Corticotropin-releasing factor antagonist blocks microwave-induced decreases in high-affinity choline uptake in the rat brain

    SciTech Connect

    Lai, H.; Carino, M.A.; Horita, A.; Guy, A.W. )

    1990-10-01

    Acute (45-min) irradiation with pulsed low-level microwaves (2450-MHz, 2 microseconds pulses at 500 pps, average power density of 1 mW/cm2, whole-body average specific absorption rate of 0.6 W/kg) decreased sodium-dependent high-affinity choline uptake (HACU) activity in the frontal cortex and hippocampus of the rat. These effects were blocked by pretreating the animals before exposure with intracerebroventricular injection of the specific corticotropin-releasing factor (CRF) receptor antagonist, alpha-helical-CRF9-41 (25 micrograms). Similar injection of the antagonist had no significant effect on HACU in the brain of the sham-exposed rats. These data suggest that low-level microwave irradiation activates CRF in the brain, which in turn causes the changes in central HACU.

  12. Regulation of atrial natriuretic peptide receptors in the rat brain

    SciTech Connect

    Saavedra, J.M.

    1987-06-01

    We have studied the localization, kinetics, and regulation of receptors for the circulating form of the atrial natriuretic peptide (ANP; 99-126) in the rat brain. Quantitative autoradiographic techniques and a /sup 125/I-labeled ligand, /sup 125/I-ANP (99-126), were employed. After in vitro autoradiography, quantification was achieved by computerized microdensitometry followed by comparison with /sup 125/I-standards. ANP receptors were discretely localized in the rat brain, with the highest concentrations in circumventricular organs, the choroid plexus, and selected hypothalamic nuclei involved in the production of the antidiuretic hormone vasopressin and in blood-pressure control. Spontaneously (genetic) hypertensive rats showed much lower numbers of ANP receptors than normotensive controls in the subfornical organ, the area postrema, the nucleus of the solitary tract, and the choroid plexus. These changes are in contrast to those observed for receptors of angiotensin II, another circulating peptide with actions opposite to those of ANP. Under conditions of acute dehydration after water deprivation, as well as under conditions of chronic dehydration such as those present in homozygous Brattleboro rats, there was an up-regulation of ANP receptors in the subfornical organ. Our results indicate that in the brain, circumventricular organs contain ANP receptors which could respond to variations in the concentration of circulating ANP. In addition, brain areas inside the blood-brain barrier contain ANP receptors probably related to the endogenous, central ANP system. The localization of ANP receptors and the alterations in their regulation present in genetically hypertensive rats and after dehydration indicate that brain ANP receptors are probably related to fluid regulation, including the secretion of vasopressin, and to cardiovascular function.

  13. The Brain Metabolome of Male Rats across the Lifespan

    PubMed Central

    Zheng, Xiaojiao; Chen, Tianlu; Zhao, Aihua; Wang, Xiaoyan; Xie, Guoxiang; Huang, Fengjie; Liu, Jiajian; Zhao, Qing; Wang, Shouli; Wang, Chongchong; Zhou, Mingmei; Panee, Jun; He, Zhigang; Jia, Wei

    2016-01-01

    Comprehensive and accurate characterization of brain metabolome is fundamental to brain science, but has been hindered by technical limitations. We profiled the brain metabolome in male Wistar rats at different ages (day 1 to week 111) using high-sensitivity and high-resolution mass spectrometry. Totally 380 metabolites were identified and 232 of them were quantitated. Compared with anatomical regions, age had a greater effect on variations in the brain metabolome. Lipids, fatty acids and amino acids accounted for the largest proportions of the brain metabolome, and their concentrations varied across the lifespan. The levels of polyunsaturated fatty acids were higher in infancy (week 1 to week 3) compared with later ages, and the ratio of omega-6 to omega-3 fatty acids increased in the aged brain (week 56 to week 111). Importantly, a panel of 20 bile acids were quantitatively measured, most of which have not previously been documented in the brain metabolome. This study extends the breadth of the mammalian brain metabolome as well as our knowledge of functional brain development, both of which are critically important to move the brain science forward. PMID:27063670

  14. Demonstration of endogenous imipramine like material in rat brain

    SciTech Connect

    Rehavi, M.; Ventura, I.; Sarne, Y.

    1985-02-18

    The extraction and partial purification of an endogenous imipramine-like material from rat brain is described. The endogenous factor obtained after gel filtration and silica chromatography inhibits (/sup 3/H) imipramine specific binding and mimics the inhibitory effect of imipramine on (/sup 3/H) serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits (/sup 3/H) imipramine binding in a competitive fashion. The factor is unevenly distributed in the brain with high concentration in the hypothalamus and low concentration in the cerebellum.

  15. Measurement of blood-brain barrier permeation in rats during exposure to 2450-MHz microwaves

    SciTech Connect

    Ward, T.R.; Elder, J.A.; Long, M.D.; Svendsgaard, D.

    1982-01-01

    Adult rats anesthesized with pentobarbital and injected intravenously with a mixture of (/sup 14/C) sucrose and (/sup 3/H) inulin were exposed for 30 min to an environment at an ambient temperature of 22, 30, or 40 degrees C, or were exposed at 22 degrees C to 2450-MHz CW microwave radiation at power densities of 0, 10, 20, or 30 mW/cm2. Following exposure, the brain was perfused and sectioned into eight regions, and the radioactivity in each region was counted. The data were analyzed by two methods. First, the data for each of the eight regions and for each of the two radioactive tracers were analyzed by regression analysis for a total of 16 analyses and Bonferroni's Inequality was applied to prevent false positive results from numerous analyses. By this conservative test, no statistically significant increase in permeation was found for either tracer in any brain region of rats exposed to microwaves. Second, a profile analysis was used for a general change in tracer uptake across all brain regions. Using this statistical method, a significant increase in permeation was found for sucrose but not for inulin. A correction factor was then derived from the warm-air experiments to correct for the increase in permeation of the brain associated with change in body temperature. This correction factor was applied to the data for the irradiated animals. After correcting the data for thermal effects of the microwave radiation, no significant increase in permeation was found.

  16. Thyroid insufficiency in developing rat brain: A genomic analysis.

    EPA Science Inventory

    Thyroid Insufficiency in the Developing Rat Brain: A Genomic Analysis. JE Royland and ME Gilbert, Neurotox. Div., U.S. EPA, RTP, NC, USA. Endocrine disruption (ED) is an area of major concern in environmental neurotoxicity. Severe deficits in thyroid hormone (TH) levels have bee...

  17. EVALUATION OF PERFLUOROOCTANE SULFONATE IN THE RAT BRAIN

    EPA Science Inventory

    Perfluorooctane Sulfonate (PFOS) is an environmentally persistent chemical that has been detected in humans and wildlife. PFOS is primarily distributed in liver and blood. The current study evaluated the level of PFOS in the adult and neonatal rat brain and determined whether t...

  18. Autoradiographic localization of relaxin binding sites in rat brain

    SciTech Connect

    Osheroff, P.L.; Phillips, H.S. )

    1991-08-01

    Relaxin is a member of the insulin family of polypeptide hormones and exerts its best understood actions in the mammalian reproductive system. Using a biologically active 32P-labeled human relaxin, the authors have previously shown by in vitro autoradiography specific relaxin binding sites in rat uterus, cervix, and brain tissues. Using the same approach, they describe here a detailed localization of human relaxin binding sites in the rat brain. Displaceable relaxin binding sites are distributed in discrete regions of the olfactory system, neocortex, hypothalamus, hippocampus, thalamus, amygdala, midbrain, and medulla of the male and female rat brain. Characterization of the relaxin binding sites in the subfornical organ and neocortex reveals a single class of high-affinity sites (Kd = 1.4 nM) in both regions. The binding of relaxin to two of the circumventricular organs (subfornical organ and organum vasculosum of the lamina terminalis) and the neurosecretory magnocellular hypothalamic nuclei (i.e., paraventricular and supraoptic nuclei) provides the anatomical and biochemical basis for emerging physiological evidence suggesting a central role for relaxin in the control of blood pressure and hormone release. They conclude that specific, high-affinity relaxin binding sites are present in discrete regions of the rat brain and that the distribution of some of these sites may be consistent with a role for relaxin in control of vascular volume and blood pressure.

  19. In vivo pink-beam imaging and fast alignment procedure for rat brain lesion microbeam radiation therapy

    PubMed Central

    Serduc, Raphaël; Berruyer, Gilles; Brochard, Thierry; Renier, Michel; Nemoz, Christian

    2010-01-01

    A fast 50 µm-accuracy alignment procedure has been developed for the radiosurgery of brain lesions in rats, using microbeam radiation therapy. In vivo imaging was performed using the pink beam (35–60 keV) produced by the ID17 wiggler at the ESRF opened at 120 mm and filtered. A graphical user interface has been developed in order to define the irradiation field size and to position the target with respect to the skull structures observed in X-ray images. The method proposed here allows tremendous time saving by skipping the swap from white beam to monochromatic beam and vice versa. To validate the concept, the somatosensory cortex or thalamus of GAERS rats were irradiated under several ports using this alignment procedure. The magnetic resonance images acquired after contrast agent injection showed that the irradiations were selectively performed in these two expected brain regions. Image-guided microbeam irradiations have therefore been realised for the first time ever, and, thanks to this new development, the ID17 biomedical beamline provides a major tool allowing brain radiosurgery trials on animal patients. PMID:20400830

  20. Prenatal Ethanol Exposure Increases Brain Cholesterol Content in Adult Rats

    PubMed Central

    Barceló-Coblijn, Gwendolyn; Wold, Loren E.; Ren, Jun; Murphy, Eric J.

    2013-01-01

    Fetal alcohol syndrome is the most severe expression of the fetal alcohol spectrum disorders (FASD). Although alterations in fetal and neonate brain fatty acid composition and cholesterol content is known to change in animal models of FASD, the persistence of these alterations into adulthood is unknown. To address this question, we determined the effect of prenatal ethanol exposure on individual phospholipid class fatty acid composition, individual phospholipid class mass, and cholesterol mass in brains from 25-week-old rats that were exposed to ethanol during gestation beginning at gestational day 2. While total phospholipid mass was unaffected, phosphatidylinositol and cardiolipin mass was decreased 14 and 43%, respectively. Exposure to prenatal ethanol modestly altered brain phospholipid fatty acid composition, and the most consistent change was a significant 1.1-fold increase in total PUFA, in the n-3/n-6 ratio, and in the 22:6 n-3 content in ethanolamine glycerophospholipids and in phosphatidylserine. In contrast, prenatal ethanol consumption significantly increased brain cholesterol mass 1.4-fold and the phospholipid to cholesterol ratio was significantly increased 1.3-fold. These results indicate that brain cholesterol mass was significantly increased in adult rats exposed prenatally to ethanol, but changes in phospholipid mass and phospholipid fatty acid composition were extremely limited. Importantly, suppression of post-natal ethanol consumption was not sufficient to reverse the large increase in cholesterol observed in the adult rats. PMID:23996454

  1. Inducible Gene Manipulations in Brain Serotonergic Neurons of Transgenic Rats

    PubMed Central

    Tews, Björn; Bartsch, Dusan

    2011-01-01

    The serotonergic (5-HT) system has been implicated in various physiological processes and neuropsychiatric disorders, but in many aspects its role in normal and pathologic brain function is still unclear. One reason for this might be the lack of appropriate animal models which can address the complexity of physiological and pathophysiological 5-HT functioning. In this respect, rats offer many advantages over mice as they have been the animal of choice for sophisticated neurophysiological and behavioral studies. However, only recently technologies for the targeted and tissue specific modification of rat genes - a prerequisite for a detailed study of the 5-HT system - have been successfully developed. Here, we describe a rat transgenic system for inducible gene manipulations in 5-HT neurons. We generated a Cre driver line consisting of a tamoxifen-inducible CreERT2 recombinase under the control of mouse Tph2 regulatory sequences. Tissue-specific serotonergic Cre recombinase expression was detected in four transgenic TPH2-CreERT2 rat founder lines. For functional analysis of Cre-mediated recombination, we used a rat Cre reporter line (CAG-loxP.EGFP), in which EGFP is expressed after Cre-mediated removal of a loxP-flanked lacZ STOP cassette. We show an in-depth characterisation of this rat Cre reporter line and demonstrate its applicability for monitoring Cre-mediated recombination in all major neuronal subpopulations of the rat brain. Upon tamoxifen induction, double transgenic TPH2-CreERT2/CAG-loxP.EGFP rats show selective and efficient EGFP expression in 5-HT neurons. Without tamoxifen administration, EGFP is only expressed in few 5-HT neurons which confirms minimal background recombination. This 5-HT neuron specific CreERT2 line allows Cre-mediated, inducible gene deletion or gene overexpression in transgenic rats which provides new opportunities to decipher the complex functions of the mammalian serotonergic system. PMID:22140568

  2. Autoradiographic localization of (3H) gepirone in the rat brain

    SciTech Connect

    Bennett, J.E.; Matheson, G.K. )

    1990-02-26

    Gepirone is an anxiolytic compound active at the 5-HT{sub 1A} receptor site. The purpose of this study was to locate the ({sup 3}H)gepirone in the rat brain and to determine the quantity of gepirone in these locations. Male Sprague-Dawley rats were injected with (3H)gepirone (200 {mu}Ci/kg, i.v.) and decapitated 10 minutes later. To determine specific binding some animals were pretreated with cold gepirone (1 mg/kg) 15 minutes before the (3H)gepirone treatment. The brains were removed, frozen, sectioned, and fixed in formaldehyde vapors. Tritium sensitive film was exposed to the sections for 106 days. Using computerized imaging technology data were obtained from 104 brain sites. Overall, the quantity of (3H)gepirone in each site correlated proportionally with known 5-HT{sub 1A} (in vitro) receptor binding.

  3. Enzyme markers of maternal malnutrition in fetal rat brain.

    PubMed

    Shambaugh, G E; Mankad, B; Derecho, M L; Koehler, R R

    1987-01-01

    The impact of maternal starvation in late gestation on development of some enzymatic mechanisms concerned with neurotransmission and polyamine synthesis was studied in fetal rat brain. Between 17 and 20 d, acetylcholinesterase and choline acetyltransferase activity increased in fetal brains of fed dams, whereas maternal starvation from day 17 to day 20 resulted in heightened acetylcholinesterase but not choline acetyltransferase activity. Ornithine decarboxylase activity on a per-gram wet-weight basis fell between 17 and 20 d in fetal brain from fed dams. Increasing the duration of maternal starvation resulted in a progressive increase in fetal brain ornithine decarboxylase. Arginine and putrescine levels in the brain were lower in fetuses of starved mothers while spermidine and spermine concentrations were unchanged. Since the Km of ornithine decarboxylase for ornithine was found to vary directly with levels of putrescine in fetal brain, lower concentrations of putrescine and greater ornithine decarboxylase activity in fetal brains from starved mothers suggested that levels of this enzyme may be controlled in part by putrescine. Changes in the maternal nutritional state had no effect on the activity of glutamate decarboxylase in fetal brain, and tissue levels of the product, gamma-aminobutyric acid, were unchanged. Thus changes in ornithine decarboxylase and acetylcholinesterase activity in fetal brain may uniquely reflect biochemical alterations consequent to maternal starvation.

  4. Pharmacological modulation of blood-brain barrier increases permeability of doxorubicin into the rat brain

    PubMed Central

    Sardi, Iacopo; la Marca, Giancarlo; Cardellicchio, Stefania; Giunti, Laura; Malvagia, Sabrina; Genitori, Lorenzo; Massimino, Maura; de Martino, Maurizio; Giovannini, Maria G

    2013-01-01

    Our group recently demonstrated in a rat model that pretreatment with morphine facilitates doxorubicin delivery to the brain in the absence of signs of increased acute systemic toxicity. Morphine and other drugs such as dexamethasone or ondansetron seem to inhibit MDR proteins localized on blood-brain barrier, neurons and glial cells increasing the access of doxorubicin to the brain by efflux transporters competition. We explored the feasibility of active modification of the blood-brain barrier protection, by using morphine dexamethasone or ondansetron pretreatment, to allow doxorubicin accumulation into the brain in a rodent model. Rats were pretreated with morphine (10 mg/kg, i.p.), dexamethasone (2 mg/kg, i.p.) or ondansetron (2 mg/kg, i.p.) before injection of doxorubicin (12 mg/kg, i.p.). Quantitative analysis of doxorubicin was performed by mass spectrometry. Acute hearth and kidney damage was analyzed by measuring doxorubicin accumulation, LDH activity and malondialdehyde plasma levels. The concentration of doxorubicin was significantly higher in all brain areas of rats pretreated with morphine (P < 0.001) or ondansetron (P < 0.05) than in control tissues. The concentration of doxorubicin was significantly higher in cerebral hemispheres and brainstem (P < 0.05) but not in cerebellum of rats pretreated with dexamethasone than in control tissues. Pretreatment with any of these drugs did not increase LDH activity or lipid peroxidation compared to controls. Our data suggest that morphine, dexamethasone or ondansetron pretreatment is able to allow doxorubicin penetration inside the brain by modulating the BBB. This effect is not associated with acute cardiac or renal toxicity. This finding might provide the rationale for clinical applications in the treatment of refractory brain tumors and pave the way to novel applications of active but currently inapplicable chemotherapeutic drugs. PMID:23977451

  5. Chronic Methamphetamine Effects on Brain Structure and Function in Rats.

    PubMed

    Thanos, Panayotis K; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J; Masad, Ihssan; Muniz, Jose A; Grant, Samuel C; Gold, Mark S; Cadet, Jean Lud; Volkow, Nora D

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  6. Chronic Methamphetamine Effects on Brain Structure and Function in Rats

    PubMed Central

    Thanos, Panayotis K.; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J.; Masad, Ihssan; Muniz, Jose A.; Grant, Samuel C.; Gold, Mark S.; Cadet, Jean Lud; Volkow, Nora D.

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  7. Developmental Vitamin D3 deficiency alters the adult rat brain.

    PubMed

    Féron, F; Burne, T H J; Brown, J; Smith, E; McGrath, J J; Mackay-Sim, A; Eyles, D W

    2005-03-15

    There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D(3) deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D(3) deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). We conclude that transient early life hypovitaminosis D(3) not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D(3) in women of child-bearing age, the public health implications of these findings warrant attention. PMID:15763180

  8. Influence of trichlorfon and fractionated irradiation on hydroproteolytic activity of pancreas and intestinal tissues of rats.

    PubMed

    Koćmierska-Grodzka, D

    1976-03-01

    Investigations into the hydroproteolytic activity of pancreas and intestinal tissues (small intestine and colon) of rats after fractionated irradiation (5 X 150 R) were carried out. There was found marked postirradiation enhancement of lipase activity in pancreas and duodenal part of intestine and increase of B-glucuronidase and acid phosphatase activity in nearly all parts of the examined intestinal tissues. Fractionated irradiation resulted in an increase of pancreatic catheptic (proteolytic) activity causing simultaneous decrease of proteolytic activity in intestine and colon. Preventive administration of Trichlorfon (ten days before irradiation) in the dose of 10 mg or 30 mg/kg evoked modification of hydroproteolytic activity in intestinal tissues of healthy and irradiated rats. Trichlorfon applied in the dose of 30 mg/kg exerted antilipolytic and anticatheptic effects in pancreas and intestinal tissues of irradiated rats. PMID:1258099

  9. Regulation of prostaglandin E{sub 2} synthesis after brain irradiation

    SciTech Connect

    Moore, Amy H.; Olschowka, John A.; Williams, Jacqueline P.; Okunieff, Paul; O'Banion, M. Kerry . E-mail: kerry_obanion@urmc.rochester.edu

    2005-05-01

    Purpose: A local tissue reaction, termed neuroinflammation, occurs after irradiation of brain tissue. Previous work suggested that cyclooxygenase (COX)-2 activity was important for changes in gene expression associated with neuroinflammation as well as increased prostaglandin E{sub 2} (PGE{sub 2}) levels seen after radiation treatment. Methods and materials: To begin to determine the contributions of other enzymes involved in PGE{sub 2} production, we examined protein levels of COX-1 and COX-2 as well as 2 PGE synthases (membrane and cytosolic PGES) 4 h after 35 Gy single dose irradiation to the brains of C3HeN mice. We also evaluated the effects of specific COX inhibitors on PGE{sub 2} production and PGES expression. Results: As expected, COX-2 expression increased after radiation exposure. Brain irradiation also increased tissue protein levels for both PGES isoforms. Specific COX-2 inhibition with NS398 lowered brain PGE{sub 2} levels by about 60%. Surprisingly, COX-1 inhibition with SC560 completely prevented the elevation of PGE{sub 2} seen after irradiation. Interestingly, NS398 reduced the membrane-associated PGES isoform, whereas SC560 treatment lowered cytosolic isoform levels below those seen in unirradiated controls. Conclusions: Taken together, these data indicate that both cyclooxygenases contribute to PGE{sub 2} production in irradiated brain and reveal dependence of PGES isoforms expression on specific cyclooxygenase activities.

  10. MR assessment of radiation-induced blood-brain barrier permeability changes in a rat glioma model

    SciTech Connect

    Krueck, W.G. Univ. of Washington School of Medicine, Seattle, WA ); Schmiedl, U.P.; Maravilla, K.R.; Starr, F.L.; Kenney, J. )

    1994-04-01

    To assess the potential of a T1-weighted, gadolinium-enhanced MR technique for quantifying radiation-induced changes of blood-brain barrier permeability in a model of stereotactically implanted intracerebral gliomas in rats. We calculated the gadolinium blood-to-tissue transport coefficient for gadopentetate dimeglumine from signal intensities in sequential MR images in nine control animals that were not irradiated and in five and three animals that had received 2500 cGy and 1500 cGy whole-brain irradiation, respectively, at 2 days before imaging. The average blood-to-tissue transport coefficient values were 9.76 mL[center dot]kg[sup [minus]1][center dot]min[sup [minus]1] in the control group, 23.41 mL[center dot]kg[sup [minus]1][center dot]min[sup [minus]1] in the 2500-cGy group, and 25.63 mL[center dot]kg[sup [minus]1][center dot]min[sup [minus]1] in the 1500-cGy group. Blood-to-tissue transport coefficients were significantly higher after irradiation, indicating increased radiation-induced blood-brain barrier permeability. Similar increased blood-brain barrier leakiness in brain tumors after high-dose irradiation has been shown by previous nuclear medicine studies using quantitative autoradiography. Contrast-enhanced dynamic MR of brain gliomas is a sensitive method to document radiation-induced blood-brain barrier breakdown. Quantitative gadolinium-enhanced MR may become a useful tool for the management of patients with brain tumors undergoing radiation therapy. 28 refs., 4 figs., 1 tab.

  11. Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats.

    PubMed

    McBride, Devin W; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H

    2015-09-01

    Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 h after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in significantly elevated frontal lobe brain water content 24 and 72 h after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study's results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 h post-SBI. PMID:25975171

  12. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

    PubMed

    Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

    2013-06-01

    Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

  13. Neuropathology of ablation of rat gliosarcomas and contiguous brain tissues using a microplanar beam of synchrotron-wiggler-generated X rays.

    PubMed

    Laissue, J A; Geiser, G; Spanne, P O; Dilmanian, F A; Gebbers, J O; Geiser, M; Wu, X Y; Makar, M S; Micca, P L; Nawrocky, M M; Joel, D D; Slatkin, D N

    1998-11-23

    Adult-rat-brain tissues display an unusually high resistance to necrosis when serially irradiated with parallel, thin slices of a microplanar (i.e., microscopically thin and macroscopically broad) beam of synchrotron-wiggler-generated, approx. 35-120 keV (median approx. 50 keV) Gd-filtered X rays at skin-entrance absorbed doses of 312 to 5000 Gy per slice. Such microplanar beams were used to irradiate young adult rats bearing right frontocerebral 9L gliosarcomas (approx. 4 mm diameter), through a volume of tissue containing the tumor and contiguous brain tissue, either in a single array or in 2 orthogonally crossed arrays of tissue slices. Each array included 101 parallel microplanar slices, 100 microm center-to-center distance, each slice being approx. 25 microm wide and 12 mm high, with skin-entrance absorbed doses of 312.5 Gy or 625 Gy per slice. Compared with unirradiated controls with a median survival time of 20 days after tumor initiation, the median survival time was extended in irradiated rats by 139 days (625 Gy, crossed arrays), 96 days (312 Gy, crossed arrays) or 24 days (625 Gy, single array). The tumors disappeared in 22 of the 36 irradiated rats, 4/11 even after unidirectional microbeam irradiation. The extent and severity of radiation damage to the normal brain in rats with or without tumor was graded histopathologically. Correlation of those grades with radiation doses shows that loss of tissue structure was confined to beam-crossing regions and that only minor damage was done to zones of the brain irradiated unidirectionally.

  14. Alterations of Amino Acid Level in Depressed Rat Brain

    PubMed Central

    Yang, Pei; Li, Xuechun; Tian, Jingchen; Jing, Fu; Qu, Changhai; Lin, Longfei; Zhang, Hui

    2014-01-01

    Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. Several studies have demonstrated the potential of amino acids as a source of neuro-specific biomarkers could be used in future diagnosis of depression. Only partial amino acids such as glycine and asparagine were determined from certain parts of rats' brain included hippocampi and cerebral cortex in previous studies. However, according to systematic biology, amino acids in different area of brain are interacted and interrelated. Hence, the determination of 34 amino acids through entire rats' brain was conducted in this study in order to demonstrate more possibilities for biomarkers of depression by discovering other potential amino acids in more areas of rats' brain. As a result, 4 amino acids (L-aspartic acid, L-glutamine, taurine and γ-amino-n-butyric acid) among 34 were typically identified as potentially primary biomarkers of depression by data statistics. Meanwhile, an antidepressant called Fluoxetine was employed to verify other potential amino acids which were not identified by data statistics. Eventually, we found L-α-amino-adipic acid could also become a new potentially secondary biomarker of depression after drug validation. In conclusion, we suggested that L-aspartic acid, L-glutamine, taurine, γ-amino-n-butyric acid and L-α-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant. PMID:25352755

  15. Rat brain acetylcholinesterase visualized with [11C]physostigmine.

    PubMed

    Planas, A M; Crouzel, C; Hinnen, F; Jobert, A; Né, F; DiGiamberardino, L; Tavitian, B

    1994-06-01

    Physostigmine, a powerful cholinesterase inhibitor, has recently been labelled with 11C in view of its potential application for in vivo imaging of cerebral acetylcholinesterase (AChE) using positron emission tomography. Here we carried out autoradiography of the rat brain using [11C]physostigmine in order to characterize the cerebral targets of this ligand. Autoradiograms were obtained using phosphor storage plates which, compared to autoradiographic films, greatly improved the quality of 11C images. Following autoradiography, brain sections were stained for AChE activity, allowing a direct comparison of autoradiographic and histoenzymatic localizations. The distributions of 11C label and of AChE activity were found to be essentially super-imposable, both after in vivo injection of and after in vitro incubation with [11C]physostigmine. Densitometric analysis showed that radioactivity and enzymatic activity distributions were regionally correlated. The fixation of [11C]physostigmine to cerebral tissue was abolished after incubation of the rat brain sections with BW 284C51, a specific AChE inhibitor, but not after incubation with iso-OMPA, a specific inhibitor of butyrylcholinesterase. Unilateral excitotoxic lesions of the striatum that eliminated local AChE expression concomitantly reduced the binding of the ligand in the lesioned area. These results indicate that autoradiographic images of the rat brain obtained with [11C]physostigmine reflect AChE distribution, thus supporting the use of this radioligand to trace cerebral AChE activity in humans with positron emission tomography.

  16. Alcohol induced changes in phosphoinositide signaling system in rat brain

    SciTech Connect

    Pandey, S.; Piano, M.; Schwertz, D.; Davis, J.; Pandey, G. )

    1991-03-11

    Agonist-induced phosphoinositide break down functions as a signal generating system in a manner similar to the C-AMP system. In order to examine if the changes produced by chronic ethanol treatment on membrane lipid composition and metabolism effect the cellular functions of the neuron, the authors have examined the effect of chronic ethanol exposure on norepinephrine (NE) serotonin (5HT) and calcium ionophore (CI) stimulated phosphoinositide (PI) hydrolysis in rat cortical slices. Rats were maintained on liber-decarli diet alcohol and control liquid diet containing isocaloric sucrose substitute for two months. They were then sacrificed and brain was removed for determination of PI turnover. 5HT stimulated {sup 3}H- inositol monophosphate ({sup 3}H-IPI) formation was significantly lower in the cortex of alcohol treated rats as compared to control rats. However, neither CI nor NE stimulated IP1 formation was significantly different from control rats. The results thus indicate that chronic exposure to ethanol decreases 5HT induced PI breakdown in rat cortex. In order to examine if this decrease is related to a decrease in 5HT2 receptors, or decreased in coupling of receptor to the effector pathway, the authors are currently determining the number and affinity of 5HT2 receptors in alcohol treated rats.

  17. Abdominal surgery activates nesfatin-1 immunoreactive brain nuclei in rats.

    PubMed

    Stengel, Andreas; Goebel, Miriam; Wang, Lixin; Taché, Yvette

    2010-02-01

    Abdominal surgery-induced postoperative gastric ileus is well established to induce Fos expression in specific brain nuclei in rats within 2-h after surgery. However, the phenotype of activated neurons has not been thoroughly characterized. Nesfatin-1 was recently discovered in the rat hypothalamus as a new anorexigenic peptide that also inhibits gastric emptying and is widely distributed in rat brain autonomic nuclei suggesting an involvement in stress responses. Therefore, we investigated whether abdominal surgery activates nesfatin-1-immunoreactive (ir) neurons in the rat brain. Two hours after abdominal surgery with cecal palpation under short isoflurane anesthesia or anesthesia alone, rats were transcardially perfused and brains processed for double immunohistochemical labeling of Fos and nesfatin-1. Abdominal surgery, compared to anesthesia alone, induced Fos expression in neurons of the supraoptic nucleus (SON), paraventricular nucleus (PVN), locus coeruleus (LC), Edinger-Westphal nucleus (EW), rostral raphe pallidus (rRPa), nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM). Double Fos/nesfatin-1 labeling showed that of the activated cells, 99% were nesfatin-1-immunoreactive in the SON, 91% in the LC, 82% in the rRPa, 74% in the EW and VLM, 71% in the anterior parvicellular PVN, 47% in the lateral magnocellular PVN, 41% in the medial magnocellular PVN, 14% in the NTS and 9% in the medial parvicellular PVN. These data established nesfatin-1 immunoreactive neurons in specific nuclei of the hypothalamus and brainstem as part of the neuronal response to abdominal surgery and suggest a possible implication of nesfatin-1 in the alterations of food intake and gastric transit associated with such a stressor. PMID:19944727

  18. Human and rat brain lipofuscin proteome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The accumulation of an autofluorescent pigment called lipofuscin in neurons is an invariable hallmark of brain aging. So far, this material has been considered to be waste material without particular relevance for cellular pathology. However, two lines of evidence argue that lipofuscin may have yet ...

  19. Local proliferation and extrahepatic recruitment of liver macrophages (Kupffer cells) in partial-body irradiated rats

    SciTech Connect

    Bouwens, L.; Knook, D.L.; Wisse, E.

    1986-06-01

    The relative significance of local proliferation and extrahepatic recruitment of Kupffer cells was investigated by partial-body irradiation before the induction of macrophage hyperplasia by zymosan. There was no difference in growth of the Kupffer cells population between nonirradiated rats and rats irradiated with the liver shielded, whereas irradiation of the liver with the rest of the body (bone marrow) shielded resulted in strong inhibition of growth (-61%). Splenectomy combined with bone marrow irradiation inhibited growth to a lesser extent as compared to liver irradiation (-38%). Monocyte and other leukocyte numbers were strongly reduced in peripheral blood and their accumulation in the liver was completely prevented by bone marrow irradiation. Our results demonstrate that local proliferation of resident Kupffer cells represents the predominant source for their increased number during hyperplasia.

  20. Nerve growth factor receptor molecules in rat brain

    SciTech Connect

    Taniuchi, M.; Schweitzer, J.B.; Johnson, E.M. Jr.

    1986-03-01

    The authors have developed a method to immunoprecipitate rat nerve growth factor (NGF) receptor proteins and have applied the method to detect NGF receptor molecules in the rat brain. Crosslinking /sup 125/I-labeled NGF to either PC12 cells or cultured rat sympathetic neurons yielded two radiolabeled molecules (90 kDa and 220 kDa) that were immunoprecipitated by monoclonal antibody 192-IgG. Further, 192-IgG precipitated two radiolabeled proteins, with the expected sizes (80 kDa and 210 kDa) of noncrosslinked NGF receptor components, from among numerous surface-iodinated PC12 cell proteins. These results demonstrate the specific immunoprecipitation of NGF receptor molecules by 192-IgG. They applied the /sup 125/I-NGF crosslinking and 192-IgG-mediated immunoprecipitation procedures to plasma membrane preparations of rat brain: NGF receptor molecules of the same molecular masses as the peripheral receptor components were consistently detected in all regions and in preparations from whole brains. Removal of the peripheral sympathetic innervation of the brain did not eliminate these NGF receptor proteins, indicating that the receptor is endogenous to central nervous system tissues. They also observed retrograde transport of /sup 125/I-labeled 192-IgG from the parietal cortex to the nucleus basalis and from the hippocampus to the nucleus of the diagonal band of Broca and the medial septal nucleus. These findings demonstrate the presence in brain of NGF receptor molecules indistinguishable from those of the peripheral nervous system.

  1. Determination of boron distribution in rat's brain, kidney and liver.

    PubMed

    Pazirandeh, Ali; Jameie, Behnam; Zargar, Maysam

    2009-07-01

    To determine relative boron distribution in rat's brain, liver and kidney, a mixture of boric acid and borax, was used. After transcardial injection of the solution, the animals were sacrificed and the brain, kidney and liver were removed. The coronal sections of certain areas of the brain were prepared by freezing microtome. The slices were sandwiched within two pieces of CR-39. The samples were bombarded in a thermal neutron field of the TRR pneumatic facility. The alpha tracks are registered on CR-39 after being etched in NaOH. The boron distribution was determined by counting these alpha tracks CR-39 plastics. The distribution showed non-uniformity in brain, liver and kidney. PMID:19375929

  2. Correlation Between Subacute Sensorimotor Deficits and Brain Edema in Rats after Surgical Brain Injury.

    PubMed

    McBride, Devin W; Wang, Yuechun; Adam, Loic; Oudin, Guillaume; Louis, Jean-Sébastien; Tang, Jiping; Zhang, John H

    2016-01-01

    No matter how carefully a neurosurgical procedure is performed, it is intrinsically linked to postoperative deficits resulting in delayed healing caused by direct trauma, hemorrhage, and brain edema, termed surgical brain injury (SBI). Cerebral edema occurs several hours after SBI and is a major contributor to patient morbidity, resulting in increased postoperative care. Currently, the correlation between functional recovery and brain edema after SBI remains unknown. Here we examine the correlation between neurological function and brain water content in rats 42 h after SBI. SBI was induced in male Sprague-Dawley rats via frontal lobectomy. Twenty-four hours post-ictus animals were subjected to four neurobehavior tests: composite Garcia neuroscore, beam walking test, corner turn test, and beam balance test. Animals were then sacrificed for right-frontal brain water content measurement via the wet-dry method. Right-frontal lobe brain water content was found to significantly correlate with neurobehavioral deficits in the corner turn and beam balance tests: the number of left turns (percentage of total turns) for the corner turn test and distance traveled for the beam balance test were both inversely proportional with brain water content. No correlation was observed for the composite Garcia neuroscore or the beam walking test. PMID:26463968

  3. Differential expression of sirtuins in the aging rat brain.

    PubMed

    Braidy, Nady; Poljak, Anne; Grant, Ross; Jayasena, Tharusha; Mansour, Hussein; Chan-Ling, Tailoi; Smythe, George; Sachdev, Perminder; Guillemin, Gilles J

    2015-01-01

    Although there are seven mammalian sirtuins (SIRT1-7), little is known about their expression in the aging brain. To characterize the change(s) in mRNA and protein expression of SIRT1-7 and their associated proteins in the brain of "physiologically" aged Wistar rats. We tested mRNA and protein expression levels of rat SIRT1-7, and the levels of associated proteins in the brain using RT-PCR and western blotting. Our data shows that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated. SIRT2 and FOXO3a protein levels increased only in the occipital lobe. SIRT3-5 expression declined significantly in the hippocampus and frontal lobe, associated with increases in superoxide and fatty acid oxidation levels, and acetylated CPS-1 protein expression, and a reduction in MnSOD level. While SIRT6 expression declines significantly with age acetylated H3K9 protein expression is increased throughout the brain. SIRT7 and Pol I protein expression increased in the frontal lobe. This study identifies previously unknown roles for sirtuins in regulating cellular homeostasis and healthy aging. PMID:26005404

  4. Spectral and lifetime domain measurements of rat brain tumours

    NASA Astrophysics Data System (ADS)

    Abi Haidar, D.; Leh, B.; Allaoua, K.; Genoux, A.; Siebert, R.; Steffenhagen, M.; Peyrot, D.; Sandeau, N.; Vever-Bizet, C.; Bourg-Heckly, G.; Chebbi, I.; Collado-Hilly, M.

    2012-02-01

    During glioblastoma surgery, delineation of the brain tumour margins remains difficult especially since infiltrated and normal tissues have the same visual appearance. This problematic constitutes our research interest. We developed a fibre-optical fluorescence probe for spectroscopic and time domain measurements. First measurements of endogenous tissue fluorescence were performed on fresh and fixed rat tumour brain slices. Spectral characteristics, fluorescence redox ratios and fluorescence lifetime measurements were analysed. Fluorescence information collected from both, lifetime and spectroscopic experiments, appeared promising for tumour tissue discrimination. Two photon measurements were performed on the same fixed tissue. Different wavelengths are used to acquire two-photon excitation-fluorescence of tumorous and healthy sites.

  5. Selective lymphoid irradiation and cyclosporin A in rat heart allografts

    SciTech Connect

    Kuromoto, N.; Hardy, M.A.; Fawwaz, R.; Reemtsma, K.; Nowygrod, R.

    1984-05-01

    Short-term peritransplant treatment utilizing 2-dose ALG and 1-dose Palladium-109-hematoporphyrin (PD-H) for selective lymphoid irradiation (SLI) leads to donor-specific permanent acceptance of heart allografts in the Fisher to Lewis rat model. The same treatment significantly prolongs survival of hearts transplanted to strongly histoincompatable , presensitized, and xenogeneic recipients. The purpose of this study was to evaluate synergistic effects of short-term, low-dose cyclosporin treatment and SLI in an attempt to develop a nontoxic protocol utilizing peritransplant treatment for immune preconditioning with minimal subsequent immunosuppression. Single-agent treatment alone with cyclosporin, ALG, or Pd-H resulted in a maximal mean graft survival time (MST) of 33 days. Immunosuppression with 1-dose Pd-H, 2-dose ALG, and low-dose cyclosporin (5 mg/kg) for 14 days doubled the MST to 78 days. Use of therapeutic-dose cyclosporin (20 mg/kg), given for just 3 days, was also quite effective, MST of 57 days with SLI and 43 days with ALG, but toxic; 3 of 12 recipients died of infection with functioning grafts. These results demonstrate that the use of low-dose cyclosporin over a short interval, when combined with peritransplant SLI, is a highly effective and safe method for prolonging heart allograft survival.

  6. Intranasal Delivery of Mesenchymal Stem Cells Significantly Extends Survival of Irradiated Mice with Experimental Brain Tumors

    PubMed Central

    Balyasnikova, Irina V; Prasol, Melanie S; Ferguson, Sherise D; Han, Yu; Ahmed, Atique U; Gutova, Margarita; Tobias, Alex L; Mustafi, Devkumar; Rincón, Esther; Zhang, Lingjiao; Aboody, Karen S; Lesniak, Maciej S

    2014-01-01

    Treatment options of glioblastoma multiforme are limited due to the blood–brain barrier (BBB). In this study, we investigated the utility of intranasal (IN) delivery as a means of transporting stem cell–based antiglioma therapeutics. We hypothesized that mesenchymal stem cells (MSCs) delivered via nasal application could impart therapeutic efficacy when expressing TNF-related apoptosis-inducing ligand (TRAIL) in a model of human glioma. 111In-oxine, histology and magnetic resonance imaging (MRI) were utilized to track MSCs within the brain and associated tumor. We demonstrate that MSCs can penetrate the brain from nasal cavity and infiltrate intracranial glioma xenografts in a mouse model. Furthermore, irradiation of tumor-bearing mice tripled the penetration of 111In-oxine–labeled MSCs in the brain with a fivefold increase in cerebellum. Significant increase in CXCL12 expression was observed in irradiated xenograft tissue, implicating a CXCL12-dependent mechanism of MSCs migration towards irradiated glioma xenografts. Finally, MSCs expressing TRAIL improved the median survival of irradiated mice bearing intracranial U87 glioma xenografts in comparison with nonirradiated and irradiated control mice. Cumulatively, our data suggest that IN delivery of stem cell–based therapeutics is a feasible and highly efficacious treatment modality, allowing for repeated application of modified stem cells to target malignant glioma. PMID:24002694

  7. Cloning and expression of a rat brain GABA transporter

    SciTech Connect

    Guastella, J.; Czyzyk, L.; Davidson, N.; Lester, H.A. ); Nelson, N.; Nelson, H.; Miedel, M.C. ); Keynan, S.; Kanner, B.I. )

    1990-09-14

    A complementary DNA clone (designated GAT-1) encoding a transporter for the neurotransmitter {gamma}-aminobutyric acid (GABA) has been isolated from rat brain, and its functional properties have been examined in Xenopus oocytes. Oocytes injected with GAT-1 synthetic messenger RNA accumulated ({sup 3}H)GABA to levels above control values. The transporter encoded by GAT-1 has a high affinity for GABA, is sodium- and chloride-dependent, and is pharmacologically similar to neuronal GABA transporters. The GAT-1 protein shares antigenic determinants with a native rat brain GABA transporter. The nucleotide sequence of GAT-1 predicts a protein of 599 amino acids with a molecular weight of 67 kilodaltons. Hydropathy analysis of the deduced protein suggests multiple transmembrane regions, a feature shared by several cloned transporters; however, database searches indicate that GAT-1 is not homologous to any previously identified proteins. Therefore, GAT-1 appears to be a member of a previously uncharacterized family of transport molecules.

  8. Comparison of the radiosensitivities of neurons and glial cells derived from the same rat brain

    PubMed Central

    KUDO, SHIGEHIRO; SUZUKI, YOSHIYUKI; NODA, SHIN-EI; MIZUI, TOSHIYUKI; SHIRAI, KATSUYUKI; OKAMOTO, MASAHIKO; KAMINUMA, TAKUYA; YOSHIDA, YUKARI; SHIRAO, TOMOAKI; NAKANO, TAKASHI

    2014-01-01

    Non-proliferating cells, such as mature neurons, are generally believed to be more resistant to X-rays than proliferating cells, such as glial and vascular endothelial cells. Therefore, the late adverse effects of radiotherapy on the brain have been attributed to the radiation-induced damage of glial and vascular endothelial cells. However, little is known about the radiosensitivities of neurons and glial cells due to difficulties in culturing these cells, particularly neurons, independently. In the present study, primary dissociated neurons and glial cultures were prepared separately from the hippocampi and cerebrum, respectively, which had been obtained from the same fetal rat on embryonic day 18. X-irradiations of 50 Gy were performed on the cultured neurons and glial cells at 7 and 21 days in vitro (DIV). The cells were fixed at 24 h after irradiation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was then performed to measure the apoptotic indices (AIs). The AIs of non-irradiated and irradiated neurons at 7 DIV were 23.7±6.7 and 64.9±4.8%, and those at 21 DIV were 52.1±17.4 and 44.6±12.5%, respectively. The AIs of non-irradiated and irradiated glial cells at 7 DIV were 5.8±1.5 and 78.4±3.3% and those at 21 DIV were 9.6±2.6 and 86.3±4.9%, respectively. Glial cells and neurons were radiosensitive at 7 DIV. However, while glial cells were radiosensitive at 21 DIV, neurons were not. PMID:25120594

  9. Induction of acute brain injury in mice by irradiation with high-LET charged particles

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Zhang, Hong

    The present study was performed to evaluate the induction of acute brain injury in mice after 235 Mev/u carbon ion irradiation. In our study, young outbred Kunming mice were divided into four treatment groups according to the penetration depth of carbon ions. Animals were irradiated with a sublethal dose of carbon ion beams prior to the Bragg curve. An experiment was performed to evaluate the acute alterations in histology, DNA double-strand breaks (DNA DSBs) as well as p53and Bax expression in the brain 96 h post-irradiation. The results demonstrated that various histopathological changes, a significant number of DNA DSBs and elevated p53 and Bax protein expression were induced in the brain following exposure to carbon ions. This was particularly true for mice irradiated with ions having a 9.1 cm-pentration depth, indicating that carbon ions can led to deleterious lesions in the brain of young animals within 96 h. Moreover, there was a remarkable increase in DNA DSBs and in the severity of histopathological changes as the penetration depths of ions increased, which may be associated with the complex track structure of heavy ions. These data reveal that carbon ions can promote serious neuropathological degeneration in the cerebral cortex of young mice. Given that damaged neurons cannot regenerate, these findings warrant further investigation of the adverse effects of the space radiation and the passage of a therapeutic heavy ion beam in the plateau region of the Bragg curve through healthy brain tissue.

  10. Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

    SciTech Connect

    Prokic, Vesna; Wiedenmann, Nicole; Fels, Franziska; Schmucker, Marianne; Nieder, Carsten; Grosu, Anca-Ligia

    2013-01-01

    Purpose: To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Methods and Materials: Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individual brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. Results: The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55 {+-} 0.62 Gy and 6.29 {+-} 0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8 {+-} 1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2 {+-} 0.7 Gy and 32.7 {+-} 0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23 {+-} 1.42 Gy in SC. Conclusions: Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.

  11. Microwave effects on energy metabolism of rat brain

    SciTech Connect

    Sanders, A.P.; Schaefer, D.J.; Joines, W.T.

    1980-01-01

    Rat brain was exposed to 591-MHz, continuous-wave (CW) microwaves at 13.8 or 5.0 mW/cm2 to determine the effect on nicotinamide adenine dinucleotide, reduced (NADH), adenosine triphosphate (ATP) and creatine phosphate (CP) levels. On initiation of the in vivo microwave exposures, fluorimetrically determined NADH rapidly increased to a maximum of 4.0%-12.5% above pre-exposure control levels at one-half minute, than decreased slowly to 2% above control at three minutes, finally increasing slowly to 5% above control level at five minutes. ATP and CP assays were performed on sham- and microwave-exposed brain at each exposure time. At 13.8 mW/cm2, brain CP level was decreased an average of 39.4%, 41.1%, 18.2%, 13.1%, and 36.4% of control at exposure points one-half, one, two three, and five minutes, respectively, and brain ATP concentration was decreased an average of 25.2%, 15.2%, 17.8%, 7.4%, and 11.2% of control at the corresponding exposure periods. ATP and CP levels of rat brain exposed to 591-MHz cw microwaves at 5mW/cm2 for one-half and one minute were decreased significantly below control levels at these exposure times, but were not significantly different from the 13.8 mW/cm2 exposures. For all exposures, rectal temperature remained constant. Heat loss through the skull aperture caused brain temperature to decrease during the five-minute exposures. This decrease was the same in magnitude for experimental and control subjects. Changes in NADH, ATP, and CP levels during microwave exposure cannot be attributed to general tissue hyperthermia. The data support the hypothesis that microwave exposure inhibits mitochondrial electron transport chain function, which results in decreased ATP and CP levels in brain.

  12. Identification of rat brain opioid (enkephalin) receptor by photoaffinity labeling

    SciTech Connect

    Yeung, C.W.

    1986-01-01

    A photoreactive, radioactive enkephalin derivative was prepared and purified by high performance liquid chromatography. Rat brain and spinal cord plasma membranes were incubated with this radioiodinated photoprobe and were subsequently photolysed. Autoradiography of the sodium dodecyl sulfate gel electrophoresis of the solubilized and reduced membranes showed that a protein having an apparent molecular weight of 46,000 daltons was specifically labeled, suggesting that this protein may be the opioid (enkephalin) receptor.

  13. Oxidative changes in brain of aniline-exposed rats

    SciTech Connect

    Kakkar, P.; Awasthi, S.; Viswanathan, P.N. )

    1992-10-01

    Oxidative stress in rat cerebellum, cortex and brain stem after a short-term high-dose exposure to aniline vapors under conditions akin to those after major chemical accidents, was studied. Significant increases in superoxide dismutase isozyme activities and formation of thiobarbituric acid reactive material along with depletion of ascorbic acid and non-protein sulfhydryl content suggest impairment of antioxidant defenses 24 h after single exposure to 15,302 ppm aniline vapors for 10 min.

  14. Multiple opiate receptors in the brain of spontaneously hypertensive rats

    SciTech Connect

    Das, S.; Bhargava, H.N.

    1986-03-01

    The characteristics of ..mu.., delta and kappa -opiate receptors in the brain of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats were determined using the receptor binding assays. The ligands used were /sup 3/H-naltrexone (..mu..), /sup 3/H-ethylketocyclazocine (EKC, kappa) and /sup 3/H-Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta). Since EKC binds to ..mu.. and delta receptors in addition to kappa, the binding was done in the presence of 100 nM each of DAGO and DADLE to suppress ..mu.. and delta sites, respectively. All three ligands bound to brain membranes of WKY rats at a single high affinity site with the following B/sub max/ (fmol/mg protein) and K/sub d/ (nM) values: /sup 3/H-naltrexone (130.5; 0.43) /sup 3/H-EKC (19.8, 1.7) and /sup 3/H-DSTLE (139, 2.5). The binding of /sup 3/H-naltrexone and /sup 3/H-DSTLE in the brain of WKY and SH did not differ. A consistent increase (22%) in B/sub max/ of /sup 3/H-EKC was found in SHR compared to WKY rats. However, the K/sub d/ values did not differ. The increase in B/sub max/ was due to increases in hypothalamus and cortex. It is concluded that SH rats have higher density of kappa-opiate receptors, particularly in hypothalamus and cortex, compared to WKY rats, and that kappa-opiate receptors may be involved in the pathophysiology of hypertension.

  15. Neuroprotection of Selective Brain Cooling After Penetrating Ballistic-like Brain Injury in Rats.

    PubMed

    Wei, Guo; Lu, Xi-Chun M; Shear, Deborah A; Yang, Xiaofang; Tortella, Frank C

    2011-01-01

    Induced hypothermia has been reported to provide neuroprotection against traumatic brain injury. We recently developed a novel method of selective brain cooling (SBC) and demonstrated its safety and neuroprotection efficacy in a rat model of ischemic brain injury. The primary focus of the current study was to evaluate the potential neuroprotective efficacy of SBC in a rat model of penetrating ballistic-like brain injury (PBBI) with a particular focus on the acute cerebral pathophysiology, neurofunction, and cognition. SBC (34°C) was induced immediately after PBBI, and maintained for 2 hours, followed by a spontaneous re-warming. Intracranial pressure (ICP) and regional cerebral blood flow were monitored continuously for 3 hours, and the ICP was measured again at 24 hours postinjury. Brain swelling, blood-brain barrier permeability, intracerebral hemorrhage, lesion size, and neurological status were assessed at 24 hours postinjury. Cognitive abilities were evaluated in a Morris water maze task at 12-16 days postinjury. Results showed that SBC significantly attenuated PBBI-induced elevation of ICP (PBBI = 33.2 ± 10.4; PBBI + SBC = 18.8 ± 6.7 mmHg) and reduced brain swelling, blood-brain barrier leakage, intracerebral hemorrhage, and lesion volume by 40%-45% for each matrix, and significantly improved neurologic function. However, these acute neuroprotective benefits of SBC did not translate into improved cognitive performance in the Morris water maze task. These results indicate that 34°C SBC is effective in protecting against acute brain damage and related neurological dysfunction. Further studies are required to establish the optimal treatment conditions (i.e., duration of cooling and/or combined therapeutic approaches) needed to achieve significant neurocognitive benefits.

  16. [Reducing late toxicity with amifostine in fractionated irradiation of the rat salivary glands].

    PubMed

    Sagowski, C; Wenzel, S; Jenicke, L; Bohuslavizki, K H; Kehrl, W; Zywietz, F; Roeser, K

    2002-09-01

    Clinical studies show that amifostine can reduce xerostomia and mucositis during radiotherapy of head and neck cancers. The aim of this study was to evaluate the radioprotective potency of amifostine with respect to late toxicity of salivary glands of rats. The head-neck-area of 8 male WAG/RijH rats (295 +/- 7 g) were irradiated with 60Co-gamma-rays (60 Gy/30 f/6 weeks). Amifostine (250 mg/m2 body surface) was applied via a venous port 15 min before each irradiation. Rats of a control group were irradiated with the same schedule with equal volumes of physiological saline. The morphological and sialoscintigraphical findings clearly demonstrate that amifostine has a remarkable cytoprotective effect on the late toxicity of irradiated salivary glands. PMID:12425136

  17. Cytosolic rat brain synapsin I is a diacylglycerol kinase.

    PubMed Central

    Kahn, D W; Besterman, J M

    1991-01-01

    The phosphorylation of diacylglycerol (DG), a reaction catalyzed by DG kinase, may be critical in the termination of effector-induced signals mediated by protein kinase C. Synapsin I is a principal target of intracellular protein kinases and is thought to be involved in the release of neurotransmitter from axon terminals. We present several lines of evidence which indicate that rat brain synapsin, in addition to this role, may function as a DG kinase. Purified rat brain DG kinase was digested with trypsin, which produced three major fragments whose sequence was identical to three regions in synapsin I. Using a rabbit anti-synapsin polyclonal antiserum, the elution profile of synapsin immunoreactivity coincided exactly with that of DG kinase activity in column fractions from the final step in the DG kinase purification procedure. As is the case with synapsin, the purified enzyme was a strongly basic protein with an isoelectric point greater than 10.0. Finally, incubating the DG kinase with highly purified bacterial collagenase, an enzyme that partially degrades the proline- and glycine-rich synapsin, resulted in the simultaneous loss of DG kinase activity and synapsin immunoreactivity. We conclude that cytosolic rat brain synapsin is capable of functioning as a DG kinase. Images PMID:1648730

  18. Methylphenidate alters NCS-1 expression in rat brain.

    PubMed

    Souza, Renan P; Soares, Eliane C; Rosa, Daniela V F; Souza, Bruno R; Réus, Gislaine Z; Barichello, Tatiana; Gomes, Karin M; Gomez, Marcus V; Quevedo, João; Romano-Silva, Marco A

    2008-07-01

    Methylphenidate has been used as an effective treatment for attention deficit hyperactivity disorder (ADHD). Methylphenidate (MPH) blocks dopamine and norepinephrine transporters causing an increase in extracellular levels. The use of psychomotor stimulants continues to rise due to both the treatment of ADHD and illicit abuse. Methylphenidate sensitization mechanism has still poor knowledge. Neuronal calcium sensor 1 was identified as a dopaminergic receptor interacting protein. When expressed in mammalian cells, neuronal calcium sensor 1 attenuates dopamine-induced D2 receptor internalization by a mechanism that involves a reduction in D2 receptor phosphorylation. Neuronal calcium sensor 1 appears to play a pivotal role in regulating D2 receptor function, it will be important to determine if there are alterations in neuronal calcium sensor 1 in neuropathologies associated with deregulation in dopaminergic signaling. Then, we investigated if methylphenidate could alter neuronal calcium sensor 1 expression in five brain regions (striatum, hippocampus, prefrontal cortex, cortex and cerebellum) in young and adult rats. These regions were chosen because some are located in brain circuits related with attention deficit hyperactivity disorder. Our results showed changes in neuronal calcium sensor 1 expression in hippocampus, prefrontal cortex and cerebellum mainly in adult rats. The demonstration that methylphenidate induces changes in neuronal calcium sensor 1 levels in rat brain may help to understand sensitization mechanisms as well as methylphenidate therapeutic effects to improve attention deficit hyperactivity disorder symptoms.

  19. Gelation and fodrin purification from rat brain extracts.

    PubMed

    Levilliers, N; Péron-Renner, M; Coffe, G; Pudles, J

    1986-06-01

    Extracts from rat brain tissue have been shown to give rise to a gel which exhibits the following features. It is mainly enriched in actin and in a high-molecular-weight protein with polypeptide chains of 235 and 240 kDa, which we identified as fodrin. Tubulin is also a major component of the gel but it appears to be trapped non-specifically during the gelation process. Gelation is pH-, ionic strength- and Ca2+-concentration-dependent, and is optimal under the conditions which promote the interaction between polymerized actin and fodrin. In a similar way to that described for the purification of rat brain actin (Levilliers, N., Péron-Renner, M., Coffe, G. and Pudles, J. (1984) Biochimie 66, 531-537), we used the gelation system as a selective means of recovering fodrin from the mixture of a low-ionic-strength extract from whole rat brain and a high-ionic-strength extract of the particulate fraction. From this gel, fodrin was purified with a good yield by a simple procedure involving gel dissociation in 0.5 M KCl and depolymerization in 0.7 M KI, Bio-Gel A-15m chromatography, followed by ammonium sulfate precipitation. PMID:3707993

  20. Ketone-body utilization by homogenates of adult rat brain

    SciTech Connect

    Lopes-Cardozo, M.; Klein, W.

