Synergistic induction of severe hypothermia (poikilothermia) by limbic seizures, acepromazine and physical restraint: role of noradrenergic alpha-1 receptors.

The maintained production of extreme reductions in core temperature (20-22 degrees C) or poikilothermia can be reliably produced by the synergistic interaction of limbic seizures (induced by lithium and pilocarpine), postseizure administration of a single injection of acepromazine, and physical restraint. Administration of the specific and nonspecific dopamine antagonists haloperidol, chlorpromazine, SCH23390, or clozapine did not simulate the effect at clinically effective dosages. Single injections of phentolamine and prazosin but not of propranolol instead of acepromazine following the seizures produced the poikilothermia. This effect was also reproduced by reducing the amount of the rats' adipose weight before the induction of the seizures and physical restraint. Rats that had been restrained or not restrained and displayed either euthermia or hypothermia exhibited significantly different patterns in brain damage within limbic and thalamic structures.

Temporal changes in neuronal dropout following inductions of lithium/pilocarpine seizures in the rat.

Estimates of neuronal dropout for approximately 100 structures as defined by Paxinos-Watson were completed for brains of male Wistar albino rats between 1 and 50 days after status epilepticus was evoked by a single systemic injection of lithium and pilocarpine. Sample estimates of neuronal loss were strongly correlated with direct measures of cell density. The most extensive immediate damage occurred within the substantia nigra reticulata, CA1 field of the hippocampus, the piriform cortex and the reuniens and paratenial nuclei of the thalamus. Neuronal dropout continued in many other structures over a 50-day period. Structures that showed the greatest 2-deoxyglucose (2-DG) uptake during discrete seizures and waxing and waning seizures within the early stages of status epilepticus but the least 2-DG uptake at the time of late continuous spiking and fast spiking with pauses [Neuroscience 64 (1995) 1057, 1075] exhibited the most neuronal dropout. Relationships between the delay of injection of acepromazine (which facilitated survival) and the amount of damage suggested that the source of the process that results in permanent brain damage may originate within the region of the piriform cortices and its subcortices.

Ventricular dilation over several weeks following induction of excitotoxic (systemic lithium/pilocarpine) lesions: potential role of damage to the substantia nigra reticulata.

Time-dependent atrophy of cerebral space and enlargement of the lateral ventricles were noted in healthy rats 1 to 100 days after the induction of seizures by a single systemic injection of lithium and pilocarpine. The rate of atrophy was most strongly correlated (0.90) with the log (base 10) of the time in days. Most of the degeneration had occurred within about 20 to 30 days after the seizure-induced brain trauma. Concomitant reduction in the area of the substantia nigra reticulata was the most powerful predictor of ventricular enlargement at the level of the caudate-putamen.

Emergent properties following brain injury: the claustrum as a major component of a pathway that influences nociceptive thresholds to foot shock in rats.

Flinch (pain) thresholds for electric current delivered to the feet were correlated with the amount of necrosis within the diencephalon and telencephalon for rats in which seizures had been induced by lithium and pilocarpine about two months before the testing. The shared variance of the quantitative damage within the claustrum, the anterior part of the paraventricular nucleus of thalamus, (central) mediodorsal thalamus, and lateral amygdala (ventromedial part) explained 81% of the variance in the nociceptive (flinch) thresholds. A primary role of the claustrum within the neuropathways that mediate the response to the interoceptive and "painful" characteristics of stimuli is indicated. The concept of primary pathways versus "emergent" pathways subsequent to excitotoxic damage within the neuromatrix is discussed.

Dissociation between conditioned taste aversion and radial maze learning following seizure-induced multifocal brain damage: quantitative tests of serial vs. parallel circuit models of memory.

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.

The sensed presence as right hemispheric intrusions into the left hemispheric awareness of self: an illustrative case study.

The hypothesis of vectorial hemisphericity predicts that left hemispheric intrusions of the right hemispheric equivalent of the sense of self should be associated with the experience of a "presence" of someone else. The neurophenomenological profile of a woman whose medical history satisfied these theoretical criteria (verified electrical anomalies that could encourage phasic discharges within the right temporal lobe and atrophy within the left temporoparietal region) is presented. In addition to interactions between electrical seizures and thinking, she reported a long history of sensed presences, ego-alien intrusions, and "sudden knowing of the subsequent sequences of seizures" before they occurred clinically. The existence of these neurocognitive processes demands a reevaluation of the psychiatric default explanations of "hysteria" and questions the belief that "awareness during seizures" or "premonition of subsequent somatosensory experience" contraindicates an epileptic process.

