lithium-chloride and Brain-Injuries

Lithium chloride (LiCl) has a significant neuroprotective effect in cerebral ischaemia. However, to date, there is a paucity of evidence on the role of LiCl in neural restoration after brain ischaemia and the signalling pathways involved remain unclear.. Therefore, to address this gap, the middle cerebral artery occlusion (MCAO) rat model was used to simulate human ischaemia stroke. Male Sprague-Dawley rats were given MCAO for 90 min followed by reperfusion, and Dickkopf-1 (DKK1, 5.0 μg/kg) was administered half an hour before MCAO. Rats were then treated with hypodermic injection of LiCl (2.0 mmol/kg) twice a day for 1 week. After treatment, cognitive impairment was assessed by the Morris water maze test. Neurological deficit score, 2,3,5-triphenyl tetrazolium chloride staining, brain water content, and histopathology were used to evaluate brain damage. Enzyme-linked immunosorbent assay was used to measure oxidative stress damage and inflammatory cytokines. Apoptosis of the hippocampal neurons was tested by western blot. The key factors of Wnt signalling pathway in the ischaemic penumbra were detected by immunofluorescence staining and quantitative real-time polymerase chain reaction.. Current experimental results showed that LiCl treatment significantly improved the impaired spatial learning and memory ability, suppressed oxidative stress, inflammatory reaction, and neuron apoptosis accompanied by attenuating neuronal damage, which subsequently decreased the brain oedema, infarct volume and neurological deficit. Furthermore, the treatment of LiCl activated Wnt signalling pathway. Interestingly, the aforementioned effects of LiCl treatment were markedly reversed by administration of DKK1, an inhibitor of Wnt signalling pathway.. These results indicate that LiCl exhibits neuroprotective effects in focal cerebral ischaemia by Wnt signalling pathway activation, and it might have latent clinical application for the prevention and treatment of ischaemic stroke.

Topics: Animals; Brain Injuries; Brain Ischemia; Humans; Infarction, Middle Cerebral Artery; Ischemia; Lithium Chloride; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Stroke

Here we studied the cytoprotective effect of lithium chloride and sodium valproate in the in vivo model of neonatal cerebral ischemia/hypoxia and analyzed the influence of these substances on the death of the major neurovascular unit components in experimental ischemia in vitro. Lithium chloride and sodium valproate effectively prevented death of neurons, astrocytes, and endothelial cells in the oxygen-glucose deprivation. This treatment protected the brain of newborn rats from ischemia/hypoxia injury. The results suggest that lithium and sodium valproate can be used for the treatment of neurodegenerative pathologies associated with hypoxia and ischemia in newborns.

Topics: Animals; Animals, Newborn; Brain Injuries; Hypoxia; Hypoxia-Ischemia, Brain; Lithium Chloride; Rats; Valproic Acid

Exendin-4 (Ex4), a glucagon-like peptide-1 receptor (GLP-1R) agonist approved to treat type 2 diabetes mellitus, is well known to induce hypophagia in human and animal models. We evaluated the contributions of the hindbrain parabrachial nucleus (PBN) to systemic Ex4-induced hypophagia, as the PBN receives gustatory and visceral afferent relays and descending input from several brain nuclei associated with feeding. Rats with ibotenic-acid lesions targeted to the lateral PBN (PBNx) and sham controls received Ex4 (1 μg/kg) before 24 h home cage chow or 90 min 0.3 M sucrose access tests, and licking microstructure was analyzed to identify components of feeding behavior affected by Ex4. PBN lesion efficacy was confirmed using conditioned taste aversion (CTA) tests. As expected, sham control but not PBNx rats developed a CTA. In sham-lesioned rats, Ex4 reduced chow intake within 4 h of injection and sucrose intake within 90 min. PBNx rats did not show reduced chow or sucrose intake after Ex4 treatment, indicating that the PBN is necessary for Ex4 effects under the conditions tested. In sham-treated rats, Ex4 affected licking microstructure measures associated with hedonic taste evaluation, appetitive behavior, oromotor coordination, and inhibitory postingestive feedback. Licking microstructure responses in PBNx rats after Ex4 treatment were similar to sham-treated rats with the exception of inhibitory postingestive feedback measures. Together, the results suggest that the PBN critically contributes to the hypophagic effects of systemically delivered GLP-1R agonists by enhancing visceral feedback.

