Electrophysiological dysfunction induced by anti-ribosomal P protein antibodies injection into the lateral ventricle of the rat brain.

Objective Anti-ribosomal P antibodies (anti-P) are strongly associated with neuropsychiatric lupus. This study was designed to determine whether these antibodies are capable of causing electro-oscillogram (EOSG) and behavior alterations in rats. Methods IgG fraction anti-P positive and affinity-purified anti-P antibodies were injected intraventricularly in rats. Sequential cortical and subcortical EOSGs were analyzed during 30 days. IgG anti-Ro/SS-A and normal IgG were used as controls. Results All 13 animals injected with IgG anti-P demonstrated a high prevalence of polyspikes, diffusely distributed in hippocampal fields and cerebral cortex. These abnormalities persisted approximately a month. Remarkably, an identical electrical disturbance was observed with the inoculation of affinity-purified anti-P antibodies. The EOSG alterations were associated with behavioral disorders with varying degrees of severity in every animal injected with anti-P. In contrast, no changes in EOSG or behavioral disturbances were observed in the control group. Conclusion Our study indicates that anti-P antibodies can directly induce electrophysiological dysfunction in central nervous system particularly in hippocampus and cortex associated with behavior disturbances.

Absence-like seizures in adult rats following pilocarpine-induced status epilepticus early in life.

Administration of pilocarpine causes epilepsy in rats if status epilepticus (SE) is induced at an early age. To determine in detail the electrophysiological patterns of the epileptogenic activity in these animals, 46 Wistar rats, 7-17 days old, were subjected to SE induced by pilocarpine and electro-oscillograms from the cortex, hippocampus, amygdala, thalamus and hypothalamus, as well as head, rostrum and vibrissa, eye, ear and forelimb movements, were recorded 120 days later. Six control animals of the same age range did not show any signs of epilepsy. In all the rats subjected to SE, iterative spike-wave complexes (8.1 0.5 Hz in frequency, 18.9 9.1 s in duration) were recorded from the frontal cortex during absence fits. However, similar spike-wave discharges were always found also in the hippocampus and, less frequently, in the amygdala and in thalamic nuclei. Repetitive or single spikes were also detected in these same central structures. Clonic movements and single jerks were recorded from all the rats, either concomitantly with or independently of the spike-wave complexes and spikes. We conclude that rats made epileptic with pilocarpine develop absence seizures also occurring during paradoxical sleep, showing the characteristic spike-wave bursts in neocortical areas and also in the hippocampus. This is in contrast to the well-accepted statement that one of the main characteristics of absence-like fits in the rat is that spike-wave discharges are never recorded from the hippocampal fields.

Absence-like seizures in adult rats following pilocarpine-induced status epilepticus early in life

Administration of pilocarpine causes epilepsy in rats if status epilepticus (SE) is induced at an early age. To determine in detail the electrophysiological patterns of the epileptogenic activity in these animals, 46 Wistar rats, 7-17 days old, were subjected to SE induced by pilocarpine and electro-oscillograms from the cortex, hippocampus, amygdala, thalamus and hypothalamus, as well as head, rostrum and vibrissa, eye, ear and forelimb movements, were recorded 120 days later. Six control animals of the same age range did not show any signs of epilepsy. In all the rats subjected to SE, iterative spike-wave complexes (8.1 ± 0.5 Hz in frequency, 18.9 ± 9.1 s in duration) were recorded from the frontal cortex during absence fits. However, similar spike-wave discharges were always found also in the hippocampus and, less frequently, in the amygdala and in thalamic nuclei. Repetitive or single spikes were also detected in these same central structures. Clonic movements and single jerks were recorded from all the rats, either concomitantly with or independently of the spike-wave complexes and spikes. We conclude that rats made epileptic with pilocarpine develop absence seizures also occurring during paradoxical sleep, showing the characteristic spike-wave bursts in neocortical areas and also in the hippocampus. This is in contrast to the well-accepted statement that one of the main characteristics of absence-like fits in the rat is that spike-wave discharges are never recorded from the hippocampal fields.