    1982-06-01

    The regulation of ketone-body metabolism and the quantitative importance of ketone bodies as lipid precursors in adult rat brain has been studied in vitro. Utilization of ketone bodies and of pyruvate by homogenates of adult rat brain was measured and the distribution of /sup 14/C from (3-/sup 14/C)ketone bodies among the metabolic products was analysed. The rate of ketone-body utilization was maximal in the presence of added Krebs-cycle intermediates and uncouplers of oxidative phosphorylation. The consumption of acetoacetate was faster than that of D-3-hydroxybutyrate, whereas, pyruvate produced twice as much acetyl-CoA as acetoacetate under optimal conditions. Millimolar concentrations of ATP in the presence of uncoupler lowered the consumption of ketone bodies but not of pyruvate. Indirect evidence is presented suggesting that ATP interferes specifically with the mitochondrial uptake of ketone bodies. Interconversion of ketone bodies and the accumulation of acid-soluble intermediates (mainly citrate and glutamate) accounted for the major part of ketone-body utilization, whereas only a small part was oxidized to CO/sub 2/. Ketone bodies were not incorporated into lipids or protein. We conclude that adult rat-brain homogenates use ketone bodies exclusively for oxidative purposes.

  1. Intrinsic optical signals of brains in rats during loss of tissue viability: effect of brain temperature

    NASA Astrophysics Data System (ADS)

    Kawauchi, Satoko; Sato, Shunichi; Ooigawa, Hidetoshi; Nawashiro, Hiroshi; Kikuchi, Makoto

    2007-07-01

    Noninvasive, real-time monitoring of brain tissue viability is crucial for the patients with stroke, traumatic brain injury, etc. For this purpose, measurement of intrinsic optical signal (IOS) is attractive because it can provide direct information about the viability of brain tissue noninvasively. We performed simultaneous measurements of IOSs that are related to morphological characteristics, i.e., light scattering, and energy metabolism for rat brains during saline infusion as a model with temporal loss of brain tissue viability. The results showed that the scattering signal was steady in an initial phase but showed a drastic, triphasic change in a certain range of infusion time, during which the reduction of CuA in cytochrome c oxidase started and proceeded rapidly. The start time of triphasic scattering change was delayed for about 100 s by lowering brain temperature from 29°C to 24°C, demonstrating the optical detection of cerebroprotection effect by brain cooling. Electron microscopic observation showed morphological changes of dendrite and mitochondria in the cortical surface tissue after the triphasic scattering change, which was thought to be associated with the change in light scattering we observed. These findings suggest that the simultaneous measurement of the intrinsic optical signals related to morphological characteristics and energy metabolism is useful for monitoring tissue viability in brain.

  2. Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury.

    PubMed

    Das, Mahasweta; Wang, Chunyan; Bedi, Raminder; Mohapatra, Shyam S; Mohapatra, Subhra

    2014-10-01

    Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CP-mag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM-tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats. Evans blue extravasation following mTBI suggested CPMM-ptd entry into the brain via the compromised blood-brain barrier. Magnetofection increased the concentration of CPMMs in the brain. RFP expression was observed in the brain (cortex and hippocampus), lung and liver 48 h after mTBI. CPMM did not evoke any inflammatory response by themselves and were excreted from the body. These results indicate the possibility of using intranasally administered CPMM as a theranostic vehicle for mTBI. From the clinical editor: In this study, chitosan and PEI-coated magnetic micelles (CPMM) were demonstrated as potentially useful vehicles in traumatic brain injury in a rodent model. Magnetofection increased the concentration of CPMMs in the brain and, after intranasal delivery, CPMM did not evoke any inflammatory response and were excreted from the body. PMID:24486465

  3. Outer brain barriers in rat and human development.

    PubMed

    Brøchner, Christian B; Holst, Camilla B; Møllgård, Kjeld

    2015-01-01

    Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post-conception) and adults using immunohistochemistry and confocal microscopy. Antibodies against claudin-11, BLBP, collagen 1, SSEA-4, MAP2, YKL-40, and its receptor IL-13Rα2 and EAAT1 were used to describe morphological characteristics and functional aspects of the outer brain barriers. Claudin-11 was a reliable marker of the arachnoid blood-CSF barrier. Collagen 1 delineated the subarachnoid space and stained pial surface layer. BLBP defined radial glial end feet layer and SSEA-4 and YKL-40 were present in both leptomeningeal cells and end feet layer, which transformed into glial limitans. IL-13Rα2 and EAAT1 were present in the end feet layer illustrating transporter/receptor presence in the outer CSF-brain barrier. MAP2 immunostaining in adult brain outlined the lower border of glia limitans; remnants of end feet were YKL-40 positive in some areas. We propose that outer brain barriers are composed of at least 3 interfaces: blood-CSF barrier across arachnoid barrier cell layer, blood-CSF barrier across pial microvessels, and outer CSF-brain barrier comprising glial end feet layer/pial surface layer.

  4. Outer brain barriers in rat and human development

    PubMed Central

    Brøchner, Christian B.; Holst, Camilla B.; Møllgård, Kjeld

    2015-01-01

    Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6–21st weeks post-conception) and adults using immunohistochemistry and confocal microscopy. Antibodies against claudin-11, BLBP, collagen 1, SSEA-4, MAP2, YKL-40, and its receptor IL-13Rα2 and EAAT1 were used to describe morphological characteristics and functional aspects of the outer brain barriers. Claudin-11 was a reliable marker of the arachnoid blood-CSF barrier. Collagen 1 delineated the subarachnoid space and stained pial surface layer. BLBP defined radial glial end feet layer and SSEA-4 and YKL-40 were present in both leptomeningeal cells and end feet layer, which transformed into glial limitans. IL-13Rα2 and EAAT1 were present in the end feet layer illustrating transporter/receptor presence in the outer CSF-brain barrier. MAP2 immunostaining in adult brain outlined the lower border of glia limitans; remnants of end feet were YKL-40 positive in some areas. We propose that outer brain barriers are composed of at least 3 interfaces: blood-CSF barrier across arachnoid barrier cell layer, blood-CSF barrier across pial microvessels, and outer CSF-brain barrier comprising glial end feet layer/pial surface layer. PMID:25852456

  5. Unraveling the fundamental molecular mechanisms of morphological and cognitive defects in the irradiated brain.

    PubMed

    Verheyde, Joris; Benotmane, Mohammed Abderrafi

    2007-02-01

    Prenatal radiation exposure may have serious consequences for normal brain development. Results of epidemiological studies clearly pointed towards an increased risk of mental retardation in children of the surviving women of the Hiroshima/Nagasaki atomic bombing when in utero exposure had occurred between weeks 8 and 15 of pregnancy or, at a lower extend between weeks 15 and 25. The high sensitivity of the developing brain, in comparison to the adult brain is related to its higher number of non-differentiated, dividing neural precursor cells. Exposure of the developing brain to ionizing radiation can lead to three main outcomes in the developing brain, depending on the radiation dose and the elapsed period after irradiation. A first event occurs early after irradiation and triggers disturbances in cell proliferation, migration, differentiation, and cell death. A second event involves the generation of morphological abnormalities in the developing brain, if the radiation dose is sufficient. A third event involves cognitive dysfunctions that are a direct consequence from a disturbance in regional brain formation. The latter results from exposure to low doses and is usually only observed in the later period of development. In order to understand the mechanisms of radiation-induced cognitive dysfunctions, it is important to track back the underlying changes in specific molecular pathways. In this review, we present the possible relationships within and between molecular pathways potentially involved in cognitive dysfunctions induced by ionizing radiation in the developing brain.

  6. Developmental disturbance of rat cerebral cortex following prenatal low-dose gamma-irradiation: a quantitative study

    SciTech Connect

    Fukui, Y.; Hoshino, K.; Hayasaka, I.; Inouye, M.; Kameyama, Y. )

    1991-06-01

    Pregnant rats were exposed to a single whole-body gamma-irradiation on Day 15 of gestation at a dose of 0.27, 0.48, 1.00, or 1.46 Gy. They were allowed to give birth and the offspring were killed at 6 or 12 weeks of age for microscopic and electron microscopic examinations of the cerebrum. Their body weight, brain weight, cortical thickness, and numerical densities of whole cells and synapses in somatosensory cortex were examined. Growth of the dendritic arborization of layer V pyramidal cells was also examined quantitatively with Golgi-Cox specimens. A significant dose-related reduction in brain weight was found in all irradiated groups. Neither gross malformation nor abnormality of cortical architecture was observed in the groups exposed to 0.27 Gy. A significant change was found in thickness of cortex in the groups exposed to 0.48 Gy or more. Cell packing density increased significantly in the group exposed to 1.00 Gy. Significant reduction in the number of intersections of dendrites with the zonal boundaries were found in the groups exposed to 0.27 Gy or more. There was no difference in the numerical density of synapses in layer I between the control and irradiated groups. These results suggested that doses as low as 0.27 Gy could cause a morphologically discernible change in the mammalian cerebrum.

  7. Relationship between Morphofunctional Changes in Open Traumatic Brain Injury and the Severity of Brain Damage in Rats.

    PubMed

    Shakova, F M; Barskov, I V; Gulyaev, M V; Prokhorenko, S V; Romanova, G A; Grechko, A V

    2016-07-01

    A correlation between the severity of morphofunctional disturbances and the volume of brain tissue injury determined by MRT was demonstrated on the model of open traumatic brain injury in rats. A relationship between the studied parameters (limb placing and beam walking tests and histological changes) and impact force (the height of load fell onto exposed brain surface) was revealed.

  8. Relationship between Morphofunctional Changes in Open Traumatic Brain Injury and the Severity of Brain Damage in Rats.

    PubMed

    Shakova, F M; Barskov, I V; Gulyaev, M V; Prokhorenko, S V; Romanova, G A; Grechko, A V

    2016-07-01

    A correlation between the severity of morphofunctional disturbances and the volume of brain tissue injury determined by MRT was demonstrated on the model of open traumatic brain injury in rats. A relationship between the studied parameters (limb placing and beam walking tests and histological changes) and impact force (the height of load fell onto exposed brain surface) was revealed. PMID:27496035

  9. Different doses of partial liver irradiation promotes hepatic regeneration in rat.

    PubMed

    Liu, Ying; Shi, Changzheng; Cui, Meng; Yang, Zhenhua; Gan, Danhui; Wang, Yiming

    2015-01-01

    The aim of this study is to investigate whether partial liver irradiation promotes hepatic regeneration in rat. Left-half liver of rat was irradiated to 10 Gy, and the Right-half to 0, 5, 10 and 15 Gy, respectively. Then, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels were evaluated on 0 day, 15-day, 30-day, 45-day and 60-day after liver irradiation. Next, the serum HGF, NF-κB and TGF-β1 levels were also analyzed on 60-day after liver irradiation. Lastly, the cyclinD1 protein expression was appraised by western blots on 60-day after liver irradiation. ALT, AST and ALP levels were reduced compared with that of controls. The serum HGF, NF-κB and TGF-β1 levels, and the cyclinD1 protein expression in liver irradiation group were increased compared with that of controls group. However, hepatic regeneration of higher dose-irradiated cirrhotic liver was triggered a more enhanced regeneration, compared with that of higher doses group. In summary, these results suggest that different doses of partial liver irradiation promotes hepatic regeneration in rat.

  10. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events. PMID:19218497

  11. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats.

    PubMed

    Zhao, Jinbing; Chen, Zhi; Xi, Guohua; Keep, Richard F; Hua, Ya

    2014-10-01

    Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron levels in brain may relate to hydrocephalus development after intracranial hemorrhage. However, the role of iron in the development of post-traumatic hydrocephalus is still unclear. This study was to determine whether or not iron has a role in hydrocephalus development after TBI. TBI was induced by lateral fluid-percussion in male Sprague-Dawley rats. Some rats had intraventricular injection of iron. Acute hydrocephalus was measured by magnetic resonance T2-weighted imaging and brain hemorrhage was determined by T2* gradient-echo sequence imaging and brain hemoglobin levels. The effect of deferoxamine on TBI-induced hydrocephalus was examined. TBI resulted in acute hydrocephalus at 24 h (lateral ventricle volume: 24.1 ± 3.0 vs. 9.9 ± 0.2 mm(3) in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm(3) in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI.

  12. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.

  13. Photoacoustic imaging for transvascular drug delivery to the rat brain

    NASA Astrophysics Data System (ADS)

    Watanabe, Ryota; Sato, Shunichi; Tsunoi, Yasuyuki; Kawauchi, Satoko; Takemura, Toshiya; Terakawa, Mitsuhiro

    2015-03-01

    Transvascular drug delivery to the brain is difficult due to the blood-brain barrier (BBB). Thus, various methods for safely opening the BBB have been investigated, for which real-time imaging methods are desired both for the blood vessels and distribution of a drug. Photoacoustic (PA) imaging, which enables depth-resolved visualization of chromophores in tissue, would be useful for this purpose. In this study, we performed in vivo PA imaging of the blood vessels and distribution of a drug in the rat brain by using an originally developed compact PA imaging system with fiber-based illumination. As a test drug, Evans blue (EB) was injected to the tail vein, and a photomechanical wave was applied to the targeted brain tissue to increase the permeability of the blood vessel walls. For PA imaging of blood vessels and EB distribution, nanosecond pulses at 532 nm and 670 nm were used, respectively. We clearly visualized blood vessels with diameters larger than 50 μm and the distribution of EB in the brain, showing spatiotemporal characteristics of EB that was transvascularly delivered to the target tissue in the brain.

  14. The AT{sub 1} Receptor Antagonist, L-158,809, Prevents or Ameliorates Fractionated Whole-Brain Irradiation-Induced Cognitive Impairment

    SciTech Connect

    Robbins, Mike E. Payne, Valerie B.S.; Tommasi, Ellen B.S.; Diz, Debra I.; Hsu, Fang-Chi; Brown, William R.; Wheeler, Kenneth T.; Olson, John; Zhao Weiling

    2009-02-01

    Purpose: We hypothesized that administration of the angiotensin type 1 (AT1) receptor antagonist, L-158,809, to young adult male rats would prevent or ameliorate fractionated whole-brain irradiation (WBI)-induced cognitive impairment. Materials and Methods: Groups of 80 young adult male Fischer 344 x Brown Norway (F344xBN) rats, 12-14 weeks old, received either: (1) fractionated WBI; 40 Gy of {gamma} rays in 4 weeks, 2 fractions/week, (2) sham-irradiation; (3) WBI plus L-158,809 (20 mg/L drinking water) starting 3 days prior, during, and for 14, 28, or 54 weeks postirradiation; and (4) sham-irradiation plus L-158,809 for 14, 28, or 54 weeks postirradiation. An additional group of rats (n = 20) received L-158,809 before, during, and for 5 weeks postirradiation, after which they received normal drinking water up to 28 weeks postirradiation. Results: Administration of L-158,809 before, during, and for 28 or 54 weeks after fractionated WBI prevented or ameliorated the radiation-induced cognitive impairment observed 26 and 52 weeks postirradiation. Moreover, giving L-158,809 before, during, and for only 5 weeks postirradiation ameliorated the significant cognitive impairment observed 26 weeks postirradiation. These radiation-induced cognitive impairments occurred without any changes in brain metabolites or gross histologic changes assessed at 28 and 54 weeks postirradiation, respectively. Conclusions: Administering L-158,809 before, during, and after fractionated WBI can prevent or ameliorate the chronic, progressive, cognitive impairment observed in rats at 26 and 52 weeks postirradiation. These findings offer the promise of improving the quality of life for brain tumor patients.

  15. Maturation of metabolic connectivity of the adolescent rat brain.

    PubMed

    Choi, Hongyoon; Choi, Yoori; Kim, Kyu Wan; Kang, Hyejin; Hwang, Do Won; Kim, E Edmund; Chung, June-Key; Lee, Dong Soo

    2015-11-27

    Neuroimaging has been used to examine developmental changes of the brain. While PET studies revealed maturation-related changes, maturation of metabolic connectivity of the brain is not yet understood. Here, we show that rat brain metabolism is reconfigured to achieve long-distance connections with higher energy efficiency during maturation. Metabolism increased in anterior cerebrum and decreased in thalamus and cerebellum during maturation. When functional covariance patterns of PET images were examined, metabolic networks including default mode network (DMN) were extracted. Connectivity increased between the anterior and posterior parts of DMN and sensory-motor cortices during maturation. Energy efficiency, a ratio of connectivity strength to metabolism of a region, increased in medial prefrontal and retrosplenial cortices. Our data revealed that metabolic networks mature to increase metabolic connections and establish its efficiency between large-scale spatial components from childhood to early adulthood. Neurodevelopmental diseases might be understood by abnormal reconfiguration of metabolic connectivity and efficiency.

  16. Detecting Behavioral Deficits Post Traumatic Brain Injury in Rats.

    PubMed

    Awwad, Hibah O

    2016-01-01

    Traumatic brain injury (TBI), ranging from mild to severe, almost always elicits an array of behavioral deficits in injured subjects. Some of these TBI-induced behavioral deficits include cognitive and vestibulomotor deficits as well as anxiety and other consequences. Rodent models of TBI have been (and still are) fundamental in establishing many of the pathophysiological mechanisms of TBI. Animal models are also utilized in screening and testing pharmacological effects of potential therapeutic agents for brain injury treatment. This chapter details validated protocols for each of these behavioral deficits post traumatic brain injury in Sprague-Dawley male rats. The elevated plus maze (EPM) protocol is described for assessing anxiety-like behavior; the Morris water maze protocol for assessing cognitive deficits in learning memory and spatial working memory and the rotarod test for assessing vestibulomotor deficits. PMID:27604739

  17. Dietary aspartame with protein on plasma and brain amino acids, brain monoamines and behavior in rats.

    PubMed

    Torii, K; Mimura, T; Takasaki, Y; Ichimura, M

    1986-01-01

    Aspartame (APM; L-aspartyl-L-phenylalanine methyl ester), was investigated for its ability to alter levels of the large neutral amino acids and monoamines in overnight fasted rats allowed to consume meals with or without protein for two hours. Additionally, the possible long term behavioral consequences of APM in 25% casein diets with or without 10% sucrose were determined. Acute APM ingestion increased both plasma and brain phenylalanine and tyrosine levels, but brain tryptophan levels were not altered regardless of dietary protein. Brain norepinephrine and dopamine levels were unaltered by any of the diet while serotonin levels were slightly increased when a protein-free diet was consumed. But APM and/or protein ingestion minimized this increase of brain serotonin levels as much as controls. Chronic APM ingestion failed to influence diurnal feeding patterns, meal size distributions, or diurnal patterns of spontaneous motor activity. The chronic ingestion of abuse doses of APM produced no significant chemical changes in brain capable of altering behavioral parameters believed to be controlled by monoamines in rats.

  18. Effect of 2,450 MHz microwave radiation on the development of the rat brain

    SciTech Connect

    Inouye, M.; Galvin, M.J.; McRee, D.I.

    1983-12-01

    Male Sprague-Dawley rats were exposed to 2,450 MHz microwave radiation at an incident power density of 10 mW/cm2 daily for 3 hours from day 4 of pregnancy (in utero exposure) through day 40 postpartum, except for 2 days at the perinatal period. The animals were killed, and the brains removed, weighed, measured, and histologically examined at 15, 20, 30, and 40 days of age. The histologic parameters examined included the cortical architecture of the cerebral cortex, the decline of the germinal layer along the lateral ventricles, the myelination of the corpus callosum, and the decline of the external germinal layer of the cerebellar cortex. In 40-day-old rats, quantitative measurements of neurons were also made. The spine density of the pyramidal cells in layer III of the somatosensory cortex, and the density of basal dendritic trees of the pyramidal cells in layer V were measured in Golgi-Cox impregnated specimens. In addition, the density of Purkinje cells and the extent of the Purkinje cell layer in each lobule were measured in midsagittal sections of the cerebellum stained with thionin. There were no remarkable differences between microwave-exposed and control (sham-irradiated) groups for any of the histologic or quantitative parameters examined; however, the findings provide important information on quantitative measurements of the brain. The data from this study failed to demonstrate that there is a significant effect on rat brain development due to microwave exposure (10 mW/cm2) during the embryonic, fetal, and postnatal periods.

  19. SPECT study of low intensity He-Ne laser intravascular irradiation therapy for brain infarction

    NASA Astrophysics Data System (ADS)

    Xiao, Xue-Chang; Dong, Jia-Zheng; Chu, Xiao-Fan; Jia, Shao-Wei; Liu, Timon C.; Jiao, Jian-Ling; Zheng, Xi-Yuan; Zhou, Ci-Xiong

    2003-12-01

    We used single photon emission computed tomography (SPECT) in brain perfusion imaging to study the changes of regional cerebral blood flow (rCBF) and cerebral function in brain infarction patients treated with intravascular laser irradiation of blood (ILIB). 17 of 35 patients with brain infarction were admitted to be treated by ILIB on the base of standard drug therapy, and SPECT brain perfusion imaging was performed before and after ILIB therapy with self-comparison. The results were analyzed in quantity with brain blood flow function change rate (BFCR%) model. Effect of ILIB during the therapy process in the other 18 patients were also observed. In the 18 patients, SPECT indicated an improvement of rCBF (both in focus and in total brain) and cerebral function after a 30 min-ILIB therapy. And the 17 patients showed an enhancement of total brain rCBF and cerebral function after ILIB therapy in comparison with that before, especially for the focus side of the brain. The enhancement for focus itself was extremely obvious with a higher significant difference (P<0.0001). The mirror regions had no significant change (P>0.05). BFCR% of foci was prominently higher than that of mirror regions (P<0.0001). In conclusion, the ILIB therapy can improve rCBF and cerebral function and activate brain cells of patients with brain infarction. The results denote new evidence of ILIB therapy for those patients with cerebral ischemia.

  20. Global profiling of influence of intra-ischemic brain temperature on gene expression in rat brain.

    PubMed

    Kobayashi, Megumi Sugahara; Asai, Satoshi; Ishikawa, Koichi; Nishida, Yayoi; Nagata, Toshihito; Takahashi, Yasuo

    2008-06-01

    Mild to moderate differences in brain temperature are known to greatly affect the outcome of cerebral ischemia. The impact of brain temperature on ischemic disorders has been mainly evaluated through pathological analysis. However, no comprehensive analyses have been conducted at the gene expression level. Using a high-density oligonucleotide microarray, we screened 24000 genes in the hippocampus under hypothermic (32 degrees C), normothermic (37 degrees C), and hyperthermic (39 degrees C) conditions in a rat ischemia-reperfusion model. When the ischemic group at each intra-ischemic brain temperature was compared to a sham-operated control group, genes whose expression levels changed more than three-fold with statistical significance could be detected. In our screening condition, thirty-three genes (some of them novel) were obtained after screening, and extensive functional surveys and literature reviews were subsequently performed. In the hypothermic condition, many neuroprotective factor genes were obtained, whereas cell death- and cell damage-associated genes were detected as the brain temperature increased. At all intra-ischemic brain temperatures, multiple molecular chaperone genes were obtained. The finding that intra-ischemic brain temperature affects the expression level of many genes related to neuroprotection or neurotoxicity coincides with the different pathological outcomes at different brain temperatures, demonstrating the utility of the genetic approach.

  1. The carcinogenic effect of localized fission fragment irradiation of rat lung.

    PubMed

    Batchelor, A L; Buckley, P; Gore, D J; Jenner, T J; Major, I R; Bailey, M R

    1980-03-01

    In a preliminary investigation of 'hot particle' carcinogenesis uranium oxide particles were introduced into the lungs of rats either by intubation of a liquid suspension of the particles or by inhalation of an aerosol. Subsequently the animals were briefly exposed to slow neutrons in a nuclear reactor, resulting in localized irradiation of the lung by fission fragments emitted from 235U atoms in the oxide particles. The uranium used in the intubation experiments was either enriched or depleted in 235U. Squamous cell carcinomas developed at the site of deposition of the enriched uranium oxide in many cases but no lung tumours occurred in the rats with the depleted uranium oxide, in which the lung tissue was exposed to very few fission fragments. Only enriched uranium oxide was used in the inhalation experiments. Pulmonary squamous cell carcinomas occurred after the fission fragment irradiation but were fewer than in the intubation experiments. Adenocarcinomas of the lung were seen in rats exposed to uranium oxide without subsequent irradiation by neutrons in the reactor and in rats irradiated with neutrons but not previously exposed to uranium oxide. It is concluded that (i) fission fragments were possibly implicated in the genesis of the squamous cell carcinomas, which only developed in those animals exposed to enriched uranium oxide and neutrons and (ii) the adenocarcinomas in the rats inhaling enriched uranium oxide only were likely to have been caused by protracted irradiation of the lung with alpha-rays emitted from the enriched uranium.

  2. Light-sheet microscopy imaging of a whole cleared rat brain with Thy1-GFP transgene

    PubMed Central

    Stefaniuk, Marzena; Gualda, Emilio J.; Pawlowska, Monika; Legutko, Diana; Matryba, Paweł; Koza, Paulina; Konopka, Witold; Owczarek, Dorota; Wawrzyniak, Marcin; Loza-Alvarez, Pablo; Kaczmarek, Leszek

    2016-01-01

    Whole-brain imaging with light-sheet fluorescence microscopy and optically cleared tissue is a new, rapidly developing research field. Whereas successful attempts to clear and image mouse brain have been reported, a similar result for rats has proven difficult to achieve. Herein, we report on creating novel transgenic rat harboring fluorescent reporter GFP under control of neuronal gene promoter. We then present data on clearing the rat brain, showing that FluoClearBABB was found superior over passive CLARITY and CUBIC methods. Finally, we demonstrate efficient imaging of the rat brain using light-sheet fluorescence microscopy. PMID:27312902

  3. Light-sheet microscopy imaging of a whole cleared rat brain with Thy1-GFP transgene.

    PubMed

    Stefaniuk, Marzena; Gualda, Emilio J; Pawlowska, Monika; Legutko, Diana; Matryba, Paweł; Koza, Paulina; Konopka, Witold; Owczarek, Dorota; Wawrzyniak, Marcin; Loza-Alvarez, Pablo; Kaczmarek, Leszek

    2016-01-01

    Whole-brain imaging with light-sheet fluorescence microscopy and optically cleared tissue is a new, rapidly developing research field. Whereas successful attempts to clear and image mouse brain have been reported, a similar result for rats has proven difficult to achieve. Herein, we report on creating novel transgenic rat harboring fluorescent reporter GFP under control of neuronal gene promoter. We then present data on clearing the rat brain, showing that FluoClearBABB was found superior over passive CLARITY and CUBIC methods. Finally, we demonstrate efficient imaging of the rat brain using light-sheet fluorescence microscopy. PMID:27312902

  4. Morphological and functional changes in the rat heart after X irradiation: Strain differences

    SciTech Connect

    Yeung, T.K.; Lauk, S.; Simmonds, R.H.; Hopewell, J.W.; Trott, K.R. )

    1989-09-01

    The hearts of mature male rats of the Wistar and Sprague-Dawley strains were locally irradiated with single doses of 17.5 and 20.0 Gy of X rays, respectively. These two dose levels had previously been shown to result in a comparable latent period between irradiation and the death of rats of these two strains from cardiac failure. Morphological changes in the myocardium and modifications in cardiac function were assessed in the animals at 28, 70, and 100 days after irradiation. The first radiation-induced change which was observed in the myocardium was a rapid decline in capillary density and a loss of alkaline phosphatase activity by the capillary endothelial cells. The capillary density was reduced to approximately 50% of that of unirradiated control values at 28 days and to approximately 40% of the control values between 70 and 100 days after irradiation. The loss of enzyme activity was also detected at 28 days. Examination of histological sections showed an increase by 70 days in the areas with negative enzyme activity up to approximately 70% of the myocardium. The reduction in capillary density and the loss of enzyme activity occurred before any marked pathological changes were seen in the myocardium. The pathological lesions seen in the myocardium at 100 days after irradiation were qualitatively and quantitatively the same in the two strains of rat. Measurements of cardiac output in Sprague-Dawley rats showed a gradual decline in output after irradiation; however, measurements in Wistar rats showed a progressive increase in cardiac output over the same period of time. It was shown by rubidium extraction that there was an increase in the percentage of the total cardiac output distributed to the ventricular muscle of Sprague-Dawley rats, while similar measurements in Wistar rats showed no significant change.

  5. Relationship between oxidative damage and colon carcinogenesis in irradiated rats: influence of dietary countermeasures

    NASA Astrophysics Data System (ADS)

    Turner, Nancy; Sanders, Lisa; Wu, Guoyao; Davidson, Laurie; Ford, John; Braby, Leslie; Carroll, Raymond; Chapkin, Robert; Lupton, Joanne

    Galactic cosmic radiation not only kills colon epithelial cells, it also generates a cellular environment that can lead to oxidative DNA damage. We previously demonstrated that a diet containing fish oil and pectin protects against initiation of colon cancer by enhancing apoptotic removal of cells with oxidative DNA adducts (8-OHdG), and that apoptosis was highly correlated with colon cancer suppression. We hypothesized this diet combination will mitigate the oxidative damage occurring from radiation and thus reduce colon cancer. The experiment tested the effect of radiation (± 1 Gy, 1 GeV/n Fe ions) on redox balance, apoptosis, and 8-OHdG levels at initiation and colon tumor incidence. Diets contained fish oil or corn oil, and cellulose or pectin (2x2 factorial design). Rats received the diets 3 wk before irradiation (half of the rats), followed by azoxymethane (AOM) injections 10 and 17 d later (all rats). Just prior to AOM injection, irradiated fish oil/pectin rats had a more reduced redox state in colonocytes (lower GSSG, P < 0.05; higher GSH/GSSG ratio), which was not observed in irradiated corn oil/cellulose rats. A shift to a more oxidative state (lower GSH and GSH/GSSG ratio, P < 0.05) occurred between 6 and 12 h after AOM in the fish oil/pectin irradiated rats. Changes in redox balance likely contributed to lower 8-OHdG levels in colonocytes from rats consuming the fish oil diets. Dietary pectin enhanced (P < 0.04) apoptosis induction 12 h after AOM injection in irradiated rats. Similar to the 8-OHdG results, colon tumor incidence was 42% higher (P < 0.05) in rats fed corn oil vs fish oil diets. In summary, fish oil/pectin diets created a more reduced colon environment in irradiated rats that was evident 10 d after irradiation. The ensuing oxidative shift in those rats after AOM injection may have enhanced apoptosis; effectively eliminating more DNA damaged cells. Thus, inclusion of fish oil and pectin in diets for long-duration space flights should help

  6. Brain fixation for analysis of brain lipid-mediators of signal transduction and brain eicosanoids requires head-focused microwave irradiation: an historical perspective.

    PubMed

    Murphy, Eric J

    2010-04-01

    To microwave or not to microwave, that is the question that has confounded the neurochemist as the quest for reducing changes in neurochemicals associated with post-mortem delay has evolved over the years. Rapid changes in brain constituents during the post-mortem delay have been recognized for years as a problem. What is real and what is artifact? What are true basal levels of molecules found in the brain? In the 1920s, neurochemists recognized this issue and determined freezing of the brain was most advantageous for halting rapid breakdown of some molecules and rapid formation of others. By the early 1970s, a number of laboratories noted that freezing the brain in situ or upon removing it from the cranial vault was not sufficient to reduce alterations in brain chemistry. Groups began experimenting with two different techniques to attack this problem, freeze-blowing and head-focused microwave irradiation. My laboratory and others have found that the utilization of head-focused microwave irradiation to halt enzymic alterations in lipids is an essential tool to limit alterations post-mortem. Recently, we and others have demonstrated that this technique is essential in reliably assessing brain eicosanoid levels, without such fixation true basal levels of eicosanoids are impossible to determine and the high concentrations seen in some paradigms may be merely an artifact produced during handling of the brain. Thus, for eicosanoid analysis and other applications in measuring brain lipid levels, head-focused microwave irradiation is an essential tool for the lipid neurochemist.

  7. Effects of extremely low frequency magnetic field on oxidative balance in brain of rats.

    PubMed

    Ciejka, Elzbieta; Kleniewska, P; Skibska, B; Goraca, A

    2011-12-01

    Extremely low frequency magnetic field (ELF-MF) may result in oxidative DNA damage and lipid peroxidation with an ultimate effect on a number of systemic disturbances and cell death. The aim of the study is to assess the effect of ELF-MF parameters most frequently used in magnetotherapy on reactive oxygen species generation (ROS) in brain tissue of experimental animals depending on the time of exposure to this field. The research material included adult male Sprague-Dawley rats, aged 3-4 months. The animals were divided into 3 groups: I - control (shame) group; II - exposed to the following parameters of the magnetic field: 7 mT, 40 Hz, 30 min/day, 10 days; III - exposed to the ELF-MF parameters of 7 mT, 40 Hz, 60 min/day, 10 days. The selected parameters of oxidative stress: thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), total free sulphydryl groups (-SH groups) and protein in brain homogenates were measured after the exposure of rats to the magnetic field. ELF-MF parameters of 7 mT, 40 Hz, 30 min/day for 10 days caused a significant increase in lipid peroxidation and insignificant increase in H(2)O(2) and free -SH groups. The same ELF-MF parameters but applied for 60 min/day caused a significant increase in free -SH groups and protein concentration in the brain homogenates indicating the adaptive mechanism. The study has shown that ELF-MF applied for 30 min/day for 10 days can affect free radical generation in the brain. Prolongation of the exposure to ELF-MF (60/min/day) caused adaptation to this field. The effect of ELF-MF irradiation on oxidative stress parameters depends on the time of animal exposure to magnetic field. PMID:22314568

  8. Assessment of MRI Parameters as Imaging Biomarkers for Radiation Necrosis in the Rat Brain

    SciTech Connect

    Wang Silun; Tryggestad, Erik; Zhou Tingting; Armour, Michael; Wen Zhibo; Fu Dexue; Ford, Eric; Zijl, Peter C.M. van; Zhou Jinyuan

    2012-07-01

    Purpose: Radiation necrosis is a major complication of radiation therapy. We explore the features of radiation-induced brain necrosis in the rat, using multiple MRI approaches, including T{sub 1}, T{sub 2}, apparent diffusion constant (ADC), cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton transfer (APT) of endogenous mobile proteins and peptides. Methods and Materials: Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X-ray beam (40 Gy; 10 Multiplication-Sign 10 mm{sup 2}) in the left brain hemisphere. MRI was acquired on a 4.7-T animal scanner at {approx}25 weeks' postradiation. The MRI signals of necrotic cores and perinecrotic regions were assessed with a one-way analysis of variance. Histological evaluation was accomplished with hematoxylin and eosin staining. Results: ADC and CBF MRI could separate perinecrotic and contralateral normal brain tissue (p < 0.01 and < 0.05, respectively), whereas T{sub 1}, T{sub 2}, MTR, and APT could not. MRI signal intensities were significantly lower in the necrotic core than in normal brain for CBF (p < 0.001) and APT (p < 0.01) and insignificantly higher or lower for T{sub 1}, T{sub 2}, MTR, and ADC. Histological results demonstrated coagulative necrosis within the necrotic core and reactive astrogliosis and vascular damage within the perinecrotic region. Conclusion: ADC and CBF are promising imaging biomarkers for identifying perinecrotic regions, whereas CBF and APT are promising for identifying necrotic cores.

  9. In utero exposure to microwave radiation and rat brain development

    SciTech Connect

    Merritt, J.H.; Hardy, K.A.; Chamness, A.F.

    1984-01-01

    Timed-pregnancy rats were exposed in a circular waveguide system starting on day 2 of gestation. The system operated at 2,450 MHz (pulsed waves; 8 microseconds PW; 830 pps). Specific absorption rate (SAR) was maintained at 0.4 W/kg by increasing the input power as the animals grew in size. On day 18 of gestation the dams were removed from the waveguide cages and euthanized; the fetuses were removed and weighed. Fetal brains were excised and weighed, and brain RNA, DNA and protein were determined. Values for measured parameters of the radiated fetuses did not differ significantly from those of sham-exposed fetuses. A regression of brain weight on body weight showed no micrencephalous fetuses in the radiation group when using as a criterion a regression line based on two standard errors of the estimate of the sham-exposed group. In addition, metrics derived from brain DNA (ie, cell number and cell size) showed no significant differences when radiation was compared to sham exposure. We conclude that 2,450-MHz microwave radiation, at an SAR of 0.4 W/kg, did not produce significant alterations in brain organogenesis.

  10. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study

    SciTech Connect

    Cakmak G.; Miller L.; Zorlu, F.; Severcan, F.

    2012-03-03

    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH{sub 2} groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH{sub 3} groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems.

  11. Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats.

    PubMed

    Gu, Xiaohuan; Wei, Zheng Zachory; Espinera, Alyssa; Lee, Jin Hwan; Ji, Xiaoya; Wei, Ling; Dix, Thomas A; Yu, Shan Ping

    2015-05-01

    Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A 6-h hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15min or 2h after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood-brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201

  12. Pharmacologically Induced Hypothermia Attenuates Traumatic Brain Injury in Neonatal Rats

    PubMed Central

    Espinera, Alyssa; Lee, Jin Hwan; Ji, Xiaoya; Wei, Ling; Dix, Thomas A.; Yu, Shan Ping

    2015-01-01

    Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A six-hour hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15 min or 2 hr after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and Caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the

  13. Autoradiographic localization of angiotensin II receptors in rat brain

    SciTech Connect

    Mendelsohn, F.A.O.; Quirion, R.; Saavedra, J.M.; Aguilera, G.; Catt, K.J.

    1984-03-01

    The /sup 125/I-labeled agonist analog (1-sarcosine)-angiotensin II ((Sar/sup 1/)AII) bound with high specificity and affinity (K/sub a/ = 2 x 10/sup 9/ M/sup -1/) to a single class of receptor sites in rat brain. This ligand was used to analyze the distribution of AII receptors in rat brain by in vitro autoradiography followed by computerized densitometry and color coding. A very high density of AII receptors was found in the subfornical organ, paraventricular and periventricular nuclei of the hypothalamus, nucleus of the tractus solitarius, and area postrema. A high concentration of receptors was found in the suprachiasmatic nucleus of the hypothalamus, lateral olfactory tracts, nuclei of the accessory and lateral olfactory tracts, triangular septal nucleus, subthalamic nucleus, locus coeruleus, and inferior olivary nuclei. Moderate receptor concentrations were found in the organum vasculosum of the lamina terminalis, median preoptic nucleus, medial habenular nucleus, lateral septum, ventroposterior thalamic nucleus, median eminence, medial geniculate nucleus, superior colliculus, subiculum, pre- and parasubiculum, and spinal trigeminal tract. Low concentrations of sites were seen in caudate-putamen, nucleus accumbens, amygdala, and gray matter of the spinal cord. These studies have demonstrated that AII receptors are distributed in a highly characteristic anatomical pattern in the brain. The high concentrations of AII receptors at numerous physiologically relevant sites are consistent with the emerging evidence for multiple roles of AII as a neuropeptide in the central nervous system. 75 references, 2 figures.

  14. Localization of histidine decarboxylase mRNA in rat brain.

    PubMed

    Bayliss, D A; Wang, Y M; Zahnow, C A; Joseph, D R; Millhorn, D E

    1990-08-01

    The recent cloning of a cDNA encoding fetal rat liver histidine decarboxylase (HDC), the synthesizing enzyme for histamine, allows the study of the central histaminergic system at the molecular level. To this end, Northern blot and in situ hybridization analyses were used to determine the regional and cellular distribution of neurons which express HDC mRNA in rat brain. Three hybridizing species which migrate as 1.6-, 2.6-, and 3.5-kb RNA were identified with Northern blots. The major (2.6 kb) and minor (3.5 kb) species, characteristic of HDC mRNA in fetal liver, were expressed at high levels in diencephalon and at just detectable levels in hippocampus, but not in other brain regions. In contrast, the 1.6-kb species was present in all brain regions examined except the olfactory bulb. Cells which contain HDC mRNA were found by in situ hybridization in the hypothalamus; HDC mRNA-containing cells were not detected in other areas, including the hippocampus. Hypothalamic neurons which express HDC mRNA were localized to all aspects of the tuberomammillary nucleus, a result consistent with previous immunohistochemical findings. PMID:19912749

  15. Administration of the peroxisomal proliferator-activated receptor {gamma} agonist pioglitazone during fractionated brain irradiation prevents radiation-induced cognitive impairment

    SciTech Connect

    Zhao Weiling; Payne, Valerie; Tommasi, Ellen; Diz, Debra I.; Hsu, F.-C.; Robbins, Mike E. . E-mail: mrobbins@wfubmc.edu

    2007-01-01

    Purpose: We hypothesized that administration of the anti-inflammatory peroxisomal proliferator-activated receptor {gamma} (PPAR{gamma}) agonist pioglitazone (Pio) to adult male rats would inhibit radiation-induced cognitive impairment. Methods and Materials: Young adult male F344 rats received one of the following: (1) fractionated whole brain irradiation (WBI); 40 or 45 Gy {gamma}-rays in 4 or 4.5 weeks, respectively, two fractions per week and normal diet; (2) sham-irradiation and normal diet; (3) WBI plus Pio (120 ppm) before, during, and for 4 or 54 weeks postirradiation; (4) sham-irradiation plus Pio; or (5) WBI plus Pio starting 24h after completion of WBI. Results: Administration of Pio before, during, and for 4 or 54 weeks after WBI prevented Radiation-induced cognitive impairment. Administration of Pio for 54 weeks starting after completion of fractionated WBI substantially but not significantly reduced Radiation-induced cognitive impairment. Conclusions: These findings offer the promise of improving the quality of life and increasing the therapeutic window for brain tumor patients.

  16. The blood-brain barrier penetration and distribution of PEGylated fluorescein-doped magnetic silica nanoparticles in rat brain

    SciTech Connect

    Ku, Shuting; Yan, Feng; Wang, Ying; Sun, Yilin; Yang, Nan; Ye, Ling

    2010-04-16

    PEGylated PAMAM conjugated fluorescein-doped magnetic silica nanoparticles (PEGylated PFMSNs) have been synthesized for evaluating their ability across the blood-brain barrier (BBB) and distribution in rat brain. The obtained nanoparticles were characterized by transmission electron microscopy (TEM), thermal gravimetry analyses (TGA), zeta potential ({zeta}-potential) titration, and X-ray photoelectron spectroscopy (XPS). The BBB penetration and distribution of PEGylated PFMSNs and FMSNs in rat brain were investigated not only at the cellular level with Confocal laser scanning microscopy (CLSM), but also at the subcellular level with transmission electron microscopy (TEM). The results provide direct evidents that PEGylated PFMSNs could penetrate the BBB and spread into the brain parenchyma.

  17. Cerebrolysin attenuates blood-brain barrier and brain pathology following whole body hyperthermia in the rat.

    PubMed

    Sharma, Hari Shanker; Zimmermann-Meinzingen, Sibilla; Sharma, Aruna; Johanson, Conrad E

    2010-01-01

    The possibility that Cerebrolysin, a mixture of several neurotrophic factors, has some neuroprotective effects on whole body hyperthermia (WBH) induced breakdown of the blood-brain barrier (BBB), blood-CSF barrier (BCSFB), brain edema formation and neuropathology were examined in a rat model. Rats subjected to a 4 h heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator exhibited profound increases in BBB and BCSFB permeability to Evans blue and radioiodine tracers compared to controls. Hippocampus, caudate nucleus, thalamus and hypothalamus exhibited pronounced increase in water content and brain pathology following 4 h heat stress. Pretreatment with Cerebrolysin (1, 2 or 5 mL/kg i.v.) 24 h before WBH significantly attenuated breakdown of the BBB or BCSFB and brain edema formation. This effect was dose dependent. Interestingly, the cell and tissue injury following WBH in cerebrolysin-treated groups were also considerably reduced. These novel observations suggest that cerebrolysin can attenuate WBH induced BBB and BCSFB damage resulting in neuroprotection.

  18. Magnetic Micelles for DNA delivery to rat brains after mild traumatic brain injury

    PubMed Central

    Das, Mahasweta; Wang, Chunyan; Bedi, Raminder; Mohapatra, Shyam S.; Mohapatra, Subhra

    2014-01-01

    Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CPmag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM - tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats. Evans blue extravasation following mTBI suggested CPMM-ptd entry into the brain via the compromised blood-brain barrier. Magnetofection increased the concentration of CPMMs in the brain. RFP expression was observed in the brain (cortex and hippocampus), lung and liver 48 hours after mTBI. CPMM did not evoke any inflammatory response by themselves and were excreted from the body. These results indicate the possibility of using intranasally administered CPMM as a theranostic vehicle for mTBI. PMID:24486465

  19. Effect of irradiation on healing of newly made colonic anastomoses in the rat

    SciTech Connect

    Biert, J.; Wobbes, T.; Hendriks, T.; Hoogenhout, J. )

    1993-12-01

    Short-term effects of radiotherapy on the healing process of newly made colonic anastomoses are investigated by measuring the anastomotic strength in a rat model. Four groups of Wistar rats were used. In all groups, rats underwent a 1 cm sigmoid resection with end-to-end anastomosis. Group I served as a control group. In group II the anastomosis was irradiated after closure of the abdominal wall with a single dose of 20 Gy of 250 kV [times] rays. Group III was irradiated with a single dose of 20 Gy while the abdominal wall was not closed, and the surrounding tissues were carefully covered by a lead plate, simulating intra-operative radiotherapy. Group IV was treated as group III, but a larger dose of 25 Gy was applied. Animals were sacrificed 3 or 7 days after the operation. General condition of the rats was determined by observation, weight loss, serum protein and albumin at sacrifice. Anastomotic healing was evaluated by inspection, bursting pressure, hydroxyproline and protein contents of the anastomotic segment. Direct postoperative externally irradiated rats (group II) showed a marked weight loss, hypoproteinaemia and hypo-albuminaemia because of involvement of small bowel in the irradiated volume. With respect to anastomotic healing there were no significant differences between control and irradiated groups. These data suggest that the application of a single dose of irradiation (20 and 25 Gy) on colonic anastomoses given in a direct postoperative or intraoperative model has no measurable side effect on the early healing of newly made colonic anastomoses. Direct postoperative external irradiation results in unwanted side effects in the adjacent bowel. 33 refs., 4 figs., 3 tabs.

  20. A Novel Technique for Image-Guided Local Heart Irradiation in the Rat

    PubMed Central

    Sharma, Sunil; Moros, Eduardo G.; Boerma, Marjan; Sridharan, Vijayalakshmi; Han, Eun Young; Clarkson, Richard; Hauer-Jensen, Martin; Corry, Peter M.

    2014-01-01

    In radiotherapy treatment of thoracic, breast and chest wall tumors, the heart may be included (partially or fully) in the radiation field. As a result, patients may develop radiation-induced heart disease (RIHD) several years after exposure to radiation. There are few methods available to prevent or reverse RIHD and the biological mechanisms remain poorly understood. In order to further study the effects of radiation on the heart, we developed a model of local heart irradiation in rats using an image-guided small animal conformal radiation therapy device (SACRTD) developed at our institution. First, Monte Carlo based simulations were used to design an appropriate collimator. EBT-2 films were used to measure relative dosimetry, and the absolute dose rate at the isocenter was measured using the AAPM protocol TG-61. The hearts of adult male Sprague-Dawley rats were irradiated with a total dose of 21 Gy. For this purpose, rats were anesthetized with isoflurane and placed in a custom-made vertical rat holder. Each heart was irradiated with a 3-beam technique (one AP field and 2 lateral fields), with each beam delivering 7 Gy. For each field, the heart was visualized with a digital flat panel X-ray imager and placed at the isocenter of the 1.8 cm diameter beam. In biological analysis of radiation exposure, immunohistochemistry showed γH2Ax foci and nitrotyrosine throughout the irradiated hearts but not in the lungs. Long-term follow-up of animals revealed histopathological manifestations of RIHD, including myocardial degeneration and fibrosis. The results demonstrate that the rat heart irradiation technique using the SACRTD was successful and that surrounding untargeted tissues were spared, making this approach a powerful tool for in vivo radiobiological studies of RIHD. Functional and structural changes in the rat heart after local irradiation are ongoing. PMID:24000983

  1. Detection of cocaine induced rat brain activation by photoacoustic tomography

    PubMed Central

    Jo, Janggun; Yang, Xinmai

    2011-01-01

    Photoacoustic tomography (PAT) was used to detect the progressive changes on the cerebral cortex of Sprague Dawley rats after the administration of cocaine hydrochloride. Different concentrations (0, 2.5, and 5.0 mg per kg body) of cocaine hydrochloride in saline solution were injected into Sprague Dawley rats through tail veins. Cerebral cortex images of the animals were continuously acquired by PAT. For continuous observation, PAT system used multi-transducers to reduce the scanning time and maintain a good signal-to-noise ratio (SNR). The obtained photoacoustic images were compared with each other and confirmed that changes in blood volume were induced by cocaine hydrochloride injection. The results demonstrate that PAT may be used to detect the effects of drug abuse-induced brain activation. PMID:21163301

  2. Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway

    SciTech Connect

    Ji, Jian-feng; Ji, Sheng-jun; Sun, Rui; Li, Kun; Zhang, Yuan; Zhang, Li-yuan; Tian, Ye

    2014-01-10

    Highlights: •Forced exercise can ameliorate WBI induced cognitive impairment in our rat model. •Mature BDNF plays an important role in the effects of forced exercise. •Exercise may be a possible treatment of the radiation-induced cognitive impairment. -- Abstract: Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating the effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male Sprague–Dawley rats received a single dose of 20 Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2 months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNF–pCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNF–pCREB signaling in non-irradiation

  3. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    PubMed Central

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-01-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue. PMID:27456312

  4. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-07-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

  5. Schisandrin B protects against solar irradiation-induced oxidative stress in rat skin tissue.

    PubMed

    Lam, Philip Y; Yan, Chung Wai; Chiu, Po Yee; Leung, Hoi Yan; Ko, Kam Ming

    2011-04-01

    Schisandrin B (Sch B) and schisandrin C (Sch C), but not schisandrin A and dimethyl diphenyl bicarboxylate, protected rat skin tissue against solar irradiation-induced oxidative injury, as evidenced by a reversal of solar irradiation-induced changes in cellular reduced glutathione and α-tocopherol levels, as well as antioxidant enzyme activities and malondialdehyde production. The cytochrome P-450-mediated metabolism of Sch B or Sch C caused ROS production in rat skin microsomes. Taken together, Sch B or Sch C, by virtue of its pro-oxidant action and the subsequent eliciting of a glutathione antioxidant response, may prevent photo-aging of skin.

  6. 2-hydroxyestradiol modifies serotonergic processes in the male rat brain

    SciTech Connect

    Kowalik, S.

    1985-01-01

    The effects of chronic (5 day) 2-hydroxyestradiol or estradiol on catecholaminergic and serotonergic neurons in the male rat brain were studied. The results indicate estrogen to be specific is inducing changes in dopaminergic systems; whereas its hydroxymetabolite appears to have a preference for serotonergic processes. In particular, in vitro 2-hydroxyestradiol appears to be a potent inhibitor of /sup 3/H-imipramine binding in brain; this inhibition is especially potent in the cortex, where it is equal in potency to serotonin. However, unlike serotonin, which is a competitive inhibitor of imipramine, 2-hydroxyestradiol is an uncompetitive inhibitor of /sup 3/H-imipramine binding in cortex and hypothalamus and a noncompetitive inhibitor in the striatum; this suggests that the inhibition of binding takes place at a point other than the site of serotonin uptake. In vitro 2-hydroxyestradiol also appears to increase the uptake of serotonin into these tissues, a change which would be expected if the imipramine binding is blocked.

  7. Neuronal damage in chick and rat embryos following X-irradiation

    SciTech Connect

    Schneider, B.F.; Norton, S.

    1980-12-01

    Exposure of rat and chick embryos to X-irradiation at the time of development of neurons at the telencephalic-diencephalic border results in prolonged damage to neurons in this area as measured by neuronal nuclear size. A dose of 100 rads to the seven-day-old chick embryo has about the same effect as 125 rads to the 15-day-old rat fetus. The nuclear volume of large, multipolar neurons in the chick paleostriatum primitivum and the rat lateral preoptic area are reduced from 10 to 15%. Larger doses of X-irradiation to the chick (150 and 200 rads) cause progressively greater reductions in nuclear size. The large neurons which were measured in the rat and chick are morphologically similar in the two species. Both contain cytoplasmic acetylcholinesterase and have several branched, spiny dendritic processes. The similarity of response of chick and rat neurons to X-irradiation diminishes the significance of maternal factors as the cause of the effects of fetal irradiation in these experiments.

  8. The impact of chronic stress on the rat brain lipidome.

    PubMed

    Oliveira, T G; Chan, R B; Bravo, F V; Miranda, A; Silva, R R; Zhou, B; Marques, F; Pinto, V; Cerqueira, J J; Di Paolo, G; Sousa, N

    2016-01-01

    Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer's disease and depression. Lipids are a major constituent of the brain and specifically signaling lipids have been shown to regulate brain function. Here, we used a mass spectrometry-based lipidomic approach to evaluate the impact of a chronic unpredictable stress (CUS) paradigm on the rat brain in a region-specific manner. We found that the prefrontal cortex (PFC) was the area with the highest degree of changes induced by chronic stress. Although the hippocampus presented relevant lipidomic changes, the amygdala and, to a greater extent, the cerebellum presented few lipid changes upon chronic stress exposure. The sphingolipid and phospholipid metabolism were profoundly affected, showing an increase in ceramide (Cer) and a decrease in sphingomyelin (SM) and dihydrosphingomyelin (dhSM) levels, and a decrease in phosphatidylethanolamine (PE) and ether phosphatidylcholine (PCe) and increase in lysophosphatidylethanolamine (LPE) levels, respectively. Furthermore, the fatty-acyl profile of phospholipids and diacylglycerol revealed that chronic stressed rats had higher 38 carbon(38C)-lipid levels in the hippocampus and reduced 36C-lipid levels in the PFC. Finally, lysophosphatidylcholine (LPC) levels in the PFC were found to be correlated with blood corticosterone (CORT) levels. In summary, lipidomic profiling of the effect of chronic stress allowed the identification of dysregulated lipid pathways, revealing putative targets for pharmacological intervention that may potentially be used to modulate stress-induced deficits.

  9. Data for mitochondrial proteomic alterations in the developing rat brain.

    PubMed

    Villeneuve, Lance M; Stauch, Kelly L; Fox, Howard S

    2014-12-01

    Mitochondria are a critical organelle involved in many cellular processes, and due to the nature of the brain, neuronal cells are almost completely reliant on these organelles for energy generation. Due to the fact that biomedical research tends to investigate disease state pathogenesis, one area of mitochondrial research commonly overlooked is homeostatic responses to energy demands. Therefore, to elucidate mitochondrial alterations occurring during the developmentally important phase of E18 to P7 in the brain, we quantified the proteins in the mitochondrial proteome as well as proteins interacting with the mitochondria. We identified a large number of significantly altered proteins involved in a variety of pathways including glycolysis, mitochondrial trafficking, mitophagy, and the unfolded protein response. These results are important because we identified alterations thought to be homeostatic in nature occurring within mitochondria, and these results may be used to identify any abnormal deviations in the mitochondrial proteome occurring during this period of brain development. A more comprehensive analysis of this data may be obtained from the article "Proteomic analysis of mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands" in the Journal of Proteomics. PMID:26217684

  10. Gene Transfer into Rat Brain Using Adenoviral Vectors

    PubMed Central

    Puntel, Mariana; Kroeger, Kurt M.; Sanderson, Nicholas S.R.; Thomas, Clare E.; Castro, Maria G.; Lowenstein, Pedro R.

    2010-01-01

    Viral vector–mediated gene delivery is an attractive procedure for introducing genes into the brain, both for purposes of basic neuroscience research and to develop gene therapy for neurological diseases. Replication-defective adenoviruses possess many features which make them ideal vectors for this purpose—efficiently transducing terminally differentiated cells such as neurons and glial cells, resulting in high levels of transgene expression in vivo. Also, in the absence of anti-adenovirus immunity, these vectors can sustain very long-term transgene expression within the brain parenchyma. This unit provides protocols for the stereotactic injection of adenoviral vectors into the brain, followed by protocols to detect transgene expression or infiltrates of immune cells by immunocytochemistry or immunofluorescence. ELISPOT and neutralizing antibody assay methodologies are provided to quantitate the levels of cellular and humoral immune responses against adenoviruses. Quantitation of adenoviral vector genomes within the rat brain using qPCR is also described. Curr. Protoc. Neurosci. 50:4.24.1–4.24.49. © 2010 by John Wiley & Sons, Inc. PMID:20066657

  11. Somatostatin receptors: identification and characterization in rat brain membranes.

    PubMed

    Srikant, C B; Patel, Y C

    1981-06-01

    We have identified and characterized specific receptors for tetradecapeptide somatostatin (SRIF; somatotropin release-inhibiting factor) in rat brain using [125I]Tyr11]SRIF as the radioligand. These receptors are present in membranes obtained from a subfraction of synaptosomes. Membranes derived from cerebral cortex bind SRIF with high affinity (Ka = 1.25 X 10(10) M-1) and have a maximum binding capacity (Bmax) of 0.155 X 10(-12) mol/mg. Neither opiates nor other neuropeptides appear to influence the binding of SRIF to brain membranes. Synthetic analogs with greater biological potency than SRIF--[D-Trp8]SRIF, [D-Cys14]SRIF, and [D-Trp8, D-Cys14]SRIF--bind to the receptors with greater avidity than SRIF, whereas inactive analogs [(2H)Ala3]SRIF and [Ala6]SRIF exhibit low binding. The ratio of receptor density to endogenous somatostatin is high in the cortex, thalamus, and striatum, low in the hypothalamus, and extremely low in the brain stem and cerebellum. Thus, SRIF receptors in the brain appear to be a distinct, new class of receptors with a regional distribution different from that of endogenous somatostatin.

