lithium-chloride and Ischemic-Attack--Transient

Previous study has indicated that chronic treatment with lithium protects brain against ischemic injury by reducing apoptotic death. To investigate whether lithium improves the behavioral disorder induced by transient global cerebral ischemia, we examined the effects of lithium treatment on the performance of rats in a set of behavioral tests, i.e. beam balance, elevated plus maze (EPM), open field and Morris water maze. Our results showed that lithium attenuated the worse general 'well-being' and the worse performance in beam balance, and hyperactivity in EPM and open field, including increased open arm entries, time spent in the open arms, squares crossed, rearing and grooming over 7 days after 15min ischemia, which were induced by four-vessel occlusion in Sprague-Dawley rats. Moreover, lithium improved the injured spatial learning and memory ability in Morris water maze at post-ischemic days 8 and 9. Histological analysis displayed that it decreased obviously cell death in hippocampal CA1 region. Our study further confirmed the protective role of lithium in the ischemia-reperfusion injury and suggested that lithium might be a helpful therapeutic approach to the treatment of stroke combining with other neuroprotective agents.

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Cell Count; Disease Models, Animal; Exploratory Behavior; Hippocampus; Ischemic Attack, Transient; Lithium Chloride; Male; Maze Learning; Mental Disorders; Psychomotor Performance; Rats; Rats, Sprague-Dawley; Survival Rate; Time Factors

Recent studies have demonstrated that lithium has a neuroprotective effect against brain ischemia. Whether this effect is mediated by hippocampal neurogenesis remains unknown. The ERK (extracellular signal-regulated kinase) pathway plays an essential role in regulating neurogenesis. The present study was undertaken to investigate whether lithium regulates hippocampal neurogenesis by the ERK pathway and improves spatial learning and memory deficits in rats after ischemia. Rats were daily injected with lithium (1 mmol/kg) and 2 weeks later subjected to 15-min ischemia induced by four-vessel occlusion method. 5-bromo-2'-deoxyuridine (Brdu; 50mg/kg) was administrated twice daily at postischemic day 6, or for 3 days from postischemic day 6 to 8. We found that lithium increased the ERK1/2 activation after ischemia by western blotting analysis. There was a significant increase in Brdu-positive cells in the hippocampal dentate gyrus after lithium treatment, compared with ischemia group at postischemic days 7 and 21; furthermore, the survival rate of Brdu-positive cells was elevated by lithium. Inhibition of the ERK1/2 activation by U0126 diminished these effects of lithium. The percentages of Brdu-positive cells that expressed a neuronal marker or an astrocytic marker were not significantly influenced by lithium. Moreover, lithium improved the impaired spatial learning and memory ability in Morris water maze, and U0126 attenuated the behavioral improvement by lithium. These results suggest that lithium up-regulates the generation and survival of new-born cells in the hippocampus by the ERK pathway and improves the behavioral disorder in rats after transient global cerebral ischemia.

Topics: Animals; Butadienes; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Hippocampus; Ischemic Attack, Transient; Learning; Lithium Chloride; Male; Memory; Neurons; Nitriles; Rats; Rats, Sprague-Dawley; Space Perception

The experiments were carried out on male Wistar rats. The influence of brain oligemic hypoxia and lithium chloride (LiCl) on some behavioural parameters was investigated. Reduction of brain blood supply was performed by surgical clamping of both carotid arteries for 60 min in general anaesthesia induced by brietal (Methoxitone sodium, 10 mg/kg i.p.). Control animals had their vessels separated, but not clamped (sham operated). 6 days after surgery animals received LiCl (2.5 mEq/kg i.p.). Behavioral experiments were performed 24 h and 7 days after lithium administration. Experimental groups consisted of 12 animals. It was found that oligemic hypoxia reduced inconsiderably spontaneous locomotor and exploratory activity in rats. Similar influence of LiCl was observed. But LiCl administered to animals after oligemic hypoxia prevented them against locomotor and exploratory impairment. In addition, LiCl strongly enhanced amphetamine-induced hyperactivity and diminished haloperidol-induced catalepsy in hypoxic animals. These effects were not observed in sham operated animals. The above results could be connected with antidepressive action of LiCl and the model of moderate oligemic hypoxia used in present work could be a useful model for investigation of new antidepressive compounds.

Topics: Amphetamine; Animals; Behavior, Animal; Brain; Catalepsy; Drug Synergism; Haloperidol; Ischemic Attack, Transient; Lithium Chloride; Male; Psychomotor Performance; Rats; Rats, Wistar

The cytoprotective effect of NBQX, a selective AMPA receptor antagonist, was tested following 10 min of severe forebrain ischemia using the 4-vessel occlusion model. Immediately, and at 15 and 30 min following reperfusion, adult Wistar rats received intraperitoneal injections of either saline (n = 5), 1 mg lithium chloride (n = 17) or 30 mg/kg of the lithium salt of NBQX (n = 18). In saline-treated animals 82 +/- 12% of CA1 hippocampal neurons were lost. Of those treated with lithium 70 +/- 23% were injured, while those given NBQX sustained only 40 +/- 34% CA1 necrosis (P less than 0.01). Twelve of 18 NBQX-treated animals had less than 30% CA1 injury as compared with 1 of 17 lithium-treated animals. The AMPA receptor may play a more important role than the NMDA receptor in selective ischemic necrosis of hippocampal neurons.

Topics: Animals; Cell Death; Chlorides; Hippocampus; Ischemic Attack, Transient; Lithium; Lithium Chloride; Neurons; Quinoxalines; Rats; Rats, Inbred Strains; Receptors, AMPA; Receptors, Neurotransmitter; Reperfusion; Sodium Chloride

It has been proposed that lithium ion desensitizes neuronal receptors that function via the inositol phospholipid signaling mechanism. We examined the effects of lithium chloride on the morphologic outcome after 5 minutes of cerebral ischemia induced in gerbils by occluding both common carotid arteries under brief halothane anesthesia. In three treated groups of 10 gerbils each, 5 meq/kg i.p. lithium chloride was given 2 days, 1 day, and 2 hours before ischemia; 2 hours before ischemia; or immediately after the end of ischemia. Corresponding control groups of nine or 10 gerbils each received equivalent volumes of saline injected at comparable times. All gerbils were perfusion-fixed 1 week later, and neuronal density of the hippocampal CA1 pyramidal cells was determined. Lithium induced very mild intraischemic systemic hypothermia, but postischemic hyperthermia developed in both treated and control groups. Neuronal densities were equal in corresponding groups. The results indicate that our regimen of lithium administration provides no benefit in survival of hippocampal neurons, and intraischemic hypothermia of less than 0.8 degrees C is not protective. Other strategies to inactivate the signal transduction system that is specific for excitatory neurotransmission should be evaluated.

Topics: Animals; Body Temperature; Brain; Calcium; Chlorides; Gerbillinae; Intracellular Membranes; Ions; Ischemic Attack, Transient; Lithium; Lithium Chloride; Male; Rectum