Anxiety and high plasma catecholamines do not impair pharmaco-induced erection of psychogenic erectile dysfunctional patients.

The aim of this study was to assess the influence of anxiety and plasma catecholamines on the pharmaco-induced erection of psychogenic erectile dysfunction (ED) patients. A total of 23 patients with psychogenic ED aged from 19 to 43 y were submitted to: (1) anxiety evaluation by the Spielberger's State and Trait Anxiety Inventory-STAI; (2) intracavernous injection of PGE1 10 microg+phentolamine 1 mg with the response monitored by Rigiscan; (3) blood sampling from cavernous bodies and cubital vein for adrenaline and noradrenaline levels determination by high performance liquid chromatography. The whole procedure was done in a single clinical setting at the same day. We found no significant correlation between the erection rigidity and the cavernous or peripheral catecholamines or between erection rigidity and anxiety scores. Some patients showed rigid erections despite high anxiety scores or penile catecholamine levels while others, with incomplete erections, had much smaller levels. These results are suggestive of a more complex mechanism controlling the penile sympathetic responsiveness in psychogenic ED patients.

The brain decade in debate: VI. Sensory and motor maps: dynamics and plasticity

This article is an edited transcription of a virtual symposium promoted by the Brazilian Society of Neuroscience and Behavior (SBNeC). Although the dynamics of sensory and motor representations have been one of the most studied features of the central nervous system, the actual mechanisms of brain plasticity that underlie the dynamic nature of sensory and motor maps are not entirely unraveled. Our discussion began with the notion that the processing of sensory information depends on many different cortical areas. Some of them are arranged topographically and others have non-topographic (analytical) properties. Besides a sensory component, every cortical area has an efferent output that can be mapped and can influence motor behavior. Although new behaviors might be related to modifications of the sensory or motor representations in a given cortical area, they can also be the result of the acquired ability to make new associations between specific sensory cues and certain movements, a type of learning known as conditioning motor learning. Many types of learning are directly related to the emotional or cognitive context in which a new behavior is acquired. This has been demonstrated by paradigms in which the receptive field properties of cortical neurons are modified when an animal is engaged in a given discrimination task or when a triggering feature is paired with an aversive stimulus. The role of the cholinergic input from the nucleus basalis to the neocortex was also highlighted as one important component of the circuits responsible for the context-dependent changes that can be induced in cortical maps

The brain decade in debate: VII. Neurobiology of sleep and dreams

This article is a transcription of an electronic symposium held on February 5, 2001 by the Brazilian Society of Neuroscience and Behavior (SBNeC) during which eight specialists involved in clinical and experimental research on sleep and dreaming exposed their personal experience and theoretical points of view concerning these highly polemic subjects. Unlike most other bodily functions, sleep and dreaming cannot, so far, be defined in terms of definitive functions that play an ascribable role in maintaining the organism as a whole. Such difficulties appear quite clearly all along the discussions. In this symposium, concepts on sleep function range from a protective behavior to an essential function for maturation of the nervous system. Kleitman's hypothesis [Journal of Nervous and Mental Disease (1974), 159: 293-294] was discussed, according to which the basal state is not the wakeful state but sleep, from which we awake to eat, to protect ourselves, to procreate, etc. Dreams, on the other hand, were widely discussed, being considered either as an important step in consolidation of learning or simply the conscious identification of functional patterns derived from the configuration of released or revoked memorized information

The brain decade in debate: VI. Sensory and motor maps: dynamics and plasticity.