  12. Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain

    NASA Astrophysics Data System (ADS)

    Ji, Ru-Rong; Schlaepfer, Thomas E.; Aizenman, Carlos D.; Epstein, Charles M.; Qiu, Dike; Huang, Justin C.; Rupp, Fabio

    1998-12-01

    Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

  13. Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

    NASA Astrophysics Data System (ADS)

    Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2010-02-01

    Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

  14. Effect of zinc supplementation on neuronal precursor proliferation in the rat hippocampus after traumatic brain injury.

    PubMed

    Cope, Elise C; Morris, Deborah R; Gower-Winter, Shannon D; Brownstein, Naomi C; Levenson, Cathy W

    2016-05-01

    There is great deal of debate about the possible role of adult-born hippocampal cells in the prevention of depression and related mood disorders. We first showed that zinc supplementation prevents the development of the depression-like behavior anhedonia associated with an animal model of traumatic brain injury (TBI). This work then examined the effect of zinc supplementation on the proliferation of new cells in the hippocampus that have the potential to participate in neurogenesis. Rats were fed a zinc adequate (ZA, 30ppm) or zinc supplemented (ZS, 180ppm) diet for 4wk followed by TBI using controlled cortical impact. Stereological counts of EdU-positive cells showed that TBI doubled the density of proliferating cells 24h post-injury (p<0.05), and supplemental zinc significantly increased this by an additional 2-fold (p<0.0001). While the survival of these proliferating cells decreased at the same rate in ZA and in ZS rats after injury, the total density of newly born cells was approximately 60% higher in supplemented rats 1wk after TBI. Furthermore, chronic zinc supplementation resulted in significant increases in the density of new doublecortin-positive neurons one week post-TBI that were maintained for 4wk after injury (p<0.01). While the effect of zinc supplementation on neuronal precursor cells in the hippocampus was robust, use of targeted irradiation to eliminate these cells after zinc supplementation and TBI revealed that these cells are not the sole mechanism through which zinc acts to prevent depression associated with brain injury, and suggest that other zinc dependent mechanisms are needed for the anti-depressant effect of zinc in this model of TBI.

  15. Effect of zinc supplementation on neuronal precursor proliferation in the rat hippocampus after traumatic brain injury.

    PubMed

    Cope, Elise C; Morris, Deborah R; Gower-Winter, Shannon D; Brownstein, Naomi C; Levenson, Cathy W

    2016-05-01

    There is great deal of debate about the possible role of adult-born hippocampal cells in the prevention of depression and related mood disorders. We first showed that zinc supplementation prevents the development of the depression-like behavior anhedonia associated with an animal model of traumatic brain injury (TBI). This work then examined the effect of zinc supplementation on the proliferation of new cells in the hippocampus that have the potential to participate in neurogenesis. Rats were fed a zinc adequate (ZA, 30ppm) or zinc supplemented (ZS, 180ppm) diet for 4wk followed by TBI using controlled cortical impact. Stereological counts of EdU-positive cells showed that TBI doubled the density of proliferating cells 24h post-injury (p<0.05), and supplemental zinc significantly increased this by an additional 2-fold (p<0.0001). While the survival of these proliferating cells decreased at the same rate in ZA and in ZS rats after injury, the total density of newly born cells was approximately 60% higher in supplemented rats 1wk after TBI. Furthermore, chronic zinc supplementation resulted in significant increases in the density of new doublecortin-positive neurons one week post-TBI that were maintained for 4wk after injury (p<0.01). While the effect of zinc supplementation on neuronal precursor cells in the hippocampus was robust, use of targeted irradiation to eliminate these cells after zinc supplementation and TBI revealed that these cells are not the sole mechanism through which zinc acts to prevent depression associated with brain injury, and suggest that other zinc dependent mechanisms are needed for the anti-depressant effect of zinc in this model of TBI. PMID:26902472

  16. Gallic acid improved behavior, brain electrophysiology, and inflammation in a rat model of traumatic brain injury.

    PubMed

    Sarkaki, Alireza; Farbood, Yaghoub; Gharib-Naseri, Mohammad Kazem; Badavi, Mohammad; Mansouri, Mohammad Taghi; Haghparast, Abbas; Mirshekar, Mohammad Ali

    2015-08-01

    Traumatic brain injury (TBI) is one of the main causes of intellectual and cognitive disabilities. In the clinic it is essential to limit the development of cognitive impairment after TBI. In this study, the effects of gallic acid (GA; 100 mg/kg, per oral, from 7 days before to 2 days after TBI induction) on neurological score, passive avoidance memory, long-term potentiation (LTP) deficits, and levels of proinflammatory cytokines including interleukin-1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in the brain have been evaluated. Brain injury was induced following Marmarou's method. Data were analyzed by one-way and repeated measures ANOVA followed by Tukey's post-hoc test. The results indicated that memory was significantly impaired (p < 0.001) in the group treated with TBI + vehicle, together with deterioration of the hippocampal LTP and increased brain tissue levels of IL-1β, IL-6, and TNF-α. GA treatment significantly improved memory and LTP in the TBI rats. The brain tissue levels of IL-1β, IL-6, and TNF-α were significantly reduced (p < 0.001) in the group treated with GA. The results suggest that GA has neuroprotective properties against TBI-induced behavioral, electrophysiological, and inflammatory disorders, probably via the decrease of cerebral proinflammatory cytokines.

  17. Increased EZH2 and decreased osteoblastogenesis during local irradiation-induced bone loss in rats

    PubMed Central

    Guo, Changjun; Li, Changwei; Yang, Kai; Kang, Hui; Xu, Xiaoya; Xu, Xiangyang; Deng, Lianfu

    2016-01-01

    Radiation therapy is commonly used to treat cancer patients but exhibits adverse effects, including insufficiency fractures and bone loss. Epigenetic regulation plays an important role in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Here, we reported local bone changes after single-dose exposure to 137CS irradiation in rats. Femur bone mineral density (BMD) and trabecular bone volume in the tibia were significantly decreased at 12 weeks after irradiation. Micro-CT results showed that tBMD, Tb.h and Tb.N were also significantly reduced at 12 weeks after irradiation exposure. ALP-positive OB.S/BS was decreased by 42.3% at 2 weeks after irradiation and was decreased by 50.8% at 12 weeks after exposure. In contrast to the decreased expression of Runx2 and BMP2, we found EZH2 expression was significantly increased at 2 weeks after single-dose 137CS irradiation in BMSCs. Together, our results demonstrated that single-dose 137CS irradiation induces BMD loss and the deterioration of bone microarchitecture in the rat skeleton. Furthermore, EZH2 expression increased and osteoblastogenesis decreased after irradiation. The underlying mechanisms warrant further investigation. PMID:27499068

  18. Propagation and titration of Alkhumra hemorrhagic fever virus in the brains of newborn Wistar rats.

    PubMed

    Madani, Tariq A; Kao, Moujahed; Abuelzein, El-Tayeb M E; Azhar, Esam I; Al-Bar, Hussein M S; Abu-Araki, Huda; Bokhary, Rana Y; Ksiazek, Thomas G

    2014-04-01

    Alkhumra hemorrhagic fever virus (AHFV) is a novel flavivirus identified first in Saudi Arabia. In this study, successful propagation of AHFV in the brains of newborn Wistar rats is described and the median rat lethal dose (RLD50) is determined. AHFV-RNA-positive human sera diluted 1:10 were injected intracerebrally into 16, ≤24h old rats. Post-inoculation, the rats were observed daily for 30 days. Brains of moribund rats were tested for AHFV-RNA using RT-PCR and cultured in LLC-MK2 cells. The titer of the isolated virus was determined and expressed in median tissue culture infectious dose (TCID50). To determine the RLD50, AHFV brain suspension was 10-fold diluted serially and each dilution was inoculated in the cerebral hemispheres of 10 rats for a total of 90 rats. Three days post-inoculation, the rats developed tremor, irritability, convulsion, opisthotonus, and spastic paresis starting in the hind limbs and ascending to involve the whole body. All infected rats died within 3-7 days with histopathologically confirmed meningoencephalitis. AHFV-RNA was detected in the brains of all infected rats and the virus titer was 10(9.4) RLD50/ml. The virus titer in LLC-MK2 was 10(8.2) TCID50/ml. In conclusion, AHFV was propagated successfully to high titers in the brains of newborn Wistar rats.

  19. Regional distribution of neuropeptide processing endopeptidases in adult rat brain.

    PubMed

    Berman, Y L; Rattan, A K; Carr, K; Devi, L

    1994-01-01

    Many peptide hormone and neuropeptide precursors undergo post-translational processing at mono- and/or dibasic residues. An enzymatic activity capable of processing prodynorphin at a monobasic processing site designated 'dynorphin converting enzyme' has been previously reported in rat rain and bovine pituitary. In this study the distribution of dynorphin converting enzyme activity in ten regions of rat brain has been compared with the distribution of subtilisin-like processing enzymes and with the immuno-reactive dynorphin peptides. The distribution of dynorphin converting enzyme activity generally matches the distribution of immuno-reactive dynorphin B-13 in most but not all brain regions. The regions that are known to have a relatively large number of immuno-reactive dynorphin-neurons also contain high levels of dynorphin converting enzyme activity. The distribution of dynorphin converting enzyme activity does not match the distribution of subtilisin-like processing enzyme or carboxypeptidase E activities. Taken together the data support the possibility that the dynorphin converting enzyme is involved in the maturation of dynorphin, as well as other neuropeptides, and peptide hormones.

  20. Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain

    PubMed Central

    2012-01-01

    Background Essential oil of Pimpinella anisum L. Apiaceae (anise oil) has been widely used in traditional Persian medicine to treat a variety of diseases, including some neurological disorders. This study was aimed to test the possible anti-seizure and anti-hypoxia effects of anise oil. Methods The effects of different concentrations of anise oil were tested on seizure attacks induced by pentylenetetrazol (PTZ) injection and neuronal hypoxia induced by oxygen withdrawal as well as on production of dark neurons and induction of long-term potentiation (LTP) in in vivo and in vitro experimental models of rat brain. Results Anise oil significantly prolonged the latency of seizure attacks and reduced the amplitude and duration of epileptiform burst discharges induced by injection of intraperitoneal PTZ. In addition, anise oil significantly inhibited production of dark neurons in different regions of the brain in epileptic rats. Anise oil also significantly enhanced the duration of the appearance of anoxic terminal negativity induced by oxygen withdrawal and inhibited induction of LTP in hippocampal slices. Conclusions Our data indicate the anticonvulsant and neuroprotective effects of anise oil, likely via inhibition of synaptic plasticity. Further evaluation of anise oil to use in the treatment of neurological disorders is suggested. PMID:22709243

  1. Distribution of beacon immunoreactivity in the rat brain.

    PubMed

    Wang, Fei; Tian, De-Run; Tian, Nan; Chen, Hui; Shi, Yu-Shun; Chang, Jaw-Kang; Yang, Jun; Yuan, Lan; Han, Ji-Sheng

    2006-01-01

    Beacon is a novel peptide isolated from the hypothalamus of Israeli sand rat. In the present study, we determined the distribution of beacon in the rat brain using immunohistochemical approach with a polyclonal antiserum directed against the synthetic C-terminal peptide fragment (47-73). The hypothalamus represented the major site of beacon-immunoreactive (IR) cell bodies that were concentrated in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON). Additional immunostained cells were found in the septum, bed nucleus of the stria terminalis, subfornical organ and subcommissural organ. Beacon-IR fibers were seen with high density in the internal layer of the median eminence and low to moderate density in the external layer. Significant beacon-IR fibers were also seen in the nucleus of the solitary tract and lateral reticular formation. The beacon neurons found in the PVN were further characterized by double label immunohistochemistry. Several beacon-IR neurons that resided in the medial PVN were shown to coexpress corticotrophin-releasing hormone (CRH) and most labeled beacon fibers in the external layer of median eminence coexist with CRH. The topographical distribution of beacon-IR in the brain suggests multiple biological activities for beacon in addition to its proposed roles in modulating feeding behaviors and pituitary hormone release.

  2. Wearable scanning photoacoustic brain imaging in behaving rats.

    PubMed

    Tang, Jianbo; Dai, Xianjin; Jiang, Huabei

    2016-06-01

    A wearable scanning photoacoustic imaging (wPAI) system is presented for noninvasive brain study in behaving rats. This miniaturized wPAI system consists of four pico linear servos and a single transducer-based PAI probe. It has a dimension of 50 mm × 35 mm × 40 mm, and a weight of 26 g excluding cablings. Phantom evaluation shows that wPAI achieves a lateral resolution of ∼0.5 mm and an axial resolution of ∼0.1 mm at a depth of up to 11 mm. Its imaging ability is also tested in a behaving rat, and the results indicate that wPAI is able to image blood vessels at a depth of up to 5 mm with intact scalp and skull. With its noninvasive, deep penetration, and functional imaging ability in behaving animals, wPAI can be used for behavior, cognition, and preclinical brain disease studies. PMID:26777064

  3. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines.

    PubMed

    Choi, Sujean; Disilvio, Briana; Fernstrom, Madelyn H; Fernstrom, John D

    2013-11-01

    Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.

  4. NO-Tryptophan: A New Small Molecule Located in the Rat Brain

    PubMed Central

    Mangas, A.; Yajeya, J.; González, N.; Duleu, S.; Geffard, M.; Coveñas, R.

    2016-01-01

    A highly specific monoclonal antibody directed against nitric oxide-tryptophan (NO-W) with good affinity (10-9 M) and specificity was developed. In the rat brain, using an indirect immunoperoxidase technique, cell bodies containing NO-W were exclusively found in the intermediate and dorsal parts of the lateral septal nucleus. No immunoreactive fibres were found in the rat brain. This work reports the first visualization and the morphological characteristics of cell bodies containing NO-W in the mammalian brain. The restricted distribution of NO-W in the rat brain suggests that this molecule could be involved in specific physiological mechanisms. PMID:27734994

  5. [Effects of total saponins of semen ziziphi Spinosae on brain damages and brain biochemical parameters under cerebral ischemia of rats].

    PubMed

    Bai, X; Huang, Z; Mo, Z; Pan, H; Ding, H

    1996-02-01

    Total saponins of Semen Ziziphi Spinosae (ZS) can reduce the contents of water and MDA in ischemic rat's brain tissues, elevate the activity of SOD, CK and LDH, cut down the content of lactate and alleviate the damages of nerve cells in brain. The study shows that ZS possesses protective effects on cerebral ischemic injuries. PMID:8758767

  6. Brain polyphosphoinositide metabolism during focal ischemia in rat cortex

    SciTech Connect

    Lin, T.N.; Liu, T.H.; Xu, J.; Hsu, C.Y.; Sun, G.Y. )

    1991-04-01

    Using a rat model of stroke, we examined the effects of focal cerebral ischemia on the metabolism of polyphosphoinositides by injecting {sup 32}Pi into both the left and right cortices. After equilibration of the label for 2-3 hours, ischemia induced a significant decrease (p less than 0.001) in the concentrations of labeled phosphatidyl 4,5-bisphosphates (66-78%) and phosphatidylinositol 4-phosphate (64-67%) in the right middle cerebral artery cortex of four rats. The phospholipid labeling pattern in the left middle cerebral artery cortex, which sustained only mild ischemia and no permanent tissue damage, was not different from that of two sham-operated controls. However, when {sup 32}Pi was injected 1 hour after the ischemic insult, there was a significant decrease (p less than 0.01) in the incorporation of label into the phospholipids in both cortices of four ischemic rats compared with four sham-operated controls. Furthermore, differences in the phospholipid labeling pattern were observed in the left cortex compared with the sham-operated controls. The change in labeling pattern was attributed to the partial reduction in blood flow following ligation of the common carotid arteries. We provide a sensitive procedure for probing the effects of focal cerebral ischemia on the polyphosphoinositide signaling pathway in the brain, which may play an important role in the pathogenesis of tissue injury.

  7. Effect of exposure to diazinon on adult rat's brain.

    PubMed

    Rashedinia, Marzieh; Hosseinzadeh, Hossein; Imenshahidi, Mohsen; Lari, Parisa; Razavi, Bibi Marjan; Abnous, Khalil

    2016-04-01

    Diazinon (DZN), a commonly used agricultural organophosphate insecticide, is one of the major concerns for human health. This study was planned to investigate neurotoxic effects of subacute exposure to DZN in adult male Wistar rats. Animals received corn oil as control and 15 and 30 mg/kg DZN orally by gastric gavage for 4 weeks. The cerebrum malondialdehyde and glutathione (GSH) contents were assessed as biomarkers of lipid peroxidation and nonenzyme antioxidants, respectively. Moreover, activated forms of caspase 3, -9, and Bax/Bcl-2 ratios were evaluated as key apoptotic proteins. Results of this study suggested that chronic administration of DZN did not change lipid peroxidation and GSH levels significantly in comparison with control. Also, the active forms of caspase 3 and caspase 9 were not significantly altered in DZN-treated rat groups. Moreover, no significant changes were observed in Bax and Bcl-2 ratios. This study indicated that generation of reactive oxygen species was probably modulated by intracellular antioxidant system. In conclusion, subacute oral administration of DZN did not alter lipid peroxidation. Moreover, apoptosis induction was not observed in rat brain.

  8. Reversal of impaired wound healing in irradiated rats by platelet-derived growth factor-BB

    SciTech Connect

    Mustoe, T.A.; Purdy, J.; Gramates, P.; Deuel, T.F.; Thomason, A.; Pierce, G.F. )

    1989-10-01

    This study examined the potential influence of platelet-derived growth factor-BB homodimers (PDGF-BB) on surgical incisions in irradiated animals with depressed wound healing. Rats were irradiated with either 800 rads total body or 2,500 rads surface irradiation. Parallel dorsal skin incisions were made 2 days later, and PDGF-BB was applied topically a single time to one of two incisions. In total body-irradiated rats, bone marrow-derived elements were severely depressed, wound macrophages were virtually eliminated, and PDGF-BB treatment was ineffective. However, in surface-irradiated rats, PDGF-BB treatment recruited macrophages into wounds and partially reversed impaired healing on day 7 (p less than 0.005) and day 12 (p less than 0.001). PDGF-BB-treated wounds were 50 percent stronger than the paired control wounds. The results suggest PDGF requires bone marrow-derived cells, likely wound macrophages, for activity and that it may be useful as a topical agent in postirradiation surgical incisions.

  9. Effects of prenatal X-irradiation on postnatal testicular development and function in the Wistar rat: development/teratology/behavior/radiation

    SciTech Connect

    Jensh, R.P.; Brent, R.L.

    1988-11-01

    It is evident that significant permanent tissue hypoplasia can be produced following radiation exposure late in fetal development. Because two organs, brain and testes, are developmentally and functionally interrelated, it was of interest to determine whether fetal testicular hypoplasia was a primary or a secondary effect of fetal brain irradiation. Twenty-four pregnant Wistar strain rats were randomly assigned to one of four groups, and a laparotomy was performed on day 18 of gestation. The fetuses received sham irradiation, whole body irradiation, or only head/thorax or pelvic body irradiation at a dosage level of 1.5 Gy. Mothers were allowed to deliver and raise their offspring until postnatal day 30, when the offspring were weaned. At 60 days of age, 74 male offspring were allowed to mate with colony control females of similar age until successful insemination or until the males reached 90 days of age, when they were killed. Testes were weighed and processed for histologic examination. Direct radiation of testes, due to whole body or pelvic exposure, resulted in testicular growth retardation and significantly reduced spermatogenesis. Breeding activity of the males and the percent of positive inseminations were also slightly reduced. However, a significant percentage of male offspring receiving direct testicular radiation did produce offspring. Head/thorax-only irradiation did not adversely affect testicular growth or spermatogenesis. Therefore, the use of histologic analysis as the sole determinant of infertility may be misleading. This study indicates that testicular growth retardation and an increased infertility rate result from direct prenatal exposure of rat testes to X-radiation and are not necessarily mediated via X-irradiation effects on the central nervous system.

  10. Heatstroke Effect on Brain Heme Oxygenase-1 in Rats

    PubMed Central

    Wen, Ya-Ting; Liu, Tsung-Ta; Lin, Yuh-Feng; Chen, Chun-Chi; Kung, Woon-Man; Huang, Chi-Chang; Lin, Tien-Jen; Wang, Yuan-Hung; Wei, Li

    2015-01-01

    Exposure to high environmental temperature leading to increased core body temperature above 40°C and central nervous system abnormalities such as convulsions, delirium, or coma is defined as heat stroke. Studies in humans and animals indicate that the heat shock responses of the host contribute to multiple organ injury and death during heat stroke. Heme oxygenase-1 (HO-1)—a stress-responsive enzyme that catabolizes heme into iron, carbon monoxide, and biliverdin—has an important role in the neuroprotective mechanism against ischemic stroke. Here, we investigated the role of endogenous HO-1 in heat-induced brain damage in rats. RT-PCR results revealed that levels of HO-1 mRNA peaked at 0 h after heat exposure and immunoblot analysis revealed that the maximal protein expression occurred at 1 h post-heat exposure. Subsequently, we detected the HO-1 expression in the cortical brain cells and revealed the neuronal cell morphology. In conclusion, HO-1 is a potent protective molecule against heat-induced brain damage. Manipulation of HO-1 may provide a potential therapeutic approach for heat-related diseases. PMID:26392811

  11. Kappa opioid receptors stimulate phosphoinositide turnover in rat brain

    SciTech Connect

    Periyasamy, S.; Hoss, W. )

    1990-01-01

    The effects of various subtype-selective opioid agonists and antagonists on the phosphoinositide (PI) turnover response were investigated in the rat brain. The {kappa}-agonists U-50,488H and ketocyclazocine produced a concentration-dependent increase in the accumulation of IP's in hippocampal slices. The other {kappa}-agonists Dynorphin-A (1-13) amide, and its protected analog D(Ala){sup 2}-dynorphin-A (1-13) amide also produced a significant increase in the formation of ({sup 3}H)-IP's, whereas the {mu}-selective agonists (D-Ala{sup 2}-N-Me-Phe{sup 4}-Gly{sup 5}-ol)-enkephalin and morphine and the {delta}-selective agonist (D-Pen{sup 2,5})-enkephalin were ineffective. The increase in IP's formation elicited by U-50,488H was partially antagonized by naloxone and more completely antagonized by the {kappa}-selective antagonists nor-binaltorphimine and MR 2266. The formation of IP's induced by U-50,488H varies with the regions of the brain used, being highest in hippocampus and amygdala, and lowest in striatum and pons-medullar. The results indicate that brain {kappa}- but neither {mu}- nor {delta}- receptors are coupled to the PI turnover response.

  12. Heatstroke Effect on Brain Heme Oxygenase-1 in Rats.

    PubMed

    Wen, Ya-Ting; Liu, Tsung-Ta; Lin, Yuh-Feng; Chen, Chun-Chi; Kung, Woon-Man; Huang, Chi-Chang; Lin, Tien-Jen; Wang, Yuan-Hung; Wei, Li

    2015-01-01

    Exposure to high environmental temperature leading to increased core body temperature above 40°C and central nervous system abnormalities such as convulsions, delirium, or coma is defined as heat stroke. Studies in humans and animals indicate that the heat shock responses of the host contribute to multiple organ injury and death during heat stroke. Heme oxygenase-1 (HO-1)-a stress-responsive enzyme that catabolizes heme into iron, carbon monoxide, and biliverdin-has an important role in the neuroprotective mechanism against ischemic stroke. Here, we investigated the role of endogenous HO-1 in heat-induced brain damage in rats. RT-PCR results revealed that levels of HO-1 mRNA peaked at 0 h after heat exposure and immunoblot analysis revealed that the maximal protein expression occurred at 1 h post-heat exposure. Subsequently, we detected the HO-1 expression in the cortical brain cells and revealed the neuronal cell morphology. In conclusion, HO-1 is a potent protective molecule against heat-induced brain damage. Manipulation of HO-1 may provide a potential therapeutic approach for heat-related diseases. PMID:26392811

  13. Neurotoxicity of Silver Nanoparticles in Rat Brain After Intragastric Exposure.

    PubMed

    Xu, Liming; Shao, Anliang; Zhao, Yanhong; Wang, Zhijie; Zhang, Cuiping; Sun, Yilin; Deng, Jie; Chou, Laisheng Lee

    2015-06-01

    It is known that the biological half-life of silver in the central nervous system is longer than in other organs. However, the potential toxicity of silver nanoparticles (NPs) on brain tissue and the underlying mechanism(s) of action are not well understood. In this study, neurotoxicity of silver NPs was examined in rat after intragastric administration. After a two-week exposure to low-dose (1 mg/kg, body weight) or high-dose (10 mg/kg) silver NPs, the pathological and ultrastructural changes in brain tissue were evaluated with H&E staining and transmission electron microscopy. The mRNA expression levels of key tight junction proteins of the blood-brain barrier (BBB) were analyzed by real-time RT-PCR, and several inflammatory factors were assessed in blood using ELISA assay. We observed neuron shrinkage, cytoplasmic or foot swelling of astrocytes, and extra-vascular lymphocytes in silver NP exposure groups. The cadherin 1 (2(-ΔΔCt): 1.45-fold/control) and Claudin-1 (2(-ΔΔCt): 2.77-fold/control) were slightly increase in mRNA expression levels, and IL-4 significantly increased after silver NP exposure. It was suggest that silver NP can induce neuronal degeneration and astrocyte swelling, even with a low-dose (1 mg/kg) oral exposure. One potential mechanism for the effects of silver NPs to the nervous cells is involved in inflammatory effects.

  14. Effect of supplemental vitamin A on colon anastomotic healing in rats given preoperative irradiation

    SciTech Connect

    Winsey, K.; Simon, R.J.; Levenson, S.M.; Seifter, E.; Demetriou, A.A.

    1987-02-01

    We studied the effect of dietary supplementation with vitamin A on the healing of colon anastomoses in irradiated bowel. Rats were divided into two groups. Those in the first group were fed a standard chow diet and those in the second group were fed the same diet supplemented with 150 IU vitamin A/g of chow. The rats were maintained on their respective diets throughout the experiment. After 7 days, half the rats in each group underwent abdominal irradiation (200 rads). Seven days later, all of the rats underwent distal colon division and anastomosis under pentobarbital anesthesia. All rats were killed 7 days postoperatively, the colons excised, and bursting strength and hydroxyproline determinations performed on both the anastomotic segment and a normal proximal segment of adjacent colon. There was a significant decrease in the bursting strength at the colon anastomosis (p less than 0.02) and in the collagen content (p less than 0.02) after preoperative irradiation. This effect was mitigated by dietary vitamin A supplementation.

  15. In vivo deep brain imaging of rats using oral-cavity illuminated photoacoustic computed tomography

    NASA Astrophysics Data System (ADS)

    Lin, Li; Xia, Jun; Wong, Terence T. W.; Zhang, Ruiying; Wang, Lihong V.

    2015-03-01

    We demonstrate, by means of internal light delivery, photoacoustic imaging of the deep brain of rats in vivo. With fiber illumination via the oral cavity, we delivered light directly into the bottom of the brain, much more than can be delivered by external illumination. The study was performed using a photoacoustic computed tomography (PACT) system equipped with a 512-element full-ring transducer array, providing a full two-dimensional view aperture. Using internal illumination, the PACT system provided clear cross sectional photoacoustic images from the palate to the middle brain of live rats, revealing deep brain structures such as the hypothalamus, brain stem, and cerebral medulla.

  16. Environmental enrichment to alleviate maze performance deficits in rats with microcephaly induced by X-irradiation

    SciTech Connect

    Shibagaki, M.; Seo, M.; Asano, T.; Kiyono, S. . Inst. for Developmental Research)

    1981-11-01

    Pregnant rats received 150 R of X-irradiation on day 17 of gestation. The male offspring were reared under environmentally enriched (EC), standard colony (SC) or impoverished conditions (IC) for 30 days after weaning. Then the Hebb-Williams maze test was carried out. The effects of X-irradiation and environment were both significant in initial, repetitive and total error scores and running time. Further analysis revealed that both EC-SC and EC-IC differences in initial, repetitive and total error scores were significant in X-irradiated animals, whereas only the EC-IC difference in initial and total error scores was significant in sham-irradiated control animals. Total protein, protein/g cortex, total benzodiazepine and muscarine cholinergic receptor bindings, and muscarinic cholinergic receptor binding/mg protein in the cerebral cortex were decreased in X-irradiated groups, compared to controls, but the effect of environment was not significant in these items. The results confirmed that environmental enrichment is a useful tool to alleviate the learning decrements in prenatally X-irradiated microcephalic rats.

  17. Effect of X-irradiation on the stomach of the rat

    SciTech Connect

    Breiter, N.; Trott, K.R.; Sassy, T. )

    1989-10-01

    A model for localized 300 kV X-irradiation of the rat stomach was developed. After irradiation with single doses, three distinct gastric disorders were observed which occurred at different latency times. Acute death 2-3 weeks after irradiation was caused by an erosive and ulcerative gastritis and occurred in all animals given 28.5 Gy without diet, in 17% of the animals given 28.5 Gy plus diet, and in 13% of the animals given 23 Gy. Subacute to chronic fatal disorders 4 weeks to 7 months after irradiation were seen as stomach dilatation and gastroparesis, associated with the replacement of the normal gastric mucosa by a hyperkeratinized multilayered squamous epithelium. These disorders occurred in 40-100% of the animals after doses between 16 Gy and 28.5 Gy (+diet). An ED 50 value of 19.2 Gy (16.5-21.2 Gy, 95% confidence interval) was calculated for this gastroparesis. Late gastric obstruction exceeding 7 months after irradiation was seen in the rats because of profound changes in the gastric wall in 13-18% of the animals after doses between 23 Gy and 14 Gy. In animals surviving these three periods, an atrophic mucosa and intestinal metaplasia developed. From functional and morphohistological studies, it can be concluded that there are differences in the pathogenesis of the fatal radiation damage for each of these periods after irradiation.

  18. Effects of laser irradiation on immature olfactory neuroepithelial explants from the rat

    SciTech Connect

    Mester, A.F.; Snow, J.B. Jr.

    1988-07-01

    The photobiological effect of low-output laser irradiation on the maturation and regeneration of immature olfactory bipolar receptor cells of the rat was studied. The maturation and regeneration of the receptor cells of rat fetuses were quantified in neuroepithelial explants with morphometric analysis. The number of explants with outgrowth and the number and length of neuritic outgrowths were determined on a regular basis for 12 days. Explants in the experimental group were irradiated with a helium-neon laser using different incident energy densities (IED). Explants in the fluorescent light control group were exposed to fluorescent light for the same periods of time as those in the experimental group were exposed to laser irradiation. Explants in another control group were not exposed to laser or fluorescent light irradiation. The IED of 0.5 J/cm2 laser irradiation has been found to increase significantly the number of explants with outgrowth and the number and length of the outgrowths. Other laser IEDs or fluorescent light irradiation did not influence maturation or regeneration.

  19. Reduction in brain immunoreactive corticotropin-releasing factor (CRF) in spontaneously hypertensive rats

    SciTech Connect

    Hashimoto, K.; Hattori, T.; Murakami, K.; Suemaru, S.; Kawada, Y.; Kageyama, J.; Ota, Z.

    1985-02-18

    The brain CRF concentration of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was examined by rat CRF radioimmunoassay. Anti-CRF serum was developed by immunizing rabbits with synthetic rat CRF. Synthetic rat CRF was also used as tracer and standard. The displacement of /sup 125/I-rat CRF by serially diluted extracts of male Wistar rats hypothalamus, thalamus, midbrain, pons, medulla oblongata, cerebral cortex, cerebellum and neurointermediate lobe was parallel to the displacement of synthetic rat CRF. In both WKY and SHR the highest levels of CRF immunoreactivity were shown by the hypothalamus and neurointermediate lobe, and considerable CRF immunoreactivity was also detected in other brain regions. The CRF immunoreactivity in the hypothalamus, neurointermediate lobe, midbrain, medulla oblongata and cerebral cortex was significantly reduced in SHR and it may suggest that CRF abnormality may be implicated in the reported abnormalities in the pituitary-adrenal axis, autonomic response and behavior of SHR.

  20. Management of solitary metastasis to the brain: the role of elective brain irradiation following complete surgical resection. [/sup 60/Co; x-rays

    SciTech Connect

    Dosoretz, D.E.; Blitzer, P.H.; Russell, A.H.; Wang, C.C.

    1980-12-01

    We examined the records of 33 patients who presented with the clinico-radiological diagnosis of solitary brain metastasis and no other evidence of tumor dissemination. Length of survival of patients and patterns of treatment failure were analyzed according to the treatment modalities that were used. Both groups were comparable regarding major parameters that affect response and survival in patients with brain metastasis. There did not appear to be any significant advantage to the use of irradiation following excision, at least at the doses employed in this study. We advocate the use of higher doses of irradiation in any curative attempt following total excision of a solitary brain metastasis.

  1. Voltammetric detection of 5-hydroxytryptamine release in the rat brain.

    PubMed

    Hashemi, Parastoo; Dankoski, Elyse C; Petrovic, Jelena; Keithley, Richard B; Wightman, R M

    2009-11-15

    5-Hydroxytryptamine (5-HT) is an important molecule in the brain that is implicated in mood and emotional processes. In vivo, its dynamic release and uptake kinetics are poorly understood due to a lack of analytical techniques for its rapid measurement. Whereas fast-scan cyclic voltammetry with carbon fiber microelectrodes is used frequently to monitor subsecond dopamine release in freely moving and anesthetized rats, the electrooxidation of 5-HT forms products that quickly polymerize and irreversibly coat the carbon electrode surface. Previously described modifications of the electrochemical waveform allow stable and sensitive 5-HT measurements in mammalian tissue slice preparations and in the brain of fruit fly larvae. For in vivo applications in mammals, however, the problem of electrode deterioration persists. We identify the root of this problem to be fouling by extracellular metabolites such as 5-hydoxyindole acetic acid (5-HIAA), which is present in 200-1000 times the concentration of 5-HT and displays similar electrochemical properties, including filming of the electrode surface. To impede access of the 5-HIAA to the electrode surface, a thin layer of Nafion, a cation exchange polymer, has been electrodeposited onto cylindrical carbon-fiber microelectrodes. The presence of the Nafion film was confirmed with environmental scanning electron microscopy and was demonstrated by the diminution of the voltammetric signals for 5-HIAA as well as other common anionic species. The modified microelectrodes also display increased sensitivity to 5-HT, yielding a characteristic cyclic voltammogram that is easily distinguishable from other common electroactive brain species. The thickness of the Nafion coating and a diffusion coefficient (D) in the film for 5-HT were evaluated by measuring permeation through Nafion. In vivo, we used physiological, anatomical, and pharmacological evidence to validate the signal as 5-HT. Using Nafion-modified microelectrodes, we present the

  2. Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway.

    PubMed

    Ji, Jian-feng; Ji, Sheng-jun; Sun, Rui; Li, Kun; Zhang, Yuan; Zhang, Li-yuan; Tian, Ye

    2014-01-10

    Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating the effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male Sprague-Dawley rats received a single dose of 20Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNF-pCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNF-pCREB signaling in non-irradiation group. These results suggest that forced running exercise offers a potentially effective treatment for radiation-induced cognitive deficits.

  3. Effects of low intensity laser acupoint irradiation on inhibiting islet beta-cell apoptosis in rats with type 2 diabetes

    NASA Astrophysics Data System (ADS)

    Xiong, Guoxin; Xiong, Leilei; Li, Xinzhong

    2016-09-01

    To investigate the effects of low intensity semiconductor laser acupoint irradiation on inhibiting islet beta-cell apoptosis in rats with type 2 diabetes, a method using a high-fat diet and low-dose intraperitoneal injections of streptozotocin established a type 2 diabetes mellitus rat model. Model rats were randomly divided into a laser acupoint irradiation group, rosiglitazone control group, and placebo group; each group had 10 rats. In addition, 10 normal male rats were selected for the normal control group. The Housanli, Neiting and Yishu acupoints of the rats in the laser acupoint irradiation group were irradiated with a 10 mW semiconductor laser; each point was irradiated for 15 min, once every 2 d over 28 d, for a total of 14 episodes of irradiation. The rosiglitazone group rats were given rosiglitazone (0.2 mg kg-1) intragastrically; the placebo group rats were given 0.9% brine (0.2 mg kg-1) intragastrically, once daily, for four consecutive weeks. The change of fasting blood glucose was determined before and after each treatment. The islet beta-cell apoptosis was determined. The islet beta-cell apoptosis rates of the laser acupoint irradiation group and the rosiglitazone group were significantly lower than the rate of the placebo group. Even though the rate was lower in the laser acupoint irradiation group than in the rosiglitazone group, there was no significant difference between them. It is shown that acupoint irradiation with a semiconductor laser can effectively inhibit islet beta-cell apoptosis in rats with type 2 diabetes.

  4. Effects of low intensity laser acupoint irradiation on inhibiting islet beta-cell apoptosis in rats with type 2 diabetes

    NASA Astrophysics Data System (ADS)

    Xiong, Guoxin; Xiong, Leilei; Li, Xinzhong

    2016-09-01

    To investigate the effects of low intensity semiconductor laser acupoint irradiation on inhibiting islet beta-cell apoptosis in rats with type 2 diabetes, a method using a high-fat diet and low-dose intraperitoneal injections of streptozotocin established a type 2 diabetes mellitus rat model. Model rats were randomly divided into a laser acupoint irradiation group, rosiglitazone control group, and placebo group; each group had 10 rats. In addition, 10 normal male rats were selected for the normal control group. The Housanli, Neiting and Yishu acupoints of the rats in the laser acupoint irradiation group were irradiated with a 10 mW semiconductor laser; each point was irradiated for 15 min, once every 2 d over 28 d, for a total of 14 episodes of irradiation. The rosiglitazone group rats were given rosiglitazone (0.2 mg kg‑1) intragastrically; the placebo group rats were given 0.9% brine (0.2 mg kg‑1) intragastrically, once daily, for four consecutive weeks. The change of fasting blood glucose was determined before and after each treatment. The islet beta-cell apoptosis was determined. The islet beta-cell apoptosis rates of the laser acupoint irradiation group and the rosiglitazone group were significantly lower than the rate of the placebo group. Even though the rate was lower in the laser acupoint irradiation group than in the rosiglitazone group, there was no significant difference between them. It is shown that acupoint irradiation with a semiconductor laser can effectively inhibit islet beta-cell apoptosis in rats with type 2 diabetes.

  5. Synchrotron X ray induced axonal transections in the brain of rats assessed by high-field diffusion tensor imaging tractography.

    PubMed

    Serduc, Raphaël; Bouchet, Audrey; Pouyatos, Benoît; Renaud, Luc; Bräuer-Krisch, Elke; Le Duc, Géraldine; Laissue, Jean A; Bartzsch, Stefan; Coquery, Nicolas; van de Looij, Yohan

    2014-01-01

    Since approximately two thirds of epileptic patients are non-eligible for surgery, local axonal fiber transections might be of particular interest for them. Micrometer to millimeter wide synchrotron-generated X-ray beamlets produced by spatial fractionation of the main beam could generate such fiber disruptions non-invasively. The aim of this work was to optimize irradiation parameters for the induction of fiber transections in the rat brain white matter by exposure to such beamlets. For this purpose, we irradiated cortex and external capsule of normal rats in the antero-posterior direction with a 4 mm×4 mm array of 25 to 1000 µm wide beamlets and entrance doses of 150 Gy to 500 Gy. Axonal fiber responses were assessed with diffusion tensor imaging and fiber tractography; myelin fibers were examined histopathologically. Our study suggests that high radiation doses (500 Gy) are required to interrupt axons and myelin sheaths. However, a radiation dose of 500 Gy delivered by wide minibeams (1000 µm) induced macroscopic brain damage, depicted by a massive loss of matter in fiber tractography maps. With the same radiation dose, the damage induced by thinner microbeams (50 to 100 µm) was limited to their paths. No macroscopic necrosis was observed in the irradiated target while overt transections of myelin were detected histopathologically. Diffusivity values were found to be significantly reduced. A radiation dose ≤ 500 Gy associated with a beamlet size of < 50 µm did not cause visible transections, neither on diffusion maps nor on sections stained for myelin. We conclude that a peak dose of 500 Gy combined with a microbeam width of 100 µm optimally induced axonal transections in the white matter of the brain.

  6. Irradiated Volume as a Predictor of Brain Radionecrosis After Linear Accelerator Stereotactic Radiosurgery

    SciTech Connect

    Blonigen, Brian J.; Steinmetz, Ryan D.; Levin, Linda

    2010-07-15

    Purpose: To investigate the correlation between volume of brain irradiated by stereotactic radiosurgery (SRS) and the incidence of symptomatic and asymptomatic brain radionecrosis (RN). Methods and Materials: A retrospective analysis was performed of patients treated with single-fraction SRS for brain metastases at our institution. Patients with at least 6-month imaging follow-up were included and diagnosed with RN according to a combination of criteria, including appearance on serial imaging and histology. Univariate and multivariate analyses were performed to determine the predictive value of multiple variables, including volume of brain receiving a specific dose (V8 Gy-V18 Gy). Results: Sixty-three patients were reviewed, with a total of 173 lesions. Most patients (63%) had received previous whole-brain irradiation. Mean prescribed SRS dose was 18 Gy. Symptomatic RN was observed in 10% and asymptomatic RN in 4% of lesions treated. Multivariate regression analysis showed V8 Gy-V16 Gy to be most predictive of symptomatic RN (p < 0.0001). Threshold volumes for significant rise in RN rates occurred between the 75th and 90th percentiles, with a midpoint volume of 10.45 cm{sup 3} for V10 Gy and 7.85 cm{sup 3} for V12 Gy. Conclusions: Analysis of patient and treatment variables revealed V8 Gy-V16 Gy to be the best predictors for RN using linear accelerator-based single-fraction SRS for brain metastases. We propose that patients with V10 Gy >10.5 cm{sup 3} or V12 Gy >7.9 cm{sup 3} be considered for hypofractionated rather than single-fraction treatment, to minimize the risk of symptomatic RN.

  7. [Effect of space flight factors simulated in ground-based experiments on the behavior, discriminant learning, and exchange of monoamines in different brain structures of rats].

    PubMed

    Shtemberg, A S; Lebedeva-Georgievskaia, K V; Matveeva, M I; Kudrin, V S; Narkevich, V B; Klodt, P M; Bazian, A S

    2014-01-01

    Experimental treatment (long-term fractionated γ-irradiation, antiorthostatic hypodynamia, and the combination of these factors) simulating the effect of space flight in ground-based experiments rapidly restored the motor and orienting-investigative activity of animals (rats) in "open-field" tests. The study of the dynamics of discriminant learning of rats of experimental groups did not show significant differences from the control animals. It was found that the minor effect of these factors on the cognitive performance of animals correlated with slight changes in the concentration ofmonoamines in the brain structures responsible for the cognitive, emotional, and motivational functions.

  8. The PPARalpha Agonist Fenofibrate Preserves Hippocampal Neurogenesis and Inhibits Microglial Activation After Whole-Brain Irradiation

    SciTech Connect

    Ramanan, Sriram; Kooshki, Mitra; Zhao Weiling; Hsu, F.-C.; Riddle, David R.; Robbins, Mike E.

    2009-11-01

    Purpose: Whole-brain irradiation (WBI) leads to cognitive impairment months to years after radiation. Numerous studies suggest that decreased hippocampal neurogenesis and microglial activation are involved in the pathogenesis of WBI-induced brain injury. The goal of this study was to investigate whether administration of the peroxisomal proliferator-activated receptor (PPAR) alpha agonist fenofibrate would prevent the detrimental effect of WBI on hippocampal neurogenesis. Methods and Materials: For this study, 129S1/SvImJ wild-type and PPARalpha knockout mice that were fed either regular or 0.2% wt/wt fenofibrate-containing chow received either sham irradiation or WBI (10-Gy single dose of {sup 137}Cs gamma-rays). Mice were injected intraperitoneally with bromodeoxyuridine to label the surviving cells at 1 month after WBI, and the newborn neurons were counted at 2 months after WBI by use of bromodeoxyuridine/neuronal nuclei double immunofluorescence. Proliferation in the subgranular zone and microglial activation were measured at 1 week and 2 months after WBI by use of Ki-67 and CD68 immunohistochemistry, respectively. Results: Whole-brain irradiation led to a significant decrease in the number of newborn hippocampal neurons 2 months after it was performed. Fenofibrate prevented this decrease by promoting the survival of newborn cells in the dentate gyrus. In addition, fenofibrate treatment was associated with decreased microglial activation in the dentate gyrus after WBI. The neuroprotective effects of fenofibrate were abolished in the knockout mice, indicating a PPARalpha-dependent mechanism or mechanisms. Conclusions: These data highlight a novel role for PPARalpha ligands in improving neurogenesis after WBI and offer the promise of improving the quality of life for brain cancer patients receiving radiotherapy.

  9. Sex Differences in Serotonin 1 Receptor Binding in Rat Brain

    NASA Astrophysics Data System (ADS)

    Fischette, Christine T.; Biegon, Anat; McEwen, Bruce S.

    1983-10-01

    Male and female rats exhibit sex differences in binding by serotonin 1 receptors in discrete areas of the brain, some of which have been implicated in the control of ovulation and of gonadotropin release. The sex-specific changes in binding, which occur in response to the same hormonal (estrogenic) stimulus, are due to changes in the number of binding sites. Castration alone also affects the number of binding sites in certain areas. The results lead to the conclusion that peripheral hormones modulate binding by serotonin 1 receptors. The status of the serotonin receptor system may affect the reproductive capacity of an organism and may be related to sex-linked emotional disturbances in humans.

  10. Estimating The Sodium Ion Diffusion Coefficient in Rat Brain

    NASA Astrophysics Data System (ADS)

    Goodman, James A.; Bretthorst, G. Larry; Kroenke, Christopher D.; Ackerman, Joseph J. H.; Neil, Jeffrey J.

    2004-04-01

    Quantifying sodium ion diffusion in the extra- and intracellular compartments will provide mechanistic insight into the as yet unexplained marked decrease in water diffusion resulting from central nervous system injury. As a first step, the apparent diffusion coefficient (ADC) of bulk brain Na+ has been determined in vivo in rat. A surface coil transmit/receive adiabatic-pulse scheme is used to provide two dimensions of volume localization, thus minimizing echo time. The third dimension is determined by slice selection gradients on the axis perpendicular to the coil plane. Signal decay in the presence of diffusion sensitizing pulsed field gradients was modeled by Bayesian Probability Theory. Preliminary findings indicate a bulk Na+ ADC of (1.16 ± .07) × 10-3 mm2/s.

  11. Label-free dopamine imaging in live rat brain slices.

    PubMed

    Sarkar, Bidyut; Banerjee, Arkarup; Das, Anand Kant; Nag, Suman; Kaushalya, Sanjeev Kumar; Tripathy, Umakanta; Shameem, Mohammad; Shukla, Shubha; Maiti, Sudipta

    2014-05-21

    Dopaminergic neurotransmission has been investigated extensively, yet direct optical probing of dopamine has not been possible in live cells. Here we image intracellular dopamine with sub-micrometer three-dimensional resolution by harnessing its intrinsic mid-ultraviolet (UV) autofluorescence. Two-photon excitation with visible light (540 nm) in conjunction with a non-epifluorescent detection scheme is used to circumvent the UV toxicity and the UV transmission problems. The method is established by imaging dopamine in a dopaminergic cell line and in control cells (glia), and is validated by mass spectrometry. We further show that individual dopamine vesicles/vesicular clusters can be imaged in cultured rat brain slices, thereby providing a direct visualization of the intracellular events preceding dopamine release induced by depolarization or amphetamine exposure. Our technique opens up a previously inaccessible mid-ultraviolet spectral regime (excitation ~270 nm, emission < 320 nm) for label-free imaging of native molecules in live tissue.

  12. Label-Free Dopamine Imaging in Live Rat Brain Slices

    PubMed Central

    2014-01-01

    Dopaminergic neurotransmission has been investigated extensively, yet direct optical probing of dopamine has not been possible in live cells. Here we image intracellular dopamine with sub-micrometer three-dimensional resolution by harnessing its intrinsic mid-ultraviolet (UV) autofluorescence. Two-photon excitation with visible light (540 nm) in conjunction with a non-epifluorescent detection scheme is used to circumvent the UV toxicity and the UV transmission problems. The method is established by imaging dopamine in a dopaminergic cell line and in control cells (glia), and is validated by mass spectrometry. We further show that individual dopamine vesicles/vesicular clusters can be imaged in cultured rat brain slices, thereby providing a direct visualization of the intracellular events preceding dopamine release induced by depolarization or amphetamine exposure. Our technique opens up a previously inaccessible mid-ultraviolet spectral regime (excitation ∼ 270 nm, emission < 320 nm) for label-free imaging of native molecules in live tissue. PMID:24661118

  13. Cholecystokinin octapeptide-like immunoreactivity: histochemical localization in rat brain.

    PubMed Central

    Innis, R B; Corrêa, F M; Uhl, G R; Schneider, B; Snyder, S H

    1979-01-01

    Cholecystokinin octapeptide-like (CCK-OP-like) immunoreactivity was localized in the rat brain by using the indirect immunofluorescence method. Specificity in immunohistochemical studies was demonstrated by the virtual elimination of staining with either preimmune sera or sera preadsorbed with CCK-OP and by the achievement of similar fluorescent patterns with two different primary anti-CCK-OP sera. CCK-OP-like fluorescence was localized in neuronal cell bodies, fibers, and varicose terminals. The most dense collections of CCK-OP cells occurred in the periaqueductal gray and in the dorsomedial hypothalamus. Substantial numbers of cells and fibers also were present in the medial/dorsal and perirhinal cortex; more limited groups of cells were found in the pyramidal layer of the hippocampus and in the dorsal raphe. Images PMID:284371

  14. A rat model for the treatment of melanoma metastatic to the brain by means of neutron capture therapy

    SciTech Connect

    Matalka, K.Z.; Bailey, M.Q.; Barth, R.F.; Staubus, A.E.; Adams, D.M.; Soloway, A.H.; James, S.M.; Goodman, J.H. ); Coderre, J.A.; Fairchild, R.G. ); Rofstad, E.K. )

    1991-01-01

    Melanoma metastatic to the brain is a serious clinical problem for which there currently is no satisfactory treatment. Boron neutron capture therapy (BNCT) has been shown by Mishima et al. to be clinically effective in the treatment of cutaneous melanoma using {sup 10}B-enriched boronophenylalaine (BPA) as the capture agent. In the present pilot study we have observed a significant prolongation in survival time of nude rats bearing intracerebral implants of the human melanoma cell line MRA 27 following administration of BPA and neutron irradiation. These findings suggest therapeutic efficacy, but unequivocal proof depends upon confirmation in a more definitive experiment using large numbers of animals with both solitary and multiple implants of melanoma. If our preliminary results are confirmed, then this will lay the groundwork for a clinical study of BNCT for the treatment of melanoma metastatic to the brain. 7 refs., 2 figs., 2 tabs.

  15. Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain.

    PubMed

    Hansen, Fernanda; Pandolfo, Pablo; Galland, Fabiana; Torres, Felipe Vasconcelos; Dutra, Márcio Ferreira; Batassini, Cristiane; Guerra, Maria Cristina; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2016-10-01

    Diabetes is associated with loss of cognitive function and increased risk for Alzheimer's disease (AD). Advanced glycation end products (AGEs) are elevated in diabetes and AD and have been suggested to act as mediators of the cognitive decline observed in these pathologies. Methylglyoxal (MG) is an extremely reactive carbonyl compound that propagates glycation reactions and is, therefore, able to generate AGEs. Herein, we evaluated persistent behavioral and biochemical parameters to explore the hypothesis that elevated exogenous MG concentrations, induced by intracerebroventricular (ICV) infusion, lead to cognitive decline in Wistar rats. A high and sustained administration of MG (3μmol/μL; subdivided into 6days) was found to decrease the recognition index of rats, as evaluated by the object-recognition test. However, MG was unable to impair learning-memory processes, as shown by the habituation in the open field (OF) and Y-maze tasks. Moreover, a single high dose of MG induced persistent alterations in anxiety-related behavior, diminishing the anxiety-like parameters evaluated in the OF test. Importantly, MG did not alter locomotion behavior in the different tasks performed. Our biochemical findings support the hypothesis that MG induces persistent alterations in the hippocampus, but not in the cortex, related to glyoxalase 1 activity, AGEs content and glutamate uptake. Glial fibrillary acidic protein and S100B content, as well as S100B secretion (astroglial-related parameters of brain injury), were not altered by ICV MG administration. Taken together, our data suggest that MG interferes directly in brain function and that the time and the levels of exogenous MG determine the different features that can be seen in diabetic patients.

  16. Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain.

    PubMed

    Hansen, Fernanda; Pandolfo, Pablo; Galland, Fabiana; Torres, Felipe Vasconcelos; Dutra, Márcio Ferreira; Batassini, Cristiane; Guerra, Maria Cristina; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2016-10-01

    Diabetes is associated with loss of cognitive function and increased risk for Alzheimer's disease (AD). Advanced glycation end products (AGEs) are elevated in diabetes and AD and have been suggested to act as mediators of the cognitive decline observed in these pathologies. Methylglyoxal (MG) is an extremely reactive carbonyl compound that propagates glycation reactions and is, therefore, able to generate AGEs. Herein, we evaluated persistent behavioral and biochemical parameters to explore the hypothesis that elevated exogenous MG concentrations, induced by intracerebroventricular (ICV) infusion, lead to cognitive decline in Wistar rats. A high and sustained administration of MG (3μmol/μL; subdivided into 6days) was found to decrease the recognition index of rats, as evaluated by the object-recognition test. However, MG was unable to impair learning-memory processes, as shown by the habituation in the open field (OF) and Y-maze tasks. Moreover, a single high dose of MG induced persistent alterations in anxiety-related behavior, diminishing the anxiety-like parameters evaluated in the OF test. Importantly, MG did not alter locomotion behavior in the different tasks performed. Our biochemical findings support the hypothesis that MG induces persistent alterations in the hippocampus, but not in the cortex, related to glyoxalase 1 activity, AGEs content and glutamate uptake. Glial fibrillary acidic protein and S100B content, as well as S100B secretion (astroglial-related parameters of brain injury), were not altered by ICV MG administration. Taken together, our data suggest that MG interferes directly in brain function and that the time and the levels of exogenous MG determine the different features that can be seen in diabetic patients. PMID:27235733

  17. The expression of aquaporins 1 and 5 in rat lung after thoracic irradiation

    PubMed Central

    Sun, Cheng-Ying; Zhao, Yu-Xia; Zhong, Wen; Liu, Da-Wei; Chen, Yan-Zhi; Qin, Li-Li; Bai, Lu; Liu, Dan

    2014-01-01

    Radiation-induced lung toxicity (RILT), leading to radiation pneumonia or fibrosis, is a primary problem of radiation therapy. The pathogenesis of RILT remains unclear. In this study, we used a rat model of RILT to examine the expression of aquaporins (AQPs) after radiation injury. Sprague Dawley rats were given a single dose of 17 Gy (dose rate of 3.0 Gy/min) of X-irradiation to the thorax. Rats that survived acute pneumonitis (at 1–4 weeks) were evaluated weekly for the expression of AQP1 and AQP5 in the lung by immunohistochemical and reverse transcription polymerase chain reaction (RT-PCR) analyses. Immunohistochemical analysis showed that AQP1 protein was expressed in the capillary endothelium, and its level was significantly decreased after irradiation. AQP5 protein was expressed in the alveolar epithelium, and its level was increased between Days 7 and 14 after irradiation but decreased at Day 28, compared with the sham group. The RT-PCR results were consistent with the immunohistochemical analysis results. In summary, this study provides the first report of AQP1 and AQP5 expression in a model of radiation-induced pulmonary inflammation and edema. Decreased levels of AQP1 and AQP5 after irradiation suggest that these proteins play a role in the pathogenesis of RILT. PMID:24570172

  18. DNA double strand breaks in rat epidermis following irradiation with electrons

    SciTech Connect

    Shulman, K.

    1986-05-01

    Although radiation induced single strand breaks in rat epidermis are repaired fairly quickly (t-1/2 = 21 minutes), the fate of DNA double strand breaks in the same cells is unclear. Here we have attempted to measure dsb's in rat epidermis by neutral elution. The DNA of 28 day old CD rats was prelabeled with 6 I.P. injections at 2.0 uCi/g body weight of /sup 3/H-TdR. The dorsal skin was irradiated with a 0.8 MeV electron beam. The epidermis was removed by trypsinization at 4/sup 0/C and a single cell suspension was made. The cells were layered onto a polycarbonate filter, lysed, and eluted at pH 9.6. Doses of at least 6000 rads were needed to detect dsb's in vivo. Dsb's were still detectable in the epidermis 3 hours after irradiation. The amount of dsb's had returned to non-irradiated levels 8 hours after irradiation. 77 refs., 2 figs., 1 tab.

