The nature and timing of excitotoxic neuronal necrosis in the cerebral cortex, hippocampus and thalamus due to flurothyl-induced status epilepticus.

Flurothyl-induced status epilepticus was studied by light and electron microscopy (LM, EM) to determine the time course and structural features of neuronal necrosis in the vulnerable brain regions in epilepsy. The cerebral cortex, hippocampus and thalamus were examined after closely spaced recovery periods of up to 1 week. The results showed that acidophilic neurons appeared simultaneously in neurons of the neocortex, hippocampus and thalamus, and that this occurred within 1 h following the end of the epilepsy.

Metabolic alterations underlying the development of hypermetabolic necrosis in the substantia nigra in status epilepticus.

The substantia nigra pars reticulata (SNPR) has previously been shown to undergo tissue necrosis following status epilepticus induced by flurothyl in the rat. Even if the rat is ventilated, the SNPR develops necrosis if the epileptic period lasts more than 30 min. Rat brains were frozen in situ after 20 and 60 min of seizure activity and after 60 min of seizure activity followed by 60 min recovery.

Sustained seizures cause circumscribed cerebral changes in glial fibrillary acidic protein, neurofilament and laminin immunofluorescence.

Sustained experimental seizures in rats have previously been shown to cause an extensive necrosis in pars reticulata of substantia nigra (SNPR) and globus pallidus (GP). In the present paper we have studied the effects of hexafluorodiethyl ether-induced seizures on the immunoreactivity seen with antibodies directed against glial fibrillary acidic protein, GFA, used to visualize astrocytes, antibodies to the glycoprotein laminin as a marker for blood vessel walls and neurofilament (NF) antibodies to monitor neuronal disturbances. Already 12 h after a 20-min seizure period a reduction in GFA immunofluorescence intensity was observed in SNPR.

Regional differences in brain glucose content in graded hypoglycemia.

Graded hypoglycemia was induced with insulin in anesthetized and artificially ventilated rats. The brains were frozen in situ, and the regional glucose concentration was determined in different areas of the brain with the bioluminescent technique. In all nine brain structures analyzed, brain tissue glucose content assessed with the bioluminescent technique correlated closely with the plasma glucose levels; the tissue/plasma glucose concentration ratios approximating 0.

Carbon dioxide narcosis: influence of short-term high concentration carbon dioxide inhalation on EEG and cortical evoked responses in the rat.

The effects of 1 min exposure to 80% CO2 inhalation was studied in rats under light general anaesthesia with N2O. It was found that 80% CO2 gave a rapid slowing of the EEG as well as a rapid decrease of the amplitude of cortical somatosensory evoked potentials. Only minor influences upon the blood pressure and heart rate were seen.

Hypotension as a complication of hypoglycemia leads to enhanced energy failure but no increase in neuronal necrosis.

The hypothesis that arterial hypotension aggravates hypoglycemic brain damage was tested. Thirty minutes of insulin induced hypoglycemia with a flat EEG ("isoelectricity") was compared in seven series of rats. In three series of animals, the energy state of the cerebral cortex was determined at blood pressures of 140, 100 and 80 mm Hg respectively.

Early axonal lesion and preserved microvasculature in epilepsy-induced hypermetabolic necrosis of the substantia nigra.

The time course of structural change in epilepsy-induced necrosis of the substantia nigra was studied by light and electron microscopy, and was correlated with previous metabolic studies. By light microscopy, tinctorial pallor appeared early, followed by pan-necrosis and macrophage infiltration. Mild lesions showed neuropil vacuolation but sparing of neurons, rather than a selective neuronal vulnerability.

Short term status epilepticus in rats causes specific behavioral impairments related to substantia nigra necrosis.

Status epilepticus (SE) was induced for 40 min by flurothyl in well oxygenated rats. This insult resulted in selective destruction of up to 65% of the substantia nigra pars reticulata. We investigated the short and long term behavioral effects of this damage.

Mechanisms of epileptic brain damage: evidence for a protective role of the noradrenergic locus coeruleus system in the rat.