This article is an edited transcription of a virtual symposium promoted by the Brazilian Society of Neuroscience and Behavior (SBNeC). Although the dynamics of sensory and motor representations have been one of the most studied features of the central nervous system, the actual mechanisms of brain plasticity that underlie the dynamic nature of sensory and motor maps are not entirely unraveled. Our discussion began with the notion that the processing of sensory information depends on many different cortical areas. Some of them are arranged topographically and others have non-topographic (analytical) properties. Besides a sensory component, every cortical area has an efferent output that can be mapped and can influence motor behavior. Although new behaviors might be related to modifications of the sensory or motor representations in a given cortical area, they can also be the result of the acquired ability to make new associations between specific sensory cues and certain movements, a type of learning known as conditioning motor learning. Many types of learning are directly related to the emotional or cognitive context in which a new behavior is acquired. This has been demonstrated by paradigms in which the receptive field properties of cortical neurons are modified when an animal is engaged in a given discrimination task or when a triggering feature is paired with an aversive stimulus. The role of the cholinergic input from the nucleus basalis to the neocortex was also highlighted as one important component of the circuits responsible for the context-dependent changes that can be induced in cortical maps.

The brain decade in debate: VII. Neurobiology of sleep and dreams.

This article is a transcription of an electronic symposium held on February 5, 2001 by the Brazilian Society of Neuroscience and Behavior (SBNeC) during which eight specialists involved in clinical and experimental research on sleep and dreaming exposed their personal experience and theoretical points of view concerning these highly polemic subjects. Unlike most other bodily functions, sleep and dreaming cannot, so far, be defined in terms of definitive functions that play an ascribable role in maintaining the organism as a whole. Such difficulties appear quite clearly all along the discussions. In this symposium, concepts on sleep function range from a protective behavior to an essential function for maturation of the nervous system. Kleitman's hypothesis [Journal of Nervous and Mental Disease (1974), 159: 293-294] was discussed, according to which the basal state is not the wakeful state but sleep, from which we awake to eat, to protect ourselves, to procreate, etc. Dreams, on the other hand, were widely discussed, being considered either as an important step in consolidation of learning or simply the conscious identification of functional patterns derived from the configuration of released or revoked memorized information.

Centrally injected atropine reduces hyperglycemia caused by 2-DG or immobilization stress in awake rats.

The physiological significance of central cholinergic neurons was investigated by verifying the effect of previous intracerebroventricular administration of atropine on the hyperglycemia induced by 2-deoxyglucose (2-DG) or by immobilization stress in unrestrained, nonanesthetized rats. Intravenous 2-DG induced a marked increase in plasma glucose that was not affected by atropine injected intracerebroventricularly 30 min before. However, the hyperglycemia induced by intracerebroventricular 2-DG was significantly reduced by previous intracerebroventricular injection of atropine. Immobilization induced a rapid increase of plasma glucose levels that was reduced by about 50% by intracerebroventricular injection of atropine. The increase in plasma lactate induced by intravenous 2-DG, or immobilization, was not significantly affected by previous intracerebroventricular injection of atropine. The data suggest that central cholinergic neurons participate in the complex neural events responsible for the hyperglycemic response to neurocytoglucopenia and to stressful situations.

Functional recovery after combined cerebral and cerebellar hemispherectomy in the rat.

The cerebellum seems to be one of the structures responsible for early neurological improvement after cerebral hemispherectomy and its consequent deficits. Considered as an accessory brain, the cerebellum may constitute a neurobiological substrate for the recovery of such extensive cortical and subcortical lesions. It may compensate for the injury by structural remodeling and plasticity. The authors observed that, indeed, rats submitted to contralateral hemicerebellectomy before cerebral hemispherectomy do not recover as well as those submitted to hemicerebellectomy 2 weeks after cerebral hemispherectomy.

Prevalence of epileptic seizures along the wakefulness-sleep cycle in adult rats submitted to status epilepticus in early life.

