The role of the temporal neocortex in the origin of convulsive activity]

Experiments on cats with cooling capsules implanted over different areas of the neocortex have shown that cooling of different intensity applied to the temporal neocortex may result in both stimulation and switching off effects. Cold stimulation (temperature dropping to 27-33 degrees C) manifested in generalized epileptiform brain electrical activity and paroxysmal states. The functional switching off the temporal area observed during its deeper cooling (20-21 degrees C) discontinues the paroxysmal state already developed and prevents the appearance of seizures, regrardless of the localization of the epileptogenic focus. The paroxysmal state weakens and ceases after repeated cooling of the temporal neocortex. The temporal neocortex, involved in the integrated activating brain system, plays a decisive role in the emergence of paroxysmal states.     

Changes in seizure activity thresholds of the cat brain in various stages of sleep and wakefulness

Changes in seizure activity of the brain evoked by electrical stimulation of the dorsal hippocampus in various stages of sleep and wakefulness were studied in adult cats. During slow sleep, when the EEG is dominated by high-voltage slow waves, near-threshold epileptogenic hippocampal stimulation evokes well-marked paroxysmal discharges. During wakefulness or the paradoxical phase of sleep, when the EEG is desynchronized, this hippocampal stimulation is less effective: either no seizure discharges are produced or they are weak. Activation of the mesencephalic reticular formation before epileptogenic hippocampal stimulation hinders the appearance of seizure activity whereas activation after hippocampal stimulation does not inhibit paroxysmal discharges already in progress; on the contrary, in some cases they are actually strengthened a little. One of the main factors limiting the appearance and spread of seizure activity is considered to be the tonic inhibitory influence of the neocortex on other parts of the brain.     

EEG evaluation of reflex testing as assessment of depth of pentobarbital anaesthesia in the rat

Electroencephalography (EEG) was applied to evaluate the validity of the paw pinch reflex as an indicator of anaesthetic depth in rats which are anaesthetized with a single intraperitoneal dose of pentobarbital. After induction of the anaesthesia, characterized by the rapid loss of the animals' ability to maintain upright posture, the EEG of 10 out of 11 rats was dominated by paroxysmal (burst suppression) activity, associated with unconsciousness. In seven out of 11 rats, the paw pinch reflex was lost after onset of paroxysmal electroencephalographic activity. However, the paw pinch reflex remained present in four out of 11 animals, demonstrating that the response is independent of cortical activity. In five out of seven rats, the EEG still showed paroxysmal activity when the paw pinch reflex was regained. However, in two other rats the EEG returned to a pattern similar to that shown by awake animals, 4 and 21 min respectively, before the reflex was regained. These data indicate that in the pentobarbital-anaesthetized rat, presence of the paw pinch reflex is not related to the level of depression of electrical activity in the cerebral cortex, and consequently is probably not related to the level of consciousness. Based upon these findings it is concluded that the paw pinch reflex is unreliable as a sole indicator of anaesthetic depth.     

Effects of EEG of the osmotic opening of the blood-brain barrier in rats

EEG activity was recorded in rats submitted to osmotic opening of the BBB by intracarotid mannitol infusion.This procedure produced an immediate short-lasting depression of the EEG and a tardive paroxysmal EEG activity. Both these phenomena were more relevant on the ipsilateral hemisphere. In some instances a tonico-clonic seizure was recorded.Pre-treatment with diazepam abolished the occurrence of the tardive EEG and behavioral modifications.In accord with previous findings, focal seizure activity is likely to be responsible for the metabolic abnormalities associated with osmotic opening of the BBB. This preparation therefore produces in the brain unphysiological states in respect to local metabolism and electrical function.     

U-54494A reduces 4-AP-induced afterdischarges of CA1 pyramidal cells in the hippocampal slice of the rat.

The anticonvulsant activity of U-54494A was studied in a 4-aminopyridine (4-AP) epilepsy model using extracellular recordings in in vitro hippocampal slices. Field potentials were evoked by stimulation of Schaffer collaterals, and recorded from the CA1 region of the hippocampus after infusion of 4-AP in the absence and presence of U-54494A. The number and the total area of after discharges (AD) in the presence of 4-AP were significantly decreased by increasing concentrations of U-54494A. In contrast, U-54494A did not significantly change the latency, duration, or area of the evoked PS in this paradigm. Phenytoin, a standard anticonvulsant, decreased the PS area without affecting either the PS latency or duration, or the AD number or area in the same paradigm. These present results provide more evidence that U-54494A is a novel and effective anticonvulsant that may be useful in the treatment of paroxysmal activity, without having generalized depressive effects.     