Topics: Analysis of Variance; Animals; Antimanic Agents; Appetitive Behavior; Brain Injuries; Eating; Excitatory Amino Acid Agonists; Exenatide; Feeding and Eating Disorders; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents; Ibotenic Acid; Lithium Chloride; Male; Parabrachial Nucleus; Peptides; Rats; Rats, Sprague-Dawley; Sucrose; Taste; Venoms; Water Deprivation

Studies in animals have provided key evidence that antagonizing TNF-α is a viable therapeutic strategy for diffuse severe brain injury. This study is planned to prevent post-traumatic secondary tissue damages in rat diffuse severe brain injury model, which is induced by alone or combined administration of Etanercept and lithium chloride (LiCl).. Male Sprague-Dawley rats were used in the current study. Rats were divided into 5 groups. Trauma was not induced and treatment was not applied to rats of Sham group. For rats of Trauma+Saline group, saline 0.9% was administered via intraperitoneal (i.p.) route at dose of 1 mg/100 g body weight 1 hour after trauma. For rats of Trauma+Etanercept group, Etanercept was administered via i.p. route at dose of 5 mg/kg body weight 1 hour after trauma. For rats of Trauma+LiCl group, LiCl was administered via i.p. route at dose of 50 mg/kg body weight 1 hour after trauma. For rats of Etanercept+LiCl group, Etanercept and LiCl were administered via i.p. route at dose of 5 mg/kg body weight and 50 mg/kg body weight, respectively, 1 hour after trauma. Serum glial fibrillary acidic protein (GFAP) and Tau levels were analyzed with ELISA. For analyses H&E, TUNEL, GFAP and TNF-α staining methods were used.. We demonstrate that Etanercept treatment reduced the TBI-induced brain tissues alteration, reduced the expression of TNF-α and improve edema and axonal swelling. We observed a significant decrease in TNF-α and GFAP positivity after LiCl was administered.. The findings obtained in this study suggest that the combination therapy with Etanercept and LiCl decreased neuronal degeneration and alleviated secondary tissue damage in post-traumatic period.

Topics: Animals; Apoptosis; Astrocytes; Brain; Brain Injuries; Disease Models, Animal; Drug Therapy, Combination; Etanercept; Glial Fibrillary Acidic Protein; Immunoglobulin G; Lithium Chloride; Male; Neurons; Neuroprotective Agents; Rats, Sprague-Dawley; Receptors, Tumor Necrosis Factor; tau Proteins; Tumor Necrosis Factor-alpha

Maternal infection during pregnancy is associated with an increased risk of neurodevelopmental injury. Our aim was to investigate whether prenatal immune challenge could alter susceptibility to seizure-induced brain injury in adulthood. Pregnant Wistar rats were injected intraperitoneally with lipopolysaccharide (LPS) or normal saline (NS) at days 15 and 16 of gestation. At postnatal day 45, seizure susceptibility was assessed in response to lithium-pilocarpine (LiPC) in adult offspring. Four groups were studied, including normal control (NS-NS), prenatal inflammation (LPS-NS), adult seizure (NS-LiPC), and "two-hit" (LPS-LiPC) groups. Our results demonstrated that adult rat offspring of LPS-exposed dams showed significantly greater susceptibility to LiPC-induced seizures, as well as enhanced hippocampal neuronal injury after seizures. Furthermore, animals in the "two-hit" group performed significantly worse than those from the NS-LiPC group in the open field test and Morris water maze. Our findings suggest that prenatal immune activation can cause a long-lasting increase in seizure susceptibility and predispose the brain to the damaging effect of seizures later in life.