Concordance of quantitative damage within the diencephalon and telencephalon following systemic pilocarpine (380 mg/kg) or lithium (3 mEq/kg)/pilocarpine (30 mg/kg) induced seizures.

We tested the hypothesis that a single systemic injection of 380 mg/kg of the muscarinic agonist pilocarpine would produce more diffuse and severe seizure-induced brain damage than a single injection of lithium (3 mEq/kg) followed 4 h later by < 1/10 the dosage of pilocarpine. The hypothesis was not supported; the pattern of quantitative brain damage 50-60 days after the seizures were elicited by either treatment was comparable within the limits of measurement error. Within the diencephalon and subcortical telencephalon the same structures were either damaged in a similar quantitative manner or were spared. Only five of the 119 damaged structures exhibited statistically significant treatment differences at P < 0.01. The results are compatible with the explanation that lithium may enhance the excitotoxic effects of subsequent muscarinic stimulation.

Deficits in working but not reference memory in adult rats in which limbic seizures had been induced before weaning: implications for early brain injuries.

Male adult rats that displayed limbic seizures between postnatal days 18 and 21 after a single s.c. injection of Li followed 4 h later by a muscarinic agent were trained in a radial arm maze; they were compared with rats that had received the Li-pilocarpine (but had not displayed overt seizures) and to nonhandled controls. Only the rats that had displayed the (preweaned) seizures displayed significant impairment for working memory but not for reference memory. Light microscopy demonstrated histological evidence of earlier damage only within select thalamic structures that are directly associated with the amygdaloid-hippocampal complex. The results are compatible with the hypothesis that early seizures during the time of CA1 hippocampal maturation can produce long-term changes in the efficacy of short-term memory.

Behaviors of rats with insidious, multifocal brain damage induced by seizures following single peripheral injections of lithium and pilocarpine.

Several domains of behavior were measured in rats (n = 465) 10 days to 100 days after induction of limbic seizures by a single subcutaneous injection of lithium and pilocarpine. These rats displayed enhanced intragroup aggression but normal muricide; gustatory neophobia and conditioned taste aversion were virtually eliminated. Severe working and reference memory deficits were evident within the radial arm maze. Both state-dependent memory and possible situation-dependent precipitation of spontaneous seizures were suggested. The behavioral changes were considered commensurate with the multifocal pattern of thalamic, hippocampal/amygdaloid, and limbic cortical damage.

Absence of maternal behavior in rats with lithium/pilocarpine seizure-induced brain damage: support of MacLean's triune brain theory.

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.

Progressive accumulation of large aggregates of calcium-containing polysaccharides and basophilic debris within specific thalamic nuclei after lithium/pilocarpine-induced seizures.

Between 30 and 50 days after the induction of seizures by a single injection of lithium and pilocarpine, large aggregates of Nissl-staining material appeared; they occupied up to 35% of the thalamic volume. Both histochemical and atomic absorption analyses indicated elevated concentrations of Ca++ (and possibly Mg++) within this substance that was also composed of polysaccharides and nucleic acids. Significant interactions between time since seizure induction and form of the material indicated a progressive accretion of this material from diffusely scattered micrometer granules to large crystalline forms. We suggest this material is composed of endoplasmic reticular debris that is bound by bivalent cations; because the severity of damage exceeds local phagocytic capacity, the material aggregates and then crystallizes. Possible relation to thalamic calcification in neonatal ischemic brains is considered.

Radial maze learning deficits and mediodorsal thalamic damage in context of multifocal seizure-induced brain lesions.

Rats were either trained 21 days after seizure induction or trained before seizure induction and tested 21 days later. The seizures, which induce insidious brain damage within a multitude of diencephalic and subcortical telencephalic structures, were induced by a single injection of lithium (3 mEq/kg sc) followed 24 hr later by pilocarpine (30 mg/kg sc). Compared with controls, the treated rats displayed significant deficits in the acquisition and recall of a radial maze task. Although there was multifocal brain damage, only the amount of damage within the mediodorsal thalamic group was significantly and strongly correlated (rho = .79) with numbers of errors.

Failure to acquire an inhibitory task following seizure-induced brain damage.

Male rats that had displayed limbic seizures following a single pair of systemic injections of lithium and pilocarpine were trained 2 months later on an operant schedule that required differential low rates of responding (DRL). The seizured rats never acquired schedules that required either 6-sec. or 12-sec. inhibition of responses following a reward; these rats displayed more perseverative responding and shorter interresponse times than controls. Histomorphology indicated severe brain damage primarily within the entorhinal cortices (and adjacent amygdala) and dorsal thalamus.