Research progress on the mechanism of pain related neural pathways above the spinal cord / 生理学报

Pain is a multi-dimensional emotional experience, and pain sensation and pain emotion are the two main components. As for pain, previous studies only focused on a certain link of the pain transmission pathway or a certain key brain region, and there is a lack of evidence that connectivity of brain regions is involved in pain or pain regulation in the overall state. The establishment of new experimental tools and techniques has brought light to the study of neural pathways of pain sensation and pain emotion. In this paper, the structure and functional basis of the neural pathways involved in the formation of pain sensation and the regulation of pain emotion in the nervous system above the spinal cord level, including thalamus, amygdala, midbrain periaqueductal gray (PAG), parabrachial nucleus (PB) and medial prefrontal cortex (mPFC), are reviewed in recent years, providing clues for the in-depth study of pain.

CX3CR1 contributes to streptozotocin-induced mechanical allodynia in the mouse spinal cord / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Patients with diabetic peripheral neuropathy experience debilitating pain that significantly affects their quality of life (Abbott et al., 2011), by causing sleeping disorders, anxiety, and depression (Dermanovic Dobrota et al., 2014). The primary clinical manifestation of painful diabetic neuropathy (PDN) is mechanical hypersensitivity, also known as mechanical allodynia (MA) (Callaghan et al., 2012). MA's underlying mechanism remains poorly understood, and so far, based on symptomatic treatment, it has no effective therapy (Moore et al., 2014).

Spinal P2X7R contributes to streptozotocin-induced mechanical allodynia in mice / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Painful diabetic neuropathy (PDN) is a diabetes mellitus complication. Unfortunately, the mechanisms underlying PDN are still poorly understood. Adenosine triphosphate (ATP)-gated P2X7 receptor (P2X7R) plays a pivotal role in non-diabetic neuropathic pain, but little is known about its effects on streptozotocin (STZ)-induced peripheral neuropathy. Here, we explored whether spinal cord P2X7R was correlated with the generation of mechanical allodynia (MA) in STZ-induced type 1 diabetic neuropathy in mice. MA was assessed by measuring paw withdrawal thresholds and western blotting. Immunohistochemistry was applied to analyze the protein expression levels and localization of P2X7R. STZ-induced mice expressed increased P2X7R in the dorsal horn of the lumbar spinal cord during MA. Mice injected intrathecally with a selective antagonist of P2X7R and P2X7R knockout (KO) mice both presented attenuated progression of MA. Double-immunofluorescent labeling demonstrated that P2X7R-positive cells were mostly co-expressed with Iba1 (a microglia marker). Our results suggest that P2X7R plays an important role in the development of MA and could be used as a cellular target for treating PDN.

Age-related changes and effects of regular low-intensity exercise on gait, balance, and oxidative biomarkers in the spinal cord of Wistar rats

The present study aimed to analyze age-related changes to motor coordination, balance, spinal cord oxidative biomarkers in 3-, 6-, 18-, 24-, and 30-month-old rats. The effects of low-intensity exercise on these parameters were also analyzed in 6-, 18-, and 24-month-old rats. Body weight, blood glucose, total cholesterol, and high-density lipoprotein (HDL) cholesterol were assessed for all rats. The soleus muscle weight/body weight ratio was used to estimate skeletal muscle mass loss. Body weight increased until 24 months; only 30-month-old rats exhibited decreased blood glucose and increased total cholesterol and HDL cholesterol. The soleus muscle weight/body weight ratio increased until 18 months, followed by a small decrease in old rats. Exercise did not change any of these parameters. Stride length and step length increased from adult to middle age, but decreased at old age. Stride width increased while the sciatic functional index decreased in old rats. Performance in the balance beam test declined with age. While gait did not change, balance improved after exercise. Aging increased superoxide anion generation, hydrogen peroxide levels, total antioxidant capacity, and superoxide dismutase activity while total thiol decreased and lipid hydroperoxides did not change. Exercise did not significantly change this scenario. Thus, aging increased oxidative stress in the spinal cord, which may be associated with age-induced changes in gait and balance. Regular low-intensity exercise is a good alternative for improving age-induced changes in balance, while beneficial effects on gait and spinal cord oxidative biomarkers cannot be ruled out because of the small number of rats investigated (n=5 or 6/group).