  19. Long-term, low-level microwave irradiation of rats.

    PubMed

    Chou, C K; Guy, A W; Kunz, L L; Johnson, R B; Crowley, J J; Krupp, J H

    1992-01-01

    Our goal was to investigate effects of long-term exposure to pulsed microwave radiation. The major emphasis was to expose a large sample of experimental animals throughout their lifetimes and to monitor them for effects on general health and longevity. An exposure facility was developed that enabled 200 rats to be maintained under specific-pathogen-free (SPF) conditions while housed individually in circularly-polarized waveguides. The exposure facility consisted of two rooms, each containing 50 active waveguides and 50 waveguides for sham (control) exposures. The experimental rats were exposed to 2,450-MHz pulsed microwaves at 800 pps with a 10-microseconds pulse width. The pulsed microwaves were square-wave modulated at 8-Hz. Whole body calorimetry, thermographic analysis, and power-meter analysis indicated that microwaves delivered at 0.144 W to each exposure waveguide resulted in an average specific absorption rate (SAR) that ranged from 0.4 W/kg for a 200-g rat to 0.15 W/kg for an 800-g rat. Two hundred male, Sprague-Dawley rats were assigned in equal numbers to radiation-exposure and sham-exposure conditions. Exposure began at 8 weeks of age and continued daily, 21.5 h/day, for 25 months. Animals were bled at regular intervals and blood samples were analyzed for serum chemistries, hematological values, protein electrophoretic patterns, thyroxine, and plasma corticosterone levels. In addition to daily measures of body mass, food and water consumption by all animals, O2 consumption and CO2 production were periodically measured in a sub-sample (N = 18) of each group. Activity was assessed in an open-field apparatus at regular intervals throughout the study. After 13 months, 10 rats from each group were euthanatized to test for immunological competence and to permit whole-body analysis, as well as gross and histopathological examinations. At the end of 25 months, the survivors (11 sham-exposed and 12 radiation-exposed rats) were euthanatized for similar analyses

  20. Multiple parallel memory systems in the brain of the rat.

    PubMed

    White, Norman M; McDonald, Robert J

    2002-03-01

    A theory of multiple parallel memory systems in the brain of the rat is described. Each system consists of a series of interconnected neural structures. The "central structures" of the three systems described are the hippocampus, the matrix compartment of the dorsal striatum (caudate-putamen), and the amygdala. Information, coded as neural signals, flows independently through each system. All systems have access to the same information from situations in which learning occurs, but each system is specialized to represent a different kind of relationship among the elements (stimulus events, responses, reinforcers) of the information that flows through it. The speed and accuracy with which a system forms a coherent representation of a learning situation depend on the correspondence between the specialization of the system and the relationship among the elements of the situation. The coherence of these stored representations determines the degree of control exerted by each system on behavior in the situation. Although they process information independently the systems interact in at least two ways: by simultaneous parallel influence on behavioral output and by directly influencing each other. These interactions can be cooperative (leading to similar behaviors) or competitive (leading to different behaviors). Experimental findings consistent with these ideas, mostly from experiments with rats, are reviewed.

  1. Ethylene glycol ethers induce oxidative stress in the rat brain.

    PubMed

    Pomierny, Bartosz; Krzyżanowska, Weronika; Smaga, Irena; Pomierny-Chamioło, Lucyna; Stankowicz, Piotr; Budziszewska, Bogusława

    2014-11-01

    Ethylene glycol ethers (EGEs) are components of many industrial and household products. Their hemolytic and gonadotoxic effects are relatively well known while their potential adverse effects on the central nervous system have not yet been clearly demonstrated. The aim of the present study was to examine the effects of 4-week administration of 2-buthoxyethanol (BE), 2-phenoxyethanol (PHE) and 2-ethoxyethanol (EE) on the total antioxidant capacity, activity of some antioxidant enzymes, such as the superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX) and glutathione reductase and lipid peroxidation in the frontal cortex and hippocampus in the rat. These studies showed that BE and PHE decreased the total antioxidant activity, SOD and GPX activity, while increased lipid peroxidation in the frontal cortex. Like in the frontal cortex, also in the hippocampus BE and PHE attenuated the total antioxidant activity, however, lipid peroxidation was increased only in animals which received BE while reduction in GPX activity was present in rats administered PHE. The obtained data indicated that 4-week administration of BE and PHE, but not EE, reduced the total antioxidant activity and enhanced lipid peroxidation in the brain. In the frontal cortex, adverse effects of PHE and BE on lipid peroxidation probably depended on reduction in SOD and GPX activity, however, in the hippocampus the changes in the total antioxidant activity and lipid peroxidation were not connected with reduction of the investigated antioxidant enzyme activity.

  2. Effect of low-energy laser (He-Ne) irradiation on embryo implantation rate in the rat

    NASA Astrophysics Data System (ADS)

    Stein, Anat; Kraicer, P. F.; Oron, Uri

    1997-12-01

    Attempts to date to increase the rate of embryo implantation, for example by assisting embryo hatching from the zona pellucida, have failed. Recently, several studies have suggested the biostimulating effect of low power laser irradiation. The objective of this study was therefore to examine the potential of low power laser irradiation of the uterus to enhance embryo implantation rate in the rat. Rat potential of low power laser irradiation of the uterus to enhance embryo implantation rate in the rat. Rat blastocysts were flushed from the uterus on day 5 of gestation. They were transferred to the uteri of pseudopregnant recipients on day 4 or 5 of pseudopregnancy. One cornu of the recipient uterus was irradiated; the other was used as control. On day 5 of pregnancy, irradiation did not change implantation rate after 10 or 30 sec of irradiation while 120 sec. of irradiation significantly decreased embryonic implantation. On the other hand, on day 4 of pregnancy, 120 sec. of radiation allowed embryonic implantation to a level similar to that seen after synchronized transfer. Conclusion: He-Ne laser irradiation of the exposed rat uterus can attenuate embryo implantation rate.

  3. Are soluble and membrane-bound rat brain acetylcholinesterase different

    SciTech Connect

    Andres, C.; el Mourabit, M.; Stutz, C.; Mark, J.; Waksman, A. )

    1990-11-01

    Salt-soluble and detergent-soluble acetylcholinesterases (AChE) from adult rat brain were purified to homogeneity and studied with the aim to establish the differences existing between these two forms. It was found that the enzymatic activities of the purified salt-soluble AChE as well as the detergent-soluble AChE were dependent on the Triton X-100 concentration. Moreover, the interaction of salt-soluble AChE with liposomes suggests amphiphilic behaviour of this enzyme. Serum cholinesterase (ChE) did not bind to liposomes but its activity was also detergent-dependent. Detergent-soluble AChE remained in solution below critical micellar concentrations of Triton X-100. SDS polyacrylamide gel electrophoresis of purified, Biobeads-treated and iodinated detergent-soluble 11 S AChE showed, under non reducing conditions, bands of 69 kD, 130 kD and greater than 250 kD corresponding, respectively, to monomers, dimers and probably tetramers of the same polypeptide chain. Under reducing conditions, only a 69 kD band was detected. It is proposed that an amphiphilic environment stabilizes the salt-soluble forms of AChE in the brain in vivo and that detergent-soluble Biobeads-treated 11 S AChE possess hydrophobic domain(s) different from the 20 kD peptide already described.

  4. Brain Pathology in Adult Rats Treated With Domoic Acid.

    PubMed

    Vieira, A C; Alemañ, N; Cifuentes, J M; Bermúdez, R; Peña, M López; Botana, L M

    2015-11-01

    Domoic acid (DA) is a neurotoxin reported to produce damage to the hippocampus, which plays an important role in memory. The authors inoculated rats intraperitoneally with an effective toxic dose of DA to study the distribution of the toxin in major internal organs by using immunohistochemistry, as well as to evaluate the induced pathology by means of histopathologic and immunohistochemical methods at different time points after toxin administration (6, 10, and 24 hours; 5 and 54 days). DA was detected by immunohistochemistry exclusively in pyramidal neurons of the hippocampus at 6 and 10 hours after dosing. Lesions induced by DA were prominent at 5 days following treatment in selected regions of the brain: hippocampus, amygdala, piriform and perirhinal cortices, olfactory tubercle, septal nuclei, and thalamus. The authors found 2 types of lesions: delayed death of selective neurons and large areas of necrosis, both accompanied by astrocytosis and microgliosis. At 54 days after DA exposure, the pathology was characterized by still-distinguishable dying neurons, calcified lesions in the thalamus, persistent astrocytosis, and pronounced microgliosis. The expression of nitric oxide synthases suggests a role for nitric oxide in the pathogenesis of neuronal degeneration and chronic inflammation induced by DA in the brain.

  5. A better mild traumatic brain injury model in the rat.

    PubMed

    Takeuchi, Satoru; Nawashiro, Hiroshi; Sato, Shunichi; Kawauchi, Satoko; Nagatani, Kimihiro; Kobayashi, Hiroaki; Otani, Naoki; Osada, Hideo; Wada, Kojiro; Shima, Katsuji

    2013-01-01

    The primary pathology associated with mild -traumatic brain injury (TBI) is selective axonal injury, which may characterize the vast majority of blast-induced TBIs. Axonal injuries in cases of mild TBI have been considered to be the main factors responsible for the long-lasting memory or attentional impairment in affected subjects. Among these axonal injuries, recent attention has been focused on the cingulum bundle (CB). Furthermore, recent studies with diffusion tensor MR imaging have shown the presence of injuries of the CB in cases of mild TBI in humans. This study aimed to provide a better laboratory model of mild TBI.Sprague-Dawley rats were subjected to mild TBI using laser-induced shock waves (LISW) (sham, 0.5 J/cm(2), or 1.0 J/cm(2); n = 4 per group). Bodian-stained brain sections 14 days after LISW at 0.5 J/cm(2) or 1.0 J/cm(2) showed a decrease in the CB axonal density compared with the sham group, whereas there were no differences in the axonal density of the corpus callosum.The present study shows that this model is capable of reproducing the histological changes associated with mild TBI. PMID:23564112

  6. [Anorexia in rats following protracted whole-body irradiation with low doses].

    PubMed

    Schraub, A; Sattler, E L; Döll, G; Kindt, A

    1975-07-01

    In our experiments, carried out hitherto, concerning the effect of incorporated and radioactive substances, weight behaviour and food uptake have proved to be a sensitive test. With regard to these experiments and the half-life of the radionuclides used, it is reported about trial series in Wistar rats. These rats were applied, with Co-60 gamma irradiation, different whole-body doses protracted over 48 hours. A total of 32 groups of experimental animals (20 animals each) was exposed to irradiation doses of lethal, medium lethal, and sublethal ranges, control and pseudo-irradiation series included. The experiments were carried out under observance of constant irradiation and attitude conditions, night and day changes, as conditioned by the season, included. Even in the inferior sublethal range (12 to 24 R), a significant trend of decreased food uptake is registered. This trend remains for a short period after the end of irradiation, but then it returns to normal conditions. Furthermore, a new decrease with subsequent increase seems to become evident-about ten days after termination of the radiotherapy (especially after several hundred R); report about these items will be made later on.

  7. [Effect of External Irradiation and Immobilization Stress on the Reproductive System of Male Rats].

    PubMed

    Vereschako, G G; Tshueshova, N V; Gorokh, G A; Kozlov, I G; Naumov, A D

    2016-01-01

    We studied the state of the reproductive system of male rats after irradiation at a dose of 2.0 Gy, immobilization stress (6 hours/day for 7 days) and their combined effects. On the 30th day after the combined treatment (37 days after irradiation) a decrease in the testicular weight by almost 50% compared with the control and lesions connected with the process of spermatogenesis are observed. In the remote period--on the 60th day (67th after irradiation) the effect of irradiation and irradiation in combination with immobilization stress leads to a sharp drop in the number of epididymal sperm (up to 18% of the control), and a reduction of their viability. The reaction ofthe reproductive system to the immobilization stress is expressed in a certain increase in the mass of the testes and epididymis, moderate imbalances in the composition of spermatogenic cells in the testis tissue, and in the long term--in the increased number of epididymal sperm and the decrease in their viability. Changes of testosterone in the blood serum, especially significant for the combined effect, reflect impairments of the regulation of the reproductive system of males under these conditions. With regard to individual indicators of the reproductive system of male rats in some cases, the- combined effects of radiation and stress had a synergistic, or, on the contrary, antagonistic character.

  8. Irradiation to the young mouse brain impaired white matter growth more in females than in males.

    PubMed

    Roughton, K; Boström, M; Kalm, M; Blomgren, K

    2013-10-31

    Modern therapy cures 80% of all children with brains tumors, but may also cause long-lasting side effects, so called late effects. Radiotherapy is particularly prone to cause severe late effects, such as intellectual impairment. The extent and nature of the resulting cognitive deficits may be influenced by age, treatment and gender, where girls suffer more severe late effects than boys. The reason for this difference between boys and girls is unknown, but very few experimental studies have addressed this issue. Our aim was to investigate the effects of ionizing radiation on the corpus callosum (CC) in both male and female mice. We found that a single dose of 8 Gray (Gy) to the brains of postnatal day 14 mice induced apoptosis in the CC and reduced the number of proliferating cells by one third, as judged by the number of phospho-histone H3 positive cells 6 h after irradiation (IR). BrdU incorporation was reduced (62% and 42% lower in females and males, respectively) and the number of oligodendrocytes (Olig2(+) cells) was lower (43% and 21% fewer in females and males, respectively) 4 months after IR, so the lack of developing and differentiated cells was more pronounced in females. The number of microglia was unchanged in females but increased in males at this late time point. The density of microvessel profiles was unchanged by IR. This single, moderate dose of 8 Gy impaired the brain growth to some extent (8.1% and 0.4% lower brain/body weight ratio in females and males, respectively) but the CC growth was even more impaired (31% and 19% smaller in females and males, respectively) 4 months after IR compared with non-irradiated mice. In conclusion, this is the first study to our knowledge demonstrating that IR to the young rodent brain affects white matter development more in females than in males.

  9. Subcellular localization and compartmentation of thiamine derivatives in rat brain.

    PubMed

    Bettendorff, L; Wins, P; Lesourd, M

    1994-05-26

    The subcellular distribution of thiamine derivatives in rat brain was studied. Thiamine diphosphate content was highest in the mitochondrial and synaptosomal fractions, and lowest in microsomal, myelin and cytosolic fractions. Only 3-5% of total thiamine diphosphate was bound to transketolase, a cytosolic enzyme. Thiamine triphosphate was barely detectable in the microsomal and cytosolic fraction, but synaptosomes were slightly enriched in this compound compared to the crude homogenate. Both myelin and mitochondrial fractions contained significant amounts of thiamine triphosphate. In order to estimate the relative turnover rates of these compounds, the animals received an intraperitoneal injection of either [14C]thiamine or [14C]sulbutiamine (isobutyrylthiamine disulfide) 1 h before decapitation. The specific radioactivities of thiamine compounds found in the brain decreased in the order: thiamine > thiamine triphosphate > thiamine monophosphate > thiamine diphosphate. Incorporation of radioactivity into thiamine triphosphate was more marked with [14C]sulbutiamine than with [14C]thiamine. The highest specific radioactivity of thiamine diphosphate was found in the cytosolic fraction of the brain, though this pool represents less than 10% of total thiamine diphosphate. Cytosolic thiamine diphosphate had a twice higher specific radioactivity when [14C]sulbutiamine was used as precursor compared with thiamine though no significant differences were found in the other cellular compartments. Our results suggest the existence of two thiamine diphosphate pools: the bound cofactor pool is essentially mitochondrial and has a low turnover; a much smaller cytosolic pool (6-7% of total TDP) of high turnover is the likely precursor of thiamine triphosphate. PMID:8186256

  10. Garlic extract attenuates brain mitochondrial dysfunction and cognitive deficit in obese-insulin resistant rats.

    PubMed

    Pintana, Hiranya; Sripetchwandee, Jirapas; Supakul, Luerat; Apaijai, Nattayaporn; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2014-12-01

    Oxidative stress in the obese-insulin resistant condition has been shown to affect cognitive as well as brain mitochondrial functions. Garlic extract has exerted a potent antioxidant effect. However, the effects of garlic extract on the brain of obese-insulin resistant rats have never been investigated. We hypothesized that garlic extract improves cognitive function and brain mitochondrial function in obese-insulin resistant rats induced by long-term high-fat diet (HFD) consumption. Male Wistar rats were fed either normal diet or HFD for 16 weeks (n = 24/group). At week 12, rats in each dietary group received either vehicle or garlic extract (250 and 500 mg·kg(-1)·day(-1)) for 28 days. Learning and memory behaviors, metabolic parameters, and brain mitochondrial function were determined at the end of treatment. HFD led to increased body weight, visceral fat, plasma insulin, cholesterol, and malondialdehyde (MDA) levels, indicating the development of insulin resistance. Furthermore, HFD rats had cognitive deficit and brain mitochondrial dysfunction. HFD rats treated with both doses of garlic extract had decreased body weight, visceral fat, plasma cholesterol, and MDA levels. Garlic extract also improved cognitive function and brain mitochondrial function, which were impaired in obese-insulin resistant rats caused by HFD consumption.

  11. Tannic acid alleviates lead acetate-induced neurochemical perturbations in rat brain.

    PubMed

    Ashafaq, Mohammad; Tabassum, Heena; Vishnoi, Shruti; Salman, Mohd; Raisuddin, Sheikh; Parvez, Suhel

    2016-03-23

    Oxidative stress has been projected as a promising mechanism involved in lead exposure. The lead predisposition catalyzes oxidative reactions and generates reactive oxygen species. The present study was carried out to investigate the effect of oral administration of tannic acid (TA) on behavioral deficit, antioxidative deterioration induced by lead acetate (LA) exposure on experimental rat brain. Male Wistar rats were treated with 50mg/kg body weight of LA and TA for three times a week for two weeks. Our data showed LA-induced profound elevation of ROS production and oxidative stress, as evidenced by increased levels of oxidative stress markers such as lipid peroxidation and protein carbonyl observed in LA treated rats, whereas significant depletion in the activity of non-enzymatic antioxidants, enzymatic antioxidants, neurotoxicity biomarker and histological changes were observed in LA treated rat brain. However, TA administration restored antioxidant status of brain significantly when compared to control. Our results demonstrate that TA exhibits potent antioxidant properties and suppresses oxidative damages in rat brain induced by LA treatment. These findings were further supported by the neurotoxicity biomarker and histopathological findings in the brain tissue showed that TA protected tissue from deleterious effects of LA exposure. It is concluded, these data suggest that LA induces oxidative stress and supplementation of TA has a powerful antioxidant effect, and it protected rat brain from poisonous effect of LA exposure in experimental rat.

  12. Tannic acid alleviates lead acetate-induced neurochemical perturbations in rat brain.

    PubMed

    Ashafaq, Mohammad; Tabassum, Heena; Vishnoi, Shruti; Salman, Mohd; Raisuddin, Sheikh; Parvez, Suhel

    2016-03-23

    Oxidative stress has been projected as a promising mechanism involved in lead exposure. The lead predisposition catalyzes oxidative reactions and generates reactive oxygen species. The present study was carried out to investigate the effect of oral administration of tannic acid (TA) on behavioral deficit, antioxidative deterioration induced by lead acetate (LA) exposure on experimental rat brain. Male Wistar rats were treated with 50mg/kg body weight of LA and TA for three times a week for two weeks. Our data showed LA-induced profound elevation of ROS production and oxidative stress, as evidenced by increased levels of oxidative stress markers such as lipid peroxidation and protein carbonyl observed in LA treated rats, whereas significant depletion in the activity of non-enzymatic antioxidants, enzymatic antioxidants, neurotoxicity biomarker and histological changes were observed in LA treated rat brain. However, TA administration restored antioxidant status of brain significantly when compared to control. Our results demonstrate that TA exhibits potent antioxidant properties and suppresses oxidative damages in rat brain induced by LA treatment. These findings were further supported by the neurotoxicity biomarker and histopathological findings in the brain tissue showed that TA protected tissue from deleterious effects of LA exposure. It is concluded, these data suggest that LA induces oxidative stress and supplementation of TA has a powerful antioxidant effect, and it protected rat brain from poisonous effect of LA exposure in experimental rat. PMID:26851560

  13. Brain sarcoma of meningeal origin after cranial irradiation in childhood acute lymphocytic leukemia. Case report

    SciTech Connect

    Tiberin, P.; Maor, E.; Zaizov, R.; Cohen, I.J.; Hirsch, M.; Yosefovich, T.; Ronen, J.; Goldstein, J.

    1984-10-01

    The authors report their experience with an unusual case of intracerebral sarcoma of meningeal cell origin in an 8 1/2-year-old girl. This tumor occurred 6 1/2 years after cranial irradiation at relatively low dosage (2200 rads) had been delivered to the head in the course of a multimodality treatment for acute lymphocytic leukemia. The tumor recurred approximately 10 months after the first surgical intervention. Macroscopic total excision of the recurrent growth followed by whole-brain irradiation (4500 rads) failed to eradicate it completely and local recurrence prompted reoperation 18 months later. This complication of treatment in long-term childhood leukemia survivors is briefly discussed, as well as the pathology of meningeal sarcomas.

  14. Schwann cell myelination of the myelin deficient rat spinal cord following X-irradiation

    SciTech Connect

    Duncan, I.D.; Hammang, J.P.; Gilmore, S.A.

    1988-01-01

    The myelin-deficient (md) rat is an X-linked myelin mutant that has an abnormality of oligodendrocytes and a severe paucity of myelin throughout the CNS. This lack of myelin makes it an ideal model in which to study the cellular interactions that occur when foreign myelinating cells are induced in the milieu of this nonmyelinated CNS. In this study, Schwann cells were induced in the lumbosacral spinal cord by exposing it to radiation, a technique demonstrated repeatedly in other nonmutant strains of rats. Md rats and their age-matched littermates were irradiated (3,000 to 4,000 R) at 3 days of age and perfused 16-22 days later after pulse labeling with tritiated thymidine. In the md rat, Schwann cell invasion progressed from the area of the spinal cord-nerve root junction and extended into the dorsal columns and adjacent gray matter. Autoradiographic evidence revealed that many of these cells incorporated 3H-thymidine, indicating that they were undergoing proliferation. Ultrastructural observations showed that there was an integration of these intraspinal Schwann cells with the cells normally occurring in this environment, i.e., oligodendrocytes and astrocytes. The extent of migration and division of Schwann cells, as well as their interactions with glial cells, were similar to those seen in the nonmutant irradiated littermates. These studies provide conclusive evidence that md rat axons are normal with respect to their ability to provide trophic and mitogenic signals to myelinating cells.

  15. Radioprotection against cataract formation by WR-77913 in gamma-irradiated rats.

    PubMed

    Menard, T W; Osgood, T B; Clark, J I; Spence, A M; Steele, J E; Krohn, K A; Livesey, J C

    1986-08-01

    Protection by WR-77913 against radiation-induced cataract formation in rats was observed following intraperitoneal (i.p.) administration of drug (1160 mg/kg) 15-30 min before exposure to 15.3 Gy of Cs-137 whole head irradiation. Control groups included irradiated, non-protected animals, and sham-irradiated aging controls. Protection was documented photographically and by analysis of eye lens constituents. All non-protected irradiated animals developed dense cataracts throughout the lens between 90-120 days post-irradiation, while WR-77913 protected animals developed minimal lens opacification through 200 days post-irradiation. No opacification in aging controls was seen. Lens protein analysis by Lowry assay and size exclusion HPLC showed radioprotected and aging control animals were similar in protein content, distribution of total and soluble protein, and degree of lens hydration. This contrasted significantly with cataractous lenses of non-protected animals. In cataractous lenses, the soluble protein concentration in the 25-43 K dalton range was approximately 10% of that found in radioprotected or aging control lenses. Hydration was substantially higher in cataractous lens. These results indicate that WR-77913 protects against lens opacification, protein insolubilization, and hydration in lenses of irradiated animals. Biodistribution studies with [S-35]-WR-77913 showed ocular uptake of drug within 15 minutes after i.p. injection, which remained relatively constant through 60 min. The relative order of drug concentration for individual eye components was: globe greater than total eye approximately equal to humor greater than lens. Although the mechanism of radioprotection observed remains to be elucidated, WR-77913 clearly prevents radiation-induced cataracts in rats. The potentially significant clinical use for this radioprotective compound is being investigated further. PMID:3019964

  16. Three-Staged Stereotactic Radiotherapy Without Whole Brain Irradiation for Large Metastatic Brain Tumors

    SciTech Connect

    Higuchi, Yoshinori Serizawa, Toru; Nagano, Osamu; Matsuda, Shinji; Ono, Junichi; Sato, Makoto; Iwadate, Yasuo; Saeki, Naokatsu

    2009-08-01

    Purpose: To evaluate the efficacy and toxicity of staged stereotactic radiotherapy with a 2-week interfraction interval for unresectable brain metastases more than 10 cm{sup 3} in volume. Patients and Methods: Subjects included 43 patients (24 men and 19 women), ranging in age from 41 to 84 years, who had large brain metastases (> 10 cc in volume). Primary tumors were in the colon in 14 patients, lung in 12, breast in 11, and other in 6. The peripheral dose was 10 Gy in three fractions. The interval between fractions was 2 weeks. The mean tumor volume before treatment was 17.6 {+-} 6.3 cm{sup 3} (mean {+-} SD). Mean follow-up interval was 7.8 months. The local tumor control rate, as well as overall, neurological, and qualitative survivals, were calculated using the Kaplan-Meier method. Results: At the time of the second and third fractions, mean tumor volumes were 14.3 {+-} 6.5 (18.8% reduction) and 10.6 {+-} 6.1 cm{sup 3} (39.8% reduction), respectively, showing significant reductions. The median overall survival period was 8.8 months. Neurological and qualitative survivals at 12 months were 81.8% and 76.2%, respectively. Local tumor control rates were 89.8% and 75.9% at 6 and 12 months, respectively. Tumor recurrence-free and symptomatic edema-free rates at 12 months were 80.7% and 84.4%, respectively. Conclusions: The 2-week interval allowed significant reduction of the treatment volume. Our results suggest staged stereotactic radiotherapy using our protocol to be a possible alternative for treating large brain metastases.

  17. State of the antioxidative enzymes of rat bone marrow cells after irradiation, fractures, and a combination of both

    SciTech Connect

    Bogdanova, I.A.; Ovchinnikov, K.G.; Torbenko, V.P.; Gerasimov, A.M.

    1987-11-01

    The authors study bone marrow levels of antioxidative (antiradical) defensive systems (ADS) enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GP), glutathione reductase (GR), and glutathione: dehydroascorbate oxidoreductase (GDAR), rats and changes in their activity in the bone marrow at various times after irradiation, mechanical trauma, and a combination of both. Development of acute radiation sickness as a result of a single irradiation was accompanied by marked changes in the enzymic antioxidative system of rat bone marrow cells.

  18. Visuospatial asymmetries and interocular transfer in the split-brain rat.

    PubMed

    Adelstein, A; Crowne, D P

    1991-06-01

    Interocular transfer (IOT), hemispheric superiority, and cerebral dominance were examined in split-brain female albino rats. Callosum-sectioned and intact animals were monocularly trained in the Morris water maze and tested in IOT and reversal phases. In the IOT phase, split-brain rats entered more nontarget quadrants and headed less accurately toward the platform than did controls. For both split-brain animals and controls, right-eye training resulted in shorter latencies and fewer nontarget entries than did left-eye training. Analyses of cerebral dominance showed shorter latencies and smaller heading errors over all 3 phases in rats that were trained with the nondominant eye. Right-eye dominant controls were less affected by platform reversal. Split-brain rats were inferior to controls in latency to find the platform and in target quadrant entries. This finding establishes a spatial cognitive deficit from callosum section.

  19. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines.

    PubMed

    Choi, Sujean; Disilvio, Briana; Fernstrom, Madelyn H; Fernstrom, John D

    2013-11-01

    Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge. PMID:23904096

  20. Changes of amino acid gradients in brain tissues induced by microwave irradiation and other means

    SciTech Connect

    Baxter, C.F.; Parsons, J.E.; Oh, C.C.; Wasterlain, C.G.; Baldwin, R.A. )

    1989-09-01

    Focused microwave irradiation to the head (FMI) has been used extensively by neurochemists for rapid inactivation of enzymatic activity in brain tissues and the preservation, for in vitro analysis, of in vivo substrate concentrations. Periodically the suitability of this technique for regional studies has been questioned. Evidence has now been obtained, on the basis of altered concentration gradients for GABA and taurine from the Substantia Nigra (SN) to an Adjacent Dorsal Area (ADJ), that FMI not only inactivates enzymes, but also facilitates rapid diffusion of small molecules from areas of high concentrations to adjacent areas of lower concentration. To a lesser extent, the implantation of plastic injection cannulas also decreased these concentration gradients. These results offer clear evidence that FMI is ill suited and unreliable for studies designed to map and compare the in vivo regional concentrations of diffusible organic molecules (such as amino acids) in brain tissues. Any invasive technique that compromises membrane barriers is likely to produce smaller similar effects.

  1. Different subcellular localization of muscarinic and serotonin (S2) receptors in human, dog, and rat brain.

    PubMed

    Luabeya, M K; Maloteaux, J M; De Roe, C; Trouet, A; Laduron, P M

    1986-02-01

    Cortex from rat, dog, and human brain was submitted to subcellular fractionation using an analytical approach consisting of a two-step procedure. First, fractions were obtained by differential centrifugation and were analyzed for their content of serotonin S2 and muscarinic receptors, serotonin uptake, and marker enzymes. Second, the cytoplasmic extracts were subfractionated by equilibration in sucrose density gradient. In human brain, serotonin and muscarinic receptors were found associated mostly with mitochondrial fractions which contain synaptosomes, whereas in rat brain they were concentrated mainly in the microsomal fractions. Density gradient centrifugation confirmed a more marked synaptosomal localization of receptors in human than in rat brain, the dog displaying an intermediate profile. In human brain, indeed, more receptor sites were found to be associated with the second peak characterized in electron microscopy by the largest number of nerve terminals. In addition, synaptosomes from human brain are denser than those from rat brain and some marker enzymes reveal different subcellular distribution in the three species. These data indicate that more receptors are of synaptosomal nature in human brain than in other species and this finding is compatible with a larger amount of synaptic contacts in human brain. PMID:2934515

  2. Through metal binding, curcumin protects against lead- and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain.

    PubMed

    Daniel, Sheril; Limson, Janice L; Dairam, Amichand; Watkins, Gareth M; Daya, Santy

    2004-02-01

    Curcumin, the major constituent of turmeric is a known, naturally occurring antioxidant. The present study examined the ability of this compound to protect against lead-induced damage to hippocampal cells of male Wistar rats, as well as lipid peroxidation induced by lead and cadmium in rat brain homogenate. The thiobarbituric assay (TBA) was used to measure the extent of lipid peroxidation induced by lead and cadmium in rat brain homogenate. The results show that curcumin significantly protects against lipid peroxidation induced by both these toxic metals. Coronal brain sections of rats injected intraperitoneally with lead acetate (20 mg/kg) in the presence and absence of curcumin (30 mg/kg) were compared microscopically to determine the extent of lead-induced damage to the cells in the hippocampal CA1 and CA3 regions, and to establish the capacity of curcumin to prevent such damage. Lead-induced damage to the neurons was significantly curtailed in the rats injected with curcumin. Possible chelation of lead and cadmium by curcumin as its mechanism of neuroprotection against such heavy metal insult to the brain was investigated using electrochemical, ultraviolet spectrophotometric and infrared spectroscopic analyses. The results of the study show that there is an interaction between curcumin and both cadmium and lead, with the possible formation of a complex between the metal and this ligand. These results imply that curcumin could be used therapeutically to chelate these toxic metals, thus potentially reducing their neurotoxicity and tissue damage.

  3. SU-E-T-457: Design and Characterization of An Economical 192Ir Hemi-Brain Small Animal Irradiator

    SciTech Connect

    Grams, M; Wilson, Z; Sio, T; Beltran, C; Tryggestad, E; Gupta, S; Blackwell, C; McCollough, K; Sarkaria, J; Furutani, K

    2014-06-01

    Purpose: To describe the design and dosimetric characterization of a simple and economical small animal irradiator. Methods: A high dose rate 192Ir brachytherapy source from a commercially available afterloader was used with a 1.3 centimeter thick tungsten collimator to provide sharp beam penumbra suitable for hemi-brain irradiation of mice. The unit is equipped with continuous gas anesthesia to allow robust animal immobilization. Dosimetric characterization of the device was performed with Gafchromic film. The penumbra from the small animal irradiator was compared under similar collimating conditions to the penumbra from 6 MV photons, 6 MeV electrons, and 20 MeV electrons from a linear accelerator as well as 300 kVp photons from an orthovoltage unit and Monte Carlo simulated 90 MeV protons. Results: The tungsten collimator provides a sharp penumbra suitable for hemi-brain irradiation, and dose rates on the order of 200 cGy/minute were achieved. The sharpness of the penumbra attainable with this device compares favorably to those measured experimentally for 6 MV photons, and 6 and 20 MeV electron beams from a linear accelerator. Additionally, the penumbra was comparable to those measured for a 300 kVp orthovoltage beam and a Monte Carlo simulated 90 MeV proton beam. Conclusions: The small animal irradiator described here can be built for under $1,000 and used in conjunction with any commercial brachytherapy afterloader to provide a convenient and cost-effective option for small animal irradiation experiments. The unit offers high dose rate delivery and sharp penumbra, which is ideal for hemi-brain irradiation of mice. With slight modifications to the design, irradiation of sites other than the brain could be accomplished easily. Due to its simplicity and low cost, the apparatus described is an attractive alternative for small animal irradiation experiments requiring a sharp penumbra.

  4. Phototherapeutic Effect of Low-Level Laser on Thyroid Gland of Gamma-Irradiated Rats.

    PubMed

    Morcos, Nadia; Omran, Manar; Ghanem, Hala; Elahdal, Mahmoud; Kamel, Nashwa; Attia, Elbatoul

    2015-01-01

    One inescapable feature of life on the earth is exposure to ionizing radiation. The thyroid gland is one of the most sensitive organs to gamma-radiation and endocrine disrupters. Low-level laser therapy (LLLT) has been used to stimulate tissue repair, and reduce inflammation. The aim of this study was to gauge the value of using Helium-Neon laser to repair the damaged tissues of thyroid gland after gamma-irradiation. Albino rats were used in this study (144 rats), divided into control, gamma, laser, and gamma plus laser-irradiated groups, each group was divided into six subgroups according to time of treatment (total six sessions). Rats were irradiated once with gamma radiation (6 Gy), and an external dose of laser (Wavelength 632.8 nm, 12 mW, CW, Illuminated area 5.73 cm(2), 2.1 mW cm(-2) 120 s, 1.4 J, 0.252 J cm(-2)) twice weekly localized on thyroid region of the neck, for a total of six sessions. Animals were sacrificed after each session. Analysis included thyroid function, oxidative stress markers, liver function and blood picture. Results revealed improvement in thyroid function, liver function and antioxidant levels, and the blood cells count after LLLT.

  5. Effects of heavy particle irradiation and diet on object recognition memory in rats

    NASA Astrophysics Data System (ADS)

    Rabin, Bernard M.; Carrihill-Knoll, Kirsty; Hinchman, Marie; Shukitt-Hale, Barbara; Joseph, James A.; Foster, Brian C.

    2009-04-01

    On long-duration missions to other planets astronauts will be exposed to types and doses of radiation that are not experienced in low earth orbit. Previous research using a ground-based model for exposure to cosmic rays has shown that exposure to heavy particles, such as 56Fe, disrupts spatial learning and memory measured using the Morris water maze. Maintaining rats on diets containing antioxidant phytochemicals for 2 weeks prior to irradiation ameliorated this deficit. The present experiments were designed to determine: (1) the generality of the particle-induced disruption of memory by examining the effects of exposure to 56Fe particles on object recognition memory; and (2) whether maintaining rats on these antioxidant diets for 2 weeks prior to irradiation would also ameliorate any potential deficit. The results showed that exposure to low doses of 56Fe particles does disrupt recognition memory and that maintaining rats on antioxidant diets containing blueberry and strawberry extract for only 2 weeks was effective in ameliorating the disruptive effects of irradiation. The results are discussed in terms of the mechanisms by which exposure to these particles may produce effects on neurocognitive performance.

  6. Vascular Injury After Whole Thoracic X-Ray Irradiation in the Rat

    SciTech Connect

    Ghosh, S.N. Wu, Q. M.S.; Maeder, M.; Fish, B.L.; Moulder, J.E.; Jacobs, E.R.; Medhora, M.; Molthen, R.C.

    2009-05-01

    Purpose: To study vascular injury after whole thoracic irradiation with single sublethal doses of X-rays in the rat and to develop markers that might predict the severity of injury. Methods and Materials: Rats that received 5- or 10-Gy thorax-only irradiation and age-matched controls were studied at 3 days, 2 weeks, and 1, 2, 5, and 12 months. Several pulmonary vascular parameters were evaluated, including hemodynamics, vessel density, total lung angiotensin-converting enzyme activity, and right ventricular hypertrophy. Results: By 1 month, the rats in the 10-Gy group had pulmonary vascular dropout, right ventricular hypertrophy, increased pulmonary vascular resistance, increased dry lung weights, and decreases in total lung angiotensin-converting enzyme activity, as well as pulmonary artery distensibility. In contrast, irradiation with 5 Gy resulted in only a modest increase in right ventricular weight and a reduction in lung angiotensin-converting enzyme activity. Conclusion: In a previous investigation using the same model, we observed that recovery from radiation-induced attenuation of pulmonary vascular reactivity occurred. In the present study, we report that deterioration results in several vascular parameters for {<=}1 year after 10 Gy, suggesting sustained remodeling of the pulmonary vasculature. Our data support clinically relevant injuries that appear in a time- and dose-related manner after exposure to relatively low radiation doses.

  7. Sensory dynamics of intense microwave irradiation: A comparative study of aversive behaviors by mice and rats

    SciTech Connect

    Justesen, D.R.

    1981-10-01

    The results of two experiments are reported, the first on 24 mice and 14 rats, all experimentally naive, that were observed for evidence of adventitious escape from faradic shock or from a potentially lethal, 2450-MHz microwave field in a multi-mode cavity. All of ten rats irradiated at a whole-body-averaged dose rate of 60 mW/g convulsed and expired, presumably from radiation-induced hyperpyrexia. Eight of ten mice irradiated at 60 mW/g survived the four sessions of irradiation, but reliable evidence of escape learning was not observed. The data of the second experiment, which was a pilot study of four rats with an extensive history of exposure to intense but intermittently applied microwave fields, revealed that the animals learned to thermoregulate behaviorally by locomoting in and out of the safe-area circle. A strong relation between dose rate (30, 60, and 120 mW/g) and proportion of time spent in the safe area was observed (r = .97). Post-exposure means of colonic temperature during three sets of sessions under the different rates of energy dosing were highly stable and averaged 39.6 deg C.

  8. Phototherapeutic Effect of Low-Level Laser on Thyroid Gland of Gamma-Irradiated Rats.

    PubMed

    Morcos, Nadia; Omran, Manar; Ghanem, Hala; Elahdal, Mahmoud; Kamel, Nashwa; Attia, Elbatoul

    2015-01-01

    One inescapable feature of life on the earth is exposure to ionizing radiation. The thyroid gland is one of the most sensitive organs to gamma-radiation and endocrine disrupters. Low-level laser therapy (LLLT) has been used to stimulate tissue repair, and reduce inflammation. The aim of this study was to gauge the value of using Helium-Neon laser to repair the damaged tissues of thyroid gland after gamma-irradiation. Albino rats were used in this study (144 rats), divided into control, gamma, laser, and gamma plus laser-irradiated groups, each group was divided into six subgroups according to time of treatment (total six sessions). Rats were irradiated once with gamma radiation (6 Gy), and an external dose of laser (Wavelength 632.8 nm, 12 mW, CW, Illuminated area 5.73 cm(2), 2.1 mW cm(-2) 120 s, 1.4 J, 0.252 J cm(-2)) twice weekly localized on thyroid region of the neck, for a total of six sessions. Animals were sacrificed after each session. Analysis included thyroid function, oxidative stress markers, liver function and blood picture. Results revealed improvement in thyroid function, liver function and antioxidant levels, and the blood cells count after LLLT. PMID:25975382

  9. The effects of celecoxib, a COX-2 selective inhibitor, on acute inflammation induced in irradiated rats.

    PubMed

    Khayyal, M T; El-Ghazaly, Mona A; El-Hazek, R M; Nada, A S

    2009-10-01

    The potential value of selective and non-selective COX-2 inhibitors in preventing some of the biochemical changes induced by ionizing radiation was studied in rats exposed to carrageenan-induced paw edema and 6-day-old air pouch models. The animals were exposed to different exposure levels of gamma-radiation, namely either to single doses of 2 and 7.5 Gy or a fractionated dose level of 7.5 Gy delivered as 0.5 Gy twice weekly for 7.5 weeks. The inflammatory response produced by carrageenan in irradiated rats was markedly higher than that induced in non-irradiated animals, and depended on the extent of irradiation. Celecoxib, a selective COX-2 inhibitor, in doses of 3, 5, 10, and 15 mg/kg was effective in reducing paw edema in irradiated and non-irradiated rats in a dose-dependent manner as well as diclofenac (3 mg/kg), a non-selective COX inhibitor. Irradiation of animals before the induction of the air pouch by an acute dose of 2 Gy led to a significant increase in leukocytic count, as well as in the level of interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), LTB(4), PGE(2) (as an index of COX-2 activity), TXB(2) (as an index of COX-1 activity), and the plasma level of MDA. This increase in level of these parameters was more marked than that observed in the non-irradiated animals subjected to the inflammagen. The blood GSH level was not affected by the dose of irradiation used, whereas superoxide dismutase (SOD) activity was suppressed. In many respects, celecoxib (5 mg/kg) was as potent as diclofenac in decreasing the elevated levels of IL-6, IL-1beta, TNF-alpha, LTB(4), PGE(2), but lacked any significant effect on TXB(2) level. Since it is mostly selective for COX-2 with a rare effect on COX-1 enzyme, both drugs at the selected dose levels showed no effect on level of MDA, GSH, and SOD activity.

  10. Effectiveness of Aloe vera on the antioxidant status of different tissues in irradiated rats.

    PubMed

    Saada, H N; Ussama, Z S; Mahdy, A M

    2003-12-01

    This study was performed to evaluate the role of Aloe vera (Aloe barbadensis Miller) on the antioxidant status in different tissues of animals whole body exposed to 7 Gy gamma radiations, delivered as a shot dose. Aloe vera (leaf juice filtrate) was supplemented daily to rats (0.25 ml/kg body weight/day), by gavage, 5 days before irradiation and 10 days after irradiation. Experimental investigations performed 3, 7 and 10 days after exposure to radiation showed that Aloe vera treatment has significantly minimized the radiation-induced increase in the amount of malondialdehyde in liver, lungs, and kidney tissues of irradiated rats. Significant amelioration in superoxide dismutase (SOD) and catalase activities was observed from the 3rd up to the 10th days for lungs, on the 7th and 10th days for kidneys and at 10 days for liver. Data obtained showed that for the different tissues, improvement in the decrease of reduced glutathione (GSH) contents was obvious on the 10th day after irradiation. Treatment with Aloe vera was also effective in minimizing the radiation-induced increase in plasma glucose levels throughout the experimental period, while it has not ameliorated the increase in plasma insulin levels. It could be concluded that the synergistic relationship between the elements found in the leaf of Aloe vera could be a useful adjunct for maintaining the integrity of the antioxidant status.

  11. Structural and functional effects of social isolation on the hippocampus of rats with traumatic brain injury.

    PubMed

    Khodaie, Babak; Lotfinia, Ahmad Ali; Ahmadi, Milad; Lotfinia, Mahmoud; Jafarian, Maryam; Karimzadeh, Fariba; Coulon, Philippe; Gorji, Ali

    2015-02-01

    Social isolation has significant long-term psychological and physiological consequences. Both social isolation and traumatic brain injury (TBI) alter normal brain function and structure. However, the influence of social isolation on recovery from TBI is unclear. This study aims to evaluate if social isolation exacerbates the anatomical and functional deficits after TBI in young rats. Juvenile male rats were divided into four groups; sham operated control with social contacts, sham control with social isolation, TBI with social contacts, and TBI with social isolation. During four weeks after brain injury in juvenile rats, we evaluated the animal behaviors by T-maze and open-field tests, recorded brain activity with electrocorticograms and assessed structural changes by histological procedures in the hippocampal dentate gyrus, CA1, and CA3 areas. Our findings revealed significant memory impairments and hyperactivity conditions in rats with TBI and social isolation compared to the other groups. Histological assessments showed an increase of the mean number of dark neurons, apoptotic cells, and caspase-3 positive cells in all tested areas of the hippocampus in TBI rats with and without social isolation compared to sham rats. Furthermore, social isolation significantly increased the number of dark cells, apoptotic neurons, and caspase-3 positive cells in the hippocampal CA3 region in rats with TBI. This study indicates the harmful effect of social isolation on anatomical and functional deficits induced by TBI in juvenile rats. Prevention of social isolation may improve the outcome of TBI.

  12. Effect of Cyclosporin A on the Uptake of D3-Selective PET Radiotracers in Rat Brain

    PubMed Central

    Tu, Zhude; Li, Shihong; Xu, Jinbin; Chu, Wenhua; Jones, Lynne A.; Luedtke, Robert R.; Mach, Robert H.

    2011-01-01

    Introduction Four benzamide analogs having a high affinity and selectivity for D3 versus D2 receptors were radiolabeled with 11C or 18F for in vivo evaluation. Methods Precursors were synthesized and the four D3 selective benzamide analogs were radiolabeled. The tissue distribution and brain uptake of the four compounds were evaluated in control rats and rats pretreated with cyclosporin A, a modulator of P-glycoprotein and an inhibitor of other ABC efflux transporters that contribute to the blood brain barrier. MicroPET imaging was carried out for [11C]6 in a control and a cyclosporin A pre-treated rat. Results All four compounds showed low brain uptake in control rats at 5 and 30 min post-injection; despite recently reported rat behavioral studies conducted on analogs 6 (WC-10) and 7 (WC-44). Following administration of cyclosporin A, increased brain uptake was observed with all four PET radiotracers at both 5 and 30 min post-i.v. injection. An increase in brain uptake following modulation/inhibition of the ABC transporters was also observed in the microPET study. Conclusions These data suggest that D3 selective conformationally-flexible benzamide analogs which contain a N-2-methoxyphenylpiperazine moiety are substrates for P-glycoprotein or other ABC transporters expressed at the blood-brain barrier, and that PET radiotracers containing this pharmacophore may display low brain uptake in rodents due to the action of these efflux transporters. PMID:21718948

  13. The Distribution of Phosphodiesterase 2a in the Rat Brain

    PubMed Central

    Stephenson, D. T.; Coskran, T. M.; Kelly, M. P.; Kleiman, R. J.; Morton, D.; O'neill, S. M.; Schmidt, C. J.; Weinberg, R. J.; Menniti, F. S.

    2015-01-01

    The phosphodiesterases (PDEs) are a superfamily of enzymes that regulate spatio-temporal signaling by the intracellular second messengers cAMP and cGMP. PDE2A is expressed at high levels in the mammalian brain. To advance our understanding of the role of this enzyme in regulation of neuronal signaling, we here describe the distribution of PDE2A in the rat brain. PDE2A mRNA was prominently expressed in glutamatergic pyramidal cells in cortex, and in pyramidal and dentate granule cells in the hippocampus. Protein concentrated in the axons and nerve terminals of these neurons; staining was markedly weaker in the cell bodies and proximal dendrites. In addition, in both hippocampus and cortex, small populations of non-pyramidal cells, presumed to be interneurons, were strongly immunoreactive. PDE2A mRNA was expressed in medium spiny neurons in neostriatum. Little immunoreactivity was observed in cell bodies, whereas dense immunoreactivity was found in the axon tracts of these neurons and their terminal regions in globus pallidus and substantia nigra pars reticulata. Immunostaining was dense in the medial habenula, but weak in other diencephalic regions. In midbrain and hindbrain, immunostaining was restricted to discrete regions of the neuropil or clusters of cell bodies. These results suggest that PDE2A may modulate cortical, hippocampal and striatal networks at several levels. Preferential distribution of PDE2A into axons and terminals of the principal neurons suggests roles in regulation of axonal excitability or transmitter release. The enzyme is also in forebrain interneurons, and in mid- and hindbrain neurons that may modulate forebrain networks and circuits. PMID:23000621

  14. Genomic responses in rat cerebral cortex after traumatic brain injury

    PubMed Central

    von Gertten, Christina; Morales, Amilcar Flores; Holmin, Staffan; Mathiesen, Tiit; Nordqvist, Ann-Christin Sandberg

    2005-01-01

    Background Traumatic brain injury (TBI) initiates a complex sequence of destructive and neuroprotective cellular responses. The initial mechanical injury is followed by an extended time period of secondary brain damage. Due to the complicated pathological picture a better understanding of the molecular events occurring during this secondary phase of injury is needed. This study was aimed at analysing gene expression patterns following cerebral cortical contusion in rat using high throughput microarray technology with the goal of identifying genes involved in an early and in a more delayed phase of trauma, as genomic responses behind secondary mechanisms likely are time-dependent. Results Among the upregulated genes 1 day post injury, were transcription factors and genes involved in metabolism, e.g. STAT-3, C/EBP-δ and cytochrome p450. At 4 days post injury we observed increased gene expression of inflammatory factors, proteases and their inhibitors, like cathepsins, α-2-macroglobulin and C1q. Notably, genes with biological function clustered to immune response were significantly upregulated 4 days after injury, which was not found following 1 day. Osteopontin and one of its receptors, CD-44, were both upregulated showing a local mRNA- and immunoreactivity pattern in and around the injury site. Fewer genes had decreased expression both 1 and 4 days post injury and included genes implicated in transport, metabolism, signalling, and extra cellular matrix formation, e.g. vitronectin, neuroserpin and angiotensinogen. Conclusion The different patterns of gene expression, with little overlap in genes, 1 and 4 days post injury showed time dependence in genomic responses to trauma. An early induction of factors involved in transcription could lead to the later inflammatory response with strongly upregulated CD-44 and osteopontin expression. An increased knowledge of genes regulating the pathological mechanisms in trauma will help to find future treatment targets. Since

  15. Rat brain endothelial cells are a target of manganese toxicity

    PubMed Central

    Marreilha dos Santos, Ana Paula; Milatovic, Dejan; Au, Catherine; Yin, Zhaobao; Batoreu, Maria Camila C.; Aschner, Michael

    2010-01-01

    Manganese (Mn) is an essential trace metal, however exposure to high Mn levels can result in neurodegenerative changes resembling Parkinson´s disease (PD). Information on Mn´s effects on endothelial cells of the blood-brain barrier (BBB) is lacking. Accordingly, we tested the hypothesis that BBB endothelial cells are a primary target for Mn-induced neurotoxicity. The studies were conducted in an in vitro BBB model of immortalized rat brain endothelial (RBE4) cells. ROS production was determined by F2-Isoprostane (F2-IsoPs) measurement. The relationship between Mn toxicity and redox status was investigated upon intracellular glutathione (GSH) depletion with diethylmaleate (DEM) or L-buthionine sulfoximine (BSO). Mn exposure (200 or 800 µM MnCl2 or MnSO4) for 4 or 24h led to significant decrease in cell viability vs. controls. DEM or BSO pre-treatment led to further enhancement in cytotoxicity vs. exposure to Mn alone, with more pronounced cell death after 24h DEM pre-treatment. F2-IsoPs levels in cells exposed to MnCl2 (200 or 800 µM), were significantly increased after 4h and remained elevated 24h after exposure compared with controls. Consistent with the effects on cell viability and F2-IsoPs, treatment with MnCl2 (200 or 800 µM) was also associated with a significant decrease in membrane potential. This effect was more pronounced in cells exposed to DEM plus MnCl2 vs. cells exposed to Mn alone. We conclude that Mn induces direct injury to mitochondria in RBE4 cells. The ensuing impairment in energy metabolism and redox status may modify the restrictive properties of the BBB compromising its function. PMID:20170646

  16. The metabolism of malate by cultured rat brain astrocytes

    SciTech Connect

    McKenna, M.C.; Tildon, J.T.; Couto, R.; Stevenson, J.H.; Caprio, F.J. )

    1990-12-01

    Since malate is known to play an important role in a variety of functions in the brain including energy metabolism, the transfer of reducing equivalents and possibly metabolic trafficking between different cell types; a series of biochemical determinations were initiated to evaluate the rate of 14CO2 production from L-(U-14C)malate in rat brain astrocytes. The 14CO2 production from labeled malate was almost totally suppressed by the metabolic inhibitors rotenone and antimycin A suggesting that most of malate metabolism was coupled to the electron transport system. A double reciprocal plot of the 14CO2 production from the metabolism of labeled malate revealed biphasic kinetics with two apparent Km and Vmax values suggesting the presence of more than one mechanism of malate metabolism in these cells. Subsequent experiments were carried out using 0.01 mM and 0.5 mM malate to determine whether the addition of effectors would differentially alter the metabolism of high and low concentrations of malate. Effectors studied included compounds which could be endogenous regulators of malate metabolism and metabolic inhibitors which would provide information regarding the mechanisms regulating malate metabolism. Both lactate and aspartate decreased 14CO2 production from malate equally. However, a number of effectors were identified which selectively altered the metabolism of 0.01 mM malate including aminooxyacetate, furosemide, N-acetylaspartate, oxaloacetate, pyruvate and glucose, but had little or no effect on the metabolism of 0.5 mM malate. In addition, alpha-ketoglutarate and succinate decreased 14CO2 production from 0.01 mM malate much more than from 0.5 mM malate. In contrast, a number of effectors altered the metabolism of 0.5 mM malate more than 0.01 mM. These included methionine sulfoximine, glutamate, malonate, alpha-cyano-4-hydroxycinnamate and ouabain.

  17. Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury.

    PubMed

    Servatius, Richard J; Marx, Christine E; Sinha, Swamini; Avcu, Pelin; Kilts, Jason D; Naylor, Jennifer C; Pang, Kevin C H

    2016-01-01

    Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone (ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post-stressor for determination of corticosterone (CORT) levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration. PMID:27616978

  18. Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

    PubMed Central

    Servatius, Richard J.; Marx, Christine E.; Sinha, Swamini; Avcu, Pelin; Kilts, Jason D.; Naylor, Jennifer C.; Pang, Kevin C. H.

    2016-01-01

    Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone (ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post-stressor for determination of corticosterone (CORT) levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration. PMID:27616978

  19. Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

    PubMed Central

    Servatius, Richard J.; Marx, Christine E.; Sinha, Swamini; Avcu, Pelin; Kilts, Jason D.; Naylor, Jennifer C.; Pang, Kevin C. H.

    2016-01-01

    Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone (ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post-stressor for determination of corticosterone (CORT) levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

  20. Pathologic findings in canine brain irradiated with fractionated fast neutrons or photons

    SciTech Connect

    Zook, B.C.; Bradley, E.W.; Casarett, G.W.; Rogers, C.C.

    1980-12-01

    Thirty-seven adult male purebred beagles received total doses of 1333, 2000, 3000, or 4500 rad of fast neutrons (15 MeV av) in 4 fractions/week for 7 weeks to the entire brain. Nineteen dogs received 4000, 6000, or 9000 rad of photons (/sup 60/Co) in an identical fractionation pattern. Dogs receiving 4500, 3000, and 2000 rad of neutrons and 9000 rad of photons developed neurologic signs and died or were euthanatized when moribund followed irradiation. Cerebrospinal fluid contained excess protein and erythrocytes during and sometimes before the generally brief course. The onset of neurologic symptoms was usually followed by a moribund state in less than 48 h. The relative biological effectiveness (RBE) as measured by onset of neurologic symptoms and mortality was greater than 4.5. Gross changes included hemorrhage, edema, and malacia primarily in the white matter, especially the corona radiata, cerebellar white matter, corpus callosum, and corpus fornicis. One beagle developed a brain tumor and died 1207 days following 1333-rad neutron irradiation.

  1. High-strain-rate brain injury model using submerged acute rat brain tissue slices.

    PubMed

    Sarntinoranont, Malisa; Lee, Sung J; Hong, Yu; King, Michael A; Subhash, Ghatu; Kwon, Jiwoon; Moore, David F

    2012-01-20

    Blast-induced traumatic brain injury (bTBI) has received increasing attention in recent years due to ongoing military operations in Iraq and Afghanistan. Sudden impacts or explosive blasts generate stress and pressure waves that propagate at high velocities and affect sensitive neurological tissues. The immediate soft tissue response to these stress waves is difficult to assess using current in vivo imaging technologies. However, these stress waves and resultant stretching and shearing of tissue within the nano- to microsecond time scale of blast and impact are likely to cause initial injury. To visualize the effects of stress wave loading, we have developed a new ex vivo model in which living tissue slices from rat brain, attached to a ballistic gelatin substrate, were subjected to high-strain-rate loads using a polymer split Hopkinson pressure bar (PSHPB) with real-time high-speed imaging. In this study, average peak fluid pressure within the test chamber reached a value of 1584±63.3 psi. Cavitation due to a trailing underpressure wave was also observed. Time-resolved images of tissue deformation were collected and large maximum eigenstrains (0.03-0.42), minimum eigenstrains (-0.33 to -0.03), maximum shear strains (0.09-0.45), and strain rates (8.4×10³/sec) were estimated using digital image correlation (DIC). Injury at 4 and 6 h was quantified using Fluoro-Jade C. Neuronal injury due to PSHPB testing was found to be significantly greater than injury associated with the tissue slice paradigm alone. While large pressures and strains were encountered for these tests, this system provides a controllable test environment to study injury to submerged brain slices over a range of strain rate, pressure, and strain loads. PMID:21970544

  2. In vivo deep brain imaging of rats using oral-cavity illuminated photoacoustic computed tomography

    NASA Astrophysics Data System (ADS)

    Lin, Li; Xia, Jun; Wong, Terence T. W.; Li, Lei; Wang, Lihong V.