In 70 adult Wistar rats submitted to pilocarpine-induced status epilepticus in early life the electro-oscillograms were recorded from neocortical areas 10, 3 and 17, from CA1 and CA3 hippocampal fields and, in 10 rats, also from the ventrolateral nuclei and amygdala. Head, eye, rostrum + vibrissae, ear and forelimb movements were recorded as well. Fifty rats were subjected to 4-hour daily recording sessions and 20 to continuous 24-hour recordings. In all the rats spike-wave discharges (SWD) were found in every site from which the electro-oscillograms were recorded, and clonic seizures were also displayed by all the animals. Most seizures (83.75%, mean = 6.59 fits/h) were concentrated in nearly 9 h and 16.25% (mean = 0. 77 fits/h) in the remaining 15 h. Eye movements occurred during 49. 2% of the total duration of motor events, the head moved in 42.8% and the rostrum + vibrissae in 8.1% of the time, departing from normal rats. Therefore, pilocarpine-induced status epilepticus produces striking changes in the wakefulness-sleep cycle characteristics.

Electro-oscillographic correlation between dorsal raphe nucleus, neocortex and hippocampus during wakefulness before and after serotoninergic inactivation.

Theta rhythm in many brain structures characterizes wakefulness and desynchronized sleep in most subprimate mammalian brains. In close relation to behaviors, theta frequency and voltage undergo a fine modulation which may involve mobilization of dorsal raphe nucleus efferent pathways. In the present study we analyzed frequency modulation (through instantaneous frequency variation) of theta waves occurring in three cortical areas, in hippocampal CA1 and in the dorsal raphe nucleus of Wistar rats during normal wakefulness and after injection of the 5-HT1a receptor agonist 8-OH-DPAT into the dorsal raphe. We demonstrated that in attentive states the variation of theta frequency among the above structures is highly congruent, whereas after 8-OH-DPAT injection, although regular signals are present, the variation is much more complex and shows no relation to behaviors. Such functional uncoupling after blockade demonstrates the influence of dorsal raphe nucleus efferent serotoninergic fibers on the organization of alertness, as evaluated by electro-oscillographic analysis.

Electro-oscillographic correlation between dorsal raphe nucleus, neocortex and hippocampus during wakefulness before and after serotoninergic inactivation

Theta rhythm in many brain structures characterizes wakefulness and desynchronized sleep in most subprimate mammalian brains. In close relation to behaviors, theta frequency and voltage undergo a fine modulation which may involve mobilization of dorsal raphe nucleus efferent pathways. In the present study we analyzed frequency modulation (through instantaneous frequency variation) of theta waves occurring in three cortical areas, in hippocampal CA1 and in the dorsal raphe nucleus of Wistar rats during normal wakefulness and after injection of the 5-HT1a receptor agonist 8-OH-DPAT into the dorsal raphe. We demonstrated that in attentive states the variation of theta frequency among the above structures is highly congruent, whereas after 8-OH-DPAT injection, although regular signals are present, the variation is much more complex and shows no relation to behaviors. Such functional uncoupling after blockade demonstrates the influence of dorsal raphe nucleus efferent serotoninergic fibers on the organization of alertness, as evaluated by electro-oscillographic analysis.

Circumscribed lesion of the medial forebrain bundle area causes structural impairment of lymphoid organs and severe depression of immune function in rats.

Interactions between the immune system and the brain are a key element in the pathophysiology of diseases such as multiple sclerosis, neuroAIDS, and Alzheimer's, which affect large numbers of individuals and are associated with a high social cost. However, the neuroanatomical basis of brain-immune interactions has not been elucidated. We report that in Wistar rats of either sex bilateral electrolytic lesion of the medial forebrain bundle reduces body weight by 28% 7 days after lesioning, and causes widespread infections, aphagia, adypsia, structural damage to the lymphoid organs and heavy depression of T lymphocytes cytotoxicity. The following alterations occur in the immune system after those lesions: the weight of the thymus, spleen and lymphonodes is reduced by 77.9%, 49.1% and 48.4%, respectively. The thymus is atrophied and contains fewer lymphoid cells in the cortex than in the medulla. In the spleen the white pulp is reduced and lymphoid cells from periarteriolar zones and at the chords are almost absent. In lymph nodes cortical small lymphocytes are depleted and primary and secondary nodules and germinal centers all but disappear. Cytotoxicity of lymphocytes is reduced by 86.2% in the thymus, 77.6% in the spleen and 70.2% in lymph nodes. The critical area of lesion is at the medialmost portion of the medial forebrain bundle, at the preoptic area and rostral part of the anterior hypothalamus. We suggest that this area contains neural circuits that are crucial for keeping the structure of lymphoid organs and the functional integrity of the immune system.