Effect of Sciatic Nerve Transection on acetylcholinesterase activity in spinal cord and skeletal muscles of the bullfrog Lithobates catesbeianus / Efeito da Secção do Nervo Isquiático sobre a atividade da acetilcolinesterase em medula espinal e músculos esqueléticos da rã-touro Lithobates catesbeianus

Abstract Sciatic nerve transection (SNT), a model for studying neuropathic pain, mimics the clinical symptoms of "phantom limb", a pain condition that arises in humans after amputation or transverse spinal lesions. In some vertebrate tissues, this condition decreases acetylcholinesterase (AChE) activity, the enzyme responsible for fast hydrolysis of released acetylcholine in cholinergic synapses. In spinal cord of frog Rana pipiens, this enzyme's activity was not significantly changed in the first days following ventral root transection, another model for studying neuropathic pain. An answerable question is whether SNT decreases AChE activity in spinal cord of frog Lithobates catesbeianus, a species that has been used as a model for studying SNT-induced neuropathic pain. Since each animal model has been created with a specific methodology, and the findings tend to vary widely with slight changes in the method used to induce pain, our study assessed AChE activity 3 and 10 days after complete SNT in lumbosacral spinal cord of adult male bullfrog Lithobates catesbeianus. Because there are time scale differences of motor endplate maturation in rat skeletal muscles, our study also measured the AChE activity in bullfrog tibial posticus (a postural muscle) and gastrocnemius (a typical skeletal muscle that is frequently used to study the motor system) muscles. AChE activity did not show significant changes 3 and 10 days following SNT in spinal cord. Also, no significant change occurred in AChE activity in tibial posticus and gastrocnemius muscles at day 3. However, a significant decrease was found at day 10, with reductions of 18% and 20% in tibial posticus and gastrocnemius, respectively. At present we cannot explain this change in AChE activity. While temporally different, the direction of the change was similar to that described for rats. This similarity indicates that bullfrog is a valid model for investigating AChE activity following SNT.

Resumo A transecção do nervo isquiático (SNT), um modelo para estudar dor neuropática, simula os sintomas clínicos do "membro fantasma", uma condição dolorosa que ocorre nos humanos após amputação ou secção completa da medula espinal. Essa condição muda a atividade da acetilcolinesterase (AChE), a enzima responsável pela rápida hidrólise da acetilcolina liberada nas sinapses colinérgicas, em alguns tecidos de vertebrados. Em medula espinal de rã Rana pipiens, a atividade da AChE não foi significativamente alterada nos primeiros dias após a secção da raiz ventral, outro modelo para o estudo da dor neuropática. Uma questão ainda não respondida é se a SNT diminui a atividade da AChE na medula espinal de rã Lithobates catesbeianus, uma espécie que vem sendo usada como modelo em estudos da dor neuropática induzida por SNT. Como cada modelo animal é criado a partir de metodologia específica, e seus resultados tendem a variar com pequenas mudanças na metodologia de indução da dor, o presente estudo avaliou a atividade da AChE em medula espinal lombossacral de rã-touro Lithobates catesbeianus, adultos, machos, 3 e 10 dias após a completa SNT. Como há diferenças temporais na maturação de placas motoras em músculos esqueléticos de ratos, nosso estudo ainda demonstrou, na rã-touro, os efeitos da SNT sobre a atividade da AChE nos músculos esqueléticos tibial posticus, um músculo postural, e gastrocnêmio, um músculo frequentemente usado em estudos do sistema motor. A atividade da AChE não mudou significativamente na medula espinal aos 3 e 10 dias após a SNT. Nos músculos, a atividade não alterou significativamente aos 3 dias após a lesão, mas reduziu de forma significativa aos 10 dias após a SNT. Aos 10 dias, a diminuição foi 18% no músculo tibial posticus e 20% no gastrocnêmio. No momento, nós não temos explicação para essa mudança na atividade da AChE. Embora temporalmente diferente, o sentido da mudança é similar ao que é descrito em ratos. Esta similaridade torna a rã-touro um modelo válido para se estudar questões ainda não respondidas da SNT sobre a AChE.