    2015-01-01

    Using internal illumination with an optical fiber in the oral cavity, we demonstrate, for the first time, photoacoustic computed tomography (PACT) of the deep brain of rats in vivo. The experiment was performed on a full-ring-array PACT system, with the capability of providing high-speed cross-sectional imaging of the brain. Compared with external illumination through the cranial skull, internal illumination delivers more light to the base of the brain. Consequently, in vivo photoacoustic images clearly reveal deep brain structures such as the hypothalamus, brain stem, and cerebral medulla.

  3. In vivo acylation of rat brain myelin proteolipid protein.

    PubMed

    Agrawal, H C; Randle, C L; Agrawal, D

    1982-04-25

    Examination of brain myelin proteins by sodium dodecyl sulfate-gel electrophoresis followed by fluorography clearly showed that both proteolipid protein (PLP) and DM-20 were acylated 24 h after the intracerebral injection of 30-day-old rats with [3H]palmitic acid. The radioactivity associated with PLP remained after purification, re-electrophoresis, and fluorography. Most of the radioactivity associated with PLP was removed when the gels were treated with hydroxylamine and then fluorographed, indicating that fatty acids were bound to PLP by ester linkage. Cleavage of purified PLP with methanolic sodium hydroxide readily released almost all protein-bound radioactivity. Thin layer chromatography of this material on both silver nitrate and reverse-phase plates provided evidence that most of the radioactivity co-migrated with methyl palmitate (77%) and methyl stearate (19%); however, some radioactivity was associated with methyl oleate (4%). Gas-liquid chromatography of the fatty acids associated with PLP distinctly revealed the presence of methyl palmitate and a detectable peak of methyl stearate. PMID:7068653

  4. Characteristics of [3H]sultopride binding to rat brain.

    PubMed

    Mizuchi, A; Kitagawa, N; Saruta, S; Miyachi, Y

    1982-10-15

    The binding of [3H]sultopride, a benzamide drug, to rat brain was investigated in vitro. Specific [3H]sultopride binding was observed in dopaminergic regions: striatum, nucleus accumbens, olfactory tubercle, substantia nigra, frontal cortex and anterior pituitary. Specific [3H]sultopride binding to striatum was saturable and had one high affinity binding site with a KD of 5.8 nM and a total density of receptors 25.7 pmol/g. [3H]Sultopride binding was stereoselectively displaced by (-)- and (+)-sultopride. Inhibition studies indicated that all neuroleptic drugs and dopamine were capable of displacing sultopride from its binding sites. A highly significant correlation was observed between IC50 values against [3H]sultopride and those against [3H]spiperone binding. Specific [3H]sultopride binding was highly dependent on the presence of sodium ions. The results suggest that the characteristics of sultopride binding sites seem to be similar to those of the D2-receptor labeled by spiperone and haloperidol. The sultopride binding site was highly dependent on the presence of sodium ions and may thus be characterized as a sodium-dependent D2-receptor.

  5. 1H homonuclear editing of rat brain using semiselective pulses

    SciTech Connect

    Hetherington, H.P.; Avison, M.J.; Shulman, R.G.

    1985-05-01

    The authors have used a semiselective Hahn spin-echo sequence of the form (1331)-tau-(2662)-tau-AQ, delivered by a surface coil to obtain high-resolution 1H NMR spectra from the brains of intact dead rats. This sequence gave suppression of the tissue water resonance by a factor of 80,000 when tau = 68 ms. Delivery of a frequency-selective Dante pulse train to the alpha-CH resonance of lactate at 4.11 ppm, simultaneously with the 2662 refocusing pulse, altered the j-modulation in the spin-coupled beta-CH3 protons. Subtraction of this spectrum from one in which the Dante was ineffective gave an edited spectrum containing only the beta-CH3 resonance of lactate at 1.31 ppm. When the position of the Dante was shifted to 3.78 ppm to selectively invert the alpha-CH protons of alanine, an edited spectrum of alanine was obtained.

  6. (/sup 3/H)-beta-endorphin binding in rat brain

    SciTech Connect

    Houghten, R.A.; Johnson, N.; Pasternak, G.W.

    1984-10-01

    The binding of (/sup 3/H)-beta-endorphin to rat brain homogenates is complex. Although Scatchard analysis of saturation studies yields a straight line, detailed competition studies are multiphasic, suggesting that even at low concentrations of the compound, the /sup 3/H-ligand is binding to more than one class of site. A portion of (/sup 3/H)-beta-endorphin binding is sensitive to low concentrations of morphine or D-Ala2-Leu5-enkephalin (less than 5 nM). The inhibition observed with each compound alone (5 nM) is the same as that seen with both together (each at 5 nM). Thus, the binding remaining in the presence of both morphine and the enkephalin does not correspond to either mu or delta sites. The portion of (/sup 3/H)-beta-endorphin binding that is inhibited under these conditions appears to be equally sensitive to both morphine and the enkephalin and may correspond to mu1 sites. Treating membrane homogenates with naloxonazine, a mu1 selective antagonist, lowers (/sup 3/H)-beta-endorphin binding to the same degree as morphine and D-Ala2-Leu5-enkephalin alone or together. This possible binding of (/sup 3/H)-beta-endorphin to mu1 sites is consistent with the role of mu1 sites in beta-endorphin analgesia and catalepsy in vivo.

  7. Angiotensin-converting enzyme inhibitors modulate kynurenic acid production in rat brain cortex in vitro.

    PubMed

    Zakrocka, Izabela; Turski, Waldemar A; Kocki, Tomasz

    2016-10-15

    It is well established that the renin-angiotensin system (RAS) is present in the brain and that glutamate activates the brain centers responsible for blood pressure control. An antagonist of glutamate, kynurenic acid (KYNA) was shown to decrease blood pressure after intracerebral administration. KYNA is an endogenous metabolite of tryptophan produced from the breakdown of kynurenine by kynurenine aminotransferases (KAT), mainly within astrocytes. The purpose of this study was to evaluate the influence of three angiotensin-converting enzyme inhibitors (lisinopril, perindopril and ramipril) on KYNA production and KAT activity in the rat brain cortex in vitro. The effect of the angiotensin-converting enzyme inhibitors on KYNA production was examined on rat brain cortical slices incubated for 2h in the presence of l-kynurenine and the angiotensin-converting enzyme inhibitors. To analyze KAT I and KAT II activity, brain cortical homogenates were incubated for 2h with L-kynurenine and the tested drugs. KYNA was separated by HPLC and quantified fluorometrically. Among the examined angiotensin-converting enzyme inhibitors, lisinopril increased KYNA production, perindopril was ineffective, and ramipril decreased KYNA synthesis in rat brain cortical slices. Lisinopril increased KAT I activity and perindopril did not affect it. However, ramipril lowered KAT I activity in rat brain cortex in vitro. Neither lisinopril nor perindopril affected KAT II activity, but ramipril decreased KAT II activity in the rat brain cortex in vitro. Our study reveals that angiotensin-converting enzyme inhibitors show various influences on KYNA production in rat brain cortical slices and activity of KATs.

  8. Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction.

    PubMed

    Liu, J; Liu, L; Chen, H

    2011-05-01

    Changes in brain ultrastructure of fetal rats with intrauterine growth restriction (IUGR) were explored and the effects of antenatal taurine supplementation on their brain ultrastructure were determined. Fifteen pregnant rats were randomly divided into three groups: control group, IUGR model group and IUGR group given antenatal taurine supplements. Taurine was added to the diet of the taurine group at a dose of 300 mg/kg/d from 12 days after conception until natural delivery. Transmission electron microscopy was used to observe ultrastructural changes in the brains of the newborn rats. At the same time, brain cellular apoptosis was detected using TUNEL, and the changes in protein expression of neuron specific enolase and glial fibrillary acidic protein were analyzed using immunohistochemistry. The results showed that: 1) The average body weight and cerebral weight were significantly lower in the IUGR group than in the control group (p<0.01) and both of them were less so after taurine was supplemented (p<0.01). 2) Transmission electron microscopy revealed that brain cortex structures were sparse IUGR rats, showing many scattered apoptotic cells, decreased numbers of synapses, lower glial cell proliferation, and fewer neurons, more sparsely arranged, while these factors were significantly improved with taurine supplementation. 3) The results of TUNEL showed that the counts of apoptotic brain cells in IUGR groups were significantly increased from those in control groups and that taurine could significantly decrease brain cell apoptosis (p<0.001). 4) The results of immunohistochemistry showed that antenatal taurine-supplementation could significantly increase the counts of neuron specific enolase and glial fibrillary acidic protein immunoreactive cells in fetal rats with IUGR (p<0.001). It can be concluded that it IUGR has a significant detrimental influence on the development of fetal rat brains, and antenatal supplement of taurine can significantly improve the IUGR

  9. Nanoparticle mediated silencing of DNA repair sensitizes pediatric brain tumor cells to γ-irradiation

    PubMed Central

    Kievit, Forrest M.; Stephen, Zachary R.; Wang, Kui; Dayringer, Christopher J.; Sham, Jonathan G.; Ellenbogen, Richard G.; Silber, John R.; Zhang, Miqin

    2015-01-01

    Medulloblastoma (MB) and ependymoma (EP) are the most common pediatric brain tumors, afflicting 3,000 children annually. Radiotherapy (RT) is an integral component in the treatment of these tumors; however, the improvement in survival is often accompanied by radiation-induced adverse developmental and psychosocial sequelae. Therefore, there is an urgent need to develop strategies that can increase the sensitivity of brain tumors cells to RT while sparing adjacent healthy brain tissue. Apurinic endonuclease 1 (Ape1), an enzyme in the base excision repair pathway, has been implicated in radiation resistance in cancer. Pharmacological and specificity limitations inherent to small molecule inhibitors of Ape1 have hindered their clinical development. Here we report on a nanoparticle (NP) based siRNA delivery vehicle for knocking down Ape1 expression and sensitizing pediatric brain tumor cells to RT. The NP comprises a superparamagnetic iron oxide core coated with a biocompatible, biodegradable coating of chitosan, polyethylene glycol (PEG), and polyethyleneimine (PEI) that is able to bind and protect siRNA from degradation and to deliver siRNA to the perinuclear region of target cells. NPs loaded with siRNA against Ape1 (NP:siApe1) knocked down Ape1 expression over 75% in MB and EP cells, and reduced Ape1 activity by 80%. This reduction in Ape1 activity correlated with increased DNA damage post-irradiation, which resulted in decreased cell survival in clonogenic assays. The sensitization was specific to therapies generating abasic lesions as evidenced by NP:siRNA not increasing sensitivity to paclitaxel, a microtubule disrupting agent. Our results indicate NP-mediated delivery of siApe1 is a promising strategy for circumventing pediatric brain tumor resistance to RT. PMID:25681012

  10. Measurement of blast wave by a miniature fiber optic pressure transducer in the rat brain.

    PubMed

    Chavko, Mikulas; Koller, Wayne A; Prusaczyk, W Keith; McCarron, Richard M

    2007-01-30

    Exposure to blast wave that is generated during an explosion may result in brain damage and related neurological impairments. The aim of this study was to investigate pressure changes induced by exposure to blast inside the rat brain. For intracranial pressure measurement we used a miniature optic fiber sensor (o.d. 550 microm) with a computer recording system. The sensor was placed in the third cerebral ventricle of anesthetized rats exposed to 40 kPa blast wave in a pneumatic-pressure driven shock tube. Short pressure waves lasting several ms were detected inside the brain with the magnitude that might result in nervous tissue damage. PMID:16949675

  11. Effects of nanoparticle zinc oxide on emotional behavior and trace elements homeostasis in rat brain.

    PubMed

    Amara, Salem; Slama, Imen Ben; Omri, Karim; El Ghoul, Jaber; El Mir, Lassaad; Rhouma, Khemais Ben; Abdelmelek, Hafedh; Sakly, Mohsen

    2015-12-01

    Over recent years, nanotoxicology and the potential effects on human body have grown in significance, the potential influences of nanosized materials on the central nervous system have received more attention. The aim of this study was to determine whether zinc oxide (ZnO) nanoparticles (NPs) exposure cause alterations in emotional behavior and trace elements homeostasis in rat brain. Rats were treated by intraperitoneal injection of ZnO NPs (20-30 nm) at a dose of 25 mg/kg body weight. Sub -: acute ZnO NPs treatment induced no significant increase in the zinc content in the homogenate brain. Statistically significant decreases in iron and calcium concentrations were found in rat brain tissue compared to control. However, sodium and potassium contents remained unchanged. Also, there were no significant changes in the body weight and the coefficient of brain. In the present study, the anxiety-related behavior was evaluated using the plus-maze test. ZnO NPs treatment modulates slightly the exploratory behaviors of rats. However, no significant differences were observed in the anxious index between ZnO NP-treated rats and the control group (p > 0.05). Interestingly, our results demonstrated minimal effects of ZnO NPs on emotional behavior of animals, but there was a possible alteration in trace elements homeostasis in rat brain.

  12. Long-term environmental enrichment leads to regional increases in neurotrophin levels in rat brain.

    PubMed

    Ickes, B R; Pham, T M; Sanders, L A; Albeck, D S; Mohammed, A H; Granholm, A C

    2000-07-01

    A number of studies have demonstrated that both morphological and biochemical indices in the brain undergo alterations in response to environmental influences. In previous work we have shown that rats raised in an enriched environmental condition (EC) perform better on a spatial memory task than rats raised in isolated conditions (IC). We have also found that EC rats have a higher density of immunoreactivity than IC rats for both low and high affinity nerve growth factor (NGF) receptors in the basal forebrain. In order to determine if these alterations were coupled with altered levels of neurotrophins in other brain regions as well, we measured neurotrophin levels in rats that were raised in EC or IC conditions. Rats were placed in the different environments at 2 months of age and 12 months later brain regions were dissected and analyzed for NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) levels using Promega ELISA kits. We found that NGF and BDNF levels were increased in the cerebral cortex, hippocampal formation, basal forebrain, and hindbrain in EC animals compared to age-matched IC animals. NT-3 was found to be increased in the basal forebrain and cerebral cortex of EC animals as well. These findings demonstrate significant alterations in NGF, BDNF, and NT-3 protein levels in several brain regions as a result of an enriched versus an isolated environment and thus provide a possible biochemical basis for behavioral and morphological alterations that have been found to occur with a shifting environmental stimulus.

  13. Pharmacokinetics and brain uptake of diazepam after intravenous and intranasal administration in rats and rabbits.

    PubMed

    Kaur, Paramjeet; Kim, Kwonho

    2008-11-19

    The purpose of this study was to investigate the plasma pharmacokinetics and brain uptake of a lipophilic benzodiazepine anticonvulsant, diazepam in New Zealand white rabbits and Sprague-Dawley rats to evaluate the possible absorption pathways after intravenous and intranasal administration. The intranasal formulation was prepared by dissolving DZ and 1% sodium glycocholate into microemulsion system composed of 15% ethyl laurate, 25% Labrasol, 37.5% Transcutol P, 12.5% ethanol, and 10% water. Diazepam was administered intravenously (1 mg/kg) or intranasally (2 mg/kg) to rats and rabbits. Drug concentrations in the plasma and six different regions of the brain tissues, i.e., olfactory bulb, olfactory tract, anterior, middle, and posterior segments of cerebrum and cerebellum were analyzed by LC/MS method after solid phase extraction. After i.n. administration, DZ was rapidly absorbed into the systemic circulation, and readily and homogeneously distributed into the different regions of brain tissues with a t(max) of 5 and 10 min in rats and rabbits, respectively. The bioavailability of DZ in rat plasma (68.4%) and brain (67.7%) were 32-47% higher than those observed in rabbit plasma (51.6%) and brain (45.9%). The AUC(brain)/AUC(plasma) ratios in rabbits after i.n. administration (3.77+/-0.17) were slightly lower than from i.v. administration (4.23+/-0.08). However, in rats the AUC(brain)/AUC(plasma) ratios after i.v. (3.03+/-0.07) and i.n. (3.00+/-0.32) administration were nearly identical. The plasma pharmacokinetic and distribution studies in the two animal models clearly showed that lipophilic DZ molecules reached the brain predominantly from the blood by crossing the blood-brain barrier after i.n. administration with no significant direct nose-to-brain transport via olfactory epithelium.

  14. Brain energy consumption in ethanol-treated, Long-Evans rats.

    PubMed

    Viña, J R; Salus, J E; DeJoseph, M R; Pallardo, F; Towfighi, J; Hawkins, R A

    1991-06-01

    The cerebral metabolic rate of glucose utilization (CMRGlc) was measured in rats fed liquid diets containing ethanol for 8 wk, after removal of ethanol from the diet and after acute ethanol intoxication. Control rats were pair fed the liquid diets containing isoenergetic amounts of dextrin-maltose. Quantitative autogradiography using [6-14C]glucose measured CMRGlc at the level of individual structures. Digital image techniques created stereograms of brain energy consumption from the autoradiographs. These techniques provided information about CMRGlc throughout the brain. Rats given the ethanol liquid diet drank constantly throughout the day and night. Neuropathological examination of brain revealed no abnormalities from ethanol consumption. Acute ethanol administration to control rats produced a decrease in CMRGlc throughout the brain that was most prominent in structures concerning auditory, visual, memory and motor functions. Chronic ethanol consumption did not reduce CMRGlc to the same degree as acute ethanol intoxication; in fact, it affected only a few structures. The removal of ethanol from chronic ethanol-treated rats for a period of 18 h caused CMRGlc to rise above control values throughout the brain. However, there were no seizures or other evidence of brain dysfunction.

  15. Prevention of GVHD by modulation of rat bone marrow with UV-B irradiation. II. Kinetics of migration of UV-B-irradiated bone marrow cells in naive and lethally irradiated rats

    SciTech Connect

    Oluwole, S.F.; Engelstad, K.; Hardy, M.A. )

    1990-06-01

    UV-B irradiation (700 J/m2) of bone marrow (BM) cells prior to transplantation into lethally gamma-irradiated (1050 rad) allogeneic rats prevents the development of GVHD and results in a stable mixed lymphohematopoietic chimerism. To better understand the underlying mechanisms of the development of stable radiation chimeras in this model, this study was designed to examine whether the dose (700 J/m2) of UV-B irradiation used for the modulation of the BM inoculum would affect the homing pattern of radiolabeled BM cells compared to that of thoracic duct lymphocytes (TDL) in the naive and lethally irradiated recipients. The results showed that intravenously administered, 111Indium-oxine-labeled, unmodified TDL home specifically to the spleen, lymph nodes, and BM compartments with a subsequent recirculation of a large number of cells from the spleen to the lymph nodes. In contrast, radiolabeled, unmodified BM cells migrate specifically to the spleen, liver, and BM with the lymph nodes, thymus, and nonlymphoid organs containing very little amounts of radioactivity. The stable concentrations of radioactivity in the lymphoid and nonlymphoid compartments between 3 and 72 hr after injection suggest that BM cells, unlike TDL, do not recirculate. The migration pattern of BM cells in the naive recipient was not significantly different from that seen in lethally irradiated animals except for the higher concentration of radioactivity in the spleen and BM of irradiated animals compared to that seen in naive recipients. The similarity of tissue localization of BM cells in naive or in irradiated syngeneic recipients to that of allogeneic recipients suggests that the homing of BM cells is not MHC restricted.

  16. Lithium Visibility in Rat Brain and Muscle in Vivoby 7Li NMR Imaging

    NASA Astrophysics Data System (ADS)

    Komoroski, Richard A.; Pearce, John M.; Newton, Joseph E. O.

    1998-07-01

    The apparent concentration of lithium (Li)in vivowas determined for several regions in the brain and muscle of rats by7Li NMR imaging at 4.7 T with inclusion of an external standard of known concentration and visibility. The average apparent concentrations were 10.1 mM for muscle, and 4.2-5.3 mM for various brain regions under the dosing conditions used. The results were compared to concentrations determinedin vitroby high-resolution7Li NMR spectroscopy of extracts of brain and muscle tissue from the same rats. The comparison provided estimates of the7Li NMR visibility of the Li cation in each tissue region. Although there was considerable scatter of the calculated visibilities among the five rats studied, the results suggested essentially full visibility (96%) for Li in muscle, and somewhat reduced visibility (74-93%) in the various brain regions.

  17. Optimization of choline administration regimen for correction of cognitive functions in rats after brain injury.

    PubMed

    Guseva, M V; Kamenskii, A A; Gusev, V B

    2013-06-01

    Choline diet promotes improvement of the brain cognitive functions in rats with moderate-to-severe traumatic brain injury. In previous studies, the rats received choline being standard (0.2%) or choline-supplemented (2%) diet for 2 weeks prior to and 2 weeks after experimental brain injury. To the end of the experiments (in 4 weeks), the post-traumatic disturbances in the cognitive functions were observed in both groups, although they were less pronounced than in the rats kept on the choline-supplemented diet. Based on original mathematical model, this paper proposes a method to calculate the most efficient use of choline to correct the brain cognitive functions. In addition to evaluating the cognitive functions, the study assessed expression of α7 nicotinic acetylcholine receptors, the amount of consumed food and water, and the dynamics of body weight.

  18. Radiation-Induced Oxidative Stress at Out-of-Field Lung Tissues after Pelvis Irradiation in Rats

    PubMed Central

    Najafi, Masoud; Fardid, Reza; Takhshid, Mohammad Ali; Mosleh-Shirazi, Mohammad Amin; Rezaeyan, Abol-Hassan; Salajegheh, Ashkan

    2016-01-01

    Objective The out-of-field/non-target effect is one of the most important phenomena of ionizing radiation that leads to molecular and cellular damage to distant non-irradiated tissues. The most important concern about this phenomenon is carcinogenesis many years after radiation treatment. In vivo mechanisms and consequences of this phenomenon are not known completely. Therefore, this study aimed to evaluate the oxidative damages to out-of-field lung tissues 24 and 72 hours after pelvic irradiation in rats. Materials and Methods In this experimentalinterventional study, Sprague-Dawleymale rats (n=49) were divided into seven groups (n=7/each group), including two groups of pelvis- exposed rats (out-of-field groups), two groups of whole bodyexposed rats (scatter groups), two groups of lung-exposed rats (direct irradiation groups), and one control sham group. Out- of-field groups were irradiated at a 2×2 cm area in the pelvis region with 3 Gy using 1.25 MeV cobalt-60 gamma-ray source, and subsequently, malondialdehyde (MDA) and glutathione (GSH) levels as well as superoxide dismutase (SOD) activity in out-of-field lung tissues were measured. Results were compared to direct irradiation, control and scatter groups at 24 and 72 hours after exposure. Data were analyzed using Mann-Whitney U test. Results SOD activity decreased in out-of-field lung tissue 24 and 72 hours after irradiation as compared with the controls and scatter groups. GSH level decreased 24 hours after exposure and increased 72 hours after exposure in the out-of-field groups as compared with the scatter groups. MDA level in out-of-field groups only increased 24 hours after irradiation. Conclusion Pelvis irradiation induced oxidative damage in distant lung tissue that led to a dramatic decrease in SOD activity. This oxidative stress was remarkable, but it was less durable as compared to direct irradiation. PMID:27602315

  19. Radiation-Induced Oxidative Stress at Out-of-Field Lung Tissues after Pelvis Irradiation in Rats

    PubMed Central

    Najafi, Masoud; Fardid, Reza; Takhshid, Mohammad Ali; Mosleh-Shirazi, Mohammad Amin; Rezaeyan, Abol-Hassan; Salajegheh, Ashkan

    2016-01-01

    Objective The out-of-field/non-target effect is one of the most important phenomena of ionizing radiation that leads to molecular and cellular damage to distant non-irradiated tissues. The most important concern about this phenomenon is carcinogenesis many years after radiation treatment. In vivo mechanisms and consequences of this phenomenon are not known completely. Therefore, this study aimed to evaluate the oxidative damages to out-of-field lung tissues 24 and 72 hours after pelvic irradiation in rats. Materials and Methods In this experimentalinterventional study, Sprague-Dawleymale rats (n=49) were divided into seven groups (n=7/each group), including two groups of pelvis- exposed rats (out-of-field groups), two groups of whole bodyexposed rats (scatter groups), two groups of lung-exposed rats (direct irradiation groups), and one control sham group. Out- of-field groups were irradiated at a 2×2 cm area in the pelvis region with 3 Gy using 1.25 MeV cobalt-60 gamma-ray source, and subsequently, malondialdehyde (MDA) and glutathione (GSH) levels as well as superoxide dismutase (SOD) activity in out-of-field lung tissues were measured. Results were compared to direct irradiation, control and scatter groups at 24 and 72 hours after exposure. Data were analyzed using Mann-Whitney U test. Results SOD activity decreased in out-of-field lung tissue 24 and 72 hours after irradiation as compared with the controls and scatter groups. GSH level decreased 24 hours after exposure and increased 72 hours after exposure in the out-of-field groups as compared with the scatter groups. MDA level in out-of-field groups only increased 24 hours after irradiation. Conclusion Pelvis irradiation induced oxidative damage in distant lung tissue that led to a dramatic decrease in SOD activity. This oxidative stress was remarkable, but it was less durable as compared to direct irradiation.

  20. Oxidative state and oxidative metabolism in the brain of rats with adjuvant-induced arthritis.

    PubMed

    Wendt, Mariana Marques Nogueira; de Sá-Nakanishi, Anacharis Babeto; de Castro Ghizoni, Cristiane Vizioli; Bersani Amado, Ciomar Aparecida; Peralta, Rosane Marina; Bracht, Adelar; Comar, Jurandir Fernando

    2015-06-01

    The purpose of the present study was to evaluate the oxidative status of the brain of arthritic rats, based mainly on the observation that arthritis induces a pronounced oxidative stress in the liver of arthritis rats and that morphological alterations have been reported to occur in patients with rheumatoid arthritis. Rats with adjuvant-induced arthritis were used. These animals presented higher levels of reactive oxygen species (ROS) in the total brain homogenate (25% higher) and in the mitochondria (+55%) when compared to healthy rats. The nitrite plus nitrate contents, nitric oxide (NO) markers, were also increased in both mitochondria (+27%) and cytosol (+14%). Arthritic rats also presented higher levels of protein carbonyl groups in the total homogenate (+43%), mitochondria (+69%) and cytosol (+145%). Arthritis caused a diminution of oxygen consumption in isolated brain mitochondria only when ascorbate was the electron donor. The disease diminished the mitochondrial cytochrome c oxidase activity by 55%, but increased the transmembrane potential by 16%. The pro-oxidant enzyme xanthine oxidase was 150%, 110% and 283% higher, respectively, in the brain homogenate, mitochondria and cytosol of arthritic animals. The same occurred with the calcium-independent NO-synthase activity that was higher in the brain homogenate (90%) and cytosol (122%) of arthritic rats. The catalase activity, on the other hand, was diminished by arthritis in all cellular fractions (between 30 and 40%). It is apparent that the brain of rats with adjuvant-induced arthritis presents a pronounced oxidative stress and a significant injury to lipids and proteins, a situation that possibly contributes to the brain symptoms of the arthritis disease.

  1. Regional Volume Decreases in the Brain of Pax6 Heterozygous Mutant Rats: MRI Deformation-Based Morphometry

    PubMed Central

    Hiraoka, Kotaro; Sumiyoshi, Akira; Nonaka, Hiroi; Kikkawa, Takako; Kawashima, Ryuta; Osumi, Noriko

    2016-01-01

    Pax6 is a transcription factor that pleiotropically regulates various developmental processes in the central nervous system. In a previous study, we revealed that Pax6 heterozygous mutant (rSey2/+) adult rats exhibit abnormalities in social interaction. However, the brain malformations underlying the behavioral abnormality are unknown. To elucidate the brain malformations in rSey2/+ rats, we morphometrically analyzed brains of rSey2/+ and wild type rats using small-animal magnetic resonance imaging (MRI). Sixty 10-week-old rats underwent brain MRI (29 rSey2/+ rats and 31 wild type rats). SPM8 software was used for image preprocessing and statistical image analysis. Normalized maps of the Jacobian determinant, a parameter for the expansion and/or contraction of brain regions, were obtained for each rat. rSey2/+ rats showed significant volume decreases in various brain regions including the neocortex, corpus callosum, olfactory structures, hippocampal formation, diencephalon, and midbrain compared to wild type rats. Among brain regions, the anterior commissure showed significant interaction between genotype and sex, indicating the effect of genotype difference on the anterior commissure volume was more robust in females than in males. The rSey2/+ rats exhibited decreased volume in various gray and white matter regions of the brain, which may contribute to manifestation of abnormal social behaviors. PMID:27355350

  2. Effect of meta-chlorobenzhydryl urea (m-ClBHU) on benzodiazepine receptor system in rat brain during experimental alcoholism.

    PubMed

    Shushpanova, T V; Solonskii, A V; Novozheeva, T P; Udut, V V

    2014-04-01

    Chronic alcohol intake induces neuroadaptive changes in benzodiazepine receptors modulating GABAA receptors that promote alcohol addiction. Analysis of benzodiazepine receptors in the brain of Wistar rats differing by alcohol preference has demonstrated that affinity of [(3)H]flunitrazepam and [(3)H]Ro5-4864 binding with membrane fraction was reduced, while the density of specific binding sites in the brain cortex of heavy drinking and low drinking rats was increased in comparison with rats nonpreferring alcohol. Administration of anticonvulsant meta-chlorobenzhydryl urea increased affinity of benzodiazepine receptors in the brain cortex of heavy drinking rats, which improved GABA neurotransmission in the brain of these animals and reduced alcohol consumption.

  3. Action of the pyrethroid insecticide cypermethrin on rat brain IIa sodium channels expressed in xenopus oocytes.

    PubMed

    Smith, T J; Soderlund, D M

    1998-12-01

    Pyrethroid insecticides bind to a unique site on voltage-dependent sodium channels and prolong sodium currents, leading to repetitive bursts of action potentials or use-dependent nerve block. To further characterize the site and mode of action of pyrethroids on sodium channels, we injected synthetic mRNA encoding the rat brain IIa sodium channel alpha subunit, either alone or in combination with synthetic mRNA encoding the rat sodium channel beta1 subunit, into oocytes of the frog Xenopus laevis and assessed the actions of the pyrethroid insecticide [1R,cis,alphaS]-cypermethrin on expressed sodium currents by two-electrode voltage clamp. In oocytes expressing only the rat brain IIa alpha subunit, cypermethrin produced a slowly-decaying sodium tail current following a depolarizing pulse. In parallel experiments using oocytes expressing the rat brain IIa alpha subunit in combination with the rat beta1 subunit, cypermethrin produced qualitatively similar tail currents following a depolarizing pulse and also induced a sustained component of the sodium current measured during a step depolarization of the oocyte membrane. The voltage dependence of activation and steady-state inactivation of the cypermethrin-dependent sustained current were identical to those of the peak transient sodium current measured in the absence of cypermethrin. Concentration-response curves obtained using normalized tail current amplitude as an index of the extent of sodium channel modification by cypermethrin revealed that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit increased the apparent affinity of the sodium channel binding site for cypermethrin by more than 20-fold. These results confirm that the pyrethroid binding site is intrinsic to the sodium channel alpha subunit and demonstrate that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit alters the apparent affinity of this site for pyrethroids.

  4. Effects of neonatal treatment with the TRPV1 agonist, capsaicin, on adult rat brain and behaviour.

    PubMed

    Newson, Penny N; van den Buuse, Maarten; Martin, Sally; Lynch-Frame, Ann; Chahl, Loris A

    2014-10-01

    Treatment of neonatal rats with the transient receptor potential vanilloid 1 (TRPV1) channel agonist, capsaicin, produces life-long loss of sensory neurons expressing TRPV1 channels. Previously it was shown that rats treated on day 2 of life with capsaicin had behavioural hyperactivity in a novel environment at 5-7 weeks of age and brain changes reminiscent of those found in subjects with schizophrenia. The objective of the present study was to investigate brain and behavioural responses of adult rats treated as neonates with capsaicin. It was found that the brain changes found at 5-7 weeks in rats treated as neonates with capsaicin persisted into adulthood (12 weeks) but were less in older rats (16-18 weeks). Increased prepulse inhibition (PPI) of acoustic startle was found in these rats at 8 and 12 weeks of age rather than the deficit commonly found in animal models of schizophrenia. Subjects with schizophrenia also have reduced flare responses to niacin and methylnicotinate proposed to be mediated by prostaglandin D2 (PGD2). Flare responses are accompanied by cutaneous plasma extravasation. It was found that the cutaneous plasma extravasation responses to methylnicotinate and PGD2 were reduced in capsaicin-treated rats. In conclusion, several neuroanatomical changes observed in capsaicin-treated rats, as well as the reduced cutaneous plasma extravasation responses, indicate that the role of TRPV1 channels in schizophrenia is worthy of investigation.

  5. Glucocorticoids modulate the NGF mRNA response in the rat hippocampus after traumatic brain injury.

    PubMed

    Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M

    2001-02-23

    Nerve growth factor (NGF) expression in the rat hippocampus is increased after experimental traumatic brain injury (TBI) and is neuroprotective. Glucocorticoids are regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on the expression of NGF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury and in situ hybridisation to evaluate the expression of NGF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomised rats (with or without CORT replacement). TBI increased expression of NGF mRNA in sham-ADX rats, but not in ADX rats. Furthermore, CORT replacement in ADX rats restored the increase in NGF mRNA induced by TBI. These findings suggest that glucocorticoids have an important role in the induction of hippocampal NGF mRNA after TBI.

  6. Induction of tolerance to cardiac allografts in lethally irradiated rats reconstituted with syngeneic bone marrow

    SciTech Connect

    Hartnett, L.C.

    1983-01-01

    Generally, organ grafts from one individual animal to another are rejected in one-two weeks. However, if the recipients are given Total Body Irradiation (TBI) just prior to grafting, followed by reconstitution of hemopoietic function with syngeneic (recipient-type) bone marrow cells, then vascularized organ grafts are permanently accepted. Initially after irradiation, it is possible to induce tolerance to many strain combinations in rats. This thesis examines the system of TBI as applied to the induction of tolerance in LEW recipients of WF cardiac allografts. These two rat strains are mismatched across the entire major histocompatibility complex. When the LEW recipient are given 860 rads, a WF cardiac allograft and LEW bone marrow on the same day, 60% of the grafts are accepted. Methods employed to improve the rate of graft acceptance include: treating either donor or recipient with small amounts of methotrexate, or waiting until two days after irradiation to repopulate with bone marrow. It seems from these investigations of some of the early events in the induction of tolerance to allografts following TBI and syngeneic marrow reconstitution that an immature cell population in the bone marrow interacts with a radioresistant cell population in the spleen to produce tolerance to completely MHC-mismatched allografts.

  7. Role of the bradykinin B2 receptor in a rat model of local heart irradiation

    PubMed Central

    Lieblong, Benjamin J.; Sridharan, Vijayalakshmi; Srivastava, Anup K.; Moros, Eduardo G.; Sharma, Sunil K.; Boerma, Marjan

    2016-01-01

    Purpose Radiation-induced heart disease (RIHD) is a delayed effect of radiotherapy for cancers of the chest, such as breast, esophageal, and lung. Kinins are small peptides with cardioprotective properties. We previously used a rat model that lacks the precursor kininogen to demonstrate that kinins are involved in RIHD. Here, we examined the role of the kinin B2 receptor (B2R) in early radiation-induced signaling in the heart. Materials and methods Male Brown Norway rats received the B2R-selective antagonist HOE-140 (icatibant) via osmotic minipump from 5 days before until 4 weeks after 21 Gy local heart irradiation. At 4 weeks, signaling events were measured in left ventricular homogenates and nuclear extracts using western blotting and real-time polymerase chain reaction. Numbers of CD68-positive (monocytes/macrophages), CD2-positive (T-lymphocytes), and mast cells were measured using immunohistochemistry. Results Radiation-induced c-Jun phosphorylation and nuclear translocation were enhanced by HOE-140. HOE-140 did not modify endothelial nitric oxide synthase (eNOS) phosphorylation or alter numbers of CD2-positive or mast cells, but enhanced CD68-positive cell counts in irradiated hearts. Conclusions B2R signaling may regulate monocyte/macrophage infiltration and c-Jun signals in the irradiated heart. Although eNOS is a main target for kinins, the B2R may not regulate eNOS phosphorylation in response to radiation. PMID:25955317

  8. Enhancement of performance for brain stimulation reward after footshock in rats.

    PubMed

    Sadowski, B; Marek, P; Panocka, I

    1984-01-01

    Rats bearing electrodes in the anterior forebrain region (AF), lateral hypothalamus (LH) or dorsal raphe (DR) nucleus were trained to press lever for brain stimulation reward. Ten minutes self- stimulation in all these placements produced a lowering of pain sensitivity as assessed by the hot-plate test. Electric footshock administered on 1 s on/4 s off paradigm for 10 min prior to self-stimulation elevated lever pressing rates in AF rats and in part of LH rats, but not in DR rats. The results are discussed in terms of opiate theory of reinforcement.

  9. Regeneration of central cholinergic neurones in the adult rat brain.

    PubMed

    Svendgaard, N A; Björklund, A; Stenevi, U

    1976-01-30

    The regrowth of lesioned central acetylcholinesterase (AChE)-positive axons in the adult rat was studied in irides implanted to two different brain sites: in the caudal diencephalon and hippocampus, and in the hippocampal fimbria. At both implantation sites the cholinergic septo-hippocampal pathways were transected. At 2-4 weeks after lesion, newly formed, probably sprouting fibres could be followed in abundance from the lesioned proximal axon stumps into the iris transplant. Growth of newly formed AChE-positive fibres into the transplant was also observed from lesioned axons in the anterior thalamus, and to a minor extent also from the dorsal and ventral tegmental AChE-positive pathways and the habenulo-interpeduncular tract. The regrowth process of the sprouting AChE-positive, presumed cholinergic fibres into the iris target was studied in further detail in whole-mount preparations of the transplants. For this purpose the irides were removed from the brain, unfolded, spread out on microscope slides, and then stained for AChE. During the first 2-4 weeks after transplantation the sprouting central fibres grew out over large areas of the iris. The new fibres branched profusely into a terminal plexus that covered maximally about half of the iris surface, and in some areas the patterning of the regenerated central fibres mimicked closely that of the normal autonomic cholinergic innervation of the iris. In one series of experiments the AChE-staining was combined with fluorescence histochemical visualization of regenerated adrenergic fibres in the same specimens. In many areas there was a striking congruence in the distributional patterns of the regenerated central cholinergic and adrenergic fibres in the transplant. This indicates that - as in the normal iris - the sprouting cholinergic axons (primarily originating in the lesioned septo-hippocampal pathways) and adrenergic axons (primarily originating in the lesioned axons of the locus neurones) regenerate together

  10. The effects of LED rectal irradiation on the experimental ulcerative colitis in rats

    NASA Astrophysics Data System (ADS)

    Zeng, Chang-Chun; Wang, Xian-Ju; Guo, Zhou-Yi; Liu, Song-Hao

    2006-01-01

    We evaluated the effects of light emitting diode(LED λ 632.8nm; power 4.0mw)applied directly to the colon on the experimental ulcerative colitis. 34 rats were divided into 3 groups, which was LED treatment group (n=12), model group (n=12), and normal control group (n=10). Given glacial acetic acid (5%) intra-anally so as to be replicated the rat model of ulcerative colitis. LED irradiation was used to curative group, with 30min each time, once per day. The period of treatment was one week. Then the activity of superoxide dismutase (SOD) and content of malondi-aldehyde (MDA) in the blood plasma were detected and the histopathological study in Colonic tissue was performed. The degree of the Colonic tissue injury in curative group was not as significant as that in the model group. Comparing with model group, the Content of MDA in LED curative group was reductive and the activity of SOD was increased significantly. We concluded that the LED irradiation can protect colonic mucosa from acetic acid induced damage in rats and the effects may be related to the photobiomodulation of LED.

  11. In vivo pink-beam imaging and fast alignment procedure for rat brain tumor radiation therapy.

    PubMed

    Nemoz, Christian; Kibleur, Astrid; Hyacinthe, Jean Noël; Berruyer, Gilles; Brochard, Thierry; Bräuer-Krisch, Elke; Le Duc, Géraldine; Brun, Emmanuel; Elleaume, Hélène; Serduc, Raphaël

    2016-01-01

    A fast positioning method for brain tumor microbeam irradiations for preclinical studies at third-generation X-ray sources is described. The three-dimensional alignment of the animals relative to the X-ray beam was based on the X-ray tomography multi-slices after iodine infusion. This method used pink-beam imaging produced by the ID17 wiggler. A graphical user interface has been developed in order to define the irradiation parameters: field width, height, number of angles and X-ray dose. This study is the first reporting an image guided method for soft tissue synchrotron radiotherapy. It allowed microbeam radiation therapy irradiation fields to be reduced by a factor of ∼20 compared with previous studies. It permitted more targeted, more efficient brain tumor microbeam treatments and reduces normal brain toxicity of the radiation treatment.

  12. Transmission of a Filterable Agent from Rat Leukaemia Induced by X-Ray Irradiation and Treatment with Methylcholanthrene

    SciTech Connect

    Sveg, F.; Hlavay, E.

    2004-07-01

    Leukemia was induced in rats by combination of x irradiation and oral application of methylcholanthrene. The rats were irradiated by a single dose of 800 r, and methylcholanthrene was applied 3 times a week by stomach tube in a dose of 1 mg for 9 months. From 60 rats, myelogenous leukemia developed in 2 and lymphatic leukemia in 1. The myelobiastic leukemia proved to be transplantable and was maintained as MR-leukemia. After irtravenous injection of 1 to 10 x 10/ sup 6/ leukemic cells, obtained from the liver and spleen, the disease developed in adult rats in 6 to 10 days. As early as the 2nd or 3rd day after inoculation, leukemic infiltration of organs, especially liver and spleen, were seen. The rats died exhibiting signs of generalized leukemia within 10 days. If cell-free filtrates from the liver and spleen of rats bearing MR leukemia were injected into newborn and 4-week-old rats, myelogenous leukemia developed in the newborn group in 24% after a latency period of 520 days and in 33% of the 4-week-old group after 570 days, on an average. The induced leukemias were transplantable into both suckling and adult rats. Many of the injected animals, which did not develop leukemia, died of cirrhosis of the liver. The results suggest that the leukemia induced by irradiation and chemical carcinogen might be caused by a submicroscopic virus-like agent.

  13. Photoacoustic imaging to detect rat brain activation after cocaine hydrochloride injection

    NASA Astrophysics Data System (ADS)

    Jo, Janggun; Yang, Xinmai

    2011-03-01

    Photoacoustic imaging (PAI) was employed to detect small animal brain activation after the administration of cocaine hydrochloride. Sprague Dawley rats were injected with different concentrations (2.5, 3.0, and 5.0 mg per kg body) of cocaine hydrochloride in saline solution through tail veins. The brain functional response to the injection was monitored by photoacoustic tomography (PAT) system with horizontal scanning of cerebral cortex of rat brain. Photoacoustic microscopy (PAM) was also used for coronal view images. The modified PAT system used multiple ultrasonic detectors to reduce the scanning time and maintain a good signal-to-noise ratio (SNR). The measured photoacoustic signal changes confirmed that cocaine hydrochloride injection excited high blood volume in brain. This result shows PAI can be used to monitor drug abuse-induced brain activation.

  14. Ontogeny of ABC and SLC transporters in the microvessels of developing rat brain.

    PubMed

    Soares, Ricardo V; Do, Tuan M; Mabondzo, Aloïse; Pons, Gérard; Chhun, Stéphanie

    2016-04-01

    The blood-brain barrier (BBB) is responsible for the control of solutes' concentration in the brain. Tight junctions and multiple ATP-binding cassette (ABC) and SoLute Carrier (SLC) efflux transporters protect brain cells from xenobiotics, therefore reducing brain exposure to intentionally administered drugs. In epilepsy, polymorphisms and overexpression of efflux transporters genes could be associated with pharmacoresistance. The ontogeny of these efflux transporters should also be addressed because their expression during development may be related to different brain exposure to antiepileptic drugs in the immature brain. We detected statistically significant higher expression of Abcb1b and Slc16a1 genes, and lower expression of Abcb1a and Abcg2 genes between the post-natal day 14 (P14) and the adult rat microvessels. P-gP efflux activity was also shown to be lower in P14 rats when compared with the adults. The P-gP proteins coded by rodent genes Abcb1a and Abcb1b are known to have different substrate affinities. The role of the Abcg2 gene is less clear in pharmacoresistance in epilepsy, nonetheless the coded protein Bcrp is frequently associated with drug resistance. Finally, we observed a higher expression of the Mct1 transporter gene in the P14 rat brain microvessels. Accordingly to our results, we suppose that age may be another factor influencing brain exposure to antiepileptics as a consequence of different expression patterns of efflux transporters between the adult and immature BBB.

  15. Epsilon Aminocaproic Acid Pretreatment Provides Neuroprotection Following Surgically Induced Brain Injury in a Rat Model.

    PubMed

    Komanapalli, Esther S; Sherchan, Prativa; Rolland, William; Khatibi, Nikan; Martin, Robert D; Applegate, Richard L; Tang, Jiping; Zhang, John H

    2016-01-01

    Neurosurgical procedures can damage viable brain tissue unintentionally by a wide range of mechanisms. This surgically induced brain injury (SBI) can be a result of direct incision, electrocauterization, or tissue retraction. Plasmin, a serine protease that dissolves fibrin blood clots, has been shown to enhance cerebral edema and hemorrhage accumulation in the brain through disruption of the blood brain barrier. Epsilon aminocaproic acid (EAA), a recognized antifibrinolytic lysine analogue, can reduce the levels of active plasmin and, in doing so, potentially can preserve the neurovascular unit of the brain. We investigated the role of EAA as a pretreatment neuroprotective modality in a SBI rat model, hypothesizing that EAA therapy would protect brain tissue integrity, translating into preserved neurobehavioral function. Male Sprague-Dawley rats were randomly assigned to one of four groups: sham (n = 7), SBI (n = 7), SBI with low-dose EAA, 150 mg/kg (n = 7), and SBI with high-dose EAA, 450 mg/kg (n = 7). SBI was induced by partial right frontal lobe resection through a frontal craniotomy. Postoperative assessment at 24 h included neurobehavioral testing and measurement of brain water content. Results at 24 h showed both low- and high-dose EAA reduced brain water content and improved neurobehavioral function compared with the SBI groups. This suggests that EAA may be a useful pretherapeutic modality for SBI. Further studies are needed to clarify optimal therapeutic dosing and to identify mechanisms of neuroprotection in rat SBI models. PMID:26463967

  16. Simultaneous NIR-EPR spectroscopy of rat brain oxygenation.

    PubMed

    Sakata, Yasuko S; Grinberg, Oleg Y; Grinberg, Stalina; Springett, Roger; Swartz, Harold M

    2005-01-01

    Changes in cerebral oxygenation were simultaneously monitored by electric paramagnetic resonance (EPR) oximetry and near-infrared spectroscopy (NIRS). The tissue oxygen tension (t-pO2) was measured with an L-band (1.2 GHz) EPR spectrometer with an external loop resonator and the concentration of oxyhemoglobin [HbO2] and deoxyhemoglobin [Hb] were measured with a full-spectral NIRS system. Mean cerebral hemoglobin saturation (SmcO2) was calculated from the absolute [HbO2] and [Hb]. Six adult male rats were implanted with lithium phthalocyanine (LiPc) crystals into the left cerebral cortex. The change in oxygenation of the brain was induced by altering the inspired oxygen fraction (FiO2) in air from 0.30 at baseline to 0.0, 0.05, 0.10, and 0.15 for 1, 2, 5, and 5 minutes, respectively, followed by reoxygenation with an FiO2 = 0.30. Although both t-pO2 and SmcO2 values showed a decrease during reduced FiO2 followed by recovery on reoxygenation, it was found that SmcO2 recovered more rapidly than t-PO2 during the recovery phase. The recovery of t-pO2 is not only related to blood oxygenation, but also to delivery, consumption, and diffusion of oxygen into the tissue from the vascular system. Further studies will be required to determine the exact mechanisms for the delay between the recovery of SmcO2 and t-pO2. PMID:16594173

  17. Mechanisms of blast induced brain injuries, experimental studies in rats.

    PubMed

    Risling, M; Plantman, S; Angeria, M; Rostami, E; Bellander, B-M; Kirkegaard, M; Arborelius, U; Davidsson, J

    2011-01-01

    Traumatic brain injuries (TBI) potentially induced by blast waves from detonations result in significant diagnostic problems. It may be assumed that several mechanisms contribute to the injury. This study is an attempt to characterize the presumed components of the blast induced TBI. Our experimental models include a blast tube in which an anesthetized rat can be exposed to controlled detonations of explosives that result in a pressure wave with a magnitude between 130 and 260 kPa. In this model, the animal is fixed with a metal net to avoid head acceleration forces. The second model is a controlled penetration of a 2mm thick needle. In the third model the animal is subjected to a high-speed sagittal rotation angular acceleration. Immunohistochemical labeling for amyloid precursor protein revealed signs of diffuse axonal injury (DAI) in the penetration and rotation models. Signs of punctuate inflammation were observed after focal and rotation injury. Exposure in the blast tube did not induce DAI or detectable cell death, but functional changes. Affymetrix Gene arrays showed changes in the expression in a large number of gene families including cell death, inflammation and neurotransmitters in the hippocampus after both acceleration and penetration injuries. Exposure to the primary blast wave induced limited shifts in gene expression in the hippocampus. The most interesting findings were a downregulation of genes involved in neurogenesis and synaptic transmission. These experiments indicate that rotational acceleration may be a critical factor for DAI and other acute changes after blast TBI. The further exploration of the mechanisms of blast TBI will have to include a search for long-term effects. PMID:20493951

  18. Monoclonal antibodies against type II rat brain protein kinase

    SciTech Connect

    Nakabayashi, C.H.; Huang, K.P.

    1987-05-01

    Three monoclonal antibodies (8/1, 10/10, and 25/3) against rat brain type II protein kinase C (PKC) were used to carry out the immunochemical characterization of this kinase. These antibodies immunoprecipitated the type II PKC in a dose-dependent manner but did neither to type I nor type III isozyme. Purified type II PKC has a molecular weight of 82,000 and consists of heterogeneous isoelectric point species, all of which are cross reactive with these antibodies. Immunoblot analysis of the tryptic fragments from PKC revealed that all three antibodies recognized the 33-38-KDa fragments, the phospholipid/phorbol ester-binding domain, but not the 45-48-KDa fragments, the kinase catalytic domain. The immune complexes of the kinase and the antibodies retained the kinase activity which was dependent on Ca/sup 2 +/ and phosphatidylserine (PS) and further activated by diacylglycerol. With antibody 8/1, the apparent Km values of the kinase for Ca/sup 2 +/ and PS were not influenced. The initial rate and final extent of autophosphorylation were reduced. The concentration of PS required for half-maximal (/sup 3/H)phorbol 12,13-dibutyrate (PDBu) binding was increased and the total PDBu binding was reduced. In the presence of optimum concentrations of Ca/sup 2 +/ and PS, the Kd of PDBu was unaffected by the antibody but the total binding was reduced. These results demonstrate that the PS/PDBu-binding domain contains the major epitope for the antibodies and the antibody mainly influences the PS/PDBu binding to the kinase.

  19. Brain capillary endothelium and choroid plexus epithelium regulate transport of transferrin-bound and free iron into the rat brain

    PubMed Central

    Deane, Rashid; Zheng, Wei; Zlokovic, Berislav V.

    2014-01-01

    Iron transport into the CNS is still not completely understood. Using a brain perfusion technique in rats, we have shown a significant brain capillary uptake of circulating transferrin (Tf)-bound and free 59Fe (1 nM) at rates of 136 ± 26 and 182 ± 23 μL/g/min, respectively, while their respective transport rates into brain parenchyma were 1.68 ± 0.56 and 1.52 ± 0.48 μL/g/min. Regional Tf receptor density (Bmax) in brain endothelium determined with 125I-holo-Tf correlated well with 59Fe-Tf regional brain uptake rates reflecting significant vascular association of iron. Tf-bound and free circulating 59Fe were sequestered by the choroid plexus and transported into the CSF at low rates of 0.17 ± 0.01 and 0.09 ± 0.02 μL/min/g, respectively, consistent with a 10-fold brain-CSF concentration gradient for 59Fe, Tf-bound or free. We conclude that transport of circulating Tf-bound and free iron could be equally important for its delivery to the CNS. Moreover, data suggest that entry of Tf-bound and free iron into the CNS is determined by (i) its initial sequestration by brain capillaries and choroid plexus, and (ii) subsequent controlled and slow release from vascular structures into brain interstitial fluid and CSF. PMID:14756801

  20. The Impact of Heart Irradiation on Dose-Volume Effects in the Rat Lung

    SciTech Connect

    Luijk, Peter van Faber, Hette; Meertens, Harm; Schippers, Jacobus M.; Langendijk, Johannes A.; Brandenburg, Sytze; Kampinga, Harm H.; Coppes, Robert P. Ph.D.

    2007-10-01

    Purpose: To test the hypothesis that heart irradiation increases the risk of a symptomatic radiation-induced loss of lung function (SRILF) and that this can be well-described as a modulation of the functional reserve of the lung. Methods and Materials: Rats were irradiated with 150-MeV protons. Dose-response curves were obtained for a significant increase in breathing frequency after irradiation of 100%, 75%, 50%, or 25% of the total lung volume, either including or excluding the heart from the irradiation field. A significant increase in the mean respiratory rate after 6-12 weeks compared with 0-4 weeks was defined as SRILF, based on biweekly measurements of the respiratory rate. The critical volume (CV) model was used to describe the risk of SRILF. Fits were done using a maximum likelihood method. Consistency between model and data was tested using a previously developed goodness-of-fit test. Results: The CV model could be fitted consistently to the data for lung irradiation only. However, this fitted model failed to predict the data that also included heart irradiation. Even refitting the model to all data resulted in a significant difference between model and data. These results imply that, although the CV model describes the risk of SRILF when the heart is spared, the model needs to be modified to account for the impact of dose to the heart on the risk of SRILF. Finally, a modified CV model is described that is consistent to all data. Conclusions: The detrimental effect of dose to the heart on the incidence of SRILF can be described by a dose dependent decrease in functional reserve of the lung.

  1. Standardized environmental enrichment supports enhanced brain plasticity in healthy rats and prevents cognitive impairment in epileptic rats.

    PubMed

    Fares, Raafat P; Belmeguenai, Amor; Sanchez, Pascal E; Kouchi, Hayet Y; Bodennec, Jacques; Morales, Anne; Georges, Béatrice; Bonnet, Chantal; Bouvard, Sandrine; Sloviter, Robert S; Bezin, Laurent

    2013-01-01

    Environmental enrichment of laboratory animals influences brain plasticity, stimulates neurogenesis, increases neurotrophic factor expression, and protects against the effects of brain insult. However, these positive effects are not constantly observed, probably because standardized procedures of environmental enrichment are lacking. Therefore, we engineered an enriched cage (the Marlau™ cage), which offers: (1) minimally stressful social interactions; (2) increased voluntary exercise; (3) multiple entertaining activities; (4) cognitive stimulation (maze exploration), and (5) novelty (maze configuration changed three times a week). The maze, which separates food pellet and water bottle compartments, guarantees cognitive stimulation for all animals. Compared to rats raised in groups in conventional cages, rats housed in Marlau™ cages exhibited increased cortical thickness, hippocampal neurogenesis and hippocampal levels of transcripts encoding various genes involved in tissue plasticity and remodeling. In addition, rats housed in Marlau™ cages exhibited better performances in learning and memory, decreased anxiety-associated behaviors, and better recovery of basal plasma corticosterone level after acute restraint stress. Marlau™ cages also insure inter-experiment reproducibility in spatial learning and brain gene expression assays. Finally, housing rats in Marlau™ cages after severe status epilepticus at weaning prevents the cognitive impairment observed in rats subjected to the same insult and then housed in conventional cages. By providing a standardized enriched environment for rodents during housing, the Marlau™ cage should facilitate the uniformity of environmental enrichment across laboratories.

  2. Effects of increasing brain GABA on the meal patterns of genetically obese vs. lean Zucker rats.

    PubMed

    Coscina, D V; Castonguay, T W; Stern, J S

    1992-06-01

    To explore recent suggestions that genetically obese Zucker rats show less anorexia when brain gamma-aminobutyric acid (GABA) is elevated, obese vs. lean littermates received 100, 50 and 0 micrograms of the GABA-transaminase inhibitor, ethanolamine-O-sulfate (EOS), intra-cisternally in a longitudinal design where their feeding patterns were monitored 24 h daily. Obese rats were refractory to EOS-induced anorexia as evidenced by less suppression of daily food intake and fewer alterations to both meal size and meal frequency, particularly in the night. This effect was not due to an inability of EOS to increase brain GABA since equivalent, specific dose-dependent increments were seen in the brains of separate obese vs. lean rats after analysis of endogenous GABA and seven other amino acids. An unexpected finding was elevated levels of brain taurine for obese rats regardless of EOS dosage, implying a hitherto unknown neurochemical trait whose potential significance is unclear. The primary data obtained provide further support for recent hypotheses that obese Zucker rats possess altered brain GABAergic mechanisms that may serve as one contributor to their over-eating.

