lithium-chloride and Hypothermia

Changes in body temperature are common features among patients with sepsis and septic shock. Similarly, systemic administration of bacterial endotoxin (lipopolysaccharide, LPS) to rats leads to an initial hypothermia followed by elevation in body temperature. These changes in body temperature are accompanied by increased levels of prostaglandin E2 (PGE2) in the hypothalamus.. This study examined the effects of lithium and SB216763 - two different glycogen synthase kinase (GSK)-3 inhibitors - on LPS-induced changes in body temperature and hypothalamic PGE2 levels in endotoxemic rats.. Endotoxemia was induced by intraperitoneal injection of LPS (10 mg/kg). Lithium (100 mg/kg) and SB216763 (5 mg/kg) were administered at 2 h before LPS. Body temperature and mortality were monitored during 48 h after LPS injection. In another protocol, rats were sacrificed at 2 h post LPS injection and then, blood, liver and hypothalamus were extracted for inflammatory mediators determination.. Lithium but not SB216763 significantly reduced LPS-induced hypothermia, while both compounds did not alter the subsequent elevation in body temperature. Moreover, only lithium significantly reduced hypothalamic PGE2 levels. On the other hand, both compounds significantly reduced plasma, hepatic and hypothalamic tumor necrosis factor-α and decreased plasma PGE2 levels. Both compounds did not alter LPS-induced mortality.. These results suggest that the attenuation of LPS-induced hypothermia by lithium may derive from its reduction of hypothalamic PGE2 levels.

Topics: Animals; Anti-Inflammatory Agents; Body Temperature; Dinoprostone; Endotoxemia; Glycogen Synthase Kinase 3; Hypothalamus; Hypothermia; Indoles; Lipopolysaccharides; Lithium Chloride; Liver; Male; Maleimides; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Tau hyperphosphorylation is one hallmark of Alzheimer's disease (AD) pathology. Pharmaceutical companies have thus developed kinase inhibitors aiming to reduce tau hyperphosphorylation. One obstacle in screening for tau kinase inhibitors is the low phosphorylation levels of AD-related phospho-epitopes in normal adult mice and cultured cells. We have shown that hypothermia induces tau hyperphosphorylation in vitro and in vivo. Here, we hypothesized that hypothermia could be used to assess tau kinase inhibitors efficacy. Hypothermia applied to models of biological gradual complexity such as neuronal-like cells, ex vivo brain slices and adult non-transgenic mice leads to tau hyperphosphorylation at multiple AD-related phospho-epitopes. We show that Glycogen Synthase Kinase-3 inhibitors LiCl and AR-A014418, as well as roscovitine, a cyclin-dependent kinase 5 inhibitor, decrease hypothermia-induced tau hyperphosphorylation, leading to different tau phosphorylation profiles. Therefore, we propose hypothermia-induced hyperphosphorylation as a reliable, fast, convenient and inexpensive tool to screen for tau kinase inhibitors.

Topics: Anesthesia; Animals; Brain; Cell Line; Cyclin-Dependent Kinase 5; Drug Evaluation, Preclinical; Female; Glycogen Synthase Kinase 3; Hypothermia; Lithium Chloride; Male; Mice; Mice, Inbred C57BL; Phosphorylation; Protein Kinase Inhibitors

Core temperature was measured in rats 24 hr. after they had been assigned to one of 8 groups in a 3-way analysis of variance design that involved (1) induction of limbic seizures by a systemic injection of lithium/pilocarpine, (2) physical restraint, and (3) administration of acepromazine. An extraordinarily powerful interaction was noted among seizures, physical restraint, and acepromazine-produced hypothermia (24 degrees C) compared to the other 7 treatments (> 35 degrees C). The putative poikilothermic response is commensurate with the loss of mammalian behaviors that follow these seizures. Implications for survival during the acute stages of brain injury are suggested.

Topics: Acepromazine; Animals; Body Temperature Regulation; Brain Injuries; Chlorides; Hypothermia; Limbic System; Lithium; Lithium Chloride; Male; Neurons; Pilocarpine; Rats; Restraint, Physical; Seizures; Status Epilepticus

Lithium compounds administered into rats' organisms in euthermia elicited accelerated urinary excretion of physiological cations, especially the Na and K ones. Homeothermic organisms in hypothermia, returnig from hypothermia and in posthypothermia showed considerable caliuresis with delayed excretion of Na during the following days. By way of gastric filling lithium load (in a form of water LiCl solution, with concentration of 0.2 n and the amount of 3.0 ml/100 cm2 ger body surface) administered to rats in deep hypothermia (17 degrees C - 19 degrees C measured high in the sigma), recovering of hypothermia (4 h) and in posthypothermia (20 h) did not elicit delayed natriuresis but efficiency of lithium and hypothermia had been summarised (clearly enhanced natriuresis and extremely enhanced caliuresis as a summarised efficiency).

Topics: Animals; Diuresis; Female; Hypothermia; Lithium Chloride; Male; Rats; Rats, Inbred Strains; Sodium

Rats were given five separate pairings (sequential IP injections) of pentobarbital and lithium chloride, both hypothermia-inducing agents. When the animals were subsequently tested with a single injection of pentobarbital alone, they exhibited an attenuated hypothermia relative to controls that had either (a) received pentobarbital-LiCl pairings spaced twenty-four hours apart, or (b) received only placebo injections of normal saline. This phenomenon provides further evidence that rats can learn an association between drug states and may help to explain why pentobarbital-LiCl pairings tend to eliminate pentobarbital's capacity to produce a conditioned flavor aversion.

Topics: Animals; Body Temperature; Body Temperature Regulation; Chlorides; Hypothermia; Lithium; Lithium Chloride; Male; Pentobarbital; Rats