lithium-chloride and Nerve-Degeneration

Transplantation of neural stem cells (NSCs) holds great potential for the treatment of spinal cord injury (SCI). However, transplanted NSCs poorly survive in the SCI environment. We injected NSCs into tibial nerve and transplanted tibial nerve into a hemisected spinal cord and investigated the effects of lithium chloride (LiCl) on the survival of spinal neurons, axonal regeneration, and functional recovery. Our results show that most of the transplanted NSCs expressed glial fibrillary acidic protein, while there was no obvious expression of nestin, neuronal nuclei, or acetyltransferase found in NSCs. LiCl treatment produced less macrosialin (ED1) expression and axonal degeneration in tibial nerve after NSC injection. Our results also show that a regimen of LiCl treatment promoted NSC differentiation into NF200-positive neurons with neurite extension into the host spinal cord. The combination of tibial nerve transplantation with NSCs and LiCl injection resulted in more host motoneurons surviving in the spinal cord, more regenerated axons in tibial nerve, less glial scar area, and decreased ED1 expression. We conclude that lithium may have therapeutic potential in cell replacement strategies for central nervous system injury due to its ability to promote survival and neuronal generation of grafted NSCs and reduced host immune reaction.

Topics: Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Cell Movement; Cell Survival; Female; Glial Fibrillary Acidic Protein; Immunohistochemistry; Lithium Chloride; Nerve Degeneration; Nerve Regeneration; Neural Stem Cells; Neurogenesis; Neurons; Rats; Spinal Cord Injuries; Tibial Nerve

Topics: Age Factors; Animals; Cerebral Cortex; Hippocampus; Lipopolysaccharides; Lithium Chloride; Male; Nerve Degeneration; Random Allocation; Rats; Rats, Sprague-Dawley; Toll-Like Receptor 4

This study tightly controlled seizure duration and severity during status epilepticus (SE) in postnatal day 10 (P10) rats, in order to isolate hyperthermia as the main variable and to study its consequences. Body temperature was maintained at 39 ± 1 °C in hyperthermic SE rats (HT+SE) or at 35 ± 1 °C in normothermic SE animals (NT+SE) during 30 min of SE, which was induced by lithium-pilocarpine (3 mEq/kg, 60 mg/kg) and terminated by diazepam and cooling to NT. All video/EEG measures of SE severity were similar between HT+SE and NT+SE pups. At 24h, neuronal injury was present in the amygdala in the HT+SE group only, and was far more severe in the hippocampus in HT+SE than NT+SE pups. Separate groups of animals were monitored four months later for spontaneous recurrent seizures (SRS). Only HT+SE animals developed convulsive SRS. Both HT+SE and NT+SE animals developed electrographic SRS (83% vs. 55%), but SRS frequency and severity were higher in hyperthermic animals (12.5 ± 3.5 vs. 4.2 ± 2.0 SRS/day). The density of hilar neurons was lower, thickness of the amygdala and perirhinal cortex was reduced, and lateral ventricles were enlarged in HT+SE over NT+SE littermates and HT/NT controls. In this model, hyperthermia greatly increased the epileptogenicity of SE and its neuropathological sequelae.

Topics: Adjuvants, Immunologic; Animals; Animals, Newborn; Anticonvulsants; Apoptosis; Brain; Cell Death; Diazepam; Disease Models, Animal; Hyperthermia, Induced; Lithium Chloride; Male; Muscarinic Agonists; Nerve Degeneration; Neurons; Neuropil; Pilocarpine; Rats; Rats, Wistar; Status Epilepticus; Time Factors