  3. Hydroxysafflor yellow A exerts antioxidant effects in a rat model of traumatic brain injury.

    PubMed

    Wang, Yang; Zhang, Chunhu; Peng, Weijun; Xia, Zian; Gan, Pingping; Huang, Wei; Shi, Yafei; Fan, Rong

    2016-10-01

    Free radical-induced oxidative damage occurs rapidly and is of primary importance during the secondary pathophysiological cascades of traumatic brain injury (TBI). Hydroxysafflor yellow A (HSYA) is a constituent of the flower petals of Carthamus tinctorius (safflower) and may represent a potential therapeutic strategy to improve outcomes following TBI. The present study aimed to identify HSYA in the brain tissues of rats exposed to TBI to determine its absorption and to investigate the underlying effects of HSYA on antioxidant enzymes in the brain tissues of TBI rats. To determine the absorption of HSYA for the investigation of the underlying antioxidant effects of HSYA in TBI, the presence of HSYA in the brain tissues of the TBI rats was identified using an ultra performance liquid chromatography‑tandem mass spectrometry method. Subsequently, the state of oxidative stress in the TBI rat model following the administration of HSYA was investigated by determining the levels of antioxidant enzymes, including superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT), and the ratio of glutathione (GSH)/glutathione disulfide (GSSG). The data obtained demonstrated that HSYA was absorbed in the brain tissues of the TBI rats. HSYA increased the activities of SOD and CAT, the level of GSH and the GSH/GSSG ratio. However, HSYA concomitantly decreased the levels of MDA and GSSG. These preliminary data suggest that HSYA has the potential to be utilized as a neuroprotective drug in cases of TBI. PMID:27599591

  4. Hydroxysafflor yellow A exerts antioxidant effects in a rat model of traumatic brain injury

    PubMed Central

    Wang, Yang; Zhang, Chunhu; Peng, Weijun; Xia, Zian; Gan, Pingping; Huang, Wei; Shi, Yafei; Fan, Rong

    2016-01-01

    Free radical-induced oxidative damage occurs rapidly and is of primary importance during the secondary pathophysiological cascades of traumatic brain injury (TBI). Hydroxysafflor yellow A (HSYA) is a constituent of the flower petals of Carthamus tinctorius (safflower) and may represent a potential therapeutic strategy to improve outcomes following TBI. The present study aimed to identify HSYA in the brain tissues of rats exposed to TBI to determine its absorption and to investigate the underlying effects of HSYA on antioxidant enzymes in the brain tissues of TBI rats. To determine the absorption of HSYA for the investigation of the underlying antioxidant effects of HSYA in TBI, the presence of HSYA in the brain tissues of the TBI rats was identified using an ultra performance liquid chromatography-tandem mass spectrometry method. Subsequently, the state of oxidative stress in the TBI rat model following the administration of HSYA was investigated by determining the levels of antioxidant enzymes, including superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT), and the ratio of glutathione (GSH)/glutathione disulfide (GSSG). The data obtained demonstrated that HSYA was absorbed in the brain tissues of the TBI rats. HSYA increased the activities of SOD and CAT, the level of GSH and the GSH/GSSG ratio. However, HSYA concomitantly decreased the levels of MDA and GSSG. These preliminary data suggest that HSYA has the potential to be utilized as a neuroprotective drug in cases of TBI. PMID:27599591

  5. Preventive effect of safranal against oxidative damage in aged male rat brain

    PubMed Central

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Samini, Fariborz

    2014-01-01

    An imbalance between production of reactive oxygen species (ROS) and its elimination by antioxidant defense system in the body has been implicated for causes of aging and neurodegenerative diseases. This study was design to assess the changes in activities of antioxidant enzymes (superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase), lipid peroxidation and reduced glutathione (GSH) levels in the brain of 2, 10 and 20 month old rats, and to determine the effect of safranal on the status of selected oxidative stress indices in the 10 and 20 month old rats. The aged rats (10 and 20 months) were given intraperitoneal injections of safranal (0.5 mg/kg day) daily for one month. The results of this study demonstrated that aging caused significant increase in the level of lipid peroxidation as well decrease in the GSH level and activities of SOD and GST in the brain of aging rats. The results of this study showed that safranal ameliorated the increased lipid peroxidation level as well as decreased GSH content of the brain of 10 and 20 month old rats. In addition, safranal treatment to the 20 month old rats, which restored the SOD and GST activities. In conclusion, safranal can be effective to protect susceptible aged brain from oxidative damage by increasing antioxidant defenses. PMID:25312506

  6. Acetaldehyde metabolism by brain mitochondria from UChA and UChB rats.

    PubMed

    Quintanilla, M E; Tampier, L

    1995-01-01

    The acetaldehyde (AcH) oxidizing capacity of total brain homogenates from the genetically high-ethanol consumer (UChB) appeared to be greater than that of the low-ethanol consumer (UChA) rats. To gain further information about this strain difference, the activity of aldehyde dehydrogenase (AIDH) in different subcellular fractions of whole brain homogenates from naive UChA and UChB rat strains of both sexes has been studied by measuring the rate of AcH disappearance and by following the reduction of NAD to NADH. The results demonstrated that the higher capacity of brain homogenates from UChB rats to oxidize AcH when compared to UChA ones was because the UChB mitochondrial low Km AIDH exhibits a much greater affinity for NAD than that of the UChA rats, as evidenced by four-to fivefold differences in the Km values for NAD. But the dehydrogenases from both strains exhibited a similar maximum rate at saturating NAD concentrations. Because intact brain mitochondria isolated from UChB rats oxidized AcH at a higher rate than did mitochondria from UChA rats only in state 4, but not in state 3, this strain difference in AIDH activity might be restricted in vivo to NAD disposition.

  7. Probing Intrinsic Resting-State Networks in the Infant Rat Brain

    PubMed Central

    Bajic, Dusica; Craig, Michael M.; Borsook, David; Becerra, Lino

    2016-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) measures spontaneous fluctuations in blood oxygenation level-dependent (BOLD) signal in the absence of external stimuli. It has become a powerful tool for mapping large-scale brain networks in humans and animal models. Several rs-fMRI studies have been conducted in anesthetized and awake adult rats, reporting consistent patterns of brain activity at the systems level. However, the evolution to adult patterns of resting-state activity has not yet been evaluated and quantified in the developing rat brain. In this study, we hypothesized that large-scale intrinsic networks would be easily detectable but not fully established as specific patterns of activity in lightly anesthetized 2-week-old rats (N = 11). Independent component analysis (ICA) identified 8 networks in 2-week-old-rats. These included Default mode, Sensory (Exteroceptive), Salience (Interoceptive), Basal Ganglia-Thalamic-Hippocampal, Basal Ganglia, Autonomic, Cerebellar, as well as Thalamic-Brainstem networks. Many of these networks consisted of more than one component, possibly indicative of immature, underdeveloped networks at this early time point. Except for the Autonomic network, infant rat networks showed reduced connectivity with subcortical structures in comparison to previously published adult networks. Reported slow fluctuations in the BOLD signal that correspond to functionally relevant resting-state networks in 2-week-old rats can serve as an important tool for future studies of brain development in the settings of different pharmacological applications or disease. PMID:27803653

  8. Effects of dietary folate deficiency on developmental increase of myelin lipids in rat brain.

    PubMed

    Hirono, H; Wada, Y

    1978-05-01

    Rats were fed a folic acid deficient purified diet from day 12 of gestation throughout the lactational period. Offsprings were fed the same diet after weaning. Control rats were given 170 microgram of folic acid per day per rat supplemented to the same diet, which was fed ad libitum or by pair-feeding. At 3 and 6 weeks of age, myelin was isolated from rat brains. It was found that in comparison with the controls, myelin yield was significantly decreased as well as the brain weight in the folic acid deficient rats at 6 weeks of age. There were no differences of gross composition of myelin, protein, ratio of cholesterol, glycolipids, phospholipids, and total lipid with or without folate deficiency either at 3 or 6 weeks of age. The hydroxy fatty acid composition of myelin lipids in brain was not changed with folate deficiency at 3 or 6 weeks of age. The developmental increase of the percentages of 22:6, 22:4, and 20:1 in nonhydroxy fatty acids of myelin lipids from the folic acid deficient rats were significantly lower at 6 weeks of age in comparison with the controls. The n-3:n-6 ratio in myelin fatty acids from the folic acid deficient rat brains was abnormally low at 3 weeks of age and was not increased at even 6 weeks of age. The implications of these findings are that folic acid may play an important role in desaturation or chain elongation of polyunsaturated fatty acids in the brain of developing rats. PMID:641593

  9. Positron Spectroscopy Investigation of Normal Brain Section and Brain Section with Glioma Derived from a Rat Glioma Model

    NASA Astrophysics Data System (ADS)

    Yang, SH.; Ballmann, C.; Quarles, C. A.

    2009-03-01

    The application of positron annihilation lifetime spectroscopy (PALS) and Doppler broadening spectroscopy (DBS) to the study of animal or human tissue has only recently been reported [G. Liu, et al. phys. stat. sol. (C) 4, Nos. 10, 3912-3915 (2007)]. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. For the rat glioma model, 200,000 C6 cells were implanted in the basal ganglion of adult Sprague Dawley rats. The rats were sacrificed at 21 days after implantation. The brains were harvested, sliced into 2 mm thick coronal sections, and fixed in 4% formalin. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. The lifetime spectra were analyzed into two lifetime components. While early results suggested a small decrease in ortho-Positronium (o-Ps) pickoff lifetime between the normal brain section and brain section with glioma, further runs with additional samples have showed no statistically significant difference between the normal and tumor tissue for this type of tumor. The o-Ps lifetime in formalin alone was lower than either the normal tissue or glioma sample. So annihilation in the formalin absorbed in the samples would lower the o-Ps lifetime and this may have masked any difference due to the glioma itself. DBS was also used to investigate the difference in positronium formation between tumor and normal tissue. Tissue samples are heterogeneous and this needs to be carefully considered if PALS and DBS are to become useful tools in distinguishing tissue samples.

  10. Positron Spectroscopy Investigation of Normal Brain Section and Brain Section with Glioma Derived from a Rat Glioma Model

    SciTech Connect

    Yang, SH.; Ballmann, C.; Quarles, C. A.

    2009-03-10

    The application of positron annihilation lifetime spectroscopy (PALS) and Doppler broadening spectroscopy (DBS) to the study of animal or human tissue has only recently been reported [G. Liu, et al. phys. stat. sol. (C) 4, Nos. 10, 3912-3915 (2007)]. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. For the rat glioma model, 200,000 C6 cells were implanted in the basal ganglion of adult Sprague Dawley rats. The rats were sacrificed at 21 days after implantation. The brains were harvested, sliced into 2 mm thick coronal sections, and fixed in 4% formalin. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. The lifetime spectra were analyzed into two lifetime components. While early results suggested a small decrease in ortho-Positronium (o-Ps) pickoff lifetime between the normal brain section and brain section with glioma, further runs with additional samples have showed no statistically significant difference between the normal and tumor tissue for this type of tumor. The o-Ps lifetime in formalin alone was lower than either the normal tissue or glioma sample. So annihilation in the formalin absorbed in the samples would lower the o-Ps lifetime and this may have masked any difference due to the glioma itself. DBS was also used to investigate the difference in positronium formation between tumor and normal tissue. Tissue samples are heterogeneous and this needs to be carefully considered if PALS and DBS are to become useful tools in distinguishing tissue samples.

  11. Metabolic mapping of the effects of the antidepressant fluoxetine on the brains of congenitally helpless rats.

    PubMed

    Shumake, Jason; Colorado, Rene A; Barrett, Douglas W; Gonzalez-Lima, F

    2010-07-01

    Antidepressants require adaptive brain changes before efficacy is achieved, and they may impact the affectively disordered brain differently than the normal brain. We previously demonstrated metabolic disturbances in limbic and cortical regions of the congenitally helpless rat, a model of susceptibility to affective disorder, and we wished to test whether administration of fluoxetine would normalize these metabolic differences. Fluoxetine was chosen because it has become a first-line drug for the treatment of affective disorders. We hypothesized that fluoxetine antidepressant effects may be mediated by decreasing metabolism in the habenula and increasing metabolism in the ventral tegmental area. We measured the effects of fluoxetine on forced swim behavior and regional brain cytochrome oxidase activity in congenitally helpless rats treated for 2 weeks with fluoxetine (5mg/kg, i.p., daily). Fluoxetine reduced immobility in the forced swim test as anticipated, but congenitally helpless rats responded in an atypical manner, i.e., increasing climbing without affecting swimming. As hypothesized, fluoxetine reduced metabolism in the habenula and increased metabolism in the ventral tegmental area. In addition, fluoxetine reduced the metabolism of the hippocampal dentate gyrus and dorsomedial prefrontal cortex. This study provided the first detailed mapping of the regional brain effects of an antidepressant drug in congenitally helpless rats. All of the effects were consistent with previous studies that have metabolically mapped the effects of serotonergic antidepressants in the normal rat brain, and were in the predicted direction of metabolic normalization of the congenitally helpless rat for all affected brain regions except the prefrontal cortex.

  12. Positron Spectroscopy Investigation of Normal Brain Section and Brain Section with Glioma Derived from a Rat Glioma Model

    NASA Astrophysics Data System (ADS)

    Quarles, C. A.; Ballmann, Charles; Yang, S. H.

    2009-04-01

    The application of positron annihilation lifetime spectroscopy (PALS) and Doppler broadening spectroscopy (DBS) to the study of animal or human tissue has only recently been reported. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. While early results suggested a small decrease in o-Ps pickoff lifetime between the normal brain section and brain section with glioma, further runs with additional samples have showed no statistically significant difference between the normal and tumor tissue for this type of tumor. DBS was also used to investigate the difference in positronium formation between tumor and normal tissue. Tissue samples are heterogeneous and this needs to be carefully considered if PALS and DBS are to become useful tools in distinguishing tissue samples.

  13. Effects of field orientation during 700-MHz radiofrequency irradiation of rats

    SciTech Connect

    Frei, M.R.; Jauchem, J.R.; Padilla, J.M. )

    1989-01-01

    Ketamine-anesthetized Sprague-Dawley rats were exposed to far-field 700-MHz continuous-wave radiofrequency radiation (RFR) in both E and H orientations. Irradiation was conducted at whole-body average specific absorption rates (SARs) of 9.2 and 13.0 W/kg (E and H, respectively) that resulted in approximately equivalent colonic specific heating rates (SHRs). Exposures were performed to repeatedly increase colonic temperature by 1 degree C (38.5 to 39.5 degrees C). Tympanic, tail, left and right subcutaneous (toward and away from RFR source), and colonic temperatures, arterial blood pressure, and respiratory rate were continuously recorded. In spite of equivalent colonic SHRs and the reduced E-orientation average SAR, the right subcutaneous, tympanic, and tail SARs, SHRs and absolute temperature increases were significantly greater in E than in H orientation. The cooling rate at all monitoring sites was also significantly greater in E than in H orientation. Heart rate and mean arterial blood pressure significantly increased during irradiation; however, changes between orientations were not different. Respiratory rate significantly increased during irradiation in H, but not in E orientation. These results indicate that during resonant frequency irradiation, differences occur in the pattern of heat deposition between E- and H-orientation exposure. When compared with previous investigations performed at supraresonant frequencies, the lower level of cardiovascular change in this study was probably related to the lower periphery-to-core thermal gradient.

  14. Effects of field orientation during 700-MHz radiofrequency irradiation of rats

    SciTech Connect

    Frei, M.R.; Jauchem, J.R.; Padilla, J.M.

    1989-01-01

    Ketamine-anesthetized Sprague-Dawley rats were exposed to far-field 700-MHz continuous-wave radiofrequency radiation (RFR) in both E and H orientations. Irradiation was conducted at whole-body average specific absorption rates (SARs) of 9.2 and 13.0 W/kg (E and H, respectively) that resulted in approximately equivalent colonic specific heating rates (SHRs). Exposures were performed to repeatedly increase colonic temperature by 1 deg C (38.5 to 39.5 deg C). Tympanic, tail, left and right subcutaneous (toward and away from RFR source), and colonic temperatures, arterial blood pressure, and respiratory rate were continuously recorded. In spite of equivalent colonic SHRs and the reduced E-orientation average SAR, the right subcutaneous, tympanic, and tail SARs, SHRs and absolute temperature increases were significantly greater in E than in H orientation. The cooling rate at all monitoring sites was also significantly greater in E than in H orientation. Heart rate and mean arterial blood pressure significantly increased during irradiation; however, changer between orientations were not different. Respiratory rate significantly increased during irradiation in H, but not in E orientation. These results indicate that during resonant frequency irradiation, differences occur in the pattern of heat deposition between E- and H-orientation exposure. When compared with previous investigations performed at supraresonant frequencies, the lower level of cardiovascular change in this study was probably related to the lower periphery-to-core thermal gradient.

  15. Rat mammary-cell survival following irradiation with 14. 3-MeV neutrons

    SciTech Connect

    Mahler, P.A.; Gould, M.N.; DeLuca, P.M. Jr.; Pearson, D.W.; Clifton, K.H.

    1982-01-01

    The survival of rat mammary gland cells irradiated in situ with either single or split doses of 14.3-MeV neutrons was determined by an in vivo transplantation assay. The single-dose data are best fit to the multitarget single-hit model by the parameters D/sub 0/ = 97 cGy and n = 0.6 while the split-dose data are best fit by the parameters D/sub 0/ = 100 cGy and n = 1.2. Analysis of the combined data sets suggests that the two survival curves are not identical. Comparison of these data with previously published results following irradiation with 250-kVp x-rays is reported.

  16. Rat mammary cell survival following irradiation with 14. 3-MeV neutrons

    SciTech Connect

    Mahler, P.A.; Gould, M.N.; DeLuca, P.M. Jr.; Pearson, D.W.; Clifton, K.H.

    1982-08-01

    The survival of rat mammary gland cells irradiated in situ with either single or split doses of 14.3-MeV neutrons was determined by an in vivo transplantation assay. The single-dose data are best fit to the multitarget single-hit model by the parameters D/sub o/ = 97 cGy and n = 0.6 while the split-dose data are best fit by the parameters D/sub o/ = 100 cGy and n = 1.2.Analysis of the combined data sets suggests that the two survival curves are not identical. Comparison of these data with previously published results following irradiation with 250-kVp X rays is reported.

  17. Low level laser therapy on injured rat muscle: assessment of irradiation parameters

    NASA Astrophysics Data System (ADS)

    Mantineo, M.; Pinheiro, J. P.; Morgado, A. M.

    2013-11-01

    Although studies show the clinical effectiveness of low level laser therapy (LLLT) in facilitating the muscle healing process, scientific evidence is still required to prove the effectiveness of LLLT and to clarify the cellular and molecular mechanisms triggered by irradiation. Here we evaluate the effect of different LLLT wavelengths, using continuous coherent Laser illumination (830 nm and 980 nm) and non-coherent LED illumination (850 nm), in the treatment of inflammation induced in the gastrocnemius muscle of Wistar rats, through the quantification of cytokines in systemic blood. We verified that all applied doses of coherent radiation produce an effect on reducing the concentration of pro-inflammatory TNF-α and IL-1β cytokines, while no treatment effect was observed after irradiation with non-coherent radiation. The best results were obtained for 40 mW at 830 nm. The results may suggest an important role of coherence properties of laser in LLLT.

  18. Effects of X irradiation on the cytoskeleton of rat alveolar macrophages in vitro

    SciTech Connect

    Ladyman, S.J.; Townsend, K.M.S.; Edwards, C.

    1984-07-01

    The three-dimensional visualization of Triton X-100 resistant cytoskeletons has been used to demonstrate that an absorbed dose of 120 Gy from X rays causes a distinctive and reproducible alteration of the cytoskeleton of intact rat alveolar macrophages in vitro. The alteration has also been shown to be rapidly and completely ''repaired'' and to be apparently similar to alterations caused by colchicine but dissimilar to those caused by cytochalasin B. From these observations and those of other workers who have studied the irradiation of extracted microtubular proteins in vitro, the authors think it likely that microtubules rather than microfilaments are the radiosensitive component of the macrophage cytoskeleton.

  19. LOW BRAIN DHA CONTENT WORSENS SENSORIMOTOR OUTCOMES AFTER TBI AND DECREASES TBI-INDUCED TIMP1 EXPRESSION IN JUVENILE RATS

    PubMed Central

    Russell, Kristin L.; Berman, Nancy E. J.; Levant, Beth

    2013-01-01

    SUMMARY The effects of dietary modulation of brain DHA content on outcomes after TBI were examined in a juvenile rat model. Long-Evans rats with normal or diet-induced decreases in brain DHA were subjected to a controlled cortical impact or sham surgery on postnatal day 17. Rats with the greatest decreases in brain DHA had the poorest sensorimotor outcomes after TBI. Ccl2, Gfap, and Mmp 9 mRNA levels, and MMP-2 and −9 enzymatic activities were increased after TBI regardless of brain DHA level. Lesion volume was not affected by brain DHA level. In contrast, TBI-induced Timp1 expression was lower in rats on the Deficient diet and correlated with brain DHA level. These data suggest that decreased brain DHA content contributes to poorer sensorimotor outcomes after TBI through a mechanism involving modulation of Timp1 expression. PMID:23796971

  20. In vivo two-photon microscopy study of short-term effects of microbeam irradiation on normal mouse brain microvasculature

    SciTech Connect

    Serduc, Raphael . E-mail: rserduc@ujf-grenoble.fr; Verant, Pascale; Vial, Jean-Claude; Farion, Regine; Rocas, Linda; Remy, Chantal; Fadlallah, Taoufik M.S.; Brauer, Elke M.S.; Bravin, Alberto; Laissue, Jean; Blattmann, Hans; Sanden, Boudewijn van der

    2006-04-01

    Purpose: The purpose of this study was to assess the early effects of microbeam irradiation on the vascular permeability and volume in the parietal cortex of normal nude mice using two-photon microscopy and immunohistochemistry. Methods and Materials: The upper part of the left hemisphere of 55 mice was irradiated anteroposteriorly using 18 vertically oriented beams (width 25 {mu}m, interdistance 211 {mu}m; peak entrance doses: 312 or 1000 Gy). At different times after microbeam exposure, the microvasculature in the cortex was analyzed using intravital two-photon microscopy after intravascular injection of fluorescein isothiocyanate (FITC)-dextrans and sulforhodamine B (SRB). Changes of the vascular volume were observed at the FITC wavelength over a maximum depth of 650 {mu}m from the dura. The vascular permeability was detected as extravasations of SRB. Results: For all times (12 h to 1 month) after microbeam irradiation and for both doses, the FITC-dextran remained in the vessels. No significant change in vascular volume was observed between 12 h and 3 months after irradiation. Diffusion of SRB was observed in microbeam irradiated regions from 12 h until 12 days only after a 1000 Gy exposure. Conclusion: No radiation damage to the microvasculature was detected in normal brain tissue after a 312 Gy microbeam irradiation. This dose would be more appropriate than 1000 Gy for the treatment of brain tumors using crossfired microbeams.

  1. Rat parotid cell function in vitro following x irradiation in vivo

    SciTech Connect

    Bodner, L.; Kuyatt, B.L.; Hand, A.R.; Baum, B.J.

    1984-02-01

    The effect of X irradiation on rat parotid acinar cell function was evaluated in vitro 1, 3, and 7 days following in vivo exposure to 2000 R. Several cellular functions were followed: protein secretion (amylase release), ion movement (K/sup +/ efflux and reuptake), amino acid transport (..cap alpha..-amino(/sup 14/C)isobutyric acid), and an intermediary metabolic response ((/sup 14/C)glucose oxidation). In addition both the morphologic appearance and in vivo saliva secretory ability of parotid cells were assessed. Our results demonstrate that surviving rat parotid acinar cells, isolated and studied in vitro 1-7 days following 2000 R, remain functionally intact despite in vivo diminution of secretory function.

  2. Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation. [X-ray

    SciTech Connect

    Hoogenhout, J.; Kazem, I.; Jerusalem, C.R.; Bakkeren, J.A.J.; de Jong, J.; Kal, H.B.; van Munster, P.J.J.

    1982-10-01

    Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21.

  3. Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation

    SciTech Connect

    Hoogenhout, J.; Kazem, I.; Jerusalem, C.R.; Bakkeren, J.A.; de Jong, J.; Kal, H.B.; van Munster, P.J.

    1982-10-01

    Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21.

  4. Acute neuroprotective effects of extremely low-frequency electromagnetic fields after traumatic brain injury in rats.

    PubMed

    Yang, Yang; Li, Ling; Wang, Yan-Gang; Fei, Zhou; Zhong, Jun; Wei, Li-Zhou; Long, Qian-Fa; Liu, Wei-Ping

    2012-05-10

    Traumatic brain injury commonly has a result of a short window of opportunity between the period of initial brain injury and secondary brain injury, which provides protective strategies and can reduce damages of brain due to secondary brain injury. Previous studies have reported neuroprotective effects of extremely low-frequency electromagnetic fields. However, the effects of extremely low-frequency electromagnetic fields on neural damage after traumatic brain injury have not been reported yet. The present study aims to investigate effects of extremely low-frequency electromagnetic fields on neuroprotection after traumatic brain injury. Male Sprague-Dawley rats were used for the model of lateral fluid percussion injury, which were placed in non-electromagnetic fields and 15 Hz (Hertz) electromagnetic fields with intensities of 1 G (Gauss), 3 G and 5 G. At various time points (ranging from 0.5 to 30 h) after lateral fluid percussion injury, rats were treated with kainic acid (administered by intraperitoneal injection) to induce apoptosis in hippocampal cells. The results were as follows: (1) the expression of hypoxia-inducible factor-1α was dramatically decreased during the neuroprotective time window. (2) The kainic acid-induced apoptosis in the hippocampus was significantly decreased in rats exposed to electromagnetic fields. (3) Electromagnetic fields exposure shortened the escape time in water maze test. (4) Electromagnetic fields exposure accelerated the recovery of the blood-brain barrier after brain injury. These findings revealed that extremely low-frequency electromagnetic fields significantly prolong the window of opportunity for brain protection and enhance the intensity of neuroprotection after traumatic brain injury.

  5. Relationship between orientation to a blast and pressure wave propagation inside the rat brain.

    PubMed

    Chavko, Mikulas; Watanabe, Tomas; Adeeb, Saleena; Lankasky, Jason; Ahlers, Stephen T; McCarron, Richard M

    2011-01-30

    Exposure to a blast wave generated during an explosion may result in brain damage and related neurological impairments. Several mechanisms by which the primary blast wave can damage the brain have been proposed, including: (1) a direct effect of the shock wave on the brain causing tissue damage by skull flexure and propagation of stress and shear forces; and (2) an indirect transfer of kinetic energy from the blast, through large blood vessels and cerebrospinal fluid (CSF), to the central nervous system. To address a basic question related to the mechanisms of blast brain injury, pressure was measured inside the brains of rats exposed to a low level of blast (~35kPa), while positioned in three different orientations with respect to the primary blast wave; head facing blast, right side exposed to blast and head facing away from blast. Data show different patterns and durations of the pressure traces inside the brain, depending on the rat orientation to blast. Frontal exposures (head facing blast) resulted in pressure traces of higher amplitude and longer duration, suggesting direct transmission and reflection of the pressure inside the brain (dynamic pressure transfer). The pattern of the pressure wave inside the brain in the head facing away from blast exposures assumes contribution of the static pressure, similar to hydrodynamic pressure to the pressure wave inside the brain. PMID:21129403

  6. Increased expression of glial fibrillary acidic protein in the brain of spontaneously hypertensive rats.

    PubMed

    Tomassoni, Daniele; Avola, Roberto; Di Tullio, Maria Antonietta; Sabbatini, Maurizio; Vitaioli, Lucia; Amenta, Francesco

    2004-05-01

    Astrogliosis, consisting in astroglial proliferation and increased expression of the specific cytoskeletal protein glial fibrillary acid protein (GFAP) is common in several situations of brain damage. Arterial hypertension, which induces cerebrovascular changes, can cause also brain damage, neurodegeneration and dementia (vascular dementia). This study was designed to assess astroglial reaction in different brain areas (frontal cortex, occipital cortex, hippocampus and striatum) of spontaneously hypertensive rats (SHR) in the pre-hypertensive phase (2 months of age), in the developing phase of hypertension (4 months of age) and in established hypertension (6 months of age). SHR were compared to age-matched normotensive Wistar-Kyoto (WKY) rats. Analysis included reverse transcription-polymerase chain reaction (RT-PCR) of GFAP mRNA, GFAP immunochemistry (Western blot analysis) and immunohistochemistry. A significant increase of GFAP mRNA and an increase of GFAP immunoreactivity were noticeable in different brain areas of SHR compared to normotensive WKY rats at 6, but not at 2 or 4 months of age. Immunohistochemistry revealed a numerical augmentation (hyperplasia) and an increase in size (hypertrophy) of GFAP-immunoreactive astrocytes in frontal cortex, occipital cortex and striatum of SHR. In the hippocampus of SHR only a numerical increase of GFAP-immunoreactive astrocytes was found. These finding demonstrating the occurrence of astrogliosis in the brain of SHR with established hypertension suggest that hypertension induces a condition of brain suffering enough to increase biosynthesis and expression of GFAP similarly as reported in several neurodegenerative disorders and in brain ischemia.

  7. Celecoxib attenuates systemic lipopolysaccharide-induced brain inflammation and white matter injury in the neonatal rats.

    PubMed

    Fan, L-W; Kaizaki, A; Tien, L-T; Pang, Y; Tanaka, S; Numazawa, S; Bhatt, A J; Cai, Z

    2013-06-14

    Lipopolysaccharide (LPS)-induced white matter injury in the neonatal rat brain is associated with inflammatory processes. Cyclooxygenase-2 (COX-2) can be induced by inflammatory stimuli, such as cytokines and pro-inflammatory molecules, suggesting that COX-2 may be considered as the target for anti-inflammation. The objective of the present study was to examine whether celecoxib, a selective COX-2 inhibitor, can reduce systemic LPS-induced brain inflammation and brain damage. Intraperitoneal (i.p.) injection of LPS (2mg/kg) was performed in postnatal day 5 (P5) of Sprague-Dawley rat pups and celecoxib (20mg/kg) or vehicle was administered i.p. 5 min after LPS injection. The body weight and wire-hanging maneuver test was performed 24h after the LPS exposure, and brain injury was examined after these tests. Systemic LPS exposure resulted in an impairment of behavioral performance and acute brain injury, as indicated by apoptotic death of oligodendrocytes (OLs) and loss of OL immunoreactivity in the neonatal rat brain. Treatments with celecoxib significantly reduced systemic LPS-induced neurobehavioral disturbance and brain damage. Celecoxib administration significantly attenuated systemic LPS-induced increments in the number of activated microglia and astrocytes, concentrations of IL-1β and TNFα, and protein levels of phosphorylated-p38 MAPK in the neonatal rat brain. The protection of celecoxib was also associated with a reduction of systemic LPS-induced COX-2+ cells which were double labeled with GFAP+ (astrocyte) cells. The overall results suggest that celecoxib was capable of attenuating the brain injury and neurobehavioral disturbance induced by systemic LPS exposure, and the protective effects are associated with its anti-inflammatory properties.

  8. DISTRIBUTION OF GLIAL FIBRILLARY ACIDIC PROTEIN IN DIFFERENT PARTS OF THE RAT BRAIN UNDER CADMIUM EXPOSURE.

    PubMed

    Kovalchuk, Yu P; Prischepa, I V; Si, U; Nedzvetsky, V S; Kot, Y G; Persky, E E; Ushakova, G A

    2015-01-01

    The chronic effects of low doses of cadmium on the distribution of soluble and filament forms of glial fibrillary acidic protein (GFAP) and their polypeptide fragments in different parts of the rat brain were investigated. Obtained results showed dose-dependent effect of cadmium on the soluble form of GFAP and more pronounced effect on the filament form and composition of the polypeptide fragments of the protein in the rat brain. Prolonged intoxication by cadmium ions in a dose of 1.0 μg/kg of body weight induced a significant decrease in soluble GFAP and an increase in the filament form in the rat brain, pointing to the development of reactive astrogliosis and the risk of neurodegeneration.

  9. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats.

    PubMed

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨ m ), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress. PMID:26180820

  10. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats

    PubMed Central

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R.; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨm), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress. PMID:26180820

  11. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats.

    PubMed

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨ m ), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

  12. Glucocorticoids modulate BDNF mRNA expression in the rat hippocampus after traumatic brain injury.

    PubMed

    Grundy, P L; Patel, N; Harbuz, M S; Lightman, S L; Sharples, P M

    2000-10-20

    Brain-derived neurotrophic factor (BDNF) expression in rat hippocampus is increased after experimental traumatic brain injury (TBI) and may be neuroprotective. Glucocorticoids are important regulators of brain neurotrophin levels and are often prescribed following TBI. The effect of adrenalectomy (ADX) on the expression of BDNF mRNA in the hippocampus after TBI has not been investigated to date. We used fluid percussion injury (FPI) and in situ hybridization to evaluate the expression of BDNF mRNA in the hippocampus 4 h after TBI in adrenal-intact or adrenalectomized rats (with or without corticosterone replacement). FPI and ADX independently increased expression of BDNF mRNA. In animals undergoing FPI, prior ADX caused further elevation of BDNF mRNA and this upregulation was prevented by corticosterone replacement in ADX rats. These findings suggest that glucocorticoids are involved in the modulation of the BDNF mRNA response to TBI.

  13. Effect of mealing on plasma and brain amino acid, and brain monoamine in rats after oral aspartame.

    PubMed

    Torii, K; Mimura, T; Takasaki, Y; Ichimura, M

    1986-01-01

    Aspartame (APM; L-aspartyl-L-phenylalanine methyl ester) was investigated for its ability to alter brain amino acids and monoamines in overnight fasted rats allowed to consume commercial diets for 60 minutes. In addition, the effects of mealing on the changes in plasma and brain amino acids and brain monoamines induced by glucose and/or insulin, and known pharmacologically active compounds, were studied. The consumption of the commercial chow largely prevented changes in blood glucose and amino acids, and brain amino acids and the monoamines dopamine, norepinephrine and serotonin that might be expected to occur following glucose with or without insulin. Feeding failed to prevent changes in the above parameters when 5-hydroxy-tryptophan, p-chlorophenylalanine and reserpine were administered. The oral administration of up to 250 mg/kg BW APM with water or glucose followed by free feeding failed to alter brain monoamines. These studies demonstrate the potent ability of food to normalize biochemical parameters in blood and brain that otherwise might occur, and clearly show the lack of effect on brain monoamine levels of abuse doses of APM when administered with food.

  14. Characterization and in vivo regulation of V sub 1 -type vasopressin receptors in the rat brain

    SciTech Connect

    Shewey, L.M.

    1988-01-01

    Specific, high affinity binding sites for ({sup 3}H)-arginine{sup 8}-vasopressin (AVP) have been characterized in Long-Evans rat septal membranes. Binding displacement studies with peptide analogs of AVP indicate that this binding site is similar to the V{sub 1} (pressor)-type receptor for AVP. When added to rat brain septal slices that had been pre-labeled with ({sup 3}H)-myoinositol, AVP stimulated the accumulation of ({sup 3}H)-inositol-1-phosphate (IP{sub 1}) in the presence of lithium in a dose-dependent manner. This stimulation was completely inhibited by the specific V{sub 1} antagonists, d(CH{sub 2}){sub 5}Tyr(Me)AVP, indicating that AVP stimulates hydrolysis of inositol phospholipids in rat brain septum through an interaction with V{sub 1}-type AVP receptors. Binding studies of AVP receptors in the septum of heterozygous (HE) and homozygous, Brattleboro (BB) rats revealed an increased number of receptors with a lower affinity for AVP in the HO-BB rat when compared to the HE-BB rat. AVP-stimulated accumulation of ({sup 3}H)-IP{sub 1} was significantly greater in the septum of the HO-BB rat than in the HE-BB rat. AVP receptor binding capacity correlated with release of ({sup 3}H)-IP{sub 1} for all three groups studied.

  15. Pharmacokinetics and distribution of fluvoxamine to the brain in rats under oxidative stress.

    PubMed

    Kobuchi, Shinji; Fukushima, Keizo; Ito, Yukako; Sugioka, Nobuyuki; Takada, Kanji

    2012-07-01

    The effects of oxidative stress (OS) on the pharmacokinetics of fluvoxamine (FLV), particularly on FLV distribution in the plasma, were studied in ferric-nitrilotriacetate-induced OS rat models (OS rats). The study protocol involved a continuous FLV infusion (25.0 μg/kg/min). The resulting mean plasma FLV concentration measured in steady state OS rats was 0.13 ± 0.01 μg/mL, which was significantly lower than plasma concentrations measured in control rats (0.19 ± 0.01 μg/mL). Moreover, the mean FLV concentration in the OS rat brain (0.51 ± 0.08 μg/g) was determined to be approximately half the concentration in control rat brains (0.95 ± 0.11 μg/g). The FLV concentrations in both the unbound fraction of plasma and erythrocytes of OS rats were significantly greater than that of control rats. These results suggest the potential attenuation of FLV's pharmacological effects in patients under OS.

  16. Studies on the radioprotective potency of amifostine on salivary glands of rats during fractionated irradiation: acute and late effects.

    PubMed

    Sagowski, Christoph; Wenzel, Soeren; Metternich, Frank Uwe; Kehrl, Wolfgang

    2003-01-01

    The purpose of this study was to evaluate the radioprotective potential of amifostine on the salivary glands of rats with respect to the acute and late effects. The head and neck area of WAG/RijH rats was irradiated with (60)Co-gamma rays (60 Gy/30f for 6 weeks). Amifostine (250 mg/m(2) body surface) or an equal volume of physiologic saline was applied intravenously 15 min before each irradiation. In the course of treatment the salivary glands were examined histopathologically. Body weight was measured sequentially during irradiation. A cytoprotective effect of amifostine on the acute toxicity of salivary glands could not be detected under fractionated irradiation. However, late effects such as fibrosis and necrosis of the glands 6 months after irradiation were less developed in the amifostine group. The weight loss of the amifostine-treated animals during fractioned irradiation was higher than in the irradiated group. Amifostine has a significant cytoprotective effect on the late toxicity of irradiated salivary glands. However, the acute toxicity of the glands during radiotherapy cannot be reduced. PMID:12520356

  17. Micro-CT evaluation of the radioprotective effect of resveratrol on the mandibular incisors of irradiated rats.

    PubMed

    Barbosa, Gabriella Lopes de Rezende; Pimenta, Luiz André; Almeida, Solange Maria de

    2016-01-01

    The purpose of this study was to perform a microcomputed tomographic evaluation of the radioprotective effect of resveratrol on the volume of mandibular incisors of irradiated rats. A second aim was to make a quantitative assessment of the effect of x-ray exposure on these dental tissues. Twenty adult male rats were divided into four groups: control, irradiated control, resveratrol, and irradiated resveratrol. The resveratrol groups received 100 mg/kg of resveratrol, whereas the irradiated groups were exposed to 15 Gy of irradiation. The animals were sacrificed 30 days after the irradiation procedure, and their mandibles were removed and scanned in a microcomputed tomography unit. The images were loaded into Mimics software to allow segmentation of the mandibular incisor and assessment of its volume. The results were compared by One-way ANOVA and Tukey's post hoc test, considering a 5% significance level. The irradiated groups showed significantly diminished volumes of the evaluated teeth, as compared with the control group (p < 0.05). The resveratrol group presented higher values than those of the irradiated groups, and volumes similar to those of the control group. High radiation doses significantly affected tooth formation, resulting in alterations in the dental structure, and thus lower volumes. Moreover, resveratrol showed no effective radioprotective impact on dental tissues. Future studies are needed to evaluate different concentrations of this substance, in an endeavor to verify its potential as a radioprotector for these dental tissues. PMID:26981750

  18. Electron-microscopic studies on the effect of calcium pantothenate upon rat liver and locally irradiated epidermis.

    PubMed

    Craciun, C; Ghircoiasiu, M; Craciun, V

    1992-01-01

    Calcium pantothenate was administered to Wistar rats in a dose of 180 mg/day/rat for 42 days, in order to investigate its effect upon the ultrastructure of the epidermis locally irradiated with a dose of 600 rep and upon partly hepatectomized liver and locally irradiated epidermis, as compared to control. The resulting data have revealed that calcium pantothenate is metabolized without entailing ultrastructural changes. Both liver and epidermis appear to be protected by calcium pantothenate, which greatly diminishes or even cancels the display of irradiation-induced negative effects. The changes brought about by irradiation are throughly presented and the subcellular mechanisms providing the radioprotection of epidermis and liver are accurately defined. PMID:1365767

  19. Persistent Impact of In utero Irradiation on Mouse Brain Structure and Function Characterized by MR Imaging and Behavioral Analysis.

    PubMed

    Verreet, Tine; Rangarajan, Janaki Raman; Quintens, Roel; Verslegers, Mieke; Lo, Adrian C; Govaerts, Kristof; Neefs, Mieke; Leysen, Liselotte; Baatout, Sarah; Maes, Frederik; Himmelreich, Uwe; D'Hooge, Rudi; Moons, Lieve; Benotmane, Mohammed A

    2016-01-01

    Prenatal irradiation is known to perturb brain development. Epidemiological studies revealed that radiation exposure during weeks 8-15 of pregnancy was associated with an increased occurrence of mental disability and microcephaly. Such neurological deficits were reproduced in animal models, in which rodent behavioral testing is an often used tool to evaluate radiation-induced defective brain functionality. However, up to now, animal studies suggested a threshold dose of around 0.30 Gray (Gy) below which no behavioral alterations can be observed, while human studies hinted at late defects after exposure to doses as low as 0.10 Gy. Here, we acutely irradiated pregnant mice at embryonic day 11 with doses ranging from 0.10 to 1.00 Gy. A thorough investigation of the dose-response relationship of altered brain function and architecture following in utero irradiation was achieved using a behavioral test battery and volumetric 3D T2-weighted magnetic resonance imaging (MRI). We found dose-dependent changes in cage activity, social behavior, anxiety-related exploration, and spatio-cognitive performance. Although behavioral alterations in low-dose exposed animals were mild, we did unveil that both emotionality and higher cognitive abilities were affected in mice exposed to ≥0.10 Gy. Microcephaly was apparent from 0.33 Gy onwards and accompanied by deviations in regional brain volumes as compared to controls. Of note, total brain volume and the relative volume of the ventricles, frontal and posterior cerebral cortex, cerebellum, and striatum were most strongly correlated to altered behavioral parameters. Taken together, we present conclusive evidence for persistent low-dose effects after prenatal irradiation in mice and provide a better understanding of the correlation between their brain size and performance in behavioral tests. PMID:27199692

  20. Persistent Impact of In utero Irradiation on Mouse Brain Structure and Function Characterized by MR Imaging and Behavioral Analysis

    PubMed Central

    Verreet, Tine; Rangarajan, Janaki Raman; Quintens, Roel; Verslegers, Mieke; Lo, Adrian C.; Govaerts, Kristof; Neefs, Mieke; Leysen, Liselotte; Baatout, Sarah; Maes, Frederik; Himmelreich, Uwe; D'Hooge, Rudi; Moons, Lieve; Benotmane, Mohammed A.

    2016-01-01

    Prenatal irradiation is known to perturb brain development. Epidemiological studies revealed that radiation exposure during weeks 8–15 of pregnancy was associated with an increased occurrence of mental disability and microcephaly. Such neurological deficits were reproduced in animal models, in which rodent behavioral testing is an often used tool to evaluate radiation-induced defective brain functionality. However, up to now, animal studies suggested a threshold dose of around 0.30 Gray (Gy) below which no behavioral alterations can be observed, while human studies hinted at late defects after exposure to doses as low as 0.10 Gy. Here, we acutely irradiated pregnant mice at embryonic day 11 with doses ranging from 0.10 to 1.00 Gy. A thorough investigation of the dose-response relationship of altered brain function and architecture following in utero irradiation was achieved using a behavioral test battery and volumetric 3D T2-weighted magnetic resonance imaging (MRI). We found dose-dependent changes in cage activity, social behavior, anxiety-related exploration, and spatio-cognitive performance. Although behavioral alterations in low-dose exposed animals were mild, we did unveil that both emotionality and higher cognitive abilities were affected in mice exposed to ≥0.10 Gy. Microcephaly was apparent from 0.33 Gy onwards and accompanied by deviations in regional brain volumes as compared to controls. Of note, total brain volume and the relative volume of the ventricles, frontal and posterior cerebral cortex, cerebellum, and striatum were most strongly correlated to altered behavioral parameters. Taken together, we present conclusive evidence for persistent low-dose effects after prenatal irradiation in mice and provide a better understanding of the correlation between their brain size and performance in behavioral tests. PMID:27199692

  1. Neuroprotective effects of consuming bovine colostrum after focal brain ischemia/reperfusion injury in rat model

    PubMed Central

    Choi, Han Sung; Ko, Young Gwan; Lee, Jong Seok; Kwon, Oh Young; Kim, Sun-Kyu; Cheong, Chul; Jang, Ki-Hyo

    2010-01-01

    To investigate the neuroprotective effects of bovine colostrums (BC), we evaluate the ability of consuming BC after focal brain ischemia/reperfusion injury rat model to reduce serum cytokine levels and infarct volume, and improve neurological outcome. Sprague-Dawley rats were randomly divided into 4 groups; one sham operation and three experimental groups. In the experimental groups, MCA occlusion (2 h) and subsequent reperfusion (O/R) were induced with regional cerebral blood flow monitoring. One hour after MCAO/R and once daily during the experiment, the experimental group received BC while the other groups received 0.9% saline or low fat milk (LFM) orally. Seven days later, serum pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) and anti-inflammatory cytokine (IL-10) levels were assessed. Also, the infarct volume was assessed by using a computerized image analysis system. Behavioral function was also assessed using a modified neurologic severity score and corner turn test during the experiment. Rats receiving BC after focal brain I/R showed a significant reduction (-26%/-22%) in infarct volume compared to LFM/saline rats, respectively (P < 0.05). Serum IL-1β, IL-6, and TNF-α levels were decreased significantly in rats receiving BC compared to LFM/saline rats (P < 0.05). In behavioral tests, daily BC intake showed consistent and significant improvement of neurological deficits for 7 days after MCAO/R. BC ingestion after focal brain ischemia/reperfusion injury may prevent brain injury by reducing serum pro-inflammatory cytokine levels and brain infarct volume in a rat model. PMID:20607064

  2. Effect of CO₂ laser irradiation on wound healing of exposed rat pulp.

    PubMed

    Suzuki, Masaya; Ogisu, Takahito; Kato, Chikage; Shinkai, Koichi; Katoh, Yoshiroh

    2011-01-01

    This study examined the effects of direct pulp capping treatment using super-pulsed CO₂ laser preirradiation on the wound healing process of exposed rat pulp on days 1, 3, 7, 14, and 28 postoperatively. Group 1 was irradiated with a CO₂ laser and directly capped with a self-etching adhesive system. The laser was operated in super-pulse mode (pulse duration, 200 μs; interval, 5800 μs; 0.003 J/pulse). The irradiation conditions were a power output of 0.5 W, an irradiation time of 3 s, and repeat mode (10 ms of irradiation at 10-ms intervals for a total beam exposure time of 1.5 s), defocused beam diameter of 0.74 mm (approximately 20 mm from the exposed pulp surface), energy density of 0.698 J/cm² per pulse, total applied energy of 0.75 J, and an activated air-cooling system. Group 2 was capped with the self-etching adhesive system. Group 3 was capped with commercially available calcium hydroxide, and the self-etching adhesive system was applied to the cavity. The following parameters were evaluated: pulp tissue disorganization, inflammatory cell infiltration, reparative dentin formation, and bacterial penetration. The results were statistically analyzed using the Kruskal-Wallis test for differences among the groups at each observation period (P < 0.05). There were no significant differences among the experimental groups in any parameters at any postoperative period (P > 0.05). CO₂ laser irradiation was effective in arresting hemorrhaging but showed a tendency to delay reparative dentin formation compared with the application of calcium hydroxide.

  3. Effect of continuous irradiation with terahertz electromagnetic waves of the NO frequency range on behavioral reactions of male albino rats under stress conditions.

    PubMed

    Kirichuk, V F; Antipova, O N; Krylova, Ya A

    2014-06-01

    We studied the effect of terahertz waves (NO frequency range, 150.176-150.664 GHz) on stress-induced variations in behavioral reactions of male albino rats during hypokinetic stress. THz irradiation was followed by partial or complete normalization of behavioral reactions of male albino rats after hypokinetic stress. The most significant effect was observed after continuous irradiation for 30 min.

  4. Intracellular pathways regulating ciliary beating of rat brain ependymal cells

    PubMed Central

    Nguyen, Thien; Chin, Wei-Chun; O’Brien, Jennifer A; Verdugo, Pedro; Berger, Albert J

    2001-01-01

    The mammalian brain ventricles are lined with ciliated ependymal cells. As yet little is known about the mechanisms by which neurotransmitters regulate cilia beat frequency (CBF). Application of 5-HT to ependymal cells in cultured rat brainstem slices caused CBF to increase. 5-HT had an EC50 of 30 μM and at 100 μM attained a near-maximal CBF increase of 52.7 ± 4.1 % (mean ± s.d.) (n= 8). Bathing slices in Ca2+-free solution markedly reduced the 5-HT-mediated increase in CBF. Fluorescence measurements revealed that 5-HT caused a marked transient elevation in cytosolic Ca2+ ([Ca2+]c) that then slowly decreased to a plateau level. Analysis showed that the [Ca2+]c transient was due to release of Ca2+ from inositol 1,4,5-trisphosphate (IP3)-sensitive stores; the plateau was probably due to extracellular Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels. Application of ATP caused a sustained decrease in CBF. ATP had an EC50 of about 50 μM and 100 μM ATP resulted in a maximal 57.5 ± 6.5 % (n= 12) decrease in CBF. The ATP-induced decrease in CBF was unaffected by lowering extracellular [Ca2+], and no changes in [Ca2+]c were observed. Exposure of ependymal cells to forskolin caused a decrease in CBF. Ciliated ependymal cells loaded with caged cAMP exhibited a 54.3 ± 7.5 % (n= 9) decrease in CBF following uncaging. These results suggest that ATP reduces CBF by a Ca2+-independent cAMP-mediated pathway. Application of 5-HT and adenosine-5′-O-3-thiotriphosphate (ATP-γ-S) to acutely isolated ciliated ependymal cells resulted in CBF responses similar to those of ependymal cells in cultured slices suggesting that these neurotransmitters act directly on these cells. The opposite response of ciliated ependymal cells to 5-HT and ATP provides a novel mechanism for their active involvement in central nervous system signalling. PMID:11179397

  5. Tail pinch induces fos immunoreactivity within several regions of the male rat brain: effects of age.

    PubMed

    Smith, W J; Stewart, J; Pfaus, J G

    1997-05-01

    Brief, intermittent stressors, such as low-level foot shock or tail pinch, induce a general excitement and autonomic arousal in rats that increases their sensitivity to external incentives. Such stimulation can facilitate a variety of behaviors, including feeding, aggression, sexual activity, parental behavior, and drug taking if the appropriate stimuli exist in the environment. However, the ability of tail pinch to induce general arousal and incentive motivation appears to diminish with age. Here we report on the ability of tail pinch to induce Fos immunoreactivity within several brain regions as a function of age. Young (2-3 months) and middle-aged (12-13 months) male rats were administered either five tail pinches (one every 2 min), one tail pinch, or zero (sham) tail pinches (n = 4 per stimulation condition). Rats were sacrificed 75 min following the onset of stimulation, and their brains were prepared for immunocytochemical detection of Fos protein. Fos immunoreactivity was induced by one and five tail pinches in several brain regions, including the anterior medial preoptic area (mPOA), paraventricular nucleus of the hypothalamus (PVN), paraventricular nucleus of the thalamus (PV-Thal), medial amygdala (MEA), basolateral amygdala (BLA), lateral habenula (LHab), and ventral tegmental area (VTA), of young rats compared with those that received zero tail pinches. In contrast to young rats, middle-aged rats had significantly less Fos induced by one and five tail pinches in the mPOA, PVN, MEA, BLA, and VTA, but an equivalent amount induced in the LHab. Fos immunoreactivity was not found within the medial prefrontal cortex, nucleus accumbens, striatum, lateral septum, or locus coeruleus in either young or old rats. Tail pinch appears to activate regions of the brain known to be involved in behavioral responses to both incentive cues and stressors. The lower level of cellular reactivity to tail pinch in middle-aged rats suggests a diminished neural responsiveness to

  6. Prostaglandin synthesis inhibitors reduce Cannabis and restraint stress induced increase in rat brain serotonin concentrations.

    PubMed

    Bhattacharya, S K; Bhattacharya, D

    1983-01-01

    Cannabis resin (CI) produced a dose-related increase in rat brain serotonin concentrations, whereas restraint stress produced maximal rise of the neurotransmitter concentrations at 1 h, followed by a tendency to normalise by 4 h. The prostaglandin (PG) synthesis inhibitors, diclofenac and paracetamol, antagonized CI and restraint stress induced rise in serotonin concentrations. The findings lend credence to earlier reports that PG synthesis inhibitors antagonize serotonin-mediated neuropharmacological actions of CI and restraint stress in rats.

  7. Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of {sup 56}Fe Irradiation on the Brain

    SciTech Connect

    Haley, Gwendolen E.; Villasana, Laura; Dayger, Catherine; Davis, Matthew J.; Raber, Jacob

    2012-11-01

    Purpose: In humans, apolipoprotein E (apoE) is encoded by three major alleles ({epsilon}2, {epsilon}3, and {epsilon}4) and, compared to apoE3, apoE4 increases the risk of developing Alzheimer disease and cognitive impairments following various environmental challenges. Exposure to irradiation, including that of {sup 56}Fe, during space missions poses a significant risk to the central nervous system, and apoE isoform might modulate this risk. Methods and Materials: We investigated whether apoE isoform modulates hippocampus-dependent cognitive performance starting 2 weeks after {sup 56}Fe irradiation. Changes in reactive oxygen species (ROS) can affect cognition and are induced by irradiation. Therefore, after cognitive testing, we assessed hippocampal ROS levels in ex vivo brain slices, using the ROS-sensitive fluorescent probe, dihydroethidium (DHE). Brain levels of 3-nitrotyrosine (3-NT), CuZn superoxide dismutase (CuZnSOD), extracellular SOD, and apoE were assessed using Western blotting analysis. Results: In the water maze, spatial memory retention was impaired by irradiation in apoE2 and apoE4 mice but enhanced by irradiation in apoE3 mice. Irradiation reduced DHE-oxidation levels in the enclosed blade of the dentate gyrus and levels of 3-NT and CuZnSOD in apoE2 but not apoE3 or apoE4 mice. Finally, irradiation increased apoE levels in apoE3 but not apoE2 or apoE4 mice. Conclusions: The short-term effects of {sup 56}Fe irradiation on hippocampal ROS levels and hippocampus-dependent spatial memory retention are apoE isoform-dependent.

  8. Neuroprotection by Vitamin C Against Ethanol-Induced Neuroinflammation Associated Neurodegeneration in the Developing Rat Brain.

    PubMed

    Ahmad, Ashfaq; Shah, Shahid A; Badshah, Haroon; Kim, Min J; Ali, Tahir; Yoon, Gwang H; Kim, Tae H; Abid, Nouman B; Rehman, Shafiq Ur; Khan, Sohail; Kim, Myeong O

    2016-01-01

    Ethanol induces oxidative stress and its exposure during early developmental age causes neuronal cell death which leads to several neurological disorders. We previously reported that vitamin C can protect against ethanol-induced apoptotic cell death in the developing rat brain. Here, we extended our study to understand the therapeutic efficacy of vitamin C against ethanol-induced oxidative stress, neuroinflammation mediated neurodegeneration in postnatal day 7 (PND7) rat. A single episode of ethanol (5g/kg) subcutaneous administration to postnatal day 7 rat significantly induced the production of reactive oxygen species (ROS), and activated both microglia and astrocytes followed by the induction of different apoptotic markers. On the other hand, due to its free radical scavenging properties, vitamin C treatment significantly reduced the production of reactive oxygen species, suppressed both activated microglia and astrocytes and reversed other changes including elevated level of Bax/Bcl-2 ratio, cytochrome c and different caspases such as caspase-9 and caspase-3 induced by ethanol in developing rat brain. Moreover, vitamin C treatment also reduced ethanol-induced activation of Poly [ADP-Ribose] Polymerase 1(PARP-1) and neurodegeneration as evident from Flouro-Jade-B and Nissl stainined neuronal cell death in PND7 rat brain. These findings suggest that vitamin C mitigated ethanol-induced oxidative stress, neuroinflammation and apoptotic neuronal loss and may be beneficial against ethanol damaging effects in brain development. PMID:26831257

  9. The effects of acute ethanol exposure and ageing on rat brain glutathione metabolism.

    PubMed

    Sommavilla, Michela; Sánchez-Villarejo, M Victoria; Almansa, Inmaculada; Sánchez-Vallejo, Violeta; Barcia, Jorge M; Romero, Francisco Javier; Miranda, María

    2012-09-01

    Binge alcohol consumption in adolescents is increasing, and it has been proposed that immature brain deals poorly with oxidative stress. The aim of our work was to study the effect of an acute dose of ethanol on glutathione (GSH) metabolism in frontal cortex, hippocampus and striatum of juvenile and adult rats. We have observed no change in levels of glutathione produced by acute alcohol in the three brain areas studied of juvenile and adult rats. Only in the frontal cortex the ratio of GSH/GSSG was increased in the ethanol-treated adult rats. GSH levels in the hippocampus and striatum were significantly higher in adult animals compared to young ones. Higher glutathione peroxidase (GPx) activity in adult rats was observed in frontal cortex and in striatum. Our data show an increased GSH concentration and GPx activity in different cerebral regions of the adult rat, compared to the young ones, suggesting that age-related variations of total antioxidant defences in brain may predispose young brain structures to ethanol-induced, oxidative stress-mediated tissue damage.

