Wyniki wyszukiwania - Biblioteka Nauki

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Bialko S100B, astrocyty i pamiec

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Kielbinski M. , Soltys Z.

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nr 1

3-13

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The effects of ketogenic and calorie restricted diets on epileptic seizure in rats with mechanical brain injury

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Osoba J. , Setkowicz-Janeczko Z. , Gzielo-Jurek K. , Kielbinski M.

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tom 73

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nr 1

EN

Traumatic brain injury (TBI) is a major cause of mortality and morbidity in children and young adults. It initiates multiple cascades of events that lead to acute metabolic dysfunction and cellular energy crisis. TBI remains one of the most common and important causes of acquired epilepsy nowadays. The ketogenic diet (KD) is a specialized high-fat low-protein and low-carbohydrate diet which mimics the anticonvulsive effects of fasting, which were known to suppress seizures. KD is used primarily in children with seizures refractory to standard anticonvulsive drugs (AEDs). Many studies on the anticonvulsant effects of a KD have been performed. Unfortunately, the mechanism of action of the ketogenic diet remains unclear. Although the ketogenic diet is the best dietary therapy for epilepsy, there are other possible approaches including overall restriction of caloric intake. Dietary restriction seems a promising alternative to classic ketogenic diet, possibly because it is associated with higher levels of ketone bodies, which are themselves neuroprotective. Caloric restriction (CR) is defined as a decrease in energy intake without lowering nutritional value. CR improves behavioral outcomes after ischemic brain injury in rats and could possibly act as a neuroprotective factor in global ischemia. It has been also shown that chronic administration of CR may provide protection in the event of TBI. The aim of this research was to study the changes in susceptibility to pilocarpine-induced epileptic seizures in rats with mechanical brain injury. In 30-day-old male Wistar rats (P30), mechanical brain injury was performed. Immediately after, the calorically unrestricted ketogenic diet (KD) and calorically restricted standard laboratory rat chow diet (CR) were introduced. In order to check how the ketogenic diet and caloric restriction alone influence the epileptic seizure susceptibility, two groups of 30-day-old rats were fed KD and CR untill postnatal day 60. At that time, seizures were induced by pilocarpine injection. During the following 6-h period, the animals were continuously observed and motor seizures intensity were rated on a 6-point scale. We have found that KD, both alone or administered to animals with history of experimental brain injury, significantly increases the maximum intensity of pilocarpine-induced seizures, compared to CR fed healthy and injured controls, respectively. Surprisingly, KD and CR seem to have opposite effects in healthy animals as well as animals with a history of experimental brain injury. We have found that KD increases the maximum intensity of pilocarpine-induced seizures, compared to both calorically restricted and unrestricted normal diets. CR, on the other hand, decreases the seizure-genic effect of pilocarpine. This results in a continuum in which calorically restricted animals exhibit the weakest, and KD-fed animals the strongest seizures. To our knowledge, the effects of calorically-restricted and ketogenic diets on pilocarpine-induced seizures have not been previously studied. In other well established models of epilepsy, KD either attenuates or has little effect on seizure intensity.

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The brain anatomy imaging after prolonged ketogenic diet feeding in rats

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Gzielo K. , Kielbinski M. , Jasinski K. , Setkowicz Z.

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nr Suppl.1

EN

INTRODUCTION: Ketogenic diet (KD) results in mild to moderate ketosis, which in turn can significantly change the metabolic balance in the brain. The effects of KD are broadly studied in search of potential clinical uses, such as reducing seizure severity in epilepsy, or providing adjunctive therapy for cancer, Alzheimer’s or Parkinson’s disease. The exact mechanism of those putative neuroprotective effects of KD is, however, still poorly understood. AIM(S): Here, we have checked if prolonged ketogenic diet changed beta hydroxy butyrate(BHB) and epididymal fat levels. The crucial thing was to determine how the ketogenic diet affects brain volume and anatomy. METHOD(S): Male Wistar rats were assigned into two experimental groups: one was given KD for 4 months (n=10), the other (n=11) was fed normal laboratory chow (N). After 4 months, rats were sacrificed. Blood samples were collected and BHB levels measured with ELISA. T2-weighed ex vivo images of extracted brains, taken with a 9.4 T magnetic resonance scanner were obtained at the Institute of Nuclear Physics, at XY resolution of 0.025 mm and voxel depth of 0.25 mm. Using a computer-assisted Cavalieri method, the volumes of the entire brain, hippocampus and brainstem structures (midbrain, pons) were estimated. Volumes were compared between groups to show differentially affected regions. Student’s t‑tests was used for statystical analysis. RESULTS: We have observed increased epididymal fat and elevated BHB levels in KD in comparison to the N group (p<0,000001). Additionally we have found a significant reduction in overall pontine volume in the KD group after the 4-month feeding period. CONCLUSIONS: Our results indicate that the prolonged ketogenic feeding was successful in inducing metabolic changes in KD animals. Observed differences in pontine volume in rats fed a ketogenic diet may lead to modification of feeding behavior. These imapairments in food-intake process may be strictly involved with parabrachial structures which are engaged in regulating appetitive behavior. FINANCIAL SUPPORT: Supported by NCS GRANT: UMO-2015/17/B/NZ7/02953.

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Alterations in brain development in rats treated with immunosuppresant drugs Sandimmune and Prograf and their vehicle components

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Uram L. , Gzielo-Jurek K. , Janeczko K. , Kielbinski M. , Setkowicz Z.

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tom 73

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nr 1

EN

Cyclosporin A and tacrolimus are powerful immunosuppressants used as post-operation medication after allogenic transplantations. Unfortunately, the drugs Sandimmune (cyclosporin A) and Prograf (tacrolimus) exhibit negative side effects. These side effects may be linked not only to the active ingredients themselves, but also to the vehicle used for their delivery – Cremophor EL and/or ethanol. Sandimmune, Prograf, ethanol, Cremophor EL or Cremophor EL with ethanol (i.e. the complete vehicle) in a saline solution were administered to male Wistar rats either on 6th and 7th or 30th and 31st day postnatally. The functional changes in the nervous system elicited by these substances were assessed by observing the intensity of seizures induced by a single i.p. injection of pilocarpine at 60th postnatal day. Brain anatomy was also analyzed by comparing brain mass, lateral ventricle relative area, thickness of cerebral hemisphere wall, relative size of the hippocampus as well as total density of cresyl violet-stained neurons in the cerebral hemisphere walls between control and experimental animals. Our data point to a significant effect of all tested substances on central nervous system development. The greatest effects on seizure severity and brain structure were associated with the complete vehicle. Such effects (although less sever) were also observed for Cremophor EL and ethanol given separately.

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ICOS gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

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Karabon L. , Jedynak A. , Tomkiewicz A. , Wolowiec D. , Kielbinski M. , Woszczyk D. , Kuliczkowski K. , Frydecka I.

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tom 49

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nr 1