This study explores the possibility that the noradrenergic locus coeruleus system influences epileptic brain damage. Bilateral 6-hydroxydopamine lesions of the locus coeruleus projection to the forebrain were found to aggravate neuronal necrosis in the neocortex following 60 min of flurothyl-induced status epilepticus. We propose that the activation of the inhibitory locus coeruleus system during status epilepticus counteracts a deleterious neuronal hyperexcitation, probably induced by excessive release of excitatory amino acids, thereby limiting neuronal necrosis.

Cerebral blood flow and metabolic rate during seizures. Relationship to epileptic brain damage.

Unlabelled: After long periods of status epilepticus, selective neuronal necrosis is incurred in the neocortex (layer III-IV), in the hippocampus (CA1 and CA4), and in the thalamus (VPL-VPM). In these areas the cerebral metabolic rate for glucose is increased to between 200-300% of control, indicating a correlation between neuronal damage and enhanced neuronal activity. Measurements of local cerebral blood flow indicate that the damage is not due to insufficient supply of oxygen.

Convulsive and non-convulsive ethanol withdrawal behaviour in rats with lesions of the noradrenergic locus coeruleus system.

The ascending noradrenergic pathways from the locus coeruleus were lesioned bilaterally in 10 rats by intracerebral 6-hydroxydopamine injections. Ten rats were sham-operated. All animals were subjected to a 4-day ethanol intoxication period using intragastric intubation.

Status epilepticus in well-oxygenated rats causes neuronal necrosis.

Neuronal necrosis in the brain resulting from status epilepticus of 15 to 120 minutes duration in ventilated and well-oxygenated rats was assessed. Seizures were induced by inhalation of the convulsant gas flurothyl, and terminated by withdrawal of flurothyl and a single injection of thiopental. The animals were allowed to recover for one week, and neuronal damage was assessed by cell counts following subserial sectioning of the brain and microscopical examination of the sections.

11C-labeled 4-isopropylantipyrine: preparation and biological evaluation as a blood flow tracer in positron emission tomography (PET).

Radiolabeled 4-isopropylantipyrine (1) has been synthesized and evaluated as a tracer for the measurement of cerebral blood flow (CBF). Methylation of 4-isopropyl-3-methyl-1-phenylpyrazol-5-one (2) with [14C]methyl iodide in acetonitrile gave [14C]-1 in radiochemical yields of 10-20%. Its blood-brain partition coefficient in rats was determined to be 0.

Cerebral metabolic changes during and following fluorothyl-induced seizures in ventilated rats.

The objective of the present study was to assess metabolic changes in the neocortex and hippocampus of well-oxygenated or moderately hypoxic rats in which fluorothyl-induced seizures were sustained for 5 or 20 min, or which were allowed recovery periods of 5, 15, or 45 min following cessation of 20-min seizure activity by withdrawal of the convulsant gas. Sustained fluorothyl-induced seizures were found to cause metabolic alterations qualitatively and quantitatively similar to those previously observed with other commonly used convulsants. Thus, although the phosphorylation state of the adenine nucleotide pool remained only moderately perturbed, if at all, there were decreases in tissue concentrations of phosphocreatine and glycogen, and increases in those of cyclic AMP, lactate, and pyruvate, with a calculated fall in intracellular pH of about 0.

Effects of ageing on local rates of cerebral protein synthesis in Sprague-Dawley rats.

The effects of ageing on local rates of protein synthesis in 39 brain structures in resting conscious rats have been examined. Young adult rats (aged 6 months) have been compared with a group of middle-aged/aged rats (aged 15-23 months). The results show that ageing is associated with significant decreases in rates of protein synthesis in the brain as a whole as well as in several specific brain regions.

Extra- and intracellular pH in the brain during seizures and in the recovery period following the arrest of seizure activity.

The objective of the study was to estimate changes in extracellular pH (pHe) and intracellular pH (pHi) during seizures and in the recovery period following the arrest of seizure activity. Seizures of 5- and 20-min duration were induced in rats by fluorothyl added to the insufflated gas mixture, and recovery for 5, 15, and 45 min was instituted by withdrawal of the fluorothyl supply following 20 min of continuous seizures. Changes in pHe were measured by double-barreled, liquid ion-exchange pH microelectrodes, and in pHi by the CO2 method, following estimation of tissue PCO2 and extracellular fluid (ECF) volume.