Corticosteroids are used in the management of several epileptic aliments; however, their effectiveness in combating seizures remains controversial, with pro- and anti-convulsive effects ascribed. The current study aimed to address the modulatory effect of dexamethasone (DEX) utilizing 3 dose levels (5, 10, and 20 mg/kg body mass of male Wistar rat) in the rat lithium-pilocarpine (Li-PIL) epilepsy model. Li-PIL induced seizures that were associated with neuronal cell loss in the CA3 region, and increased prostaglandin (PG)E(2), tumor necrosis factor (TNF)-α, interleukin (IL)-10, nitric oxide, and neutrophil infiltration in the hippocampus. However, Li-PIL compromised the oxidant-antioxidant balance of the hippocampus. Effective anticonvulsant activity was only observed with 10 mg DEX/kg body mass, which reduced seizure production and incidence, as well as neuronal cell loss in the CA3 region. At this anticonvulsant dose, enhancements in the antioxidant system and IL-10, as well as suppression of altered inflammatory markers were observed. Conversely, doubling the dose showed a tendency to shorten seizure latency, and neither affected seizure incidence nor CA3 neuronal cell loss. These effects were associated with an increase in levels of PGE(2) and TNF-α. The present study found a lack of protection at 5 mg DEX/kg body mass, an anticonvulsant effect at 10 mg/kg, and a loss of protection at 20 mg/kg in the Li-PIL epilepsy model, which indicates that there is an optimal dose of DEX for preventing the induction of seizures.

Topics: Animals; Anticonvulsants; Antioxidants; CA3 Region, Hippocampal; Dexamethasone; Dinoprostone; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Interleukin-10; Lithium Chloride; Male; Nerve Degeneration; Neutrophil Activation; Nitric Oxide; Oxidative Stress; Pilocarpine; Rats; Rats, Wistar; Seizures; Tumor Necrosis Factor-alpha

Fetal alcohol exposure can cause developmental defects in offspring known as fetal alcohol spectrum disorder (FASD). FASD symptoms range from obvious facial deformities to changes in neuroanatomy and neurophysiology that disrupt normal brain function and behavior. Ethanol exposure at postnatal day 7 in C57BL/6 mice induces neuronal cell death and long-lasting neurobehavioral dysfunction. Previous work has demonstrated that early ethanol exposure impairs spatial memory task performance into adulthood and perturbs local and interregional brain circuit integrity in the olfacto-hippocampal pathway. Here we pursue these findings to examine whether lithium prevents anatomical, neurophysiological, and behavioral pathologies that result from early ethanol exposure. Lithium has neuroprotective properties that have been shown to prevent ethanol-induced apoptosis. Here we show that mice co-treated with lithium on the same day as ethanol exposure exhibit dramatically reduced acute neurodegeneration in the hippocampus and retain hippocampal-dependent spatial memory as adults. Lithium co-treatment also blocked ethanol-induced disruption in synaptic plasticity in slice recordings of hippocampal CA1 in the adult mouse brain. Moreover, long-lasting dysfunctions caused by ethanol in olfacto-hippocampal networks, including sensory-evoked oscillations and resting state coherence, were prevented in mice co-treated with lithium. Together, these results provide behavioral and physiological evidence that lithium is capable of preventing or reducing immediate and long-term deleterious consequences of early ethanol exposure on brain function.

Topics: Animals; Animals, Newborn; Behavior, Animal; Central Nervous System Depressants; Ethanol; Female; Hippocampus; Lithium Chloride; Male; Mice; Mice, Inbred C57BL; Nerve Degeneration; Neuronal Plasticity; Neuroprotective Agents

Transcranial direct current stimulation (tDCS) is a recently available, noninvasive brain stimulation technique. The effects of cathodal tDCS on convulsions and spatial memory after status epilepticus (SE) in immature animals were investigated.. Rats underwent lithium-pilocarpine-induced SE at postnatal day (P) 20-21 and received daily 30-min cathodal tDCS for 2 weeks at P23-36 through a unilateral epicranial electrode at 200μA. After tDCS, convulsions over 2 weeks were estimated by 20-h/day video monitoring. The rats were tested in a water maze for spatial learning at P50-53 and the brains were examined for cell loss and mossy fiber sprouting.. Long-term treatment with weak cathodal tDCS reduced SE-induced hippocampal cell loss, supragranular and CA3 mossy fiber sprouting, and convulsions (reduction of 21%) in immature rats. The tDCS treatment also rescued cognitive impairment following SE.. These findings suggested that cathodal tDCS has neuroprotective effects on the immature rat hippocampus after pilocarpine-induced SE, including reduced sprouting and subsequent improvements in cognitive performance. Such treatment might also have an antiepileptic effect.