Topics: Age Factors; Animals; Animals, Newborn; Brain Injuries; Disease Models, Animal; Disease Susceptibility; Exploratory Behavior; Female; Hippocampus; Learning Disabilities; Lipopolysaccharides; Lithium Chloride; Male; Maze Learning; Muscarinic Agonists; Pilocarpine; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Seizures; Time Factors

To test the feasibility that whole body exposure to structurally matched, physiologically patterned magnetic fields could reduce cellular injury within specific regions of the brain, young rats were seized with lithium and pilocarpine and then exposed to a sham field or to one of three computer-generated magnetic field patterns. They were digitized equivalents of the pulsed patterns of electric current known to produce long-term potential (LTP) in slices of hippocampus or entorhinal cortices. Histological analyses of their brains as adults indicated the earlier exposure to the LTP-patterned fields produced a robust reduction of damage within the primary and association areas of the right temporal cortices and the CA1/CA2 hippocampal fields. The results suggest physiologically patterned magnetic fields could be employed to target specific nuclei anywhere within the brain by matching intrinsic activity.

Topics: Animals; Brain Injuries; Dose-Response Relationship, Radiation; Epilepsy; Lithium Chloride; Long-Term Potentiation; Magnetic Field Therapy; Male; Pilocarpine; Rats; Rats, Wistar; Temporal Lobe

Rats suppress intake of a normally preferred 0.15% saccharin conditioned stimulus (CS) when it is paired with an aversive agent like lithium chloride (LiCl) or a preferred substance such as sucrose or a drug of abuse. The reward comparison hypothesis suggests that rats avoid intake of a saccharin cue following pairings with a drug of abuse because the rats are anticipating the availability of the rewarding properties of the drug. The present study used bilateral ibotenic acid lesions to examine the role of the gustatory cortex in the suppression of CS intake induced by cocaine, morphine, and LiCl. The results show that bilateral lesions of the insular gustatory cortex (1) fully prevent the suppressive effects of both a 15 and a 30 mg/kg dose of morphine, (2) attenuate the suppressive effect of a 10 mg/kg dose of cocaine, but (3) are overridden by a 20 mg/kg dose of the drug. Finally, these same cortical lesions had no impact on LiCl-induced conditioned taste aversion. The current data show that the insular taste cortex plays an integral role in drug-induced avoidance of a gustatory CS.

Topics: Adjuvants, Immunologic; Analgesics; Analysis of Variance; Animals; Behavior, Animal; Brain Injuries; Cerebral Cortex; Cocaine; Conditioning, Operant; Dose-Response Relationship, Drug; Food Preferences; Inhibition, Psychological; Lithium Chloride; Male; Morphine; Phosphopyruvate Hydratase; Rats; Rats, Sprague-Dawley

Different ratios of normal male rats and male rats in which limbic seizures had been induced by a single systemic injection of lithium and pilocarpine were housed in groups of six. The group ratios ranged along the continuum from all normal rats to all experimental rats. The average numbers of episodes of boxing, biting and mounting--thrusting per rat per hour per group were recorded by direct observation (red light) for 1 h during the midscotophase. Groups that contained less than two normal rats exhibited significantly elevated amounts of agonistic (boxing, biting) behavior but not mounting behavior. Multiple regression analyses showed that combinations of neuronal loss within only two to three areas accommodated at least 50% of the variance in the numbers of these behaviors.

Topics: Agonistic Behavior; Animals; Antimanic Agents; Behavior, Animal; Brain Injuries; Cerebral Cortex; Corpus Striatum; Data Interpretation, Statistical; Epilepsy; Limbic System; Lithium Chloride; Male; Muscarinic Agonists; Nerve Degeneration; Pilocarpine; Rats; Rats, Wistar

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