Functional reactivation of the deafferented hippocampus by embryonic septal grafts as assessed by measurements of local glucose utilization.

Transection of the septo-hippocampal connections through fimbria-fornix damage in the rat results in profound hippocampal cholinergic deafferentation, and, when applied bilaterally, leads to severe and long-lasting impairments in learning and memory. Previous studies have shown that intrahippocampal septal grafts can reestablish a new cholinergic in the initially denervated hippocampal formation and at least partly compensate for the lesion-induced learning impairments in fimbria-fornix lesioned rats. The purpose of the present study was to determine the magnitude of lesion-induced alterations in cerebral function as reflected in local glucose use measured by (14C)-2-deoxyglucose (2-DG) autoradiography, and the degree to which this index of functional activity could be normalized following reinnervation from transplants of fetal cerebral tissue from the primordial septal region.

Models for studying long-term recovery following forebrain ischemia in the rat. 1. Circulatory and functional effects of 4-vessel occlusion.

The article describes findings obtained by the application of the Pulsinelli-Brierley 4-vessel occlusion ischemic model in 2 rat strains. In one, a high incidence of respiratory arrest was observed after carotid occlusion. In the other, no such problems were encountered but a large fraction of the animals failed to lose consciousness upon arterial occlusion.

Metabolic, circulatory, and structural alterations in the rat brain induced by sustained pentylenetetrazole seizures.

Previous studies have demonstrated that bicuculline-induced seizures of 1-2 h in duration lead to structural, metabolic, and circulatory alterations in the rat brain. Such alterations were observed even though cerebral oxygenation seemed adequate. In the present study, we explored whether pentylenetetrazole, a convulsant which interferes with gamma-aminobutyric acid inhibition by mechanisms other than that of bicuculline, leads to similar structural alterations and to similar cerebral metabolic and circulatory changes.

Regional cerebral blood flow in conscious stroke-prone spontaneously hypertensive rats.

Regional cerebral blood flow (rCBF) was measured autoradiographically with [14C]iodoantipyrine as a diffusible tracer in two strains of conscious normotensive rats (Wistar Kyoto and local Wistar) and in two groups of spontaneously hypertensive stroke-prone rats (SHRSP) with a mean arterial pressure (MAP) below or above 200 mm Hg. In spite of the large differences in arterial pressure, rCBF did not differ significantly between the hypertensive and the normotensive groups in any of the 14 specified brain structures measured. However, rCBF increased asymmetrically within part of the caudate-putamen in two of nine SHRSP with a MAP above 200 mm Hg, indicating a regional drop in the elevated cerebrovascular resistance.

Cerebral metabolic and circulatory effects of 1,1,1-trichloroethane, a neurotoxic industrial solvent. 1. Effects on local cerebral glucose consumption and blood flow during acute exposure.

The effects of inhaled 1,1,1-trichloroethane (3500, 6000, and 7800 ppm) on behavior, local cerebral blood flow, and local cerebral glucose consumption were studied in awake rats. The effect of the solvent inhalation on the EEG pattern and local cerebral blood flow was also studied in paralyzed animals under N2O analgesia. Exposure of awake animals to 6000 ppm 1,1,1-trichloroethane induced a decrease in motility and exploratory behavior.

Regional differences in vascular autoregulation in the rat brain in severe insulin-induced hypoglycemia.

The present experiments were undertaken to determine if loss of vascular autoregulation during severe hypoglycemia shows regional differences that could help to explain the localization of hypoglycemic cell damage. Artificially ventilated rats (70% N2O) were subjected to a 30-min insulin-induced hypoglycemic coma (with cessation of EEG activity), with mean arterial blood pressure being maintained at 140, 120, 100, and 80 mm Hg. After 30 min of hypoglycemia, local cerebral blood flow (CBF) in 25 brain structures was measured autoradiographically with a [14C]iodoantipyrine technique.