Fisiología de la perfusión medular / Physiology of spinal perfusion

Introducción: En las últimas décadas ha aumentado el interés por el estudio de la fisiología de la perfusión a nivel de la médula espinal. Muchos de los tratamientos en pacientes con lesión medular han sido basados en el paralelismo de la dinámica vascular entre el cerebro y la médula. Conocer estos aspectos así como los métodos relacionados con su monitoria resulta favorable para la adecuada intervención del paciente con lesión a nivel medular. Objetivo: Realizar una revisión en la literatura científica de los aspectos más importantes que intervienen en la perfusión de la médula espinal, los mecanismos de autorregulación y su aplicación clínica dentro del estudio de la fisiología medular. Métodos: Con las palabras claves, se realizó una revisión no sistemática en las bases de datos correspondientes a OVID, Medline/PubMed, Science Direct. Resultados y Conclusiones: El papel de la autorregulación es vital en la conservación de la integridad de la médula espinal, realizar un adecuado control de ella así como de otros factores químicos y metabólicos son determinantes en el control del flujo sanguíneo medular y minimiza el riesgo de lesión medular secundaria. Las curvas de autorregulación para el cerebro y la médula espinal son virtualmente idénticas; dentro de un rango de 60-150 mmHg.

Introduction: Over the past decades the interest in the study of the physiology of perfusion at the level of the spinal cord has increased. Many treatments in patients with spinal cord injury have been based on the parallelism of the vascular dynamics between the brain and the spinal. Knowing about these aspects and methods related to their monitoring practice is favorable for a proper intervention of the patient with spinal cord injury. Objective: To do a scientific literature review on the most important aspects involved in spinal cord perfusion, autoregulatory mechanisms and their clinical applications in the study of spinal cord physiology. Methods: Using the keywords, a non-systematic review on the OVID, Medline/PubMed and Science Direct databases, was performed. Results and Conclusion: The role of autoregulation is vital in maintaining the integrity of the spinal cord, an adequate control of it as well as other chemical and metabolic factors are important in the control of medullary blood flow and minimizes the risk of secondary spinal cord injury. The autoregulation curves for the brain and spinal cord are virtually identical, within a range of 60-150 mmHg.

Brown-Sequard, a restless mind / Brown-Sequard, uma mente inquieta

Brown-Séquard, a remarkable medical personality of the 19 th century, was born in a small island of the Indian Ocean. He travelled over the world exerting his skills: a successful physician, and an innovative researcher, with a very ample range of interests. His favored subject was the nervous system. The spinal cord was studied extensively, with novel and important discoveries on the sensory pathways. He identified cases with spinal cord hemisection, and described the clinical presentation corresponding to a syndrome which bears his name (Brown-Séquard syndrome), for which he is best known among neurologists. Regarding the brain, he proposed nine mental and physical functions (organs) related to dynamically interconnected cell clusters, in harmony with the “ réseau de cellules anastomosées ”, “ activités dynamogeniques et inhibitrices ”, and “ action à distance ” concepts. Finally, he is considered by some as the “father” of endocrinology, due to his studies on glands and their secretions.

Brown-Séquard, notável personalidade médica do século 19, nasceu em uma pequena ilha do Oceano Índico. Viajou pelo mundo exercendo suas habilidades: médico de sucesso e pesquisador ousado, com gama muito extensa de interesses. Seu assunto favorito era o sistema nervoso. A medula foi estudada de modo amplo, com descobertas novas e importantes sobre as vias sensitivas. Identificou casos com hemisseção medular e descreveu o quadro clínico correspondente a uma síndrome que leva seu nome (síndrome de Brown-Séquard), motivo pelo qual é melhor conhecido entre os neurologistas. Considerando o cérebro, propôs nove funções (órgãos) mentais e físicas relacionadas de modo dinâmico a conglomerados celulares, em harmonia com seus conceitos de “ réseau de cellules anastomosées ”, “ activités dynamogeniques et inhibitrices ” e “ action à distance ”. Finalmente, ele é considerado por alguns como “pai” da endocrinologia, devido seus estudos sobre glândulas e suas secreções.