Effect of chemical stimulation of the dorsomedial hypothalamic nucleus on blood plasma glucose, triglycerides and free fatty acids in rats.

The effects of chemical stimulation of the dorsomedial hypothalamic nucleus (DMH) on blood plasma concentration of glucose, triglycerides, insulin, and free fatty acids (FFA) were investigated in anesthetized adult Wistar rats. Microinjection of 12.5 nmol of norepinephrine into the DMH increased blood plasma concentration of glucose and FFA, decreased triglycerides, and did not change plasma insulin within 5 min; after 20 min, blood glucose and FFA reached control values. Microinjection of epinephrine (12.5 nmol) into the DMH also increased blood plasma glucose concentration and decreased triglycerides after 5 min. These effects are probably mediated by beta-adrenergic mechanisms, because they were prevented by beta-adrenergic antagonist propranolol, but not by alpha-adrenergic antagonist prazosin. Microinjection into the DMH of glutamate, dopamine, or acetylcholine failed to cause any change in those metabolic parameters, corroborating the hypothesis that the DMH is part of a beta-adrenergic pathway involved in short-term modulation of the availability of glucose and FFA.

The relevance of patient individuality in the evaluation and treatment of aphasia. Case report.

The usual approach to language disorders relies on standardised evaluations in which pattern-tests characterise the subject's status according to the classical aphasiological typology. Those data are then analysed to support a traditional prevalent criterion for the distinction between "normal" and "pathological" linguistic performance, which is strictly focused on a quantitative approach. In the present study a method for evaluation and treatment of aphasia is proposed in which socio-cultural conditions are emphasised, in order to expand this conventional criterion as to encompass a qualitative (individualised) one. Although the methodology draws the attention, the results here obtained also point to the importance of re-evaluating what is presently considered as the most appropriate criterion for "normal" cognitive processes, particularly those related to language.

Correlation between concomitant theta waves in nucleus reticularis pontis oralis and in hippocampus, thalamus and neocortex during dreaming in rats.

Theta waves, which are the main electrophysiological expression of dreaming activity in many brain structures of rats, often undergo specific changes in voltage and frequency according to the oniric patterns. Much is known about their mechanisms but little is known regarding their origin, which has been ascribed to a specific activation of either the reticular formation or the septal nuclei or nucleus reticularis pontis oralis. In the present study, rats were prepared for chronic recording of the electro-oscillograms of cortical areas 10, 3 and 17, of hippocampal CA1 and CA3 fields, of nucleus reticularis thalami, nucleus reticularis pontis oralis and occasionally of nucleus reticularis caudalis. Head, rostrum, eye and forelimb movements were also recorded, so that the oniric behaviors could be precisely identified. The scatter diagrams and the corresponding correlation coefficients (r) of the voltage of concomitant waves were determined for each possible pair of leads. The potentials were analyzed at a frequency of 256 Hz over a period of 1 to 3 sec. A very high degree of correlation was observed between theta waves in nucleus reticularis pontis oralis, hippocampal fields and nucleus reticularis pontis caudalis; sometimes r approached unity. Although these data cannot be taken as proof of nucleus reticularis pontis oralis being the source of theta waves, they are at least compatible with this hypothesis.