Electroencephalographic analysis of manifestations of latent forms of paroxysmal syndrome in the wakefulness-sleep cycle in rats

An electroencephalographic study of the brain activity in the wakefulness-sleep cycle was carried out on rats of Krushinskii-Molodkina line (KM) with hereditary predisposition to audiogenic convulsions and on Wistar rats that were insensitive to the convulsiogenic sound effect, but with epileptiform manifestations appearing on the background of cadmium intoxication and administration of kainic acid into the caudate nucleus head. There were revealed several EEG patterns whose presence was an indicator of formation of disorders of the CNS activity of the paroxysmal character in the animals. It has been established that in the phase of the rat rapid-wave sleep, a high representation of episodes with predominance of a-diapason EEG oscillations can be considered a specific non-paroxysmal abnormality due to the presence of convulsive syndrome in these animals. It was shown the long steady decrease of sensitivity of KM rats to the convulsiogenic sound effect, which appeared after multiple audiogenic generalized tonicoclonic convulsive attacks, correlated with a decrease of the degree of theta-diapason oscillations and with an increase of representation of alpha-diapason waves on EEG in the state of the animal quiet consciousness. A role of disintegration in activity of the ascending activating brain systems in the animal and human paroxysmal syndromes is discussed.     

Electroencephalographic analysis of manifestations of hidden forms of paroxysmal syndrome in the wakefulness-sleep cycle in rats

An electroencephalographic study of the brain activity in the wakefulness-sleep cycle was carried out on rats of Krushinskii-Molodkina line (KM) with hereditary predisposition to audiogenic convulsions and on Wistar rats that were insensitive to the convulsiogenic sound effect, but with epileptiform manifestations appearing on the background of cadmium intoxication and administration of kainic acid into the caudate nucleus head. There were revealed several EEG patterns whose presence was an indicator of formation of disorders of the CNS activity of the paroxysmal character in the animals. It has been established that in the phase of the rat rapid-wave sleep, a high representation of episodes with predominance of α-diapason EEG oscillations can be considered a specific non-paroxysmal abnormality due to the presence of convulsive syndrome in these animals. There was shown a long steady decrease of sensitivity of KM rats to the convulsiogenic sound effect, which appeared after multiple audiogenic generalized tonicoclonic convulsive attacks, correlated with a decrease of the degree of ?-diapason oscillations and with an increase of representation of α-diapason waves on EEG in the state of the animal quiet wakefulness. The role of disintegration in activity of the ascending activating brain systems in the animal and human paroxysmal syndromes is discussed.     

Time-dependent changes in the serum levels of prolactin, nesfatin-1 and ghrelin as a marker of epileptic attacks young male patients

A relationship between hormones and seizures has been reported in animals and humans. Therefore, the purpose of this study was to investigate the association between serum levels of prolactin, nesfatin-1 and ghrelin measured different times after a seizure or non-epileptic event and compared with controls. The study included a total of 70 subjects, and of whom 18 patients had secondary generalized epilepsy (SGE), 16 patients had primary generalized epilepsy (PGE), 16 patients exhibited paroxysmal event (psychogenic) and 20 healthy males were control subjects. The first sample was taken within 5 min of a seizure, with further samples taken after 1, 24, and 48 h so long as the patient did not exhibit further clinically observable seizures; blood samples were taken once from control subjects. Prolactin was measured immediately using TOSOH Bioscience hormone assays. Nesfatin-1 and ghrelin peptides were measured using a commercial immunoassay kit. Patients suffering from focal epilepsy with secondary generalization and primary generalized epilepsy presented with significantly higher levels of serum prolactin and nesfatin-1 and lower ghrelin levels 5 min, 1 and 24 h after a seizure than patients presenting with paroxysmal events (psychogenic) and control subjects; the data were similar but not statistically significant after 48 h. The present study suggests that increased serum prolactin and nesfatin-1 concentrations, decreased ghrelin concentrations could be used as markers to identify patients that have suffered a recent epileptic seizure or other paroxysmal event (psychogenic).     

Nitroprusside modulates pulmonary vein arrhythmogenic activity

Background  

Pulmonary veins (PVs) are the most important sources of ectopic beats with the initiation of paroxysmal atrial fibrillation, or the foci of ectopic atrial tachycardia and focal atrial fibrillation. Elimination of nitric oxide (NO) enhances cardiac triggered activity, and NO can decrease PV arrhythmogensis through mechano-electrical feedback. However, it is not clear whether NO may have direct electrophysiological effects on PV cardiomyocytes. This study is aimed to study the effects of nitroprusside (NO donor), on the ionic currents and arrhythmogenic activity of single cardiomyocytes from the PVs.     

