Neural substrate of defensive behavior in the midbrain tectum.

It has been shown that the gradual increase in the intensity of electrical stimulation of the dorsal periaqueductal gray (DPAG), deep layers of the superior colliculus (DLSC) and inferior colliculus of rats induces, in a progressive manner, characteristic aversive responses such as arousal, freezing, and escape behavior. The DPAG-DLSC together with the periventricular gray substance of the diencephalon, amygdala and the inferior colliculus, constitute the neural substrate of aversion in the brain. In general, the behavioral responses induced by midbrain tectum stimulation are accompanied by increases in the mean arterial blood pressure, heart rate, and respiration. Both the behavioral and autonomic consequences of electrical stimulation of the mesencephalic tectum have been shown to be attenuated by minor tranquilizers, probably through enhancement of GABAergic neurotransmission. Besides GABAergic mechanisms several lines of evidence have clearly implicated opioid, serotonergic, and excitatory amino acids-mediated mechanisms in the control of the neural substrates commanding defensive behavior in the brain aversive system.

Mechanisms of defense in the inferior colliculus.

The inferior colliculus (IC) is a well known relay station for auditory pathways in the brainstem. In the present review we are suggesting that aversive states are also generated and elaborated in the inferior colliculus and that this structure may be part of a brain system commanding defensive behavior. The evidences presented in this review have been obtained from experiments carried out with the combined use of intracerebral microinjections and of electrical stimulation of the inferior colliculus. This electrical stimulation caused a behavioral activation together with autonomic reactions usually observed as part of the defense reaction. NMDA--an excitatory amino acid--, or bicuculline--a GABAA antagonist--injected into the IC mimicked the effects of its electrical stimulation. The IC electrical stimulation showed clear aversive properties as rats submitted to a switch-off paradigm quickly learned to interrupt it. Systemic administration as well as IC microinjections of the anxiolytic compound midazolam caused dose-dependent increases in the latency and reductions in the frequency of switch-off responses to the inferior colliculus electrical stimulation. Similar results were obtained following microinjections into this brainstem structure of the GABAA agonist muscimol. These results suggest that neural substrates responsible for defensive behavior in the inferior colliculus may be depressed by benzodiazepines as part of the anxiolytic action of these compounds. This anti-aversive action may be produced by the enhancement of GABAA mechanisms. Serotonergic mechanisms seem also to be involved in the modulation of these aversive states as IC microinjections of zimelidine, a 5-HT uptake blocker, caused a significant inhibition of the switch-off responses in the shuttle-box.(ABSTRACT TRUNCATED AT 250 WORDS)

Defensive reactions evoked by activation of NMDA receptors in distinct sites of the inferior colliculus.

The inferior colliculus (IC) is primarily involved in conveying auditory information to higher cortical structures. Recently we have shown that this structure may also be part of a brain system commanding defensive behaviour. There is evidence that the neural substrates responsible for defensive behaviour in the inferior colliculus are regulated by GABAergic, serotonergic and opioid mechanisms and that these substrates may also be depressed by benzodiazepines as part of their anxiolytic action. Here we present evidence for the involvement of excitatory amino acids in the IC in the expression of defensive reactions. Microinjections of NMDA (5-40 nmol)--an excitatory amino acid--into the ventrolateral division of the central nucleus of the IC of rats placed inside a circular arena induced aversive reactions, characterized by running, rearing, and jumping. This hyperactivity was interspersed by immobility states which often progressed to convulsive seizures. These reactions were inhibited by the NMDA specific antagonist AP7 previously microinjected into the IC. It is suggested that NMDA receptor mediated mechanisms are called into play during the display of the defensive behaviour.

Opposite effects of low and high doses of morphine on neural substrates of aversion in the inferior colliculus.

