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Journal Article 2001; 22(1): 53-73 PubMed PMID: 11393163 Citation  Keywords:  Adrenal Glands:physiology, Animals, Biological Clocks, Blood Pressure:physiology, Chronobiology Disorders:physiopathology, Chronobiology Phenomena, Chronotherapy, Circadian Rhythm:physiology, Drug Administration Schedule, Genomics, Homeostasis, Humans, Pi.   

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Journal Article 2012; 33(8): 782-786 PubMed PMID: 23391979 Citation  Keywords:  Animals, Axons:drug effects, Blood-Brain Barrier:drug effects, Brain Edema:drug therapy, Female, Glucocorticoids:pharmacology, Male, Methylprednisolone:pharmacology, Myelin Sheath:drug effects, Nerve Fibers, Myelinated:drug effects, Neuroprotective Agents.   

OBJECTIVES: Our previous experiments proved that methylprednisolone (MP) can significantly reduce axonal impairment accompanying extracellular oedema induced by the osmotic challenge (load) on the blood-brain barrier (BBB). The aim of the present work was to identify whether MP can affect myelin impairment accompanying intracellular oedema induced by water intoxication.

METHODS: For induction of cellular brain oedema, the standard model of water intoxication was chosen. Animals received distilled water in amount corresponding to 15% of the animal's body weight. The volume was divided into three parts and administered intraperitoneally in 8 hours interval. Axonal changes were recognized as signs of myelin disintegration (oedematous distensions, axonal swelling, vesicles, varicosities) at histological sections stained with Black Gold and classified into four grades of myelin degradation. Hippocampal CA1 and CA3 areas and the dentate gyrus were selected for the study. Methylprednisolone was administered either intraperitoneally or intracarotically. Its effect was studied in two different time intervals: in the acute group (30 minutes after hyperhydration and MP application) and in chronic one (1 week after hyperhydration and MP application).

RESULTS: In both the acute and chronic groups, cellular oedema induced by water intoxication brought about apparent damage of myelin (compared to control animals p<0.0001). Intracarotic injection of MP was not able to influence myelin integrity changes either in the acute or in chronic group. However, intraperitoneal administration of MP increased the level of myelin deterioration in the acute group (p 0.05), but improved myelin changes in the chronic group (p<0.005).

CONCLUSION: The effect of MP on axonal impairment during cellular brain oedema induced by water intoxication differs from that during the extracellular osmotic oedema. In the extracellular oedema, cellular metabolism is not significantly affected and myelin changes can be influenced by the neuroprotective effect of MP. The primary cause of cellular oedema is a disorder of cellular metabolism and myelin impairment is one of the structural consequences of such disorder. That is why the myelin changes are not affected by MP administration in a consistent and specific manner....

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Journal Article 2012; 33(8): 749-756 PubMed PMID: 23391977 Citation  Keywords:  Animals, Endocrine System:physiology, Endocrine System Diseases:metabolism, Energy Metabolism:physiology, Ghrelin:physiology, Humans,.   

: Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor. It is mainly secreted by stomach cells but has also been shown to be present in the hypothalamus, pituitary, gonads and many other organs. Ghrelin is a regulator of energy homeostasis and GH secretion. Many studies have been done examining the influence of ghrelin on different organs. Ghrelin may play an important role in pathophysiology of some endocrine diseases. The relationship between ghrelin and pituitary, gonads and thyroid function appears to be specially interesting....

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Journal Article 2012; 33(8): 736-748 PubMed PMID: 23391975 Citation  Keywords:  Animals, Brain:immunology, Fatty Acids, Omega-3:metabolism, Humans, Mental Disorders:immunology, Neuroimmunomodulation:physiology, Oxidative Stress:physiology,.   

