| 81. |
- Andersson, Helena
(författare)
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Heavy metal neurotoxicity : on trimethyltin-, methylmercury- and cadmium-induced disturbances of neurotransmitter systems and neurotrophins
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organic and inorganic metal compounds produced by human activities often reach the environment where they are associated with a plethora of potential health hazards. Of particular concern is the risk for CNS disturbances during development or in the adult. While considerable documentation exists concerning lead compounds, methodology needs to be developed to better understand the mechanisms of actions of many other heavy metal compounds. The present work studies the effects of tin, mercury and cadmium compounds inthe developing and adult rat. Trimethyltin (TMT) was chosen as a model organic metal compound with a specific neurotoxic profile in adult rats. Its actions were characterized using histological, histochemical, in situ hybridization, receptor binding and biochemical methods. A single injection causes neurodegenerative changes in the limbic system including a severe transient gliosis, neuronal degeneration, selective losses of NMDA and kainate receptors, an early transient decrease of BDNF followed by an up-regulation of BDNF and the immediate-early gene c-fos and hsp70 concomitant with a decrease in the BDNF trkB receptor mRNA. Astrocytes also show increased GABA immunoreactivity and an increase of the glial glutamate transporter mRNA, perhaps reflecting enhanced glial glutamate uptake. TMT also caused decreases of serotonin and noradrenalin levels in several brain regions while dopamine appeared not to be affected. Reduced levels of 5-HT were paralleled by reduced 5-HT nerve terminal densities in hippocampus and cortex. Attempting to block and/or counteract TMT toxicity, it was found that the non-NMDA antagonist DNQX was able to protect selected animals, and that PBN, a spin-trapping agent, offered partial protection, while the NMDA antagonist MK-801 and the GABA function enhancer chlormethiazole were without effects. Subtoxic doses of methylmercury (MeHg) caused specific decreases of hippocampal BDNF mRNA levels within hours, recovering after three days. The related neurotrophin NT-3 and trkB did not show mRNA changes. C-fos mRNA increased in a specific hippocampal cell population and in cerebral cortex and cerebellum even after very low doses of MeHg. The changes of BDNF mRNA expression were unlike those caused by many other CNS perturbations in which BDNF is up-regulated, and were not associated with major neuronal or glial damage at the chosen doses. Finally, long-term low-level exposure to mercury and cadmium during development was studied. MeHg exposure via the dams and the diet leading to brain concentrations of <1.5 mg Hg/kg caused no general toxic effects in neurons and no changes of GFAP-immunoreactive astrocytes. However, significant changes of cerebellar noradrenaline were found, underlining the importance of detailed and multifaceted biochemical and morphological analysis to detect possible negative effects of long-term low dosage exposure. Exposure to 5 ppm cadmium chloride in the drinking water during development led to significant changes of serotonin and noradrenalin levels in the cerebral cortex. BDNF mRNA was increased in cerebral cortex, while trkB mRNA was decreased in hippo-campus. Hence, chronic exposure to very low levels of cadmium chloride during development led to complex neurochemical disturbances of neurotransmitters as well as neurotrophins. It is concluded that morphological and biochemical analyses of brain tissue using markers of neurons and glial cells including transmitter systems, neurotrophic systems and immediate-early genes, together constitute a sensitive battery of techniques able to detect brain disturbances caused by very low level exposure of animals to heavy metals in cases where the use of a single technique is likely to miss the neurotoxic damage. Applying these and similar methods to rodents constitutes a general system capable of generating early warnings about the potential neurotoxic hazards of xenobiotics.
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| 87. |
- Andersson, Helena M., 1973-, et al.
(författare)
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Active recovery training does not affect the antioxidant response to soccer games in elite female players
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Changes in plasma endogenous and dietary antioxidants and oxidative stress markers were studied following two 90-min elite female soccer games separated by 72 h of either active or passive recovery. The active recovery group (n=8) trained for one hour at 22 and 46 h after the first game (low-intensity cycling and resistance training)while the passive group rested(n=8). Blood samples were taken before, immediately after, 21, 45 and 69 h after the first and immediately after the second game. The oxidative stress markers and antioxidants were not affected by active recovery. The oxidative stress marker oxidized glutathione increased by the same extent after both games, while the lipid peroxidation marker diacrons reactive-oxygen metabolites remained unchanged. The endogenous antioxidants total glutathione, uric acid and ferric reducing/antioxidant power assay increased immediately after both games with the same amplitude, while increases in cysteine, cysteine-glycine and total thiols reached significant levels only after the second game. The changes in dietary antioxidants after the first game were either rapid and persistent (tocopherols, ascorbic acid increased; polyphenols decreased) or delayed (carotenoids). This resulted in high pre-second game levels of tocopherols, ascorbic acid and carotenoids. Polyphenols returned to baseline at 69 h and were not affected by the second game. In conclusion, the soccer-associated dietary but not endogenous antioxidant defence is persistent. Similar acute oxidative stress and endogenous antioxidant responses and dissimilar dietary antioxidant reactions occur during two repeated female soccer games. Finally, the complex antioxidant response to soccer is not affected by active recovery training.
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| 88. |
- Cubo, Rubén
(författare)
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Calculating Directional Deep Brain Stimulation Settings by Constrained Optimization
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Deep Brain Stimulation (DBS) consists of delivering electrical stimuli to a brain target via an implanted lead to treat neurodegenerative conditions. Individualized stimulation is vital to ensure therapeutic results, since DBS may otherwise become ineffective or cause undesirable side effects. Since the DBS pulse generator is battery-driven, power consumption incurred by the stimulation is important. In this study, target coverage and power consumption are compared over a patient population for clinical and model-based patient-specific settings calculated by constrained optimization. Methods: Brain models for five patients undergoing bilateral DBS were built. Mathematical optimization of activated tissue volume was utilized to calculate stimuli amplitudes, with and without specifying the volumes, where stimulation was not allowed to avoid side effects. Power consumption was estimated using measured impedance values and battery life under both clinical and optimized settings. Results: It was observed that clinical settings are generally less aggressive than the ones suggested by unconstrained model-based optimization, especially under asymmetrical stimulation. The DBS settings satisfying the constraints were close to the clinical values. Conclusion: The use of mathematical models to suggest optimal patient-specific DBS settings that observe technological and safety constraints can save time in clinical practice. It appears though that the considered anatomy-related safety constraints depend on the patient and further research is needed in this regard. Power consumption is important to consider since it increases with the square of the stimuli amplitude and critically affects battery life. Significance: This work highlights the need of specifying the brain volumes to be avoided by stimulation while optimizing the DBS amplitude, in contrast to minimizing general stimuli overspill, and applies the technique to a cohort of patients. It also stresses the importance of taking power consumption into account.
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