  10. Neuroprotection by Vitamin C Against Ethanol-Induced Neuroinflammation Associated Neurodegeneration in the Developing Rat Brain.

    PubMed

    Ahmad, Ashfaq; Shah, Shahid A; Badshah, Haroon; Kim, Min J; Ali, Tahir; Yoon, Gwang H; Kim, Tae H; Abid, Nouman B; Rehman, Shafiq Ur; Khan, Sohail; Kim, Myeong O

    2016-01-01

    Ethanol induces oxidative stress and its exposure during early developmental age causes neuronal cell death which leads to several neurological disorders. We previously reported that vitamin C can protect against ethanol-induced apoptotic cell death in the developing rat brain. Here, we extended our study to understand the therapeutic efficacy of vitamin C against ethanol-induced oxidative stress, neuroinflammation mediated neurodegeneration in postnatal day 7 (PND7) rat. A single episode of ethanol (5g/kg) subcutaneous administration to postnatal day 7 rat significantly induced the production of reactive oxygen species (ROS), and activated both microglia and astrocytes followed by the induction of different apoptotic markers. On the other hand, due to its free radical scavenging properties, vitamin C treatment significantly reduced the production of reactive oxygen species, suppressed both activated microglia and astrocytes and reversed other changes including elevated level of Bax/Bcl-2 ratio, cytochrome c and different caspases such as caspase-9 and caspase-3 induced by ethanol in developing rat brain. Moreover, vitamin C treatment also reduced ethanol-induced activation of Poly [ADP-Ribose] Polymerase 1(PARP-1) and neurodegeneration as evident from Flouro-Jade-B and Nissl stainined neuronal cell death in PND7 rat brain. These findings suggest that vitamin C mitigated ethanol-induced oxidative stress, neuroinflammation and apoptotic neuronal loss and may be beneficial against ethanol damaging effects in brain development.

  11. Element distribution in the brain sections of rats measured by synchrotron radiation X-ray fluorescence

    NASA Astrophysics Data System (ADS)

    Liu, N. Q.; Zhang, F.; Wang, X. F.; Zhang, Z. Y.; Chai, Z. F.; Huang, Y. Y.; He, W.; Zhao, X. Q.; Zuo, A. J.; Yang, R.

    2004-02-01

    The concentration of trace elements in brain sections was measured by synchrotron radiation X-ray fluorescence. The relative concentration was calculated by means of the normalization of Compton scattering intensity approximately 22 keV, after the normalization for collecting time of X-ray spectrum and the counting of the ion chamber, and subtracting the contribution of the polycarbonate film for supporting sample. Furthermore, the statistical evaluation of the element distribution in various regions of the brain sections of the 20-day-old rats was tested. For investigating the distribution of elements in the brain of iodine deficient rats, Wistar rats were fed with iodine deficient diet and deionized water (ID group). The rats were fed the same iodine deficient diet, but drank KIO 3 solution as control (CT group). The results showed that the contents of calcium (Ca) in thalamus (TH) and copper (Cu) and iron (Fe) in cerebral cortex (CX) of ID rats were significantly lower than that of control rats, while the contents of phosphor (P), sulfur (S), potassium (K), rubidium (Rb), bromine (Br), chlorine (Cl), zinc (Zn), Ca and Cu of ID in hippocampus (H) and the contents of Br, Cl, Zn and Ca in cerebral cortex of ID rats were significantly higher. Especially, the difference of Br, Cl, Zn and Ca in H between ID and CT was more significant. The contents of all elements measured in H were higher than (or equal to) CX and/or TH for both groups, except low Cl of the control rats. Furthermore Zn and Cu contents along the hippocampal fissure in both groups were 1.5 ( P<0.001) and 0.87( P<0.03) times higher than in hippocampus, respectively. Considering the results of cluster analysis our study shows that the marked alterations in the spatial distribution of Zn and Ca of ID rats brain during brain development stages. In addition, the effect of the perfusion with 0.9% NaCl solution before taking brain on the distribution of elements in the brain sections was observed and

  12. Imaging of water distribution in the rat brain by activation autoradiography

    SciTech Connect

    Kogure, K.; Kawashima, K.; Iwata, R.; Ido, T. )

    1990-01-01

    Regional water distribution in the rat brain was obtained autoradiographically by activation analysis. The autoradiogram obtained for the normal rat brain showed high accumulation of water in the areas of sensory-motor cortex, hippocampus, thalamus, and amygdaloid cortex, whereas corpus callosum and internal capsule showed low water contents as expected. The estimated values of water content were 78.6 +/- 4.9 weight % for gray matter, and 73.5 +/- 4.9 weight % for white matter, respectively. The mean values of the water content were consistent with those obtained by a conventional drying-weighing method.

  13. Effects of cervical-lymphatic blockade on brain edema and infarction volume in cerebral ischemic rats.

    PubMed

    Si, Jinchao; Chen, Lianbi; Xia, Zuoli

    2006-10-31

    To observe the effects of cervical-lymphatic blockade (CLB) on brain edema and infarction volume of ischemic (MCAO) rat, we examined changes in cerebral water content, Ca2+ and glutamate concentrations, cerebral infarction volume and mRNA expression levels of N-methyl-D-aspartame receptor 1 (NMDA receptor 1) in the ischemic (left) hemisphere. The present results demonstrated that all the above indices in rats with middle cerebral artery occlusion plus cervical lymphatic blockade (MCAO+CLB) were markedly higher than those with only middle cerebral artery occlusion (MCAO) at different time points. These results indicated [corrected] that CLB can aggravate cerebral ischemia by increasing brain edema and infarction volume.

  14. Investigation of irradiated rats DNA in the presence of Cu(II) chelates of amino acids Schiff bases.

    PubMed

    Karapetyan, N H; Torosyan, A L; Malakyan, M; Bajinyan, S A; Haroutiunian, S G

    2016-01-01

    The new synthesized Cu(II) chelates of amino acids Schiff bases were studied as a potential radioprotectors. Male albino rats of Wistar strain were exposed to X-ray whole-body irradiation at 4.8 Gy. This dose caused 30% mortality of the animals (LD30). The survival of animals exposed to radiation after preliminary administration of 10 mg/kg Cu(II)(Nicotinyl-L-Tyrosinate)2 or Cu(II)(Nicotinyl-L-Tryptophanate)2 prior to irradiation was registered about 80 and 100% correspondingly. Using spectrophotometric melting and agarose gel electrophoresis methods, the differences between the DNA isolated from irradiated rats and rats pretreated with Cu(II) chelates were studied. The fragments of DNA with different breaks were revealed in DNA samples isolated from irradiated animals. While, the repair of the DNA structure was observed for animals pretreated with the Cu(II) chelates. The results suggested that pretreatment of the irradiated rats with Cu(II)(Nicotinyl-L-Tyrosinate)2 and Cu(II)(Nicotinyl-L-Tryptophanate)2 compounds improves the liver DNA characteristics.

  15. Evaluation of radioprotective effect of aloe vera and zinc/copper compounds against salivary dysfunction in irradiated rats.

    PubMed

    Nejaim, Yuri; I V Silva, Amaro; V Vasconcelos, Taruska; J N L Silva, Emmanuel; M de Almeida, Solange

    2014-09-01

    The aim of this study was to evaluate the radioprotective and reparative effects of compounds based on aloe vera, zinc, and copper against salivary gland dysfunction in Wistar rats. A total of 150 Wistar rats were randomly divided into 12 groups, in which the animals received aloe vera and/or zinc and copper. In eight of these groups the animals were also subjected to irradiation before or after administration of the substances. After 27 days, sialometry tests were performed. Data were analyzed using ANOVA and the Tukey test (P < 0.05). Rats that had been administered aloe vera before or after irradiation showed a significantly higher salivary flow rate than rats that had been simply irradiated. When both substances were administered, a statistically significant difference in the salivary flow rate was observed in comparison with the irradiation alone group seven days after irradiation. The present results suggest that aloe vera exerts positive protective and reparative effects, and can be considered a potential radioprotective substance.

  16. Compartmental analysis of washout effect in rat brain: in-beam OpenPET measurement using a 11C beam

    NASA Astrophysics Data System (ADS)

    Hirano, Yoshiyuki; Kinouchi, Shoko; Ikoma, Yoko; Yoshida, Eiji; Wakizaka, Hidekazu; Ito, Hiroshi; Yamaya, Taiga

    2013-12-01

    In-beam positron emission tomography (PET) is expected to enable visualization of a dose verification using positron emitters (β+ decay). For accurate dose verification, correction of the washout of the positron emitters should be made. In addition, the quantitative washout rate has a potential usefulness as a diagnostic index, but modeling for this has not been studied yet. In this paper, therefore, we applied compartment analyses to in-beam PET data acquired by our small OpenPET prototype, which has a physically opened field-of-view (FOV) between two detector rings. A rat brain was located at the FOV and was irradiated by a 11C beam. Time activity curves of the irradiated field were measured immediately after the irradiations, and the washout rate was obtained based on two models: the two-washout model (medium decay, k2m; slow decay, k2s) developed in a study of rabbit irradiation; and the two-compartment model used in nuclear medicine, where efflux from tissue to blood (k2), influx (k3) and efflux (k4) from the first to second compartments in tissue were evaluated. The observed k2m and k2s were 0.34 and 0.005 min-1, respectively, which was consistent with the rabbit study. Also k2m was close to the washout rate in cerebral blood flow (CBF) measurements by dynamic PET with 15O-water, while, k2, k3, and k4 were 0.16, 0.15 and 0.007 min-1. Our present work suggested the dynamics of 11C might be relevant to CBF or permeability of a molecule containing 11C atoms might be regulated by a transporter because the k2 was relatively low compared with a simple diffusion tracer.

  17. Brain macrophages in rats following intravenous labelling of mononuclear leucocytes with colloidal carbon.

    PubMed Central

    Ling, E A

    1978-01-01

    Intravenous injections of colloidal carbon were used to label circulating mononuclear leucocytes. In the neonatal rats (3-5 days old), either 24 or 48 hours later, carbon-labelled macrophages were seen in the brain tissue. In the areas examined, notably the corpus callosum and the cerebral cortex, labelled macrophages were distributed randomly. They were either perivascular, perineuronal or lay between the nerve fibres. The labelled cells were mostly spindle-shaped with an eccentric nucleus and the cytoplasm at one pole of the cell was engorged with dark carbon particles. Abundant labelled cells were also seen over the brain surface in the layers of meninges. There was no evidence of leucocytic infiltration into the brain tissue of mature animals. It is concluded from the present work that a proportion (but not all) of the macrophages in the neonatal rat brain are derived from the blood stream. Images Figs. 1-8 PMID:632205

  18. Testosterone does not influence opiate binding sites in the male rat brain.

    PubMed

    Cicero, T J; Newman, K S; Meyer, E R

    1983-09-26

    It has been reported previously that castration produces testosterone-reversible increases in the density of 3H-naltrexone binding sites in the male rat brain. Unfortunately, we were unable to replicate these observations in a comprehensive series of studies. Specifically, we found that castration failed to produce changes in the Kd or Bmax of opiate binding sites in whole male rat brain, or in the hypothalamus, utilizing 3H-dihydromorphine (a mu receptor ligand), 3H-D-alanine, D-leucine enkephalin (delta) or 3H-naltrexone (ubiquitous). Furthermore, we found that the relative proportion of mu and delta binding sites in brain was unchanged by castration. The reasons for the discrepancy between the present results and those previously reported are unclear, but it appears that the provocative hypothesis that testosterone influences opioid receptors in brain must be carefully reevaluated. PMID:6310295

  19. Putrescine as a marker of the effects of 2-chloropropionic acid in the rat brain.

    PubMed

    de Vera, Núria; Camón, Lluïsa; Martínez, Emili

    2004-05-27

    The neurotoxin 2-chloropropionic acid (2CPA, 750 mg/kg, per os) induces ataxia in rats causing neuropathological changes (necrosis and edema) localized mainly in the cerebellum (CB). It has been described that putrescine (PUT) is a good marker of severe brain damage. We measured the concentration of PUT (by HPLC) in ataxic rat brains 3 days after 2CPA dosing. PUT was 9-fold higher than normal values in CB, 5-fold higher in midbrain (MB) and medulla oblongata + pons (MO) and 3-fold higher in the remaining areas studied. Treatment with glycerol, a reducer of brain edema, lowered the concentration of PUT only in CB, MB and MO. Histological damage was found in CB and the spinal trigeminal nucleus (located in the pontomedullar brainstem). We suggest that PUT can act as a marker of both neuronal necrosis and brain edema.

  20. Effect of acute and chronic hypernatremia on myoinositol and sorbitol concentration in rat brain and kidney.

    PubMed

    Lohr, J W; McReynolds, J; Grimaldi, T; Acara, M

    1988-01-01

    In animal models of hypernatremia, increases in brain electrolyte content account for the entire increase in osmolality in acute but not chronic hypernatremia, suggesting that there is generation of additional intracellular solutes ("idiogenic osmoles") in chronic hypernatremic states. In the present study, the concentration of the polyols myoinositol and sorbitol and water content were determined in the brain and kidneys of rats made acutely (2 hours) and chronically (72 hours) hypernatremic by intraperitoneal injection of NaCl and water restriction. Both the brain and the kidney responded to chronic hypernatremia with increased levels of myoinositol. Sorbitol levels increased in the kidney in response to both acute and chronic hypernatremia. Water content dropped in acute hypernatremia, but remained unchanged during chronic hyperosmolar challenge. We conclude that the polyols, myoinositol and sorbitol, may play a significant role in cellular osmoregulation in brain and kidney during chronic hypernatremia in the rat.

  1. CARBONYL SULFIDE INHALATION PRODUCES BRAIN LESIONS IN F344 RATS.

    EPA Science Inventory

    Carbonyl sulfide (COS) is an intermediate in the production of pesticides and herbicides, and is a metabolite of the neurotoxicant carbon disulfide. The potential neurotoxicity of inhaled COS was investigated in F344 rats. Male rats were exposed to 0, 75, 150, 300, or 600 ppm COS...

  2. Regional distribution of sultopride and sulpiride in rat brain measured by radioimmunoassay.

    PubMed

    Mizuchi, A; Kitagawa, N; Miyachi, Y

    1983-01-01

    Sensitive and specific radioimmunoassays for both sultopride and sulpiride were developed. Using these radioimmunoassays, the regional distributions of sultopride and sulpiride in rat brain after intraperitoneal administration were investigated. Although relatively small amounts of both drugs were detected in the brain, sultopride appears to pass the blood-brain barrier more easily than sulpiride. Relatively high concentrations of sultopride were seen in hypothalamus, striatum, the mesolimbic area and hippocampus, while sulpiride accumulated mainly in brain areas such as hypothalamus, medulla oblongata and cerebellum, where the blood-brain barrier is less effective. Both drugs seem to be concentrated by the pituitary and pineal body. These differences between sultopride and sulpiride in penetration to the brain may depend on their different lipid solubilities, since sultopride has a higher lipid solubility compared with sulpiride.

  3. Acetylcholine content in the brain of rats treated with paraoxon and obidoxime

    PubMed Central

    Milošević, M. P.

    1970-01-01

    1. The effect of obidoxime on the rise in brain acetylcholine caused by the anticholinesterase paraoxon was studied in the rat. 2. In animals poisoned with a sublethal dose of paraoxon and thereafter treated with obidoxime the levels of both “free” and total brain acetylcholine were practically the same as those in rats injected with paraoxon only. 3. After poisoning with doses of paraoxon which are lethal unless an oxime is also given, the total acetylcholine in the brain of obidoxime-protected rats continued to accumulate, reaching a peak 2 h after injection of paraoxon. At this time no signs of central effects such as convulsions or tremor were seen. 4. Atropine, given 30 min before paraoxon, markedly reduced the rise in total brain acetylcholine seen when the anticholinesterase is given alone. 5. In rats pretreated with atropine and obidoxime excessive doses of paraoxon which are lethal in the absence of the antidotes produced a rise in total brain acetylcholine which was directly proportional to the dose of paraoxon administered. PMID:5485148

  4. Extremely low-frequency magnetic field induces manganese accumulation in brain, kidney and liver of rats.

    PubMed

    Çelik, Mustafa Salih; Güven, Kemal; Akpolat, Veysi; Akdağ, Mehmet Zulkuf; Nazıroğlu, Mustafa; Gül-Güven, Reyhan; Çelik, M Yusuf; Erdoğan, Sait

    2015-06-01

    The aim of the present study was to determine the effects of extremely low-frequency magnetic field (ELF-MF) on accumulation of manganese (Mn) in the kidney, liver and brain of rats. A total of 40 rats were randomly divided into eight groups. Four control groups received 0, 3.75, 15 and 60 mg Mn per kg body weight orally every 2 days for 45 days, respectively. The remaining four groups received same concentrations of Mn and were also exposed to ELF-MF (1.5 mT; 50 Hz) for 4 h for 5 days a week during 45 days. Following the last exposure, kidney, liver and brain were taken from all rats and they were analyzed for Mn accumulation levels using an inductively coupled plasma-optical emission spectrometer. In result of the current study, we observed that Mn levels in brain, kidney and liver were higher in Mn groups than in control groups. Mn levels in brain, kidney and liver were also higher in Mn plus ELF-MF groups than in Mn groups. In conclusion, result of the current study showed that the ELF-MF induced manganese accumulation in kidney, liver and brain of rats.

  5. Aging and sex influence the permeability of the blood-brain barrier in the rat

    SciTech Connect

    Saija, A.; Princi, P.; D'Amico, N.; De Pasquale, R.; Costa, G.

    1990-01-01

    The aim of the present study was to investigate the existence of aging- and sex-related alterations in the permeability of the blood-brain barrier (BBB) in the rat, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer ({sup 14}C)-{alpha}-aminoisobutyric acid. The authors observed that: (a) the permeability of the BBB significantly increased within the frontal and temporo-parietal cortex, hypothalamus and cerebellum in 28-30 week old rats, in comparison with younger animals; (b) in several brain areas of female intact rats higher Ki values (even though not significantly different) were calculated at oestrus than at proestrus; (c) in 1-week ovariectomized rats there was a marked increase of Ki values at the level of the frontal, temporo-parietal and occipital cortex, cerebellum and brain-stem. One can speculate that aging and sex-related alterations in thee permeability of the BBB reflect respectively changes in brain neurochemical system activity and in plasma steroid hormone levels.

  6. Brain oxidative damage restored by Sesbania grandiflora in cigarette smoke-exposed rats.

    PubMed

    Ramesh, Thiyagarajan; Sureka, Chandrabose; Bhuvana, Shanmugham; Begum, Vavamohaideen Hazeena

    2015-08-01

    Cigarette smoking has been associated with high risk of neurological diseases such as stroke, Alzheimer's disease, multiple sclerosis, etc., The present study was designed to evaluate the restorative effects of Sesbania grandiflora (S. grandiflora) on oxidative damage induced by cigarette smoke exposure in the brain of rats. Adult male Wistar-Kyoto rats were exposed to cigarette smoke for a period of 90 days and consecutively treated with S. grandiflora aqueous suspension (SGAS, 1000 mg/kg body weight per day by oral gavage) for a period of 3 weeks. The levels of protein carbonyl, nitric oxide, and activities of cytochrome P450, NADPH oxidase and xanthine oxidase were significantly increased, whereas the levels of total thiol, protein thiol, non-protein thiol, nucleic acids, tissue protein and the activities of Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase were significantly diminished in the brain of rats exposed to cigarette smoke as compared with control rats. Also cigarette smoke exposure resulted in a significant alteration in brain total lipid, total cholesterol, triglycerides and phospholipids content. Treatment of SGAS is regressed these alterations induced by cigarette smoke. The results of our study suggest that S. grandiflora restores the brain from cigarette smoke induced oxidative damage. S. grandiflora could have rendered protection to the brain by stabilizing their cell membranes and prevented the protein oxidation, probably through its free radical scavenging and anti-peroxidative effect.

  7. Measurement of the optical properties of rat brain tissue using contact spatially resolved spectroscopy

    NASA Astrophysics Data System (ADS)

    Gysbrechts, Barbara; Nguyen Do Trong, Nghia; Wang, Ling; Cabral, Henrique; Navratilova, Zaneta; Battaglia, Francesco P.; Saeys, Wouter; Bartic, Carmen

    2014-05-01

    Nowadays, biophotonics is widely used in neuroscience. The effectiveness of biophotonic techniques, such as fluorescence imaging and optogenetics, is affected by the optical properties of the examined tissue. Therefore, knowledge of these properties is essential to carefully plan experiments. Mice and rats are widely used in neuroscience studies. However, reports about optical properties of their brains are very rare. We measured optical absorption μa and reduced scattering μ's coefficients of native rat brain in the visible and near-infrared wavelength region, using contact spatially resolved spectroscopy (SRS). In this study, we estimate μa and μ's for the rat cortex and discuss their stability in time. Additionally, variations in optical properties within and between samples were characterized. The results extend the range of known optical properties for the rat cortex, especially in the visible range, relevant to optogenetics. μa and μ's are stable within a time span of four hours, and show low variation in and between brain samples. This indicates that a suitable protocol was used to estimate optical properties of rodent brain tissue. Since contact SRS is a non-destructive method, this technique could be used also to measure μa and μ's in living animals. Moreover, the probe has small dimensions, allowing the characterization of optical properties in different structures of the brain.

  8. Spontaneous Wheel Running Exercise Induces Brain Recovery via Neurotrophin-3 Expression Following Experimental Traumatic Brain Injury in Rats.

    PubMed

    Koo, Hyun Mo; Lee, Sun Min; Kim, Min Hee

    2013-09-01

    [Purpose] The aim of the present study was to investigate the expression of neurotrophin-3 (NT-3) after applying spontaneous wheel running exercises (SWR) after experimental traumatic brain injury (TBI). [Subjects and Methods] Thirty male Sprague-Dawley rats were divided into 3 groups; 20 rats were subjected to controlled cortical impact for TBI, and then, animals were randomly collected from the SWR group and subjected to wheel running exercise for 3 weeks. Ten rats were not subjected to any injury or running exercise to compare with the effect of TBI and SWR. Immunohistochemistry, Western blotting, skilled ladder rung walking test, and 2,3,5-triphenyltetrazolium chloride staining analysis for the evaluation of NT-3 expression were used to assess brain damage and recovery. [Results] The TBI-induced decrease in NT-3 expression was recovered by wheel running exercise. Moreover, decreased ischemic volume and progressive neurobehavioral outcome were observed in the SWR group. [Conclusion] Spontaneous running exercise promotes brain recovery and motor function through an increase in expression of NT-3. PMID:24259924

  9. Effects of heavy particle irradiation and diet on amphetamine- and lithium chloride-induced taste avoidance learning in rats

    NASA Technical Reports Server (NTRS)

    Rabin, Bernard M.; Shukitt-Hale, Barbara; Szprengiel, Aleksandra; Joseph, James A.

    2002-01-01

    Rats were maintained on diets containing either 2% blueberry or strawberry extract or a control diet for 8 weeks prior to being exposed to 1.5 Gy of 56Fe particles in the Alternating Gradient Synchrotron at Brookhaven National Laboratory. Three days following irradiation, the rats were tested for the effects of irradiation on the acquisition of an amphetamine- or lithium chloride-induced (LiCl) conditioned taste avoidance (CTA). The rats maintained on the control diet failed to show the acquisition of a CTA following injection of amphetamine. In contrast, the rats maintained on antioxidant diets (strawberry or blueberry extract) continued to show the development of an amphetamine-induced CTA following exposure to 56Fe particles. Neither irradiation nor diet had an effect on the acquisition of a LiCl-induced CTA. The results are interpreted as indicating that oxidative stress following exposure to 56Fe particles may be responsible for the disruption of the dopamine-mediated amphetamine-induced CTA in rats fed control diets; and that a reduction in oxidative stress produced by the antioxidant diets functions to reinstate the dopamine-mediated CTA. The failure of either irradiation or diet to influence LiCl-induced responding suggests that oxidative stress may not be involved in CTA learning following injection of LiCl.

  10. Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation-Induced Damage in Wistar Rats.

    PubMed

    Li, Jianzhong; Xu, Jing; Xu, Weiheng; Qi, Yang; Lu, Yiming; Qiu, Lei; Hu, Zhenlin; Chu, Zhiyong; Chai, Yifeng; Zhang, Junping

    2015-08-12

    Hong Shan Capsule (HSC), a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. In this study, we investigated its protection in rats against acute lethal total-body irradiation (TBI). Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. Pretreatment with HSC prevented differential expression of 66% (1398 genes) of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway. Our analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. Our data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage.

  11. Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation-Induced Damage in Wistar Rats

    PubMed Central

    Li, Jianzhong; Xu, Jing; Xu, Weiheng; Qi, Yang; Lu, Yiming; Qiu, Lei; Hu, Zhenlin; Chu, Zhiyong; Chai, Yifeng; Zhang, Junping

    2015-01-01

    Hong Shan Capsule (HSC), a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. In this study, we investigated its protection in rats against acute lethal total-body irradiation (TBI). Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. Pretreatment with HSC prevented differential expression of 66% (1398 genes) of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway. Our analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. Our data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage. PMID:26274957

  12. Cholestasis induced antinociception and decreased gene expression of MOR1 in rat brain.

    PubMed

    Ahmadi, S; Karami, Z; Mohammadian, A; Khosrobakhsh, F; Rostamzadeh, J

    2015-01-22

    We examined antinociception and gene expression of mu-opioid receptor 1 (MOR1) in some brain areas of cholestatic rats, 21 days after common bile duct ligation (BDL). Cholestasis was induced in male Wistar rats during laparotomy and common BDL. Pain behavior was assessed on days 7, 14 or 21 of BDL using a hotplate test in control, sham and cholestatic groups. On day 21 of BDL, other groups of rats were sacrificed, whole brains were extracted, and the hypothalamus, prefrontal cortex (PFC), hippocampus and striatum in control, sham and cholestatic rats were dissected. We used a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method for evaluating MOR1 gene expression. The results revealed that cholestatic rats showed significant antinociception on days 14 and 21 of ligation with the most significant effect on day 21, which was prevented by naloxone (1 mg/kg). On the other hand, the expression of MOR1 gene compared to the sham group was decreased by 42% in the hypothalamus, 41% in the PFC, and 67% in the hippocampus after 21 days of BDL, while no significant change in its expression in the striatum was observed. It can be concluded that a change in endogenous opioid levels and its subsequent influence on the gene expression of MOR in some areas of the rat brain may underlie the altered nociception and other possible pathological changes such as pruritus after induction of cholestasis. PMID:25290008

  13. Biophotonic effect of diode laser irradiance on tensile strength of diabetic rats.

    PubMed

    Lau, Pik Suan; Bidin, Noriah; Krishnan, Ganesan; Nassir, Zaleha; Bahktiar, Hazri

    2015-04-01

    Low-energy laser irradiance at certain wavelengths is able to stimulate the tissue bio-reaction and enhance the healing process. Collagen deposition is one of the important aspects in healing process because it can increase the strength of the skin. This study was designed to examine the biophotonic effect of irradiance on collagen production of diabetic wound in rat model. The tensile strength of skin was employed as a parameter to describe the wound. Diabetic rat models were induced by streptozotocin via intravenous injection. Skin-breaking strength was measured using an Instron tensile test machine. The experimental animals were treated with 808-nm diode laser at two different powers-0.1 and 0.5 W/cm(2)-and 30, 60, and 120 s for each session. The tensile strength was optimized after treated with high-power diode laser. The photostimulation effect was revealed by accelerated healing process and enhanced tensile strength of wound. Laser photostimulation on tensile strength in diabetic wound suggests that such therapy facilitates collagen production in diabetic wound healing.

  14. Biophotonic effect of diode laser irradiance on tensile strength of diabetic rats.

    PubMed

    Lau, Pik Suan; Bidin, Noriah; Krishnan, Ganesan; Nassir, Zaleha; Bahktiar, Hazri

    2015-04-01

    Low-energy laser irradiance at certain wavelengths is able to stimulate the tissue bio-reaction and enhance the healing process. Collagen deposition is one of the important aspects in healing process because it can increase the strength of the skin. This study was designed to examine the biophotonic effect of irradiance on collagen production of diabetic wound in rat model. The tensile strength of skin was employed as a parameter to describe the wound. Diabetic rat models were induced by streptozotocin via intravenous injection. Skin-breaking strength was measured using an Instron tensile test machine. The experimental animals were treated with 808-nm diode laser at two different powers-0.1 and 0.5 W/cm(2)-and 30, 60, and 120 s for each session. The tensile strength was optimized after treated with high-power diode laser. The photostimulation effect was revealed by accelerated healing process and enhanced tensile strength of wound. Laser photostimulation on tensile strength in diabetic wound suggests that such therapy facilitates collagen production in diabetic wound healing. PMID:25260140

  15. Brain structure volumes in the mole rat, Spalax ehrenbergi (Spalacidae, Rodentia) in comparison to the rat and subterrestrial insectivores.

    PubMed

    Frahm, H D; Rehkämper, G; Nevo, E

    1997-01-01

    Natural blindness and a subterranean, digging mode of life demand peculiar adaptations of the central nervous system in the mole rat Spalax ehrenbergi, which are the focus of this quantitative investigation. Volumes of 25 brain structures in Spalax were evaluated allometrically, using the least encephalized mammalian species, the Madagassian hedgehog-like tenrecs (Tenrecinae) as a reference base, and their sizes compared with those of the rat (as a more generalized representative of rodents) and of some subterranean Insectivora. The allometric approach reveals that Spalax has a larger brain than tenrecs and the rat. Within the brain, the neocortex and diencephalon are well developed, an observation also made in other mammalian species with a relatively high encephalization. An unique feature in Spalax is the enlargement of motor structures of the brain, such as the cerebellum (and cerebellar nuclei), and the striatum. Most conspicuous is the large size of the nucleus motorius nervi trigemini, reflecting the importance of masticatory muscles for the special digging technique, which demand an intense use of the teeth for loosening the soil.

  16. Downregulation of toll-like receptor 4 and IL-6 following irradiation of the rat urinary bladder.

    PubMed

    Giglio, D; Wasén, C; Mölne, J; Suchy, D; Swanpalmer, J; Jabonero Valbuena, J; Tobin, G; Ny, L

    2016-07-01

    The pathophysiology behind radiation cystitis is poorly understood. Here we investigated whether bladder irradiation affects the immune system of the rat urinary bladder. Female rats were sedated and exposed to one single radiation dose of 20 Gy or only sedated (controls) and killed 16 h to 14 days later. Rats were placed in a metabolic cage at 16 h, 3 days, 7 days and 14 days following bladder irradiation. The urinary bladders were harvested and analysed with qPCR, immunohistochemistry and/or Western blot for the expression of interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, nitric oxide synthases (eNOS, iNOS and nNOS), tumour necrosis factor (TNF)-α and toll-like receptor 4 (TLR4). Urine was collected and analysed for IL-6 and nitrite (reflecting nitric oxide activity) with ELISA and the Griess reaction, respectively. Irradiation increased bladder frequency and decreased voiding volumes 14 days following bladder irradiation. Bladder irradiation increased the expression of IL-10 and collagen in the bladder, while TLR4 and IL-6 expressions were decreased in the urothelium concomitantly with a decrease in mast cells in the submucosa and urine levels of IL-6 and nitrite. The present findings show that bladder irradiation leads to urodynamic changes in the bladder and may suppress important immunoregulatory pathways in the urinary bladder. PMID:27117224

  17. Effect of compensating filters on the isodose charts of rat and guinea-pig phantoms irradiated with "fission-neutrons".

    PubMed

    Zaránd, P

    1976-01-01

    Isodose charts were calculated for rat and guinea-pig phantoms exposed to a modified fission spectrum with a most probable energy of 1.3 MeV. Infinite tissue equivalent cylinders (r = 2.5 and 3.3 cm) and a plane source emitting neutrons according to a cosine distribution were assumed and an albedo code was used. Combined effect of (tissue-equivalent or polyethylene) compensating filters (or simply filters) and a bilateral irradiation or rotation was studied. Bilateral irradiation and the use of a filter resulted in a uniform irradiation of a rat phantom (Dmax/Dmin less than 1.15), while a uniform irradiation of a guinea-pig phantom could be obtained by the combined use of filters and rotation. If rotation is possible a Dmax/Dmin less than 1.05 ratio can be achieved. Filters + rotation should be used in all circumstances when geometrical restrictions do not prevent the installation of a rotation equipment. In this case bilateral irradiation + compensating filters are advisable. Unilateral irradiation of small laboratory animals (mouse, rat, guinea-pig) should be avoided. PMID:1007885

  18. Age-dependent changes in material properties of the brain and braincase of the rat.

    PubMed

    Gefen, Amit; Gefen, Nurit; Zhu, Qiliang; Raghupathi, Ramesh; Margulies, Susan S

    2003-11-01

    Clinical and biomechanical evidence indicates that mechanisms and pathology of head injury in infants and young children may be different from those in adults. Biomechanical computer-based modeling, which can be used to provide insight into the thresholds for traumatic tissue injury, requires data on material properties of the brain, skull, and sutures that are specific for the pediatric population. In this study, brain material properties were determined for rats at postnatal days (PND) 13, 17, 43, and 90, and skull/suture composite (braincase) properties were determined at PND 13, 17, and 43. Controlled 1 mm indentation of a force probe into the brain was used to measure naive, non-preconditioned (NPC) and preconditioned (PC) instantaneous (G(i)) and long-term (G( infinity )) shear moduli of brain tissue both in situ and in vitro. Brains at 13 and 17 PND exhibited statistically indistinguishable shear moduli, as did brains at 43 and 90 PND. However, the immature (average of 13 and 17 PND) rat brain (G(i) = 3336 Pa NPC, 1754 Pa PC; G( infinity )= 786 Pa NPC, 626 Pa PC) was significantly stiffer (p < 0.05) than the mature (average of 43 and 90 PND) brains (G(i) = 1721 Pa NPC, 1232 Pa PC; G( infinity ) = 508 Pa NPC, 398 Pa PC). A "reverse engineering" finite element model approach, which simulated the indentation of the force probe into the intact braincase, was used to estimate the effective elastic moduli of the braincase. Although the skull of older rats was significantly thicker than that of the younger rats, there was no significant age-dependent change in the effective elastic modulus of the braincase (average value = 6.3 MPa). Thus, the increase in structural rigidity of the braincase with age (up to 43 PND) was due to an increase in skull thickness rather than stiffening of the tissue. These observations of a stiffer brain and more compliant braincase in the immature rat compared with the adult rat will aid in the development of age-specific experimental

  19. Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.

    PubMed

    Fridén, Markus; Winiwarter, Susanne; Jerndal, Gunilla; Bengtsson, Ola; Wan, Hong; Bredberg, Ulf; Hammarlund-Udenaes, Margareta; Antonsson, Madeleine

    2009-10-22

    New experimental methodologies were applied to measure the unbound brain-to-plasma concentration ratio (K(p,uu,brain)) and the unbound CSF-to-plasma concentration ratio (K(p,uu,CSF)) in rats for 43 structurally diverse drugs. The relationship between chemical structure and K(p,uu,brain) was dominated by hydrogen bonding. Contrary to popular understanding based on the total brain-to-plasma concentration ratio (logBB), lipophilicity was not a determinant of unbound brain exposure. Although changing the number of hydrogen bond acceptors is a useful design strategy for optimizing K(p,uu,brain), future improvement of in silico prediction models is dependent on the accommodation of active drug transport. The structure-brain exposure relationships found in the rat also hold for humans, since the rank order of the drugs was similar for human and rat K(p,uu,CSF). This cross-species comparison was supported by K(p,uu,CSF) being within 3-fold of K(p,uu,brain) in the rat for 33 of 39 drugs. It was, however, also observed that K(p,uu,CSF) overpredicts K(p,uu,brain) for highly effluxed drugs, indicating lower efflux capacity of the blood-cerebrospinal fluid barrier compared to the blood-brain barrier.

  20. Preventive and therapeutic effects of low level laser irradiation on gentamicin vestibulotoxicity in rat utricle

    NASA Astrophysics Data System (ADS)

    Rhee, Chung-Ku; Oh, Yang Hee; Ahn, Jin-Chul; Jung, Min-Sang; Kim, Yeong-Sik; Suh, Myung-Whan

    2009-02-01

    Purpose: To investigate the effects of low level laser (LLL) irradiation for the prevention and treatment of aminoglycoside-induced vestibular ototoxicity. Materials and Methods: An organotypic culture of 2 to 4 days old rat utricular maculae hair cells was used. The cultured utricular hair cells were divided into 6 groups. Group C: the hair cells were cultured for 14 days. Group G: cultured hair cells were treated with 1 mM gentamicin (GM) for 48 hours. Group L: LLL irradiation with 670 nm diode laser 3 mW/cm2 for 60 min (10.8 J/cm2)/day for 14 days. Group LG: LLL irradiation 10.8 J/ cm2/day for 2 days followed by GM insult. Group GL: treated with GM and followed by LLL irradiation 10.8 J/ cm2/day for 12 days. LGL group: LLL irradiation 10.8 J/ cm2/day for 2 days, then GM insulted, followed by the LLLT 10.8 J/ cm2/day for 10 days. The hair cells in each group were examined and counted by confocal laser scanning electron microscope on 7th and 14th days after FM1-43 staining and observed by scanning electron microscope (SEM). Results: The number of vestibular hair cells of group G was significantly less than those in group C. Group L showed no difference compared to group C. Significantly higher numbers of cells were seen in Group LG and GL comparing to group G. The cells were more in LG than group GL. Group LGL showed the most vestibular hair cells compared to the G, LG, and GL groups. SEM showed damaged hair cells in group G while they were well preserved in groups C, L, LG, GL, and LGL. Conclusion: LLL irradiation before and after GM insult on utricular hair cells were most effective to prevent and treat GM ototoxicity. This study indicates that LLL irradiation may have clinical implications to treat various vestibular and cochlear inner ear diseases.

  1. Cranial grafting of stem cell-derived microvesicles improves cognition and reduces neuropathology in the irradiated brain.

    PubMed

    Baulch, Janet E; Acharya, Munjal M; Allen, Barrett D; Ru, Ning; Chmielewski, Nicole N; Martirosian, Vahan; Giedzinski, Erich; Syage, Amber; Park, Audrey L; Benke, Sarah N; Parihar, Vipan K; Limoli, Charles L

    2016-04-26

    Cancer survivors face a variety of challenges as they cope with disease recurrence and a myriad of normal tissue complications brought on by radio- and chemotherapeutic treatment regimens. For patients subjected to cranial irradiation for the control of CNS malignancy, progressive and debilitating cognitive dysfunction remains a pressing unmet medical need. Although this problem has been recognized for decades, few if any satisfactory long-term solutions exist to resolve this serious unintended side effect of radiotherapy. Past work from our laboratory has demonstrated the neurocognitive benefits of human neural stem cell (hNSC) grafting in the irradiated brain, where intrahippocampal transplantation of hNSC ameliorated radiation-induced cognitive deficits. Using a similar strategy, we now provide, to our knowledge, the first evidence that cranial grafting of microvesicles secreted from hNSC affords similar neuroprotective phenotypes after head-only irradiation. Cortical- and hippocampal-based deficits found 1 mo after irradiation were completely resolved in animals cranially grafted with microvesicles. Microvesicle treatment was found to attenuate neuroinflammation and preserve host neuronal morphology in distinct regions of the brain. These data suggest that the neuroprotective properties of microvesicles act through a trophic support mechanism that reduces inflammation and preserves the structural integrity of the irradiated microenvironment. PMID:27044087

  2. Cranial grafting of stem cell-derived microvesicles improves cognition and reduces neuropathology in the irradiated brain

    PubMed Central

    Baulch, Janet E.; Acharya, Munjal M.; Allen, Barrett D.; Ru, Ning; Chmielewski, Nicole N.; Martirosian, Vahan; Giedzinski, Erich; Syage, Amber; Park, Audrey L.; Benke, Sarah N.; Parihar, Vipan K.; Limoli, Charles L.

    2016-01-01

    Cancer survivors face a variety of challenges as they cope with disease recurrence and a myriad of normal tissue complications brought on by radio- and chemotherapeutic treatment regimens. For patients subjected to cranial irradiation for the control of CNS malignancy, progressive and debilitating cognitive dysfunction remains a pressing unmet medical need. Although this problem has been recognized for decades, few if any satisfactory long-term solutions exist to resolve this serious unintended side effect of radiotherapy. Past work from our laboratory has demonstrated the neurocognitive benefits of human neural stem cell (hNSC) grafting in the irradiated brain, where intrahippocampal transplantation of hNSC ameliorated radiation-induced cognitive deficits. Using a similar strategy, we now provide, to our knowledge, the first evidence that cranial grafting of microvesicles secreted from hNSC affords similar neuroprotective phenotypes after head-only irradiation. Cortical- and hippocampal-based deficits found 1 mo after irradiation were completely resolved in animals cranially grafted with microvesicles. Microvesicle treatment was found to attenuate neuroinflammation and preserve host neuronal morphology in distinct regions of the brain. These data suggest that the neuroprotective properties of microvesicles act through a trophic support mechanism that reduces inflammation and preserves the structural integrity of the irradiated microenvironment. PMID:27044087

  3. Brain acetylcholinesterase activity in Wistar and August rats with low and high motor activity (a cytochemical study).

    PubMed

    Sergutina, A V; Rakhmanova, V I

    2014-08-01

    Acetylcholinesterase activity was quantitatively evaluated by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampus CA3 field) of August and Wistar rats demonstrating high and low motor activity in the open field test. In August rats, acetylcholinesterase activity in the analyzed brain structures prevailed in animals with high motor activity in comparison with rats with low motor activity. In Wistar rats, the differences between the animals demonstrating high and low motor activity were less pronounced, but varied depending on the experimental series of studies. Comparisons of August rats with low motor activity and Wistar rats with high motor activity (maximum difference of motor function in these animals) revealed significant excess of acetylcholinesterase activity in layer III of the sensorimotor cortex in August rats and no differences in other brain structures of the examined animals.

  4. Compromised Blood-Brain Barrier Competence in Remote Brain Areas in Ischemic Stroke Rats at Chronic Stage

    PubMed Central

    Garbuzova-Davis, Svitlana; Haller, Edward; Williams, Stephanie N.; Haim, Eithan D.; Tajiri, Naoki; Hernandez-Ontiveros, Diana G.; Frisina-Deyo, Aric; Boffeli, Sean M.; Sanberg, Paul R.; Borlongan, Cesario V.

    2014-01-01

    Stroke is a life threatening disease leading to long-term disability in stroke survivors. Cerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from initial ischemic lesion, i.e. diaschisis. Previously, we showed that the damaged blood-brain barrier (BBB) was implicated in subacute diaschisis. The present study investigated BBB competence in chronic diaschisis using a transient middle cerebral artery occlusion (tMCAO) rat model. Our results demonstrated significant BBB damage mostly in the ipsilateral striatum and motor cortex in rats at 30 days after tMCAO. The BBB alterations were also determined in the contralateral hemisphere via ultrastructural and immunohistochemical analyses. Major BBB pathological changes in contralateral remote striatum and motor cortex areas included: (1) vacuolated endothelial cells containing large autophagosomes, (2) degenerated pericytes displaying mitochondria with cristae disruption, (3) degenerated astrocytes and perivascular edema, (4) Evans Blue extravasation, and (5) appearance of parenchymal astrogliosis. Importantly, discrete analyses of striatal and motor cortex areas revealed significantly higher autophagosome accumulation in capillaries of ventral striatum and astrogliosis in dorsal striatum in both cerebral hemispheres. These widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggest persistent and/or continued BBB damage in chronic ischemia. The pathological changes in remote brain areas likely indicate chronic ischemic diaschisis, which should be considered in the development of treatment strategies for stroke. PMID:24610730

  5. Leydig cells contribute to the inhibition of spermatogonial differentiation after irradiation of the rat.

    PubMed

    Shetty, G; Zhou, W; Weng, C C Y; Shao, S H; Meistrich, M L

    2016-05-01

    Irradiation with 6 Gy produces a complete block of spermatogonial differentiation in LBNF1 rats that would be permanent without treatment. Subsequent suppression of gonadotropins and testosterone (T) restores differentiation to the spermatocyte stage; however, this process requires 6 weeks. We evaluated the role of Leydig cells (LCs) in maintenance of the block in spermatogonial differentiation after exposure to radiation by specifically eliminating functional LCs with ethane dimethane sulfonate (EDS). EDS (but not another alkylating agent), given at 10 weeks after irradiation, induced spermatogonial differentiation in 24% of seminiferous tubules 2 weeks later. However, differentiation became blocked again at 4 weeks as LCs recovered. When EDS was followed by treatment with GnRH antagonist and flutamide, sustained spermatogonial differentiation was induced in >70% of tubules within 2 weeks. When EDS was followed by GnRH antagonist plus exogenous T, which also inhibits LC recovery but restores follicle stimulating hormone (FSH) levels, the spermatogonial differentiation was again rapid but transient. These results confirm that the factors that block spermatogonial differentiation are indirectly regulated by T, and probably FSH, and that adult and possibly immature LCs contribute to the production of such inhibitory factors. We tested whether insulin-like 3 (INSL3), a LC-produced protein whose expression correlated with the block in spermatogonial differentiation, was indeed responsible for the block by injecting synthetic INSL3 into the testes and knocking down its expression in vivo with siRNA. Neither treatment had any effect on spermatogonial differentiation. The Leydig cell products that contribute to the inhibition of spermatogonial differentiation in irradiated rats remain to be elucidated. PMID:26991593

  6. DNA Methylation Patterns in Rat Mammary Carcinomas Induced by Pre- and Post-Pubertal Irradiation

    PubMed Central

    Takabatake, Masaru; Blyth, Benjamin J.; Daino, Kazuhiro; Imaoka, Tatsuhiko; Nishimura, Mayumi; Fukushi, Masahiro; Shimada, Yoshiya

    2016-01-01

    Several lines of evidence indicate one’s age at exposure to radiation strongly modifies the risk of radiation-induced breast cancer. We previously reported that rat mammary carcinomas induced by pre- and post-pubertal irradiation have distinct gene expression patterns, but the changes underlying these differences have not yet been characterized. The aim of this investigation was to see if differences in CpG DNA methylation were responsible for the differences in gene expression between age at exposure groups observed in our previous study. DNA was obtained from the mammary carcinomas arising in female Sprague-Dawley rats that were either untreated or irradiated (γ-rays, 2 Gy) during the pre- or post-pubertal period (3 or 7 weeks old). The DNA methylation was analyzed using CpG island microarrays and the results compared to the gene expression data from the original study. Global DNA hypomethylation in tumors was accompanied by gene-specific hypermethylation, and occasionally, by unique tumor-specific patterns. We identified methylation-regulated gene expression candidates that distinguished the pre- and post-pubertal irradiation tumors, but these represented only 2 percent of the differentially expressed genes, suggesting that methylation is not a major or primary mechanism underlying the phenotypes. Functional analysis revealed that the candidate methylation-regulated genes were enriched for stem cell differentiation roles, which may be important in mammary cancer development and worth further investigation. However, the heterogeneity of human breast cancer means that the interpretation of molecular and phenotypic differences should be cautious, and take into account the co-variates such as hormone receptor status and cell-of-origin that may influence the associations. PMID:27711132

  7. Immunocytochemistry of formalin-fixed human brain tissues: microwave irradiation of free-floating sections.

    PubMed

    Shiurba, R A; Spooner, E T; Ishiguro, K; Takahashi, M; Yoshida, R; Wheelock, T R; Imahori, K; Cataldo, A M; Nixon, R A

    1998-01-01

    antigens. Theory and practice of microwave antigen retrieval are covered extensively in the handbook Microwave Cookbook for Microscopists. A concise overview of microwave methods in the neurosciences has been published, and clinical applications have been reviewed. In this context, it should be noted that fresh tissues may be stabilized for immunocytochemistry by reversible, non-chemical binding processes such as cryosectioning after microwave treatment and freeze-drying. Thus, it may be possible to enhance immunostaining for some antigens by microwave irradiation of unfixed as well as fixed specimens. Parameters to be optimized for microwave retrieval of specific antigens include temperature, irradiation time, tissue buffer composition, salt concentration, and pH. Temperature, irradiation time, and pH are key variables. With this in mind, an optimal method was developed for retrieval of a wide variety of antigens in human brain tissues. Typical microwave protocols employ elevated temperatures that may reach 100 degrees C, where denaturation causes irreversible uncoiling and disruption of protein secondary and tertiary structures. Under these conditions, stable covalent bonds securing methylene crosslinks between polypeptides remain intact, but more reactive links formed by Schiff bases may be hydrolyzed. Resultant conformational changes presumably expose buried loops of continuous amino acids and protruding regions, increasing accessibility of their epitopes. Protein denaturation seems to be a reasonable explanation for the effects of microwaves on antigen retrieval. This idea is supported by the observation that denaturing solutions such as 6 M urea increase immunoreactivity of some antigens. Still, the molecular basis of these effects remains unresolved, in part due to the complex chemistry of formaldehyde reactions with tissue constituents. Indeed, some methylene bridges between similar groups such as NH2 and NH may be hydrolyzed by washing fixed tissues in distilled

  8. [The change of some indices of coagulogram in rats in experimental pancreonecrosis under the influence of electromagnet irradiation of extremely high frequencies].

    PubMed

    Boĭko, V V; Ivanova, Iu V; Mushenko, E V

    2011-12-01

    The dynamics of changes of some coagulogram indices under the influence of electromagnet irradiation of extremely high frequencies was studied in rats in conditions of experimental pancreonecrosis. Irradiation of abdominal cavity in animals, using electromagnet irradiation with the 6.5 mm wave length, reduces hypercoagulation shifts essentially and raises the plasm anticoagulant and fibrinolytic activity.

  9. Fos expression in brain stem nuclei of pregnant rats after hydralazine-induced hypotension.

    PubMed

    Curtis, K S; Cunningham, J T; Heesch, C M

    1999-08-01

    Fos and dopamine beta-hydroxylase immunoreactivity were evaluated in the brain stems of 21-day pregnant and virgin female rats injected with either hydralazine (HDZ; 10 mg/kg iv) or vehicle. HDZ produced significant hypotension in both groups, although baseline blood pressure was lower in pregnant rats (96 +/- 2.5 mmHg) than in virgin female rats (121 +/- 2.8 mmHg). There were no differences in Fos immunoreactivity in the brain stems of pregnant and virgin female rats after vehicle treatment. HDZ-induced hypotension significantly increased Fos expression in both groups; however, the magnitude of the increases differed in the caudal ventrolateral medulla (CVL), the area postrema (AP), and the rostral ventrolateral medulla (RVL). Fos expression after HDZ in pregnant rats was augmented in noncatecholaminergic neurons of the CVL but was attenuated in the AP and in noncatecholaminergic neurons in the RVL. These results are consistent with differences in the sympathetic response to hypotension between pregnant and virgin female rats and indicate that the central response to hypotension may be different in pregnant rats.

  10. Water maze training in aged rats: effects on brain metabolic capacity and behavior.

    PubMed

    Villarreal, J S; Gonzalez-Lima, F; Berndt, J; Barea-Rodriguez, E J

    2002-06-01

    The effects of Morris water maze training on brain metabolism and behavior were compared between aged (20-22 months) and young (2-4 months) Fischer 344 male rats. Each group had yoked controls, which swam the same amount of time as the trained rats but without the platform. This was followed after 9 days by quantitative histochemical mapping of brain cytochrome oxidase, the terminal enzyme for cellular respiration. The aged rats spent a significantly lower percent of time in the correct quadrant and had a longer latency to escape to the hidden platform, relative to the young rats. Metabolic differences between trained aged and young rats were found in regions related to escape under stress: perirhinal cortex, basolateral amygdala and lateral habenula; and vestibular nuclei that guide orientation in three-dimensional space. These differences were not found in the yoked swimming rats. The results suggest that, at the time point investigated, water maze training in aged Fischer 344 rats produces altered oxidative energy metabolism in task-relevant limbic and vestibular regions.

  11. Binding sites for atrial natriuretic factor (ANF) in brain: alterations in Brattleboro rats

    SciTech Connect

    McCarty, R.; Plunkett, L.M.

    1986-12-01

    Binding sites for atrial natriuretic factor (ANF-28) were analyzed in discrete brain areas of Brattleboro rats with hereditary diabetes insipidus and Long-Evans (LE) controls by quantitative autoradiography. The maximum binding capacity (Bmax) and affinity constant (Ka) for /sup 125/I-ANF-28 were elevated significantly in the subfornical organ of Brattleboro rats compared to matched LE controls. In contrast, values for Bmax and Ka for /sup 125/I-ANF-28 binding in choroid plexus and area postrema were similar for rats of the two strains. These findings are consistent with a selective upregulation of ANF-28 binding sites in the subfornical organ of Brattleboro rats which exhibit a profound disturbance in body fluid homeostasis. These alterations in ANF-28 binding sites in the subfornical organ may represent a compensatory response to the absence of vasopressin in the Brattleboro rat.

  12. Effects of gamma-irradiation on biosynthesis of different types of ribonucleic acids in normal and regenerating rat liver.

    PubMed Central

    Markov, G G; Dessev, G N; Russev, G C; Tsanev, R G

    1975-01-01

    1. The effect of gamma-irradiation (4000rd) on the synthesis of ribosomal (pre-rRNA) and heterogeneous nuclear RNA (pre-mRNA) in normal and in regenerating rat liver was studied by using 40 min labelling with [6(-14)C]orotic acid. 2. Partial hepatectomy caused a sharp transient increase in the specific radioactivity of the endogenous low-molecular-weight RNA precursors in the livers of both normal and irradiated rats. Irradiation of intact animals did not affect the pool. 3. Irradiation enhanced the synthesis of pre-rRNA for at least 12h. The synthesis of pre-mRNA was also enhanced, but only in the first 3h after irradiation. 4. Partial hepatectomy strongly stimulated the synthesis of both pre-rRNA and pre-mRNA. 5. The synthesis of pre-rRNA was enhanced also in regenerating liver of animals irradiated before or after the operation. The conclusion can be drawn that the early increase in the synthesis of ribosomal RNA is a non-specific cellular response to different injuring factors. 6. The only case where irradiation caused an early inhibition of RNA synthesis was that of pre-mRNA in regenerating liver. This supports the hypothesis that ionizing radiation does not suppress the transcription per se but affects the mechanisms of activation of new genes (cellular programming). PMID:1147904

  13. Brain renin-angiotensin system and sympathetic hyperactivity in rats after myocardial infarction.

    PubMed

    Zhang, W; Huang, B S; Leenen, F H

    1999-05-01

    Blockade of brain "ouabain" prevents the sympathetic hyperactivity and impairment of baroreflex function in rats with congestive heart failure (CHF). Because brain "ouabain" may act by activating the brain renin-angiotensin system (RAS), the aim of the present study was to assess whether chronic treatment with the AT1-receptor blocker losartan given centrally normalizes the sympathetic hyperactivity and impairment of baroreflex function in Wistar rats with CHF postmyocardial infarction (MI). After left coronary artery ligation (2 or 6 wk), rats received either intracerebroventricular losartan (1 mg. kg-1. day-1, CHF-Los) or vehicle (CHF-Veh) by osmotic minipumps. To assess possible peripheral effects of intracerebroventricular losartan, one set of CHF rats received the same rate of losartan subcutaneously. Sham-operated rats served as control. After 2 wk of treatment, mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) at rest and in response to air-jet stress and intracerebroventricular injection of the alpha2-adrenoceptor-agonist guanabenz were measured in conscious animals. Arterial baroreflex function was evaluated by ramp changes in MAP. Compared with sham groups, CHF-Veh groups showed impaired arterial baroreflex control of HR and RSNA, increased sympathoexcitatory and pressor responses to air-jet stress, and increased sympathoinhibitory and hypotensive responses to guanabenz. The latter is consistent with decreased activity in sympathoinhibitory pathways. Chronic intracerebroventricular infusion of losartan largely normalized these abnormalities. In CHF rats, the same rate of infusion of losartan subcutaneously was ineffective. In sham-operated rats, losartan intracerebroventricularly or subcutaneously did not affect sympathetic activity. We conclude that the chronic increase in sympathoexcitation, decrease in sympathoinhibition, and desensitized baroreflex function in CHF all appear to depend on the brain RAS, since

  14. Protective effect of Xingnaojia formulation on rats with brain and liver damage caused by chronic alcoholism

    PubMed Central

    LI, SHUANG; WANG, SU; GUO, ZHI-GANG; HUANG, NING; ZHAO, FAN-RONG; ZHU, MO-LI; MA, LI-JUAN; LIANG, JIN-YING; ZHANG, YU-LIN; HUANG, ZHONG-LIN; WAN, GUANG-RUI

    2015-01-01

    The aim of this study was to observe the effect of a formulation of traditional Chinese medicine extracts known as Xingnaojia (XNJ) on the liver function, learning ability and memory of rats with chronic alcoholism and to verify the mechanism by which it protects the brain and liver. A rat model of chronic alcoholism was used in the study. The spatial learning ability and memory of the rats were tested. The rats were then sacrificed and their brains and hepatic tissues were isolated. The activity of superoxide dismutase (SOD) and levels of glutamate (Glu), N-methyl D-aspartate receptor subtype 2B (NR2B), cyclin-dependent kinase 5 (CDK5) and cannabinoid receptor 1 (CB1) in the hippocampus were analyzed. The ultrastructure of the hepatic tissue was observed by electron microscopy. In addition, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum were tested and the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TCHOL) were analyzed. XNJ enhanced the learning and memory of rats with chronic alcoholism. Treatment with XNJ increased the activity of SOD, and decreased the expression levels of NR2B mRNA and NR2B, CB1 and CDK5 proteins in the brain tissues compared with those in the model rats. It also increased the activity of ALDH in the serum and liver, decreased the serum levels of LDL, TG and TCHOL and increased the serum level of HDL. These results indicate that XNJ exhibited a protective effect against brain and liver damage in rats with chronic alcoholism. PMID:26640531

  15. Adverse effects of brain irradiation correlated with MR and CT imaging

    SciTech Connect

    Constine, L.S.; Konski, A.; Ekholm, S.; McDonald, S.; Rubin, P.