The inferior colliculus (IC) is a well known relay station for auditory pathways in the brainstem. Much evidence has implicated this structure as part of a brain system mediating aversive states, and changes in its functioning as responsible for the occurrence of audiogenic seizures. Rats were implanted with chemitrodes, devices which allow electrical stimulation and microinjections of drugs in the same brain sites. Stepwise increases in the intensity of electrical stimulation of the IC of rats placed inside a circular arena allowed the determination of thresholds for freezing and escape behavior. Morphine (10-40nmol) caused dose-dependent increases in both aversive thresholds. A systemic injection of naloxone reversed the effects of morphine on the centrally induced aversive responses. These data suggest that neural substrates controlling defensive behavior in this structure are under opioid inhibitory control. Higher doses of morphine (80nmol) induced a non-naloxone reversible fearful hyper activity. It is suggested that opioid mechanisms exert an inhibitory control on the neural substrates of aversion in the IC and that high doses of morphine microinjected into IC cause pro-aversive actions probably through non-opioid mechanisms.

Antiaversive action of benzodiazepines on escape behavior induced by electrical stimulation of the inferior colliculus.

In the present work, evidence is presented for the involvement of inferior colliculus in the generation and elaboration of aversive responses which suggests that this structure may be part of a brain system that commands aversive states. Electrical stimulation of the inferior colliculus of rats placed inside an open field allowed the determination of thresholds for the escape response. Afterward these rats were placed inside a shuttle box and submitted to a switch-off paradigm. Electrical stimulation of the inferior colliculus was applied at a current intensity 5% below the escape threshold. This electrical stimulation showed clear aversive properties: the rats quickly learned to interrupt it. Systemic administration (3 and 5.6 mg/kg) as well as inferior colliculus microinjections (10 and 20 nmol) of the anxiolytic compound midazolam caused dose-dependent increases in the latency and reductions in the frequency of switch-off responses to the inferior colliculus electrical stimulation. Similar results were obtained following microinjections into this brainstem structure of the GABA-A agonist muscimol (0.1 and 0.5 nmol). These results suggest that neural substrates commanding defensive behavior in the inferior colliculus may be depressed by benzodiazepines as part of the anxiolytic action of these compounds. This antiaversive action may be produced by the enhancement of GABA-A mechanisms.

[Organophosphate poisoning and myocardial necrosis]. / Intoxicação por órgano-fosforado e necrose miocárdica.

A man (46 years-old) was admitted to the intensive care unit (ICU) with a history that eight hours before he had voluntarily drank 100 ml of malathion. He complained of a burning pain on the anterior thorax and was confused. His cardiovascular evaluation was normal and his breathing was heavy with some rales on the pulmonary auscultation. He was treated with atropine and contrathion and rapidly evolved into coma. Electrocardiogram showed subendocardial lesion in the inferior wall with diffuse ly altered ventricular repolarization and increase QT interval. During the ICU period his cardiac enzyme levels also raised. The patient died in the 8th day after admission. The pathological evaluation of the heart revealed foci of myocardial necrosis. This is the 1st case of medical literature with histological confirmation of myocardial necrosis from organophosphate intoxication.

[Upper gastrointestinal hemorrhage caused by a fistula from a right anomalous subclavian artery to the esophagus]. / Hemorragia digestiva por fístula de artéria subclávia direita anômala com o esôfago.

Bleeding from an arterio-esophageal fistula is a rare and nearly lethal condition and surgical treatment is the only curative option. We report a case of bleeding from a fistula from an aberrant right subclavian artery to the esophagus. Diagnosis was made only at necropsy, despite of three previous laparotomies. This anatomical variation is found in 0.5% of the general population. Development of a communication between this artery and the esophagus, secondary to aneurysmatic dilatation or to prolonged nasogastric intubation, as probably occurred with this patient, is a extremely rare condition. Surgical treatment depends on the early recognition of clinical signs of the arterio-esophageal communication, before the onset of systemic complications of hypovolemic shock.

Bovine pericardium used as a cardiovascular patch.