: The lipids constitute majority of dry weight of mature human brain. From lipids, 35% is comprised of PUFA with long chain (LC-PUFA), especially docosahexaenoic acid (DHA) of n-3 family and arachidonic acid (AA) of n-6 family. Humans are dependent on dietary intake of both AA and DHA. Interestingly, the dietary n-6/n-3 ratio increased considerably during last century. LC-PUFAs play numerous roles in the brain, including structural (forming the physico-chemical properties in the lipid bilayer of cellular membranes) and signaling ones. Moreover, they influence neurogenesis and neurotransmission within the nervous tissue. The metabolites of PUFA modulate immune and inflammatory processes in the brain, oxidative stress as well as its consequences. Of high importance is also their connection with several metabolic factors involved in the proper function of the brain and/or were discovered to play a role in the pathogenesis of neuropsychiatric diseases - melatonin, homocysteine, leptin, and adiponectin. This review gives short view of the metabolism and possible mechanisms of PUFA n-3 action in the brain, and their role in the pathogenesis of psychiatric diseases....

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Journal Article 2012; 33(7): 713-721 PubMed PMID: 23391884 Citation  Keywords:  Acute-Phase Reaction:chemically induced, Animals, Anti-Inflammatory Agents, Non-Steroidal:pharmacology, Body Temperature:drug effects, Brain:drug effects, Dopamine:biosynthesis, Fever:chemically induced, Indomethacin:pharmacology, Lipopolysaccharides:toxi.   

OBJECTIVES: The antipyretic and neuroprotective potential of the nonsteroidal anti-inflammatory drug "indomethacin" was tested against lipopolysaccharide-produced hyperthermia and biosynthesis of norepinephrine and dopamine, in six brain regions of male rat.

METHODS: Observations were based on a single intraperitoneal injection of each of lipopolysaccharide (250 µg Kg-1 body wt) and indomethacin (20 mg Kg-1 body wt) followed by sampling and assaying of brain specimens after 2, 8, 12 and 24 hrs. lipopolysaccharide induced a general hyperthermia (8-24 hr) that was completely abolished by pretreatment with indomethacin.

RESULTS: In virtually all brain regions tested, lipopolysaccharide stimulated the biosynthesis of norepinephrine and dopamine. Yet, pretreatment with indomethacin provoked substantial mitigation predominantly after 24 hrs. A time-based manner attended by a regionally nonselective manner characterized lipopolysaccharide-induced monoamine biosynthesis; whereas, indomethacin alleviation seems to proceed in a time-dependent and regionally-selective pathway since the pons proved the fastest and/or most responsive brain region to indomethacin action. A role of prostaglandin synthesis in the development of lipopolysaccharide-induced fever and catecholamine biosynthesis was suggested, given that both responses were abolished by the cyclooxygenase-inhibitor indomethacin.

CONCLUSION: Accordingly, our data verified the potent therapy potential of indomethacin in protecting cerebral noradrenergic and dopaminergic systems against lipopolysaccharide-induced acute phase reactions....

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Journal Article 2012; 33(7): 709-712 PubMed PMID: 23391882 Citation  Keywords:  Analgesics, Opioid:pharmacology, Animals, Behavior, Animal:drug effects, Choice Behavior:drug effects, Conditioning (Psychology):drug effects, Male, Mice, Morphine:pharmacology, Morphine Dependence:physiopathology, Music, Nucleus Accumbens:drug effects, R.   

OBJECTIVES: This research aims at studying the neuroendocrine effects of music on creating morphine dependence in mice using conditioned place preference (CPP).

METHODS: The mice treated with 10 mg/kg morphine subcutaneously, fast music and slow music. Morphine was used to create dependence. In order to recognize the morphine rewarding effects, CPP technique was used. In the conditioning stage that lasted for 8 days, different groups of mice, after receiving the treatment were randomly placed in compartment for 30 minutes. The post-conditioning stage included the fourth day, the ninth day, the 12th day and the 16th day.

RESULTS: Comparing place preference between morphine group and the control group, a significant increase (p<0.05) was observed in the place preference of morphine group, while a significant decrease (p<0.05) was demonstrated in the place preferences of morphine + taxi girl music group compared with morphine group alone. In addition morphine + alone in the rain music group demonstrated a significantly increased conditioned place preference (p<0.05) compared with the morphine group.