    1988-08-01

    Forty-one patients treated for primary malignancies of the brain at the University of Rochester Cancer Center since 1970 were assessed for adverse effects of irradiation clinically, and by computerized tomography (CT) and magnetic resonance (MR) imaging. At diagnosis, patients ranged in age from 1-65 years (median 19 years) and the most common tumor (in 30) was astrocytoma. Radiation doses ranged from 45 to 81.3 Gy (median 56.8 Gy). White matter changes visible on MR were graded on a scale of 1-4, with grades 1-2 known to occur in some normal patients. Areas of increased signal intensity not associated with the tumor or surgery were visible in all patients (gr 1 = 37%, gr 2 = 32%, gr 3 = 17%, gr 4 = 15%) whereas only 35% had regions of abnormality (hypodensity) on CT. Sulci enlargement and ventricular abnormalities (asymmetry or dilatation) were present in approximately 50% of patients by each technique. Higher grade MR lesions were associated with radiation to large volumes and high doses. For the 36 patients treated with 1.5-2.0 Gy daily fractions, the mean radiation dose by grade was as follows: gr 1 = 55.1 Gy, gr 2 = 58.8 Gy, gr 3 = 60.0 Gy, gr 4 = 63.5 Gy. All 5 patients treated on a hyperfractionated schedule had gr 1-2 changes despite receiving greater than 70 Gy. Fifty percent of patients treated to the whole brain (+/- boost) had gr 3-4 changes, compared with 14% treated with local fields (peak dose regions similar in both groups). Among the children (less than or equal to 13 years), 20% had gr 3-4 changes compared with 56% of adults (excluding hyperfractionated patients). This finding may be due entirely or in part to the lower radiation doses used for children (mean 54.4 Gy vs. 63.7 Gy in adults). Clinical abnormalities attributable to irradiation included an impairment in mental functioning in 7 adults, and learning disabilities in 5 children.

  16. The neuroprotection of hypoxic preconditioning on rat brain against traumatic brain injury by up-regulated transcription factor Nrf2 and HO-1 expression.

    PubMed

    Shu, Longfei; Wang, Chunlin; Wang, Jinbiao; Zhang, Yongming; Zhang, Xing; Yang, Yanyan; Zhuo, Jianwei; Liu, Jiachuan

    2016-01-12

    Hypoxic preconditioning (HPC) increases the inherent tolerance of brain tissue suffering from severe hypoxia or ischemia insult by stimulating the protective ability of the brain. However, little is known concerning the effect of HPC on traumatic brain injury (TBI). We designed this study to investigate the effect of HPC on TBI and explore its underlying mechanisms. We found that HPC significantly alleviates neurological dysfunction, lessens brain edema, reduces cell apoptosis, increases neuronal survival, up-regulates the expressions of Nrf2 and HO-1, and decreases the inducer of protein carbonyls, 4-hydroxy-2-nonenal, and 8-hydroxy-2-deoxyguanosine in the brain tissue of rats 24h after brain injury. However, no influence was observed in normal rats after only 3d of hypoxic training. Results further indicated that HPC protects the brain against traumatic damage. This protective effect may be achieved by up-regulating Nrf2 and HO-1 expression and alleviating oxidative stress damage. PMID:26590328

  17. Effects of hyperbaric oxygen and irradiation on experimental skin flaps in rats

    SciTech Connect

    Nemiroff, P.M.; Merwin, G.E.; Brant, T.; Cassisi, N.J.

    1985-08-01

    This study investigated the effects of hyperbaric oxygen (HBO) and irradiation (RT) on experimental skin flaps in rats under varying conditions. Animals were assigned at random to 1 of 15 groups that represented all possible ordering effects of HBO, RT, and flap, as well as controls that included flap-only, RT-only, and HBO-only groups. Cranially based skin flaps measuring 3 x 9 cm were elevated on the dorsum. The surviving length was evaluated with fluorescein dye 7 days after the operation. Depending on the treatment condition, HBO was given either 48 hours or 24 hours before flap elevation, or within 4 hours or 48 hours after flap elevation. Rats receiving RT (WCo) were given a single dose of 1000 rads to the dorsum. Results showed that all groups receiving HBO within 4 hours after flap elevation had significantly greater flap survival length, with as much as a 22% greater length of surviving flap. HBO given 48 hours before flap elevation also significantly improved flap survival over controls. RT appeared to have no immediate significant effect on flap survival. However, rats receiving RT, regardless of other factors, gained significantly less weight than did controls. Findings clearly indicate that, to be effective, HBO needs to be given as soon after surgery as possible.

  18. Neuroprotective effect of EGb761® and low-dose whole-body γ-irradiation in a rat model of Parkinson's disease.

    PubMed

    El-Ghazaly, Mona A; Sadik, Nermin A H; Rashed, Engy R; Abd-El-Fattah, Amal A

    2015-12-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. The present study was undertaken to investigate the pretreatment effects of standardized Ginkgo biloba extract (EGb761(®)) and low-dose whole-body γ-irradiation on the neurological dysfunction in the reserpine model of PD. Male Wistar rats were pretreated orally with EGb761 or fractionated low-dose whole-body γ-irradiation or their combination, then subjected to intraperitoneal injection of reserpine (5 mg/kg body weight) 24 h after the final dose of EGb761 or radiation. Reserpine injection resulted in the depletion of striatal dopamine (DA) level, increased catalepsy score, increased oxidative stress indicated via depletion of glutathione (GSH), increased malondialdehyde (MDA) and iron levels, decreased DA metabolites metabolizing enzymes; indicated by inhibition by glutathione-S-transferase, and nicotinamide adenine dinucleotide phosphate (NADPH)-quinone oxidoreductase (NQO) activities, mitochondrial dysfunction; indicated by declined complex I activity, and adenosine triphosphate (ATP) level and increased apoptosis; indicated by decreased mitochondrial B cell lymphoma-2 (Bcl-2) protein level and by transmission electron microscope. EGb761 and low-dose γ-radiation ameliorated the reserpine-induced state of oxidative stress, mitochondrial dysfunction, and apoptosis in brain. It can be concluded that EGb761, a widely used herbal medicine and low dose of γ-irradiation have protective effects for combating Parkinsonism possibly via replenishment of GSH levels.

  19. Brain receptors for thyrotropin releasing hormone in morphine tolerant-dependent rats

    SciTech Connect

    Bhargava, H.N.; Das, S.

    1986-03-01

    The effect of chronic treatment of rats with morphine and its subsequent withdrawal on the brain receptors for thyrotropin releasing hormone (TRH) labeled with /sup 3/H-(3MeHis/sup 2/)TRH (MeTRH). Male Sprague Dawley rats were implanted with 4 morphine pellets (each containing 75 mg morphine base) during a 3-day period. Placebo pellet implanted rats served as controls. Both tolerance to and dependence on morphine developed as a result of this procedure. For characterization of brain TRH receptors, the animals were sacrificed 72 h after the implantation of first pellet. In another set of animals the pellets were removed and were sacrificed 24 h later. The binding of /sup 3/H-MeTRH to membranes prepared from brain without the cerebellum was determined. /sup 3/H-MeTRH bound to brain membranes prepared from placebo pellet implanted rats at a single high affinity site with a B/sub max/ value of 33.50 +/- 0.97 fmol/mg protein and a K/sub d/ of 5.18 +/- 0.21 nM. Implantation of morphine pellets did not alter the B/sub max/ value of /sup 3/H-MeTRH but decreased the K/sub d/ value significantly. Abrupt or naloxone precipitated withdrawal of morphine did not alter B/sub max/ or the K/sub d/ values. The binding of /sup 3/H-MeTRH to brain areas was also determined. The results suggest that the development of tolerance to morphine is associated with enhanced sensitivity of brain TRH receptors, however abrupt withdrawal of morphine does not change the characteristics of brain TRH receptors.

  20. Aqueous Date Fruit Efficiency as Preventing Traumatic Brain Deterioration and Improving Pathological Parameters after Traumatic Brain Injury in Male Rats

    PubMed Central

    Badeli, Hamze; Shahrokhi, Nader; KhoshNazar, Mahdieosadat; Asadi-Shekaari, Majid; Shabani, Mohammad; Eftekhar Vaghefi, Hassan; Khaksari, Mohammad; Basiri, Mohsen

    2016-01-01

    Objective Following traumatic brain injury, disruption of blood-brain-barrier and consequent brain edema are critical events which might lead to increasing intracranial pressure (ICP), and nerve damage. The current study assessed the effects of aqueous date fruit extract (ADFE) on the aforementioned parameters. Materials and Methods In this experimental study, diffused traumatic brain injury (TBI) was generated in adult male rats using Marmarou’s method. Experimental groups include two pre-treatment (oral ADFE, 4 and 8 mL/kg for 14 days), vehicle (distilled water, for 14 days) and sham groups. Brain edema and neuronal injury were measured 72 hours after TBI. Veterinary coma scale (VCS) and ICP were determined at -1, 4, 24, 48 and 72 hours after TBI. Differences among multiple groups were assessed using ANOVA. Turkey’s test was employed for the ANOVA post-hoc analysis. The criterion of statistical significance was sign at P<0.05. Results Brain water content in ADFE-treated groups was decreased in comparison with the TBI+vehicle group. VCS at 24, 48 and 72 hours after TBI showed a significant increase in ADFE groups in comparison with the TBI+vehicle group. ICP at 24, 48 and 72 hours after TBI, was decreased in ADFE groups, compared to the TBI+vehicle. Brain edema, ICP and neuronal injury were also decreased in ADFE group, but VCS was increased following on TBI. Conclusion ADFE pre-treatment demonstrated an efficient method for preventing traumatic brain deterioration and improving pathological parameters after TBI.

  1. Aqueous Date Fruit Efficiency as Preventing Traumatic Brain Deterioration and Improving Pathological Parameters after Traumatic Brain Injury in Male Rats

    PubMed Central

    Badeli, Hamze; Shahrokhi, Nader; KhoshNazar, Mahdieosadat; Asadi-Shekaari, Majid; Shabani, Mohammad; Eftekhar Vaghefi, Hassan; Khaksari, Mohammad; Basiri, Mohsen

    2016-01-01

    Objective Following traumatic brain injury, disruption of blood-brain-barrier and consequent brain edema are critical events which might lead to increasing intracranial pressure (ICP), and nerve damage. The current study assessed the effects of aqueous date fruit extract (ADFE) on the aforementioned parameters. Materials and Methods In this experimental study, diffused traumatic brain injury (TBI) was generated in adult male rats using Marmarou’s method. Experimental groups include two pre-treatment (oral ADFE, 4 and 8 mL/kg for 14 days), vehicle (distilled water, for 14 days) and sham groups. Brain edema and neuronal injury were measured 72 hours after TBI. Veterinary coma scale (VCS) and ICP were determined at -1, 4, 24, 48 and 72 hours after TBI. Differences among multiple groups were assessed using ANOVA. Turkey’s test was employed for the ANOVA post-hoc analysis. The criterion of statistical significance was sign at P<0.05. Results Brain water content in ADFE-treated groups was decreased in comparison with the TBI+vehicle group. VCS at 24, 48 and 72 hours after TBI showed a significant increase in ADFE groups in comparison with the TBI+vehicle group. ICP at 24, 48 and 72 hours after TBI, was decreased in ADFE groups, compared to the TBI+vehicle. Brain edema, ICP and neuronal injury were also decreased in ADFE group, but VCS was increased following on TBI. Conclusion ADFE pre-treatment demonstrated an efficient method for preventing traumatic brain deterioration and improving pathological parameters after TBI. PMID:27602324

  2. Field orientation effects during 5. 6-GHz radiofrequency irradiation of rats

    SciTech Connect

    Frei, M.R.; Jauchem, J.R.; Price, D.L.; Padilla, J.M. )

    1990-12-01

    Ketamine-anesthetized Sprague-Dawley rats were exposed in E and H orientations (long axis parallel to electric and magnetic fields, respectively) to far-field 5.6-GHz continuous-wave radio-frequency radiation (RFR). Power densities were used that resulted in equivalent whole-body average specific absorption rates of 14 W/kg in both orientations (90 mW/cm2 for E and 66 mW/cm2 for H). Irradiation was conducted to increase colonic temperature by 1 degree C (from 38.5 to 39.5 degrees C). During experimentation, arterial blood pressure and respiratory rate and colonic, tympanic, left and right subcutaneous (sides toward and away from RFR source), and tail temperatures were continuously recorded. Results showed no significant difference in the times required to cause a 1 degree C increase or to recover to the initial temperature when irradiation was stopped. Significant differences between E- and H-orientation exposure were seen in the patterns of localized heating. The tail and left subcutaneous temperature increases were significantly greater during E-orientation exposure, the tympanic site showed no difference, and the right subcutaneous temperature increase was significantly greater during H-orientation exposure. Under both exposure conditions, heart rate and mean arterial blood pressure significantly increased during irradiation; however, there were no significant differences between E and H orientation responses. These findings at 5.6 GHz are in contrast to the significant cardiovascular response differences between E- and H-orientation exposure noted during a previous study of irradiation at 2.45 GHz.

  3. Rapid and widespread distribution of doxycycline in rat brain: a mass spectrometric imaging study.

    PubMed

    Munyeza, Chiedza F; Shobo, Adeola; Baijnath, Sooraj; Bratkowska, Dominika; Naiker, Suhashni; Bester, Linda A; Singh, Sanil D; Maguire, Glenn E M; Kruger, Hendrik G; Naicker, Tricia; Govender, Thavendran

    2016-01-01

    1. The penetration of tetracyclines into the brain has been widely documented. The aim of this work was to develop a matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI MSI) method for the molecular histology of doxycycline (DOX) in the healthy rat brain. 2. The time-dependent distribution was investigated after an i.p. dose of 25 mg/kg at 0, 5, 30, 120, 240, 360 and 480 min postdose. LCMS/MS was used to quantify the drug in plasma and brain homogenates and MALDI MSI was used to determine the distribution of the analyte. 3. Within the first-hour postdose, the drug showed slow accumulation into the plasma and brain tissues. DOX brain concentration gradually increased and reached a peak (Cmax) of 1034.9 ng/mL at 240 min postdose, resulting in a brain plasma ratio of 31%. The images acquired by MSI matched the quantification results and clearly showed drug distribution over the entire rat brain coronal section from 5 min and its slow elimination after 360-min postdose. 4. Our findings confirm that MALDI MSI provides an advanced, label-free and faster alternative technique for xenobiotic distribution such as DOX in tissues, making it an essential drug discovery tool for other possible neuroprotective agents. PMID:26327274

  4. 65zinc uptake from blood into brain and other tissues in the rat

    SciTech Connect

    Pullen, R.G.; Franklin, P.A.; Hall, G.H. )

    1990-10-01

    Zinc is essential for normal growth, development and brain function although little is known about brain zinc homeostasis. Therefore, in this investigation we have studied 65Zn uptake from blood into brain and other tissues and have measured the blood-brain barrier permeability to 65Zn in the anaesthetized rat in vivo. Adult male Wistar rats within the weight range 500-600 g were used. 65ZnCl2 and (125I)albumin, the latter serving as a vascular marker, were injected in a bolus of normal saline I.V. Sequential arterial blood samples were taken during experiments that lasted between 5 min and 5 hr. At termination, samples from the liver, spleen, pancreas, lung, heart, muscle, kidney, bone, testis, ileum, blood cells, csf, and whole brain were taken and analysed for radio-isotope activity. Data have been analysed by Graphical Analysis which suggests 65Zn uptake from blood by all tissues sampled was unidirectional during this experimental period except brain, where at circulation times less than 30 min, 65Zn fluxes were bidirectional. In addition to the blood space, the brain appears to contain a rapidly exchanging compartment(s) for 65Zn of about 4 ml/100g which is not csf.

  5. Analysis of intracranial pressure pulse waveform and brain capillary morphology in type 2 diabetes mellitus rats.

    PubMed

    Onodera, Hidetaka; Oshio, Kotaro; Uchida, Masashi; Tanaka, Yuichiro; Hashimoto, Takuo

    2012-06-15

    Diabetes mellitus in neurosurgical patients is known to be a disease with high risks and severe outcomes. However, the mechanism by which diabetes mellitus induces dysfunction of brain tissue is not well known. The hypothesis of this study was that the damage to brain microvasculature in diabetes mellitus results in impaired compliance of the brain. Pathological changes associated with type II diabetes were investigated using a rat model. Pathophysiological changes in diabetic brain tissue were also investigated to confirm cerebral compliance by analyzing intracranial pressure waveforms. Pathologic findings revealed thickening of the basement membrane and fibrous collagen infiltration into the inner basement membrane of the brain microvasculature in diabetes mellitus. Analysis of intracranial pressure waveforms revealed that the P2 portion increased in diabetic rats compared to the control and was increased further with the increase in intracranial pressure. Analysis of the differential pressure curve, with respect to time, demonstrated that intracranial elasticity showed a concomitant increase. Pathologic findings and intracranial pressure waveforms were consistent with changes in brain microvasculature in diabetes mellitus. The increase of elasticity of brain tissue in diabetes mellitus may exacerbate the damage of intracranial disease.

  6. Levels of S100B in brain and blood of rats with diabetic ketoacidosis.

    PubMed

    Glaser, Nicole; Lo, Weei; Tancredi, Daniel; Orgain, Myra; Puvenna, Vikram; Janigro, Damir; O'Donnell, Martha

    2015-10-22

    Diabetic ketoacidosis (DKA) frequently causes subtle brain injuries in children. Rarely, these injuries can be severe and life threatening. The physiological processes leading to brain injury during DKA are poorly understood. S100B is a calcium-binding protein secreted by astrocytes. Elevated serum S100B levels are documented in several types of brain injuries. S100B may have either neuroprotective or neurotoxic effects, depending upon the concentration. We undertook the current studies to measure alterations in S100B production and secretion during DKA. We measured serum S100B concentrations in juvenile rats during and after DKA, and used immunohistochemistry to measure S100B expression in the hippocampus, cortex and striatum. Compared to levels in both normal and hyperglycemic control rats, serum S100B levels during DKA were significantly reduced. Serum S100B gradually rose after DKA, returning to levels of hyperglycemic controls by 72 h. S100B expression in the hippocampus was also significantly reduced 24h after DKA. There were no significant changes in S100B expression in other brain regions. Our findings contrast with those for other types of brain injuries in which both serum S100B levels and astrocyte S100B expression are typically elevated. These data suggest that serum S100B measurement cannot be used as an indicator of brain injury during DKA. Whether reduced S100B production or secretion is involved in the pathogenesis of DKA-related brain injury should be investigated.

  7. Increased folate uptake prevents dietary development of folate deficiency in the rat brain

    SciTech Connect

    McMartin, K.E.; Collins, T.D.; Eisenga, B.H.; Bhandari, S.D. )

    1990-02-26

    Folic acid and folate deficiency have been implicated in disorders of the central nervous system. In a study of the mechanism for the effects of chronic ethanol on folate homeostasis, the uptake of {sup 3}H-folic acid by the rat brain has been studied. Male Sprague-Dawley rats were fed sulfonamide-supplemented folate-sufficient and folate-deficient liquid diets containing either ethanol or isoenergic carbohydrate as a control. After 16 weeks, severe folate depletion occurred in tissues (liver, kidney, spleen, lung intestine, testes), but not in the brain. Tissue retention of {sup 3}H-folic acid was increased four-fold in the brain of folate-deficient rats. A smaller increase in uptake was observed in the other tissues, except for the liver, in which the retention of {sup 3}H-folic acid was slightly decreased. Chronic ethanol feeding decreased hepatic folate uptake, but not that by the increase the uptake of folate from the plasma of folate-deficient rats, thereby inhibiting the development of brain folate deficiency.

  8. The Physiochemistry of Capped Nanosilver Predicts Its Biological Activity in Rat Brain Endothelial Cells (REBEC4)

    EPA Science Inventory

    The “capping” or coating of nanosilver (nanoAg) extends its potency by limiting its oxidation and aggregation and stabilizing its size and shape. The ability of such coated nanoAg to alter the permeability and activate oxidative stress pathways in rat brain endothelia...

  9. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats.

    PubMed

    Iyyaswamy, Ashok; Rathinasamy, Sheeladevi

    2012-09-01

    This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

  10. THYROID INSUFFICIENCY AND GENE EXPRESSION IN DEVELOPING RAT BRAIN: A DOSE RESPONSE STUDY.

    EPA Science Inventory

    Thyroid Insufficiency and Gene Expression in Developing Rat Brain: A Dose Response Study. JE Royland and ME Gilbert, Neurotox. Div., U.S. EPA, RTP, NC, USA. Endocrine disruption is an area of major concern in environmental neurotoxicity. Deficits in thyroid hormone (TH) levels h...

  11. Blueberry treatment decreased D-galactose-induced oxidative stress and brain damage in rats.

    PubMed

    Çoban, Jale; Doğan-Ekici, Işın; Aydın, A Fatih; Betül-Kalaz, Esra; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2015-06-01

    D-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of whole fresh blueberry (BB) (Vaccinium corymbosum L.) treatment on oxidative stress in age-related brain damage model. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with 5 % (BB1) and 10 % (BB2) BB containing chow for two months. Malondialdehyde (MDA),protein carbonyl (PC) and glutathione (GSH) levels, and Cu Zn-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities as well as acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brain by immunohistochemistry. MDA and PC levels and AChE activity increased, but GSH levels, SOD and GSH-Px activities decreased together with histopathological structural damage in the brain of GAL-treated rats. BB treatments, especially BB2 reduced MDA and PC levels and AChE activity and elevated GSH levels and GSH-Px activity. BB1 and BB2 treatments diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. These results indicate that BB partially prevented the shift towards an imbalanced prooxidative status and apoptosis together with histopathological amelioration by acting as an antioxidant (radical scavenger) itself in GAL-treated rats.

  12. Effects of preshock experience on enhancement of rat brain noradrenaline turnover induced by psychological stress.

    PubMed

    Tsuda, A; Tanaka, M; Ida, Y; Tsujimaru, S; Ushijima, I; Nagasaki, N

    1986-01-01

    The present study examined alterations of brain noradrenaline (NA) turnover as a function of preshock and psychological stress treatments, by measuring contents of NA metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in discrete brain regions of male Wistar rats. Psychological stress induced by exposing to the sight, sound and odor of other rats being shocked produced higher levels of MHPG-SO4 in the hypothalamus, amygdala and locus coeruleus (LC) region, as well as higher levels of plasma corticosterone. Preshock experienced rats also showed marked increases of MHPG-SO4 levels in the same regions described above and elevated plasma corticosterone levels when placed but not shocked in the same environment in which the rats had previously received shocks. The effects of psychological stress on brain NA turnover were affected by the animal's shock history preferentially in the hypothalamus and amygdala. These results suggest that: a purely psychological stressor caused acutely enhanced NA turnover in specific brain regions; regional NA activity appeared to be reinstated simply by reexposure to the environment previously associated with shock; preshock experience further intensified the enhancement of amygdaloid NA turnover evoked by psychological stress. An additional experiment, studying the aftereffects of preshock experience, clearly showed that these findings result from sensitization or conditioning to the environment previously paired with shock, and not merely from the aftereffects of the shock per se. PMID:3945655

  13. Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

    PubMed Central

    Herrera-Pérez, José Jaime; Fernández-Guasti, Alonso; Martínez-Mota, Lucía

    2013-01-01

    In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT) expression associated with low testosterone (T) levels. The objectives of this study were to establish (1) if brain SERT expression is reduced by aging and (2) if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months) and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population. PMID:26317087

  14. [Sorption of sulfophthaleinic dyes by the brain synaptosomes of rats deprived of parodoxical sleep].

    PubMed

    Nilova, N S

    1984-12-01

    The influence of paradoxical sleep deprivation on sorption of bromphenol blue, bromcresol green and bromthymol blue by rat's brain synaptosomes was studied. Effect of sleep disturbance (increase in the number of dye bindings) was shown to augment with the increase in hydrophobicity of the sulfophtaleinic dye. PMID:6528362

  15. The primary structure of rat brain (cytoplasmic) dynein heavy chain, a cytoplasmic motor enzyme.

    PubMed Central

    Zhang, Z; Tanaka, Y; Nonaka, S; Aizawa, H; Kawasaki, H; Nakata, T; Hirokawa, N

    1993-01-01

    Overlapping cDNA clones encoding the heavy chain of rat brain cytoplasmic dynein have been isolated. The isolated cDNA clones contain an open reading frame of 13,932 bp encoding 4644 aa (M(r), 532,213). The deduced protein sequence of the heavy chain of rat brain dynein shows significant similarity to sea urchin flagellar beta-dynein (27.0% identical) and to Dictyostelium cytoplasmic dynein (53.5% identical) throughout the entire sequence. The heavy chain of rat brain (cytoplasmic) dynein contains four putative nucleotide-binding consensus sequences [GX4GK(T/S)] in the central one-third region that are highly similar to those of sea urchin and Dictyostelium dyneins. The N-terminal one-third of the heavy chain of rat brain (cytoplasmic) dynein shows high similarity (43.8% identical) to that of Dictyostelium cytoplasmic dynein but poor similarity (19.4% identical) to that of sea urchin flagellar dynein. These results suggested that the C-terminal two-thirds of the dynein molecule is conserved and plays an essential role in microtubule-dependent motility activity, whereas the N-terminal regions are different between cytoplasmic and flagellar dyneins. Images Fig. 1 PMID:7690137

  16. PRENATAL EXPOSURE TO CHLORPYRIFOS ALTERS NEUROTROPHIN IMMUNOREACTIVITY AND APOPTOSIS IN RAT BRAIN.

    EPA Science Inventory

    In the present study, the effects of the organophosphate pesticide chlorpyrifos [CPF; O,O'diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate] on the regional distribution of three neurotrophic factors and on levels of apoptosis in gestational rat brain were characterized. P...

  17. Blood-ocular and blood-brain barrier function in streptozocin-induced diabetes in rats

    SciTech Connect

    Maeepea, O.; Karlsson, C.; Alm, A.

    1984-09-01

    Edetic acid labeled with chromium 51 was injected intravenously in normal rats and in rats with streptozocin-induced diabetes. One hour after the injection the animals were killed and the concentrations of edetic acid 51Cr in vitreous body, retina, and brain were determined. No significant difference was observed between the two groups for either tissue. In a second series, a mixture of tritiated 1-glucose and aminohippuric acid tagged with carbon 14 was injected instead of edetic acid. A substantial accumulation of aminohippuric acid 14C compared with tritiated 1-glucose was observed in the vitreous body and the brain of diabetic rats in comparison with the control group. It is concluded that untreated streptozocin-induced diabetes in rats for one to two weeks will not cause a generalized increase in the permeability of the blood-ocular or the blood-brain barriers, but organic acids may accumulate in the vitreous body as well as in the brain as a consequence of reduced outward transport through these barriers.

  18. Radial glia-like cells persist in the adult rat brain.

    PubMed

    Gubert, Fernanda; Zaverucha-do-Valle, Camila; Pimentel-Coelho, Pedro M; Mendez-Otero, Rosalia; Santiago, Marcelo F

    2009-03-01

    During development, radial glia cells contribute to neuronal migration and neurogenesis, and differentiate into astrocytes by the end of the developmental period. Recently, it was demonstrated that during development, radial glia cells, in addition to their role in migration, also give rise to neuroblasts. Furthermore, radial glial cells remain in the adult brain as adult neural stem cells (NSC) in the subventricular zone (SVZ) around the lateral ventricles (LVs), and generate new neurons continuously throughout adulthood. In this study, we used immunohistochemical and morphological methods to investigate the presence of radial glia-like cells around the LVs during the postnatal development period until adulthood in rats. In all ages of rats studied, we identified cells with morphological and immunocytochemical features that are similar to the radial glia cells found in the embryonic brain. Similarly to the radial glia, these cells express nestin and vimentin, and have a radial morphology, extending perpendicularly as processes from the ventricle wall. These cells also express GFAP, GLAST, and Pax6, and proliferate. In the brains of adult rats, we identified cells with relatively long processes (up to 600 mum) in close apposition with migrating neuroblasts. Our results showed that the radial glia-like cells present in the adult rat brain share several morphological and functional characteristics with the embryonic radial glia. We suggest that the embryonic radial glia cells located around the LV walls do not complete their transformation into astrocytes, but rather persist in adulthood.

  19. Curcumin alleviates brain edema by lowering AQP4 expression levels in a rat model of hypoxia-hypercapnia-induced brain damage

    PubMed Central

    YU, LIN-SHENG; FAN, YAN-YAN; YE, GUANGHUA; LI, JUNLI; FENG, XIANG-PING; LIN, KEZHI; DONG, MIUWU; WANG, ZHENYUAN

    2016-01-01

    The present study aimed to investigate the therapeutic effects of curcumin (CU) against brain edema in a rat model of hypoxia-hypercapnia (HH)-induced brain damage (HHBD). Male Sprague-Dawley rats were divided into five groups, including a control group and four treatment groups. The rats in the control group were raised under normal laboratory conditions and were injected with water, whereas the rats in the treatment groups were exposed to a low O2/high CO2 environment simulating HH conditions, and were injected with water, CU, dimethyl sulfoxide (solvent control) or monosialoganglioside GM1. After 2 weeks, the morphological characteristics of the brain tissues were analyzed using optical and electron microscopy. In addition, aquaporin (AQP)-4 protein expression levels in brain tissue samples were analyzed using streptavidin-biotin complex immunohistochemistry and western blotting, and mRNA expression levels were detected using reverse transcription-quantitative polymerase chain reaction. Severe brain edema, tissue structure disruption and increased AQP4 expression levels were detected in the brain tissues of the HH rats. Conversely, the rats treated with CU or GM1 exhibited attenuated HHBD-induced brain edema and tissue structure disruption, and decreased mRNA and protein expression levels of AQP4. The results of the present study suggested that CU treatment was able to attenuate HHBD-induced brain edema by downregulating the expression levels of AQP4 in a rat model. Therefore, CU may be considered a potential therapeutic drug for the treatment of patients with brain edema. PMID:26997983

  20. Acute effect of aspartame-induced oxidative stress in Wistar albino rat brain.

    PubMed

    Ashok, Iyaswamy; Sheeladevi, Rathinasamy; Wankhar, Dapkupar

    2015-09-01

    The present study was carried out to investigate the acute effect of aspartame on oxidative stress in the Wistar albino rat brain. We sought to investigate whether acute administration of aspartame (75 mg/kg) could release methanol and induce oxidative stress in the rat brain 24 hours after administration. To mimic human methanol metabolism, methotrexate treated rats were used to study aspartame effects. Wistar strain male albino rats were administered with aspartame orally as a single dose and studied along with controls and methotrexate treated controls. Blood methanol and formate level were estimated after 24 hours and rats were sacrificed and free radical changes were observed in discrete regions by assessing the scavenging enzymes, reduce dglutathione (GSH), lipid peroxidation and protein thiol levels. There was a significant increase in lipid peroxidation levels, superoxide dismutase activity (SOD), glutathione peroxidase levels (GPx), and catalase activity (CAT) with a significant decrease in GSH and protein thiol. Aspartame exposure resulted in detectable methanol even after 24 hours. Methanol and its metabolites may be responsible for the generation of oxidative stress in brain regions. The observed alteration in aspartame fed animals may be due to its metabolite methanol and elevated formate. The elevated free radicals due to methanol induced oxidative stress. PMID:26445572

  1. Effects of Ligusticum chuanxiong and Gastrodia elata on blood-brain barrier permeability in migraine rats.

    PubMed

    Wang, Qiang; Shen, Lan; Ma, Shiyu; Chen, Meiwan; Lin, Xiao; Hong, Yanlong; Liang, Shuang; Feng, Yi

    2015-06-01

    The two herbs Ligusticum chuanxiong (LC) Hort. (Umbelliferae) and Gastrodia elata (GE) Blume (Orchidaceae), are widely used in the clinic for the treatment of migraine. This article aims to understand the effects of LC and GE on blood-brain barrier (BBB) permeability in migraine rats. Serotonin, excitatory amino acids (EAAs) and matrix metalloproteinase-9 (MMP-9) were determined at different sampling times to assess BBB disruption during a migraine attack. BBB permeability was examined by fluorescence imaging and Evans blue dye (EBD) extravasation. The results showed that the expression of serotonin in migraine rat brain was enhanced from 30 min to 120 min and glutamate (Glu) was suppressed from 30 min to 60 min in LC-GE group compared with the model group (p < 0.05 or 0.01), while the MMP-9 levels in migraine rat blood was increased at 30 min as well as decreased at 120 min in LC-GE group compared with the model group (p < 0.05 or 0.01). EBD levels in rat brain were significantly lower at 30-60 min and 120-150 min in LC-GE group than that of the model group (p < 0.05 or 0.01). Our findings demonstrated that LC and GE might decrease BBB permeability and maintain its integrity through regulating serotonin, EAAs and MMP-9 in migraine rats. PMID:26189306

  2. Acute effect of aspartame-induced oxidative stress in Wistar albino rat brain.

    PubMed

    Ashok, Iyaswamy; Sheeladevi, Rathinasamy; Wankhar, Dapkupar

    2015-09-01

    The present study was carried out to investigate the acute effect of aspartame on oxidative stress in the Wistar albino rat brain. We sought to investigate whether acute administration of aspartame (75 mg/kg) could release methanol and induce oxidative stress in the rat brain 24 hours after administration. To mimic human methanol metabolism, methotrexate treated rats were used to study aspartame effects. Wistar strain male albino rats were administered with aspartame orally as a single dose and studied along with controls and methotrexate treated controls. Blood methanol and formate level were estimated after 24 hours and rats were sacrificed and free radical changes were observed in discrete regions by assessing the scavenging enzymes, reduce dglutathione (GSH), lipid peroxidation and protein thiol levels. There was a significant increase in lipid peroxidation levels, superoxide dismutase activity (SOD), glutathione peroxidase levels (GPx), and catalase activity (CAT) with a significant decrease in GSH and protein thiol. Aspartame exposure resulted in detectable methanol even after 24 hours. Methanol and its metabolites may be responsible for the generation of oxidative stress in brain regions. The observed alteration in aspartame fed animals may be due to its metabolite methanol and elevated formate. The elevated free radicals due to methanol induced oxidative stress.

  3. Cocaine induces DNA damage in distinct brain areas of female rats under different hormonal conditions.

    PubMed

    de Souza, Marilise F; Gonçales, Tierre A; Steinmetz, Aline; Moura, Dinara J; Saffi, Jenifer; Gomez, Rosane; Barros, Helena M T

    2014-04-01

    We evaluated levels of neuronal DNA damage after acute or repeated cocaine treatment in different brain areas of female rats after ovariectomy or sham surgery. Rats in the control and acute groups were given saline i.p., whereas in the repeated group were given 15 mg/kg, i.p., cocaine for 8 days. After a 10 day washout period, the control group was given saline i.p., whereas rats in the acute and repeated groups were given a challenge dose of 15 mg/kg, i.p., cocaine. After behavioural assessment, rats were killed and the cerebellum, hippocampus, hypothalamus, prefrontal cortex and striatum were dissected for the Comet assay. Acute cocaine exposure induced DNA damage in all brain areas. This effect persisted after repeated administration, except in the hypothalamus, where repeated treatment did not cause increased DNA damage. Sexual hormones exhibited a neuroprotective effect, decreasing cocaine-induced DNA damage in cycling rats in all brain areas. PMID:24552452

  4. Short Communication: Rheological properties of blood serum of rats after irradiation with different gamma radiation doses in vivo.

    PubMed

    Abdelhalim, Mohamed Anwar K; Moussa, Sherif Aa; Ms, Al-Ayed

    2016-01-01

    The blood serum rheological properties open the door to find suitable radio-protectors and convenient therapy for many cases of radiation exposure. The present study aimed to investigate the rheological properties of rat blood serum at wide range of shear rates after whole body irradiation with different gamma radiation doses in vivo. Healthy male rats were divided into five groups; one control group and 4 irradiated groups. The irradiation process was carried out using Co60 source with dose rate of 0.883cG/sec. Several rheological parameters were measured using Brookfield LVDV-III Programmable rheometer. A significant increase in viscosity and shear stress was observed with 25 and 50Gy corresponding to each shear rate compared with the control; while a significant decrease observed with 75 and 100Gy. The viscosity exhibited a Non-Newtonian behaviour with the shear rate while shear stress values were linearly related with shear rate. The decrease in blood viscosity might be attributed to changes in molecular weight, pH sensitivity and protein structure. The changes in rheological properties of irradiated rats' blood serum might be attributed to destruction changes in the haematological and dimensional properties of rats' blood products. PMID:27005501

  5. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

    PubMed

    Li, Fang; Teng, Hui-Yun; Liu, Jing; Wang, Hua-Wei; Zeng, Li; Zhao, Li-Fang

    2014-09-01

    This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P < 0.01), respectively, and (2) that taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) μg/g (F = 24.828, P < 0.01), respectively. Overall, our results indicated that taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR.

  6. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

    PubMed

    Li, Fang; Teng, Hui-Yun; Liu, Jing; Wang, Hua-Wei; Zeng, Li; Zhao, Li-Fang

    2014-09-01

    This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P < 0.01), respectively, and (2) that taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) μg/g (F = 24.828, P < 0.01), respectively. Overall, our results indicated that taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR. PMID:24676564

  7. Aberrant changes of somatostatin and neuropeptide Y in brain of a genetic rat model for epilepsy: tremor rat.

    PubMed

    Xu, Xiaoxue; Guo, Feng; Cai, Xinze; Yang, Jun; Zhao, Jiuhan; Min, Dongyu; Wang, Qianhui; Hao, Liying; Cai, Jiqun

    2016-01-01

    Excessive excitation or loss of inhibitory neurotransmission has been closely related to epileptic activity. Somatostatin (SST) and Neuropeptide Y (NPY) are members of endogenous neuropeptides which are recognized as important modulator of classical neurotransmitter, distributed abundantly in mammalian central nervous system. Abnormal expression of these two neuropeptides evidenced in some epileptic models highlights the relevance of SST or NPY in the pathogenesis of epilepsy. The tremor rat (TRM) is a genetic epileptic animal model which can manifest tonic convulsions without any external stimuli. The present study aimed to investigate the distribution and expression of SST and NPY in TRM brains, including hippocampus, temporal lobe cortex and cerebellum. Our RT‑PCR data showed that up-regulated mRNA expression of SST and NPY was discovered in TRM hippocampus and temporal lobe cortex compared with control (Wistar) rats. The peptide levels of these neuropeptides in brain areas mentioned above were both apparently higher than that in normal Wistar rats as well. However, in cerebellums, neither SST nor NPY was significantly changed compared with control group. The immunohistochemical data showed that SST and NPY were widely present throughout CA1, CA3 and the hilus of hippocampus, the entorhinal cortex of temporal lobe cortex, as well as cerebellar Purkinje layer. In conclusion, our results discovered the aberrant changes of SST and NPY in several TRM brain regions, suggesting that the peptidergic system might be involved in TRM epileptiform activity. PMID:27685769

  8. Lasting neuropathological changes in rat brain after intermittent neonatal administration of thimerosal.

    PubMed

    Olczak, Mieszko; Duszczyk, Michalina; Mierzejewski, Paweł; Wierzba-Bobrowicz, Teresa; Majewska, Maria D

    2010-01-01

    Thimerosal, an organomercurial added as a preservative to some vaccines, is a suspected iatrogenic factor, possibly contributing to paediatric neurodevelopmental disorders including autism. We examined the effects of early postnatal administration of thimerosal (four i.m. injections, 12 or 240 μg THIM-Hg/kg, on postnatal days 7, 9, 11 and 15) on brain pathology in Wistar rats. Numerous neuropathological changes were observed in young adult rats which were treated postnatally with thimerosal. They included: ischaemic degeneration of neurons and "dark" neurons in the prefrontal and temporal cortex, the hippocampus and the cerebellum, pathological changes of the blood vessels in the temporal cortex, diminished synaptophysin reaction in the hippocampus, atrophy of astroglia in the hippocampus and cerebellum, and positive caspase-3 reaction in Bergmann astroglia. These findings document neurotoxic effects of thimerosal, at doses equivalent to those used in infant vaccines or higher, in developing rat brain, suggesting likely involvement of this mercurial in neurodevelopmental disorders. PMID:21225508

  9. Effect of neuroleptics on phospholipase A2 activity in the brain of rats.

    PubMed

    Trzeciak, H I; Kalaciński, W; Małecki, A; Kokot, D

    1995-01-01

    The effect of neuroleptics on phospholipase A2 (PLA2) activity in rat brain plasma membranes was studied. Chlorpromazine (10 mg/kg), fluphenazine (5 mg/kg), thioridazine (5 mg/kg), trifluoperazine (5 mg/kg), haloperidol (2 mg/kg), and sulpiride (100 mg/kg) were administered to rats intraperitoneally as a single dose or long-term treatment (4 weeks). The PLA2 activity was determined 24, 48, and 72 h after the last injection of a drug. The enzyme activity was decreased after a single or 4-week administration of chlorpromazine, trifluoperazine, haloperidol, and sulpiride. Fluphenazine and thioridazine caused an increase of PLA2 activity in rat brain both after a single dose and long-term administration. For the first time it was shown that neuroleptics cannot only inhibit but also increase, PLA2 activity. Elucidation of this fact requires further studies. PMID:7669826

  10. Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure.

    PubMed

    Mishra, D; Flora, S J S

    2008-05-01

    Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain - parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50A ppm sodium arsenite in drinking water) for 10A months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes.

  11. Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats

    PubMed Central

    Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

    2014-01-01

    Background & objectives: Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Methods: Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. Results: SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. Interpretation & conclusions: The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney. PMID:24927349

  12. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

    SciTech Connect

    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir; Richardson, Jason R.; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2014-08-15

    The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.

  13. Autoradiographic visualization of insulin-like growth factor-II receptors in rat brain

    SciTech Connect

    Mendelsohn, L.G.; Kerchner, G.A.; Clemens, J.A.; Smith, M.C.

    1986-03-01

    The documented presence of IGF-II in brain and CSF prompted us to investigate the distribution of receptors for IGF-II in rat brain slices. Human /sup 125/-I-IGF-II (10 pM) was incubated for 16 hrs at 4/sup 0/C with slide-mounted rat brain slices in the absence and presence of unlabeled human IGF-II (67 nM) or human insulin (86 nM). Slides were washed, dried, and exposed to X-ray film for 4-7 days. The results showed dense labeling in the granular layers of the olfactory bulbs, deep layers of the cerebral cortex, pineal gland, anterior pituitary, hippocampus (pyramidal cells CA/sub 1/-CA/sub 2/ and dentate gyrus), and the granule cell layers of the cerebellum. Unlabeled IGF-II eliminated most of the binding of these brain regions while insulin produced only a minimal reduction in the amount of /sup 125/I-IGF-II bound. These results indicate that a specific neural receptor for IGS-II is uniquely distributed in rat brain tissue and supports the notion that this peptide might play an important role in normal neuronal functioning.

  14. Propofol anesthesia reduces Lempel-Ziv complexity of spontaneous brain activity in rats.

    PubMed

    Hudetz, Anthony G; Liu, Xiping; Pillay, Siveshigan; Boly, Melanie; Tononi, Giulio

    2016-08-15

    Consciousness is thought to scale with brain complexity, and it may be diminished in anesthesia. Lempel-Ziv complexity (LZC) of field potentials has been shown to be a promising measure of the level of consciousness in anesthetized human subjects, neurological patients, and across the sleep-wake states in rats. Whether this relationship holds for intrinsic networks obtained by functional brain imaging has not been tested. To fill this gap of knowledge, we estimated LZC from large-scale dynamic analysis of functional magnetic resonance images (fMRI) in conscious sedated and unconscious anesthetized rats. Blood oxygen dependent (BOLD) signals were obtained from 30-min whole-brain resting-state scans while the anesthetic propofol was infused intravenously at constant infusion rates of 20mg/kg/h (conscious sedated) and 40mg/kg/h (unconscious). Dynamic brain networks were defined at voxel level by sliding window analysis of regional homogeneity (ReHo) of the BOLD signal. From scans performed at low to high propofol dose, the LZC was significantly reduced by 110%. The results suggest that the difference in LZC between conscious sedated and anesthetized unconscious subjects is conserved in rats and this effect is detectable in large-scale brain network obtained from fMRI. PMID:27291459

  15. The effects of training and detraining on memory, neurotrophins and oxidative stress markers in rat brain.

    PubMed

    Radak, Zsolt; Toldy, Anna; Szabo, Zsofia; Siamilis, Savvas; Nyakas, Csaba; Silye, Gabriella; Jakus, Judit; Goto, Sataro

    2006-09-01

    In the current investigation we tested how swimming training (T) (8 week, 5 times/week, 2 h/day), and detraining (DT) affects brain functions and oxidative stress markers in rat brain. The free radical concentration, measured by electron paramagnetic resonance, decreased in brain of T and DT rats compared to controls (C). The level of brain-derived neurotrophic factor (BDNF) increased as a result of training, but decreased below the control level after 6 weeks of detraining. In addition, the concentration of nerve growth factor (NGF) also declined with DT. The passive avoidance test was used to assess the memory of rats, and training-induced improvement was observed but the enhancement disappeared with detraining. When the content of mitochondrial electron transport complexes, as a potent free radical generator, was evaluated by the blue native gel method, no significant alterations were observed. The repair of nuclear and mitochondrial 8-oxodeoxyguanosine, as measured by the activity of OGG1, showed no significant difference. Therefore, the results suggest that regular exercise training improves memory, decreases the level of reactive oxygen species, and increase the production of BDNF and NGF. On the other hand, it appears that the beneficial effects of training are reversible in the brain, since detraining down-regulates the neurotrophin level, and memory. It is suggested that exercise training is more likely to beneficially effect the production of reactive oxygen species and the related oxidative damage.

  16. Combination Cell Therapy with Mesenchymal Stem Cells and Neural Stem Cells for Brain Stroke in Rats

    PubMed Central

    Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

    2015-01-01

    Objectives Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. Method and Materials The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. Result The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. Conclusions The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats. PMID:26019759

  17. Acute effects of oral or parenteral aspartame on catecholamine metabolism in various regions of rat brain.

    PubMed

    Yokogoshi, H; Wurtman, R J

    1986-03-01

    Hypertensive (SHR) and nonhypertensive [Wistar-Kyoto (WKY); Sprague-Dawley (SD)] strains of rats received the dipeptide sweetener aspartame (200 mg/kg) or, as a positive control, tyrosine (200 mg/kg) by gavage or parenterally, after a brief (2-h) fast. Two hours later, compared with those of saline controls brain levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylethyleneglycol (MHPG) sulfate were significantly higher in the hypothalamus (WKY), locus coeruleus (SD and SHR) and brain stem (SHR) in tyrosine-treated animals, and in the locus coeruleus (SD) of those given aspartame. Brain norepinephrine levels were also higher, compared with those of saline-treated control rats, in the cerebral cortex (SD and SHR), amygdala (SD) and locus coeruleus (WKY) after tyrosine administration, and in the amygdala (SD) and cerebral cortex (SHR) after aspartame administration. In another study, oral aspartame was found to be at least as effective as the parenterally administered sweetener in raising regional brain levels of tyrosine or MHPG sulfate (i.e., compared with corresponding levels in saline-treated rats). Animals receiving oral aspartame also exhibited higher plasma tyrosine and phenylalanine ratios (i.e., the ratios of their plasma concentrations to the summed concentrations of other large neutral amino acids that compete with them for uptake into the brain), than animals receiving saline.

  18. Alterations in the molecular weight distribution of proteins in rat brain synaptosomes during aging and centrophenoxine treatment of old rats.

    PubMed

    Nagy, K; Nagy, I

    1984-12-01

    Properly prepared membrane proteins of brain synaptosomes of 2-, 12- and 24-month-old CFY female rats were filtrated on a Sepharose 2B gel. The molecular weight distribution showed an age-dependence: there was a clear shift toward the higher molecular weights in the adult and old rats. The observed alterations reflect an increased cross-linking of the proteins during aging due most probably to the OH free radical damage of the cell components. Centrophenoxine treatment for 2 months reversed this phenomenon in the old animals: the high molecular weight fractions decreased and the lower ones increased in the treated animals as compared to the old, untreated rats. The results support the membrane hypothesis of aging and contribute to a better understanding of the biological effects of centrophenoxine.

  19. Dietary n-6 polyunsaturated fatty acid deprivation increases docosahexaenoic acid metabolism in rat brain.

    PubMed

    Igarashi, Miki; Kim, Hyung-Wook; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I

    2012-03-01

    Dietary n-6 polyunsaturated fatty acid (PUFA) deprivation in rodents reduces brain arachidonic acid (20:4n-6) concentration and 20:4n-6-preferring cytosolic phospholipase A(2) (cPLA(2) -IVA) and cyclooxygenase (COX)-2 expression, while increasing brain docosahexaenoic acid (DHA, 22:6n-3) concentration and DHA-selective calcium-independent phospholipase A(2) (iPLA(2) )-VIA expression. We hypothesized that these changes are accompanied by up-regulated brain DHA metabolic rates. Using a fatty acid model, brain DHA concentrations and kinetics were measured in unanesthetized male rats fed, for 15 weeks post-weaning, an n-6 PUFA 'adequate' (31.4 wt% linoleic acid) or 'deficient' (2.7 wt% linoleic acid) diet, each lacking 20:4n-6 and DHA. [1-(14) C]DHA was infused intravenously, arterial blood was sampled, and the brain was microwaved at 5 min and analyzed. Rats fed the n-6 PUFA deficient compared with adequate diet had significantly reduced n-6 PUFA concentrations in brain phospholipids but increased eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid n-3 (DPAn-3, 22:5n-3), and DHA (by 9.4%) concentrations, particularly in ethanolamine glycerophospholipid (EtnGpl). Incorporation rates of unesterified DHA from plasma, which represent DHA metabolic loss from brain, were increased 45% in brain phospholipids, as was DHA turnover. Increased DHA metabolism following dietary n-6 PUFA deprivation may increase brain concentrations of antiinflammatory DHA metabolites, which with a reduced brain n-6 PUFA content, likely promotes neuroprotection and alters neurotransmission.

  20. Uptake and biodistribution of rizatriptan to blood and brain following different routes of administration in rats.

    PubMed

    Wang, Chun; Quan, Li-Hui; Guo, Yi; Liu, Chun-Yu; Liao, Yong-Hong

    2007-06-01

    The objective of the present study was to investigate the biodistribution profiles of rizatriptan in the blood and brain of Wistar rats after peroral, subcutaneous, intranasal and intratracheal administration with a particular view to determining the applicability of inhalation delivery to achieve rapid and high availability of the drug in both blood and the brain. Following the intratracheal administration of the drug (4.0mg/kg) to the rats, the absolute bioavailability was found to be 91.2%, significantly higher than those from intranasal or peroral routes, and T(max) in plasma and brain was attained within 2 min, significantly shorter than the T(max) of intranasal ( approximately 10 min in both plasma and brain), subcutaneous (16.7 min in plasma and 22.5 min in brain) and peroral (30.0 min in plasma and 45.0 min in brain) administration. In addition, other pharmacokinetic parameters associated with rapid onset of action including AUC(plasma/brain) and C(max), of intratracheal instillated rizatriptan appeared also to be comparable or superior to those of other delivered routes. Although AUC(brain)/AUC(plasma) ratios after intranasal delivery (43.4%) differed significantly from the ratios shown after intratracheal instillation (23.2%), the AUC(brain 0-120 min) via the latter routes was slightly but not significantly higher than that from the former routes. The results in the present study indicated that pulmonary delivery of rizatriptan may achieve maximum plasma and brain concentrations significantly more rapidly compared with intranasal, subcutaneous and peroral administration and be a promising delivery method with extremely rapid onset of action in the pain relief of migraine. PMID:17267150

  1. Neurobehavioral tests in rat models of degenerative brain diseases.

    PubMed

    Urbach, Yvonne K; Bode, Felix J; Nguyen, Huu Phuc; Riess, Olaf; von Hörsten, Stephan

    2010-01-01

    Each translational approach in medical research forces the establishment of neurobehavioral screening systems, dedicated to fill the gap between postgenomic generation of state-of-the-art animal models (i.e. transgenic rats) on the one hand and their added value for really predictive experimental preclinical therapy on the other. Owing to these developments in the field, neuroscientists are frequently challenged by the task of detecting discrete behavioral differences in rats. Systematic, comprehensive phenotyping covers these needs and represents a central part of the process. In this chapter, we provide an overview on theoretical issues related to comprehensive neurobehavioral phenotyping of rats and propose specific classical procedures, protocols (similar to the SHIRPA approach in mice), as well as techniques for repeated, intraindividual phenotyping. Neurological testing of rats, motorfunctional screening using the accelerod approach, emotional screening using the social interaction test of anxiety, and testing of sensorimotoric gating functions by prepulse inhibition of the startle response are provided in more detail. This description is completed by an outlook on most recent developments in the field dealing with automated, intra-home-cage technologies, allowing continuous screening in rats in various behavioral and physiological dimensions on an ethological basis.

  2. Low-level laser irradiation, cyclooxygenase-2 (COX-2) expression and necrosis of random skin flaps in rats.

    PubMed

    Esteves Junior, Ivaldo; Masson, Igor B; Oshima, Celina T F; Paiotti, Ana Paula R; Liebano, Richard E; Plapler, Helio

    2012-05-01

    Skin flaps are still a matter of concern among surgeons, as failures can occur leading to flap necrosis. However, low-level laser irradiation has been reported as an effective tool to improve the viability of ischemic flaps, yet its mechanisms of action remain unclear. We investigated the effect of low-level laser irradiation on the viability of random skin flaps in rats and determined COX-2 expression in the flap pedicle. The study animals comprised 24 EPM-1 Wistar rats which were randomly allocated into three equal groups. A cranially based dorsal random skin flap measuring 10 × 4 cm was created in all the animals. In one group, laser irradiation was simulated (sham group), and in the other two groups the animals were irradiated at 12 points with 0.29 J at 20 mW (energy density 10.36 J/cm(2), irradiance 0.71 W/cm(2)), or with 7.3 J at 100 mW (energy density 260.7 J/cm(2), irradiance 3.57 W/cm(2)). These procedures were applied to the cranial half of the flap immediately after surgery and were repeated on days 2 and 5 after surgery. The percentage necrotic area was determined on day 7 after surgery by the paper template method. The immunohistochemical expression of COX-2 in the samples was given scores from 0 to 3. The necrotic area was smaller in group irradiated at 7.3 J compared to sham-treated group and to the group irradiated at 0.29 J (P < 0.05); there was no difference between the sham-treated group and group irradiated at 0.29 J. COX-2 expression was lower in the group irradiated at 7.3 J than in the sham-treated group and the group irradiated at 0.29 J (P < 0.001). Low-level laser therapy was effective in decreasing random skin flap necrosis in rats using a laser energy of 7.30 J per point. Laser irradiation also decreased the expression of COX-2 in the flap pedicle.

  3. Inhibition of rat brain monoamine oxidase by repeated administration of pirlindol

    SciTech Connect

    Verevkina, I.V.; Asnina, V.V.; Gorkin, V.Z.; Mashovskii, M.D.

    1985-10-01

    Since pirlindol, like other antidepressants, is used for a long time and since its therapeutic effect usually appears 5-7 days or more after the beginning of treatment, the authors investigate its action on activity of MAO of types A and B in rat brain when administered repeatedly. MAO activity was determined in 50% homogenates of rat brain, made up in 10 mM phosphate buffer, pH 7.4, containing 2% detergent Triton X-100. It is shown that an important role in the antidepressant effect of pirlindol is played by its property of selectively blocking deamination of neurotrans mitters such as serotonin and noradrenalin in the human brain.

  4. Kainic acid induces expression of caveolin-1 in activated microglia in rat brain.

    PubMed

    Takeuchi, Shigeko; Matsuda, Wakoto; Tooyama, Ikuo; Yasuhara, Osamu

    2013-01-01

    Caveolin-1, a major constituent of caveolae, has been implicated in endocytosis, signal transduction and cholesterol transport in a wide variety of cells. In the present study, the expression of caveolin-1 was examined by immunohistochemistry in rat brain with or without systemic injection of kainic acid (KA). Caveolin-1 immunoreactivity was observed in capillary walls in brains of control rats. From one to seven days after KA injection, caveolin-1 immunoreactivity appeared in activated microglia in the cerebral cortex, hippocampus and other brain regions. The strongest immunoreactivity of microglia was seen after 3 days after KA administration. The expression of caveolin-1 was confirmed by RT-PCR and Western blot analysis, respectively. The induction of caveolin-1 expression in microglia activated in response to kainic acid administration suggests its possible role in a modulation of inflammation. PMID:23690214

  5. Brain damage in a new hemorrhagic shock model in the rat using long-term recovery

    SciTech Connect

    Yamauchi, Y.; Kato, H.; Kogure, K. )

    1990-03-01

    A new shock model in the <