lithium-chloride and Brain-Damage--Chronic

The aims of the present study were to ascertain whether nonconvulsive status epilepticus (NCSE) could give rise to long-term behavioral deficits and permanent brain damage. Two months after NCSE was elicited with pilocarpine (15 mg/kg i.p.) in LiCl-pretreated adult male rats, animals were assigned to either behavioral (spontaneous behavior, social interaction, elevated plus-maze, rotorod, and bar-holding tests) or EEG studies. Another group of animals was sacrificed and their brains were processed for Nissl and Timm staining as well as for parvalbumin and calbindin immunohistochemistry. Behavioral analysis revealed motor deficits (shorter latencies to fall from rotorod as well as from bar) and disturbances in the social behavior of experimental animals (decreased interest in juvenile conspecific). EEGs showed no apparent abnormalities. Quantification of immunohistochemically stained sections revealed decreased amounts of parvalbumin- and calbindin-immunoreactive neurons in the motor cortex and of parvalbumin-positive neurons in the dentate gyrus. Despite relatively inconspicuous manifestations, NCSE may represent a risk for long-term deficits.

Topics: Animals; Arousal; Behavior, Animal; Brain; Brain Damage, Chronic; Brain Mapping; Calbindins; Convulsants; Electroencephalography; Limbic System; Lithium Chloride; Male; Maze Learning; Motor Activity; Motor Skills; Neocortex; Parvalbumins; Pilocarpine; Postural Balance; Rats; Rats, Wistar; Reaction Time; S100 Calcium Binding Protein G; Social Behavior; Status Epilepticus; Video Recording

The gross behavioural, electrocortical and neuropathological effects of kainate (10 mg/kg i.p,) and ouabain (1 micrograms, given into one dorsal hippocampus) were studied in rats. The effects of these treatments on nitric oxide synthase (NOS) activity in homogenates of hippocampus and cortex were also studied. Administration of kainate or ouabain produced motor and electrocortical seizures similar for latency to onset (approximately 15 min) and intensity (in all instances 80-100% of the treated rats showed behavioural and electrographic seizures). These effects were accompanied at 24 h by severe damage to all subsectors of the hippocampal formation and this concerned a similar proportion of the treated rats (n = 4-8 per treatment). No significant changes in nitric oxide synthase (NOS) activity were noted in the cerebral cortex and hippocampus of rats receiving injections of kainate and ouabain. In addition, pretreatment with N omega-Nitro-L-arginine methyl ester (300 micrograms, given into one lateral cerebral ventricle 15 min previously) was ineffective in preventing the effects of kainate and ouabain. In conclusion, present data suggest that excessive production of NO is not involved in the mechanisms triggering seizures and neurodegeneration produced by kainate or ouabain.

Topics: Amino Acid Oxidoreductases; Animals; Arginine; Brain Damage, Chronic; Hippocampus; Kainic Acid; Lithium Chloride; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Ouabain; Rats; Rats, Wistar; Seizures; Tacrine

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