BACKGROUND: The use of glutaraldehyde preserved bovine pericardium in valvular prostheses is well known. Although widely used clinically as patch material, bovine pericardium has not been extensively studied in this setting. METHODS: With this objective, 21 dogs received a standard bovine pericardial patch to partially replace the aortic, left atrial, or pericardial walls. The dogs were randomly divided into three groups according to implant duration. Group 1 consisted of 6 dogs evaluated surgically after 33 to 43 postoperative days, Group 2 with 7 dogs reoperated after 120 to 165 days, and Group 3 with 8 dogs reoperated after 225 to 305 days. RESULTS: Microscopic and macroscopic evaluation demonstrated: 1) the wrinkled surface of the bovine pericardium adhered to neighboring structures whereas the smooth surface did not adhere to the epicardium; 2) the bovine pericardial patch did not show structural changes in any of the implant sites; 3) the final left atrial patch was significantly smaller than the aortic and pericardial patches for Group 2 and Group 3 dogs; 4) the atrial patch area decreased significantly, whereas the aortic and pericardial areas did not change over time; 5) the pericardial implant was significantly thinner than the aortic and left atrial patches for Group 3 dogs; 6) a layer of fibrous connective tissue was formed on the smooth surface of the left atrial and aortic patches. The internal apposition fibrasis was significantly thicker in the left atrium than in the aorta in Groups 1 and 2; 7) the internal fibrasis layer of the atrial and aortic patches was calcified in Groups 2 and 3; and 8) the internal apposition tissue of the atrial and aortic patches showed neoformation of elastic fibers which clearly increased with implant duration. CONCLUSIONS: The fate of implanted glutaraldehyde-preserved bovine pericardial patches in cardiovascular applications depends on three factors: 1) the contact surface, 2) the tension it is subjected to, and 3) contact with blood flow.

Intoxicaçäo por órgano-fosforado e necrose miocárdica / Organophosphate Intoxication and Myocardial Necrosis

Paciente masculino, de 46 anos, foi internado no centro de terapia com quadro de ingestäo voluntária de 100ml há 8h. Queixava-se de ardor na face anterior do tórax. Estava torporoso. O exame cardiovascular era normal e a ventilaçäo espontânea com muitos roncos na ausculta pulmonar. Foi medicado com atropina e cotrathion, evoluindo para o coma. O eletrocardiograma apresentou lesäo subendocárdica em parede inferior, alteraçöes difusas da repolarizaçäo ventricular e aumento do intervalo QT. As enzimas cardíacas se elevaram. No 8§ dia o paciente foi a óbito e a análise anatomopatológica do coraçäo revelou: artérias coronárias normais em toda a extensäo, e focos difusos de necrose niocárdica comprovada por anatomopatológico em intoxicaçäo por órgano-fosforado. A necrose miocárdica difusa pode ser a responsável pelas alteraçöes cardíacas comumente encontradas.

Hemorragia digestiva por fístula de artéria subclávia direta anômala com o esôfago / Upper gastrointestinal hemorrhage from a fistula of a right anomalous subclavian artery to the esophagus

As hemorragias decorrentes das comunicaçoes arteriais com o esôfago sao raras e letais em praticamente todos os casos. O tratamento cirúrgico imediato é a única opçao terapêutica curativa. Os autores apresentam um caso de hemorragia por fístula de artéria subclávia direita anômala com o esôfago, no qual o diagnóstico foi esclarecido apenas na necropsia, após três operaçoes. Esta alteraçao anatômica é encontrada em 0,5 por cento da populaçao geral. Raramente se estabelece comunicaçao desta artéria com esôfago, como conseqüência de dilataçao aneurismática ou de traumatismo provocado pela permanência prolongada de sonda nasogástrica, como, provavelmente, ocorreu com esse doente. O tratamento cirúrgico dependerá do reconhecimento precoce dos sinais diagnósticos sugestivos de comunicaçao arterial com o esôfago antes que a hemorragia traga repercussao sistêmica.

Glioblastoma multiforme do cerebelo.Relato de um caso em crianca. / Glioblastoma multiforme of the cerebellum Report of a case in a child

Os autores relatam um caso de glioblastoma multiforme em uma crianca com 12 anos de idade e com sintomatologia ha um mes. Os autores tentaram correlacionar s sintomatologia e o quadro clinico com os trabalhos anteriormente publicados. O diagnostico foi constatado post-mortem e parece ser o primeiro caso descrito na literatura brasileira nesta localizacao e faixa etaria

Os efeitos da cocaína no cérebro

Artigo publicado na revista 'Cérebro e Mente', do Núcleo de Informática Biomédica da Unicamp. Mostra breve histórico e propriedades primárias da cocaína e descreve, com ilustrações e animações, os efeitos da droga no cérebro.