CONCLUSIONS: Alone in the rain music acts as a positive pleasant emotion increasing the dopaminergic activity in the Nucleus Accumbens (NAc) and Ventral Tegmental Area (VTA) and through associated learning mechanisms of reward-related behavior increases morphine addiction. However, taxi girl music may act as unpleasant experiences producing negative emotions and reducing morphine addiction....

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Journal Article 2012; 33(7): 703-708 PubMed PMID: 23391881 Citation  Keywords:  Animals, Antithyroid Agents:pharmacology, Body Temperature:drug effects, Body Weight:drug effects, Brain Chemistry:drug effects, Eating:drug effects, Energy Metabolism:drug effects, Hypothalamus:drug effects, Hypothyroidism:chemically induced, Male, Methi.   

OBJECTIVES: We evaluated the contribution of the thyroid hormones to the long-term maintenance of feeding behavior and body weight, while distinguishing their direct central effects from those resulting from the metabolic rate in the peripheral tissues.

METHODS: We assessed the effect of hypothyroidism on the long-term (6 months) regulation of food intake, body weight, and energy expenditure in rats. We then generated the recovery of a euthyroid condition in the brain while maintaining a low T3 availability for the peripheral organs, i.e. a combined condition of central euthyroidism with peripheral hypothyroidism, with the aid of a pharmacological combination.

RESULTS: Hypothyroidism caused a decrease in the daily food intake, body weight, and body temperature. The food intake and body temperature stabilized at a lower value, whereas body weight kept decreasing at a constant rate. The administration of exogenous T4 increased food intake and body-weight gain, but had no effect on body temperature.

CONCLUSIONS: The thyroid hormones are necessary for the long-term regulation of energy intake, storage, and expenditure by different mechanisms. The feeding behavior seems to be partially dependent on a direct action of the thyroid hormones on the brain and this effect is independent of the energy expenditure in the peripheral organs. The body weight is closely dependent on the thyroid status and its maintenance seems to involve thyroid action on mechanisms other than feeding and metabolic rate....

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Journal Article 2012; 33(7): 689-696 PubMed PMID: 23391880 Citation  Keywords:  Animals, CA1 Region, Hippocampal:pathology, Cerebral Cortex:pathology, Disease Models, Animal, Disease Progression, Excitatory Postsynaptic Potentials:drug effects, Male, Neurodegenerative Diseases:chemically induced, Neurotoxins:toxicity, Rats, Rats, Wis.   

BACKGROUND: Trimethyltin (TMT), a potent neurotoxicant, elicits neuronal death in the limbic system and causes damage particularly in the hippocampus. Current interest relates to the opportunity to use TMT as an experimental model of neurodegeneration in the study of Alzheimer-like diseases.

OBJECTIVE: In light of recently found species-specific and strain-specific differences in TMT intoxication, the aim of this study was to characterise the model of TMT-induced neurodegeneration in the brain of Wistar rats during early (days 1-3) and late (days 22-24) stage of neuronal damage.

RESULTS: Reduced neurotransmission at the CA3-CA1 synapse and reduced number of cells accompanied with reduced width of CA1 pyramidal cell layer were observed at the late stage of TMT intoxication (7 mg/kg, i.p.). Long-term potentiation of excitatory postsynaptic potential, elicited by train stimulation (100 Hz, 1s), was not impaired by the dose of TMT tested. Activation of pro-apoptotic caspase-3 suggests involvement of apoptosis in neuronal cell death in the hippocampus at the late stage of TMT intoxication. Increased protein carbonyl formation was proved in the cortex at the early stage of TMT intoxication compared both to controls in the early and late stage and to the late stage of TMT action.

CONCLUSIONS: TMT-induced neurodegeneration was proved in the brain of Wistar rats. Changes found in the parameters examined may be reliable indicators of neurodegeneration. The increased level of carbonyls in the cortex at the early stage indicates that particularly at the onset of progressive neurodegeneration compounds with antioxidative properties may be effective in slowing down brain injury....

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