Topics: Animals; Disease Models, Animal; Electric Stimulation Therapy; Hippocampus; Lithium Chloride; Male; Maze Learning; Memory Disorders; Mossy Fibers, Hippocampal; Nerve Degeneration; Pilocarpine; Rats; Rats, Wistar; Seizures; Status Epilepticus

Status epilepticus-induced hippocampal neuronal loss is mainly associated with excitotoxicity induced by increased levels of extracellular glutamate which is normally neutralized by high-affinity uptake mechanism. The energy source for the glutamate uptake is the electrochemical Na(+) gradient maintained by Na(+)/K(+) ATPase pump. In this study, we investigated the effect of early-life-induced status epilepticus on hippocampal Na(+)/K(+) ATPase activity and glutamate uptake. Rat pups 15 days old were injected i.p. with LiCl (3 mEq/kg) 12-18 h prior to s.c. pilocarpine administration (60 mg/kg). Hippocampal Na(+)/K(+) ATPase activity and glutamate uptake were evaluated 1.5, 12 and 24 h after SE induction. LiCl-pilocarpine-induced SE decreased Na(+)/K(+) ATPase activity and glutamate uptake by 42 and 38%, respectively, 1.5 h after SE induction. However, 12 and 24 h after SE induction the pump activity and glutamate uptake returned to control levels. SE early in life increased hippocampal number of degenerating neurons in the CA1 subfield and dentate gyrus 24 h after SE induction. In conclusion, SE induced early in life causes short-term disruption in hippocampal Na(+)/K(+) ATPase activity and glutamate uptake, which may be related to neuronal death found in CA1 subfield.

Topics: Animals; Convulsants; Enzyme Activation; Glutamic Acid; Hippocampus; Lithium Chloride; Male; Nerve Degeneration; Pilocarpine; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Status Epilepticus

In this study, we performed immunohistochemistry for somatostatin (SS), neuropeptide Y (NPY), and parvalbumin (PV) in LiCl-pilocarpine-treated rats to observe quantitative changes and axonal sprouting of GABAergic interneurons in the hippocampus, especially in the sclerotic hippocampus. Fluoro-Jade B (FJB) was performed to detect the specific degeneration of GABAergic interneurons. Compared with age-matched control rats, there were fewer SS/NPY/PV-immunoreactive (IR) interneurons in the hilus of the sclerotic hippocampus in pilocarpine-treated rats; hilar dentritic inhibitory interneurons were most vulnerable. FJB stain revealed degeneration was evident at 2 months after status epilepticus. Some SS-IR and NPY-IR interneurons were also stained for FJB, but there was no evidence of degeneration of PV-IR interneurons. Axonal sprouting of GABAergic interneurons was present in the hippocampus of epileptic rats, and a dramatic increase of SS-IR fibers was observed throughout all layers of CA1 region in the sclerotic hippocampus. These results confirm selective loss and degeneration of a specific subset of GABAergic interneurons in specific subfields of the hippocampus. Axonal sprouting of inhibitory GABAergic interneurons, especially numerous increase of SS-IR neutrophils within CA1 region of the sclerotic hippocampus, may constitute the aberrant inhibitory circum and play a significant role in the generation and compensation of temporal lobe epilepsy.

Topics: Animals; Axons; Disease Models, Animal; gamma-Aminobutyric Acid; Hippocampus; Interneurons; Lithium Chloride; Male; Nerve Degeneration; Neuropeptide Y; Parvalbumins; Pilocarpine; Rats; Rats, Sprague-Dawley; Sclerosis; Somatostatin; Status Epilepticus