Both social and ecological factors predict ungulate brain size

Among mammals, the members of some Orders have relatively large brains. Alternative explanations for this have emphasized either social or ecological selection pressures favouring greater information-processing capacities, including large group size, greater foraging efficiency, higher innovation rates, better invasion success and complex problem solving. However, the focal taxa for these analyses (primates, carnivores and birds) often show both varied ecological competence and social complexity. Here, we focus on the specific relationship between social complexity and brain size in ungulates, a group with relatively simple patterns of resource use, but extremely varied social behaviours. The statistical approach we used, phylogenetic generalized least squares, showed that relative brain size was independently associated with sociality and social complexity as well as with habitat use, while relative neocortex size is associated with social but not ecological factors. A simple index of sociality was a better predictor of both total brain and neocortex size than group size, which may indicate that the cognitive demands of sociality depend on the nature of social relationships as well as the total number of individuals in a group.     

Characteristics of cerebral electrical activity in rabbits with experimental herpetic encephalitis]

Examinations carried out on 33 rabbits with an experimental herpetic encpehalitis showed changes in the electrical activity of the brain correlating with the clinical picture of the disease. A diffus slowing down of the biopotentials and paroxysmal activity of two types--the paroxysmal periodic complexes and the complexes 'spike +the paroxysmal 3/sec' was revealed during the acute period of encephalitis.     

Motor Enrichment and the Induction of Plasticity Before or After Brain Injury

Voluntary exercise, treadmill activity, skills training, and forced limb use have been utilized in animal studies to promote brain plasticity and functional change. Motor enrichment may prime the brain to respond more adaptively to injury, in part by upregulating trophic factors such as GDNF, FGF-2, or BDNF. Discontinuation of exercise in advance of brain injury may cause levels of trophic factor expression to plummet below baseline, which may leave the brain more vulnerable to degeneration. Underfeeding and motor enrichment induce remarkably similar molecular and cellular changes that could underlie their beneficial effects in the aged or injured brain. Exercise begun before focal ischemic injury increases BDNF and other defenses against cell death and can maintain or expand motor representations defined by cortical microstimulation. Interfering with BDNF synthesis causes the motor representations to recede or disappear. Injury to the brain, even in sedentary rats, causes a small, gradual increase in astrocytic expression of neurotrophic factors in both local and remote brain regions. The neurotrophic factors may inoculate those areas against further damage and enable brain repair and use-dependent synaptogenesis associated with recovery of function or compensatory motor learning. Plasticity mechanisms are particularly active during time-windows early after focal cortical damage or exposure to dopamine neurotoxins. Motor and cognitive impairments may contribute to self-imposed behavioral impoverishment, leading to a reduced plasticity. For slow degenerative models, early forced forelimb use or exercise has been shown to halt cell loss, whereas delayed rehabilitation training is ineffective and disuse is prodegenerative. However, it is possible that, in the chronic stages after brain injury, a regimen of exercise would reactivate mechanisms of plasticity and thus enhance rehabilitation targeting residual functional deficits.     

Distinguishing soft-tissue hemangiomas from vascular malformations using technetium-labeled red blood cell scintigraphy.

Soft-tissue vascular lesions in children can be classified as either hemangiomas or vascular malformations. The distinction between the two has important prognostic and therapeutic implications. Over the past 8 years, we have evaluated 64 vascular lesions with the technetium-labeled red blood cell (Tc-RBC) scan. Twenty-eight lesions imaged as hemangiomas with intense focal uniform uptake. This diagnosis was confirmed in 27 lesions, or 96 percent. Thirty-six lesions imaged as vascular malformations with abnormal vessels or diffusely increased activity. This diagnosis was confirmed in 35 lesions, or 97 percent. Overall, the Tc-RBC scan was 97 percent accurate in distinguishing hemangiomas from vascular malformations. It is particularly useful when the clinical diagnosis of the lesion may not be evident. Not only can biopsy be avoided, but parents can be reassured at an earlier age and given accurate information regarding prognosis.     