Correlation between concomitant theta waves in nucleus reticularis pontis oralis and in hippocampus, thalamus and neocortex during dreaming in rats

Theta waves, which are the main electrophysiological expression of dreaming activity in many brain structures of rats, often undergo specific changes in voltage and frequency according to the oniric patterns. Much is known about their mechanisms but little is known regarding their origin, which has been ascribed to a specific activation of either the reticular formation or the septal nuclei or nucleus reticularis pontis oralis. In the present study, rats were prepared for chronic recording of the electro-oscillograms of cortical areas 10, 3 and 17, of hippocampal CA1 and CA3 fields, of nucleus reticularis thalami, nucleus reticularis pontis oralis and occasionally of nucleus reticularis caudalis. Head, rostrum, eye and forelimb movements were also recorded, so that the oniric behaviors could be precisely identified. The scatter diagrams and the corresponding correlation coefficients (r) of the voltage of concomitant waves were determined for each possible pair of leads. The potentials were analyzed at a frequency of 256 Hz over a period of 1 to 3 sec. A very high degree of correlation was observed between theta waves in nucleus reticularis pontis oralis, hippocampal fields and nucleus reticularis pontis caudalis; sometimes r approached unity. Although these data cannot be taken as proof of nucleus reticularis pontis oralis being the source of theta waves, they are at least compatible with this hypothesis.

Cardiovascular adjustments in limb retraction provoked by noxious stimulation in decerebrate and spinal cats. Evidence for a somatotopic organization.

Arterial blood pressure, heart rate and iliac blood flow were continuously recorded in 61 adult cats and their alteration induced by noxious stimulation of the interdigital spaces of the four limbs was studied in intact (anesthetized) and in decerebrate and spinal preparations. Noxious stimulation of any limb in the decerebrate animals provoked retraction 61% of the times and an increase of blood pressure and heart rate in approximately 80% of the stimulations. Stimulation of a hindlimb provoked an increase of blood flow in the same limb in about 80% of the stimulations, due to active vasodilation. Contralateral stimulation provoked a smaller increase of blood flow but with an increase in vascular resistance, indicating some degree of vasoconstriction. Stimulation of the forelimbs induced small increases of blood flow in the hindlimbs but the calculated vascular resistance was higher than the basal values, also indicating vasoconstriction. Neuromuscular blockade with gallamine did not affect the increase of hindlimb blood flow, suggesting a central regulation of the intricate distribution of blood to the limbs. The vasodilation was not due to activation of sympathetic cholinergic vasodilator neurons inasmuch as the blood flow responses were not affected by cholinergic blockade with atropine. In spinal animals, stimulation of any limb provoked small increases of blood pressure, extremely low degrees of tachycardia and an increase of hindlimb blood flow, with active vasodilation. Neuromuscular paralysis, however, abolished the adjustments of blood flow in the hindlimbs, indicating that metabolites and/or sensory information caused by muscle contraction induced them. In intact cats anesthetized with sodium pentobarbiturate, blood pressure and heart rate increased under noxious stimulation, although less than in the decerebrate animals. Nearly 40% of the stimulations provoked hypotension rather than hypertension. Blood flow increased due to stimulation of any limb but, as in the decerebrate preparation, there was active vasodilation in the ipsilateral hindlimb and vasoconstriction in the contralateral one.

Platelet activating factor and histamine effects in synovial blood flow evaluated by laser-Doppler flowmetry.

OBJECTIVE: To investigate platelet activating factor (PAF) and histamine effects in synovial circulation of rabbits. METHODS: A laser-Doppler flowmeter was adapted to study the synovial blood flow. Either PAF or histamine were infused in the first femoral artery branch. The effects of PAF and histamine antagonists as well as of inhibitors of cyclooxygenase products were evaluated. RESULTS: PAF induced a vasoconstriction in synovial circulation, which was inhibited by the PAF antagonist, WEB 2170, a cyclooxygenase inhibitor, indomethacin or a thromboxane synthesis inhibitor, dazmegrel. Histamine induced vasoconstriction in the synovial vessels. Promethazine not only inhibited this vasoconstriction but also induced a vasodilation, that was blocked by a combined treatment with promethazine and cimetidine. Pretreatment with WEB 2170 did not interfere with histamine effect. CONCLUSIONS: Our data indicate that PAF induces vasoconstriction in synovial blood flow through a receptor mediated mechanism and that thromboxane is involved in this effect. Histamine induces constriction or dilation in synovial vessels, through action on H1 or H2 receptors, respectively. This effect is not dependent on PAF.