Status epilepticus (SE) leads to serious damage in hippocampus of the adult brain. Much less is known about immature brain where neuronal degeneration may have different localization and time course. Lithium-pilocarpine SE was induced in 12-day-old male Wistar rats. Six different intervals after SE (from 4 h to 1 week) were studied using Fluoro-Jade B staining. Three to four animals were used for every interval. Severity of damage in individual parts of hippocampal formation was semi-quantified. A consistent neuronal damage occurred in all hippocampal fields (CA 1, CA 3, dentate gyrus) at all survival intervals. Hippocampal fields CA 1 and CA 3 exhibited degeneration of interneurons located mainly in stratum oriens and pyramidale at shorter intervals (4-12h). Massive degeneration of pyramidal cells started at 24h in CA 1 and at 48 h in CA 3. Dentate gyrus exhibited degenerating neurons in granular layer with a peak at short intervals (4-8 h), and molecular layer was spared. The lower blade of dentate gyrus was more affected than the upper blade. Damage of hilar neurons was negligible. Our results demonstrate that SE elicited in immature rats causes acute neurodegeneration in the hippocampus. Time course of this degeneration is different for individual parts of hippocampal formation and for individual cell types.

Topics: Animals; Animals, Newborn; Dentate Gyrus; Disease Models, Animal; Hippocampus; Lithium Chloride; Male; Nerve Degeneration; Pilocarpine; Pyramidal Cells; Rats; Rats, Wistar; Status Epilepticus; Time Factors

Whether status epilepticus (SE) in early infancy, rather than the underlying illness, leads to temporal lobe neurodegeneration and volume reduction remains controversial.. SE was induced with LiCl-pilocarpine in P12 rats. To assess acute neuronal damage, brains (five controls, five with SE) were investigated at 8 h after SE by using silver and Fluoro-Jade B staining. Some brains from the early phase were processed for electron microscopy. To assess chronic changes, brains from nine controls and 13 rats with SE at P12 were analyzed after 3 months by using histology and magnetic resonance imaging (MRI).. MRI analysis of the temporal lobe of adult animals with SE at P12 indicated that 23% of the rats had hippocampal, 15% had amygdaloid, and 31% had perirhinal volume reduction. Histologic analysis of sections from the MR-imaged brains correlated with the MRI data. Analysis of neurodegeneration 8 h after SE by using both silver and Fluoro-Jade B staining revealed degenerating neurons located in the same temporal lobe regions as the volume reduction in chronic samples. Electron microscopic analysis revealed irreversible ultrastructural alterations. As with the chronic histologic and MRI findings, interanimal variability was seen in the distribution and severity of acute damage.. Our data indicate that SE at P12 can cause acute neurodegeneration in the hippocampus as well as in the adjacent temporal lobe. It is likely that acute neuronal death contributes to volume reduction in temporal lobe regions that is detected with MRI in a subpopulation of animals in adulthood.

Topics: Amygdala; Animals; Animals, Newborn; Apoptosis; Disease Models, Animal; Entorhinal Cortex; Fluoresceins; Hippocampus; Lithium Chloride; Magnetic Resonance Imaging; Male; Microscopy, Electron; Nerve Degeneration; Neurons; Organic Chemicals; Pilocarpine; Rats; Rats, Wistar; Silver Staining; Status Epilepticus; Temporal Lobe

Glutamate excitotoxicity has been involved in the pathophysiology of epilepsy. Normal functioning of glutamate transporters clears the synaptically released glutamate to prevent excitotoxic neuronal death. Using densitometric immunohistochemical analysis, we examined the temporal expression of the neuronal glutamate transporter (EAAC1) in the lithium-pilocarpine rat model of temporal lobe epilepsy. During the acute period of lithium-pilocarpine-induced status epilepticus, EAAC1 transporter expression increased in the pyramidal neurons of cornus ammonis (CA)1, CA2 and CA3 (fields of the hippocampus), in dentate gyrus (DG) granule cells and in olfactory tubercle (Tu). During the latent period, EAAC1 expression was strongly expressed in the DG granular and molecular layers, Tu, cerebral cortex and septum, and went back to control levels in CA1, CA2 and CA3 layers. The overexpression of EAAC1 occurred mainly in structures prone to develop Fluoro-Jade-B-positive degenerating neurons. It is, however, not clear to what extent the overexpression of EAAC1 contributes to epileptogenesis and in which area it may represent a preventive or compensatory or response to injury.