EEG markers of the disturbed systemic brain activity in hypoxia

Specific rearrangements of the brain bioelectric potential field and the structures where the components (waves) of the main EEG rhythms interact, as well as the stereotactic location and power of the equivalent electrical dipole sources (EEDSs), were studied at various stages of acute experimental hypoxia (breathing for 15–30 min a hypoxic gas mixture containing 8% oxygen in nitrogen). The disrupted intercentral relationships that ensure the formation of the dynamic “morphological equivalent” to support the integrative brain activity, rearrangements of this activity, and the adaptive functions of the whole brain proved to account for partial or complete disintegration of systemic brain activity during acute hypoxia. EEDS tomography showed that EEDSs responsible for the generation of the basic brain rhythmic pattern are normally located in the thalamic structures. At the initial stages of hypoxia, the distribution of the EEDS foci is changed so that the density of EEDSs is increased on the sections that include the hypothalamic region structures, basal nuclei of the forebrain, and the limbic system; the basal, frontal, and medial regions of the temporal lobes of both hemispheres are also involved. With increasing hypoxia, EEDSs appeared in the basal and medial regions of the frontal lobes. At this time, both the surface and deep regions of the frontal lobes of the brain hemispheres are the major targets of the hypoxic effect. At the stages of severe hypoxia, pronounced functional changes in the CNS are observed, including the phenomenon of movement of multiple EEDS foci primarily through the basal and mediobasal regions of the frontal and temporal lobes and in the limbic system structures. Thus, despite the generalized high-amplitude paroxysmal activity that is observed in EEG, a functional disintegration (disruption) of interactions between individual brain regions appears and leads to disturbed regulation of the brain and systemic brain activity. Spatiotemporal EEG markers have been identified that make it possible to assess the individual sensitivity and resistance to hypoxia, as well as the degree of disintegration of his systemic brain activity at different stages of hypoxia.     

Focal adhesion kinase and p130Cas mediate both sarcomeric organization and activation of genes associated with cardiac myocyte hypertrophy

Hypertrophic terminally differentiated cardiac myocytes show increased sarcomeric organization and altered gene expression. Previously, we established a role for the nonreceptor tyrosine kinase Src in signaling cardiac myocyte hypertrophy. Here we report evidence that p130Cas (Cas) and focal adhesion kinase (FAK) regulate this process. In neonatal cardiac myocytes, tyrosine phosphorylation of Cas and FAK increased upon endothelin (ET) stimulation. FAK, Cas, and paxillin were localized in sarcomeric Z-lines, suggesting that the Z-line is an important signaling locus in these cells. Cas, alone or in cooperation with Src, modulated basal and ET-stimulated atrial natriuretic peptide (ANP) gene promoter activity, a marker of cardiac hypertrophy. Expression of the C-terminal focal adhesion-targeting domain of FAK interfered with localization of endogenous FAK to Z-lines. Expression of the Cas-binding proline-rich region 1 of FAK hindered association of Cas with FAK and impaired the structural stability of sarcomeres. Collectively, these results suggest that interaction of Cas with FAK, together with their localization to Z-lines, is critical to assembly of sarcomeric units in cardiac myocytes in culture. Moreover, expression of the focal adhesion-targeting and/or the Cas-binding proline-rich regions of FAK inhibited ANP promoter activity and suppressed ET-induced ANP and brain natriuretic peptide gene expression. In summary, assembly of signaling complexes that include the focal adhesion proteins Cas, FAK, and paxillin at Z-lines in the cardiac myocyte may regulate, either directly or indirectly, both cytoskeletal organization and gene expression associated with cardiac myocyte hypertrophy.     

Phosphorylated Thiamine Derivatives and Cortical Activity in the Baboon Papio papio: Effect of Intermittent Light Stimulation

The effect of intermittent light stimulation (ILS) on the distribution of thiamine derivatives in three brain areas (occipital, motor, and premotor) was compared in photosensitive and nonphotosensitive baboons. ILS induces paroxysmal discharges in the motor and premotor areas of photosensitive animals only. In baboons submitted to ILS, thiamine triphosphate (TTP) decreases in both photosensitive and nonphotosensitive animals; thiamine monophosphate (TMP) increases in photosensitive animals, which present ILS-induced paroxysmal discharges, whereas it is unaffected in nonphotosensitive animals. The variations are the most significant in the occipital (visual) cortex. A consumption of TTP may result from electrical activity induced by light stimulation in the occipital area. No correlation between ILS-induced paroxysmal activity and a decrease in TTP contents was found. However, photosensitive animals are affected differently from nonphotosensitive animals, as their content of TMP in the cerebral cortex increases on stimulation. However, as long as the exact role of thiamine compounds in relation to membrane excitability in the nervous system remains unknown, it is impossible to conclude whether the differences observed in the metabolism of thiamine compounds are the cause or the consequence of the photosensitivity in the baboon Papio papio.     

An avian model of genetic reflex epilepsy

The Fayoumi strain of chickens (Fepi) carries a recessive autosomal gene mutation in which homozygotes are afflicted with a photogenic and audiogenic reflex epilepsy. Seizures consist of stimulus-locked motor symptoms followed by generalized self sustained convulsions. EEG recordings show spikes and spike and waves patterns at rest which are suppressed during seizures and replaced by a desynchronized pattern of activity. Neurones of the prosencephalon discharge in bursts at rest, while neurones of the mesencephalon are bursting during seizures. Living neural chimeras were obtained by replacing specific embryonic brain vesicles in a normal chicken embryo with equivalent vesicles from a Fepi donor. These chimeras show that the epileptic phenotype can be totally or partially transferred from the Fepi to the normal chickens. Total transfer of photogenic and audiogenic seizures was obtained by substitution of both the prosencephalon and mesencephalon, while substitution of the prosencephalon alone resulted in transfer of interictal paroxysmal activity and substitution of the mesencephalon alone resulted principally in transfer of ictal motor symptoms. Increased expression of the c-fos protooncogene, as revealed by the western blot technique, confirmed the distinct encephalic localizations of the symptoms of the photogenic and audiogenic reflex epilepsy of the Fepi shown with the methods of electrophysiology and brain chimeras. We conclude that the Fepi is a good model of brain stem reflex epilepsy and suggest that the brain stem is a generator of some other animal and human genetic reflex "epileptic syndromes".     

Repetitive pseudoseizures incorrectly managed as status epilepticus.

Pseudoseizures should be considered in the differential diagnosis of intractable seizures. Incorrect diagnosis may result in incorrect management, with the patient unnecessarily exposed to side effects of drugs. The authors report on three patients who presented with uncontrolled seizures originally diagnosed and managed as status epilepticus. Electroencephalography performed during provoked attacks led to a diagnosis of pseudoseizures. Psychiatric assessment revealed psychologic disorders. The patients received supportive therapy, and the pseudoseizures stopped.     

Effect of Noncompetitive Blockade of N-Methyl-d-Aspartate Receptors on the Neurochemical Sequelae of Experimental Brain Injury

Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global and focal ischemia and hypoglycemia, and improves neurological outcome after experimental spinal cord injury. The present study examined the effects of the noncompetitive N-methyl-D-aspartate receptor blocker MK-801 on neurochemical sequelae following experimental fluid-percussion brain injury in the rat. Fifteen minutes after fluid-percussion brain injury (2.8 atmospheres), animals received either MK-801 (1 mg/kg, i.v.) or saline. MK-801 treatment significantly attenuated the development of focal brain edema at the site of injury 48 h after brain injury, significantly reduced the increase in tissue sodium, and prevented the localized decline in total tissue magnesium that was observed in injured tissue of saline-treated animals. Using phosphorus nuclear magnetic resonance spectroscopy, we also observed that MK-801 treatment improved brain metabolic status and promoted a significant recovery of intracellular free magnesium concentrations that fell precipitously after brain injury. These results suggest that excitatory amino acid neurotransmitters may be involved in the pathophysiological sequelae of traumatic brain injury and that noncompetitive N-methyl-D-aspartate receptor antagonists may effectively attenuate some of the potentially deleterious neurochemical sequelae of brain injury.     

Failure of Intravenous or Intracardiac Delivery of Mesenchymal Stromal Cells to Improve Outcomes after Focal Traumatic Brain Injury in the Female Rat

Mesenchymal stromal cells secrete a variety of anti-inflammatory factors and may provide a regenerative medicine option for the treatment of traumatic brain injury. The present study investigates the efficacy of multiple intravenous or intracardiac administrations of rat mesenchymal stromal cells or human mesenchymal stromal cells in female rats after controlled cortical impact by in vivo MRI, neurobehavior, and histopathology evaluation. Neither intravenous nor intracardiac administration of mesenchymal stromal cells derived from either rats or humans improved MRI measures of lesion volume or neurobehavioral outcome compared to saline treatment. Few mesenchymal stromal cells (<0.0005% of injected dose) were found within 3 days of last dosage at the site of injury after either delivery route, with no mesenchymal stromal cells being detectable in brain at 30 or 56 days post-injury. These findings suggest that non-autologous mesenchymal stromal cells therapy via intravenous or intracardiac administration is not a promising treatment after focal contusion traumatic brain injury in this female rodent model.