Topics: Animals; Brain; Brain Chemistry; Epilepsy, Temporal Lobe; Excitatory Amino Acid Transporter 3; Fluoresceins; Immunohistochemistry; Lithium Chloride; Nerve Degeneration; Organic Chemicals; Pilocarpine; Rats; Rats, Sprague-Dawley; Status Epilepticus

To study cortical excitability after status epilepticus induced in two age groups of immature rats.. Lithium-pilocarpine status epilepticus was elicited in 12- (SE12) or 25-day-old (SE25) rats. Control siblings received saline instead of pilocarpine. Interhemispheric responses were elicited by stimulation of sensorimotor region of cerebral cortex 3, 6, 9, 13, or 26 days after status. Single biphasic pulses with intensities from 0.2 to 4 mA were used for stimulation; eight responses were always averaged. Amplitude of the first positive and negative waves (i.e., monosynaptic transcallosal responses) was measured and used for construction of input-output (I/O) curves. FluoroJade B was used to visualize degenerating neurons 24 h after status in both age groups.. No significant changes were found at short intervals, but only a tendency to lower amplitudes 3 days after status in SE12 group. Marked changes appeared 26 days after status. The younger group exhibited lower amplitudes than did control rats, whereas SE25 animals generated responses with higher amplitude than did controls (i.e., the I/O curve was steeper. FluoroJade B-positive neurons were scarce in SE12 rats, whereas a substantial number of positive neurons was found in SE25 animals. The positive neurons exhibited characteristics of interneurons, and their distribution in cortical layers differed in the two groups.. Status epilepticus resulted in neuronal death in both SE12 and SE25 animals. Changes in transcallosal evoked potentials were opposite in the two age groups. Augmented amplitude of responses in SE25 rats may indicate an increased cortical excitability.

Topics: Animals; Cerebral Cortex; Corpus Callosum; Electric Stimulation; Fluoresceins; Fluorescent Dyes; Functional Laterality; Interneurons; Lithium Chloride; Male; Nerve Degeneration; Organic Chemicals; Pilocarpine; Rats; Rats, Wistar; Status Epilepticus

Glycogen synthase kinase-3beta (GSK-3beta) is a multifunctional enzyme involved in a variety of biological events including development, glucose metabolism and cell death. Its activity is inhibited by phosphorylation of the Ser9 residue and up-regulated by Tyr216 phosphorylation. Activated GSK-3beta increases phosphorylation of tau protein and induces cell death in a variety of cultured neurons, whereas phosphorylation of phosphatidylinositol-3 (PI-3) kinase-dependent protein kinase B (Akt), which inhibits GSK-3beta activity, is one of the best characterized cell survival signaling pathways. In the present study, the cholinergic immunotoxin 192 IgG-saporin was used to address the potential role of GSK-3beta in the degeneration of basal forebrain cholinergic neurons, which are preferentially vulnerable in Alzheimer's disease (AD) brain. GSK-3beta co-localized with a subset of forebrain cholinergic neurons and loss of these neurons was accompanied by a transient decrease in PI-3 kinase, phospho-Ser473Akt and phospho-Ser9GSK-3beta levels, as well as an increase in phospho-tau levels, in the basal forebrain and hippocampus. Total Akt, GSK-3beta, tau and phospho-Tyr216GSK-3beta levels were not significantly altered in these brain regions in animals treated with 192 IgG-saporin. Systemic administration of the GSK-3beta inhibitor LiCl did not significantly affect cholinergic marker or phospho-Ser9GSK-3beta levels in control rats but did preclude 192-IgG saporin-induced alterations in PI-3 kinase/phospho-Akt, phospho-Ser9GSK-3beta and phospho-tau levels, and also partly protected cholinergic neurons against the immunotoxin. These results provide the first evidence that increased GSK-3beta activity, via decreased Ser9 phosphorylation, can mediate, at least in part, 192-IgG saporin-induced in vivo degeneration of forebrain cholinergic neurons by enhancing tau phosphorylation. The partial protection of these neurons following inhibition of GSK-3beta kinase activity suggests a possible therapeutic role for GSK-3beta inhibitors in attenuating the loss of basal forebrain cholinergic neurons observed in AD.

Topics: Animals; Antibodies, Monoclonal; Cholinergic Agents; Cholinergic Fibers; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Immunotoxins; Injections, Intraventricular; Lithium Chloride; Male; N-Glycosyl Hydrolases; Nerve Degeneration; Neurons; Neuroprotective Agents; Phosphorylation; Prosencephalon; Rats; Rats, Sprague-Dawley; Ribosome Inactivating Proteins, Type 1; Saporins; tau Proteins

The causes of sporadic Parkinson's disease (PD) are poorly understood. 6-Hydroxydopamine (6-OHDA), a PD mimetic, is widely used to model this neurodegenerative disorder in vitro and in vivo; however, the underlying mechanisms remain incompletely elucidated. We demonstrate here that 6-OHDA evoked endoplasmic reticulum (ER) stress, which was characterized by an up-regulation in the expression of GRP78 and GADD153 (Chop), cleavage of procaspase-12, and phosphorylation of eukaryotic initiation factor-2 alpha in a human dopaminergic neuronal cell line (SH-SY5Y) and cultured rat cerebellar granule neurons (CGNs). Glycogen synthase kinase-3 beta (GSK3beta) responds to ER stress, and its activity is regulated by phosphorylation. 6-OHDA significantly inhibited phosphorylation of GSK3beta at Ser9, whereas it induced hyperphosphorylation of Tyr216 with little effect on GSK3beta expression in SH-SY5Y cells and PC12 cells (a rat dopamine cell line), as well as CGNs. Furthermore, 6-OHDA decreased the expression of cyclin D1, a substrate of GSK3beta, and dephosphorylated Akt, the upstream signaling component of GSK3beta. Protein phosphatase 2A (PP2A), an ER stress-responsive phosphatase, was involved in 6-OHDA-induced GSK3beta dephosphorylation (Ser9). Blocking GSK3beta activity by selective inhibitors (lithium, TDZD-8, and L803-mts) prevented 6-OHDA-induced cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP), DNA fragmentations and cell death. With a tetracycline (Tet)-controlled TrkB inducible system, we demonstrated that activation of TrkB in SH-SY5Y cells alleviated 6-OHDA-induced GSK3beta dephosphorylation (Ser9) and ameliorated 6-OHDA neurotoxicity. TrkB activation also protected CGNs against 6-OHDA-induced damage. Although antioxidants also offered neuroprotection, they had little effect on 6-OHDA-induced GSK3beta activation. These results suggest that GSK3beta is a critical intermediate in pro-apoptotic signaling cascades that are associated with neurodegenerative diseases, thus providing a potential target site amenable to pharmacological intervention.

Topics: Animals; Apoptosis; Brain-Derived Neurotrophic Factor; CCAAT-Enhancer-Binding Proteins; Cells, Cultured; Cerebellar Cortex; Cyclin D1; Endoplasmic Reticulum Chaperone BiP; Enzyme Inhibitors; Eukaryotic Initiation Factor-2; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Heat-Shock Proteins; Humans; Lithium Chloride; Molecular Chaperones; Nerve Degeneration; Nerve Tissue Proteins; Neurons; Oxidopamine; Parkinson Disease; PC12 Cells; Phosphoprotein Phosphatases; Phosphorylation; Protein Phosphatase 2; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Rats; Receptor, trkB; Signal Transduction; Thiadiazoles; Transcription Factor CHOP; Transcription Factors

Activation of the tumor suppressor gene, p53, has been strongly implicated in selective neuronal cell death. This study investigated p53 expression in the immature and adult rat brain following status epilepticus induced by the administration of lithium-pilocarpine (LPSE). Both p53 mRNA and protein were examined in relation to neuronal degeneration using in situ hybridization and immunohistochemistry, respectively. Injured cells with eosinophilic cytoplasm with increased p53 mRNA were observed in hippocampal subfields, piriform cortex, amygdala and thalamus. p53 mRNA levels reached a peak by 8 h and returned to baseline by 24 h after the onset of LPSE. The magnitude of p53 mRNA induction was greatest in 21-day-old rats. In contrast to the cellular expression pattern of p53 mRNA, immunohistochemistry demonstrated that p53 protein was increased in all of the eosinophilic cells. Further, double-labeling studies revealed that p53 protein was elevated in neurons that were degenerating. This was supported by colocalization of activated caspase 3 in some cells with damaged DNA. These results provide additional evidence for a critical role for the p53 pathway in excitotoxic neuronal cell death due to status epilepticus.

Topics: Aging; Animals; Animals, Newborn; Antimanic Agents; Brain; Caspase 3; Caspases; Cholinergic Agents; Immunohistochemistry; Lithium Chloride; Nerve Degeneration; Neurons; Pilocarpine; Rats; Rats, Wistar; RNA, Messenger; Status Epilepticus; Tumor Suppressor Protein p53

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

Multivariate analyses between conditioned taste aversion (CTA) and radial maze acquisition (RMA) scores and percentages of neuronal dropout within thalamic and telencephalic structures were completed for rats in which overt seizures had been evoked following a single systemic injection of lithium/pilocarpine. Despite multifocal damage, only the amount of damage within the hippocampus (CA1) and the basolateral amygdala was most strongly associated with attenuated CTA, whereas damage within the mediodorsal thalamus was primarily associated with RMA. There was no significant correlation between CTA or RMA. Multiple regression analyses for specific Paxinos and Watson structures and their traditional aggregates supported more precise delineation of neuronal substrates of learning/memory and a multimodal (parallel) model for these processes.

Topics: Animals; Avoidance Learning; Brain Damage, Chronic; Brain Mapping; Conditioning, Classical; Dose-Response Relationship, Drug; Evoked Potentials; Lithium Chloride; Male; Maze Learning; Mental Recall; Nerve Degeneration; Nerve Net; Pilocarpine; Rats; Rats, Wistar; Seizures; Synaptic Transmission; Taste; Telencephalon; Thalamic Nuclei

Female rats, with and without maternal experience, received limbic seizure-inducing (SC) injections of lithium and pilocarpine. Following the subsequent parturitions, these rats displayed a complete absence of maternal behavior. Rats that did not display seizures after receiving the lithium/pilocarpine injections displayed behaviors that were comparable to normal controls. Although the multifocal limbic, thalamic, and cingulate damage abolished maternal care, there was no evidence of aberrant effects upon fecundity, litter size, or mammary function; infanticide was negligible. The pattern of brain damage involves the evolutionarily more recent thalamocingulate system of mammals and supports MacLean's theory that these pathways are required for normal mother-offspring interaction.

Topics: Animals; Brain; Brain Mapping; Cerebral Cortex; Chlorides; Electroencephalography; Evoked Potentials; Female; Hypothalamus; Kindling, Neurologic; Limbic System; Lithium; Lithium Chloride; Maternal Behavior; Nerve Degeneration; Pilocarpine; Rats; Rats, Wistar

The functional relation between restricted damage to ventral primary somatosensory neocortex and the ability of rats to acquire conditioned taste aversion (CTA( was examined by a combination of behavioral and neurohistological techniques. Lesions confined exclusively to the established gustatory neocortex (GN) did not disrupt CTA acquisition, nor did lesions confined to suprarhinal cortical areas ventral to the GN. Lesions that encroached on dorsal prepiriform and insular cortices produced CTA acquisition deficits and damaged a large proportion of efferent projections to the prefrontal and precentral neocortex. In a second experiment, lesions of dorsal prepiriform and insular cortices did not modify taste preference-aversion threshold to any of the four taste modalities. It is concluded tha ventral somatosensory neocortical fields, including the established GN, do not mediate CTA acquisition and that rhinal cortices ventral and posterior to the GN are preferentially involved in associative learning for tastes and illness.

Topics: Animals; Avoidance Learning; Axons; Brain Mapping; Chlorides; Conditioning, Classical; Lithium; Lithium Chloride; Male; Muridae; Nerve Degeneration; Nerve Fibers; Neural Pathways; Somatosensory Cortex; Taste