Intraoperative Neurophysiologic Monitoring: Basic Principles and Recent Update

The recent developments of new devices and advances in anesthesiology have greatly improved the utility and accuracy of intraoperative neurophysiological monitoring (IOM). Herein, we review the basic principles of the electrophysiological methods employed under IOM in the operating room. These include motor evoked potentials, somatosensory evoked potentials, electroencephalography, electromyography, brainstem auditory evoked potentials, and visual evoked potentials. Most of these techniques have certain limitations and their utility is still being debated. In this review, we also discuss the optimal stimulation/recording method for each of these modalities during individual surgeries as well as the diverse criteria for alarm signs.

Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathway

We have shown that the peripheral and spinal cord heme oxygenase (HO)-carbon monoxide (CO)-soluble guanylate cyclase-cGMP pathways play an important role in antinociception in the rat experimental formalin model. Our objective was to determine if there is synergism between peripheral (paw) and spinal HO-CO pathways in nociception. Rats were handled and adapted to the experimental environment for a few days before the formalin test, in which 50 µL of a 1 percent formalin was injected subcutaneously into the dorsal surface of the right hind paw. The animals were then observed for 1 h and the frequency of flinching behavior was taken to represent the nociceptive response. Thirty minutes before the test, rats were pretreated with intrathecal injections of the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) or heme-lysinate, which is a substrate of the HO pathway. The paw treatments took place 20 min before the test. Low doses of ZnDPBG did not increase nociception, while a low heme-lysinate dose did not change flinching behavior after paw or spinal injections. Combined subactive spinal (50 nmol) and peripheral (40 nmol) low doses of ZnDPBG induced hypernociception (increase of 80 percent in the first and 25 percent in the second phase flinching), whereas combined spinal-peripheral heme-lysinate (50 and 30 nmol) led to second phase antinociception (40 percent reduction in flinching). These findings suggest a synergy between the peripheral and spinal HO-CO pathways. Local activation of the HO system probably regulates the nociception initiation in peripheral tissue and participates in buffering the emerging nociceptive signals at the peripheral and spinal sites of action. In short, an antinociceptive synergy exists between peripheral and spinal HO pathways, which may reduce the doses required and side effects.

Nicotinamide adenine dinucleotide phosphate-diaphorase and c-fos expression in spinal cord neurons following noxious stimulation

To investigate nicotinamide adenine dinucleotide phosphate-diaphorase [NADPH-d] and fos expression in spinal cord dorsal horn neurons following noxious peripheral stimulation. Expression of the immediate-early gene c-fos and nitric oxide containing neurons one hour after unilateral formalin injection to the dorsal hind paw was investigated in rat lumbar spinal cord, using fos immunohistochemistry and NADPH-d histochemical techniques. The experiments were performed in 2004 and 2006 at Ege University Center for Brain Research in Izmir, Turkey. In 10 adult male Sprague-Dawley rats, an increase in fos-immunoreactive neurons was observed ipsilateral, and NADPH-d positive neurons equally ipsi- and contralateral to the formalin injection site. Approximately 20% of fos-immunoreactive neurons were NADPH-d positive ipsilateral to the formalin injection, whereas no double labeling was observed in the contralateral side. Also, a close relation of NADPH-d positive processes with fos-immunoreactive nuclei were also observed. The results of this study support the hypothesis that nitric oxide synthase blocking agents may serve as a possible alternative in treatment of hyperalgesia following inflammation and peripheral nerve injury

Spinal motoneuron excitability in iron deficiency anaemia.

Decreased tissue oxygenation resulting from iron deficiency anaemia produces generalized weakness and fatigue. The precise physiological mechanism underlying this weakness is unknown and studies in this regard have been scarce. One possible underlying mechanism has been suggested to be reduction of spinal motoneuron excitability. F waves are low amplitude motor responses to nerve stimulation, produced by antidromic activation of the peripheral motor fibers, resulting in recurrent discharge of motoneurons. F waves have been established as an efficient tool to assess spinal motoneuron excitability. 15 patients of iron deficiency anaemia using inclusion criteria of hemoglobin level < 9 g/dL and serum ferritin < 15 microg/L were studied. 8 controls with hemoglobin levels > 12 g/ dL were also included. Bilateral median and common peroneal F wave studies were performed. F wave mean latency, chronodispersion, persistence and mean amplitude were studied. They were within the normal range and no significant differences between the patients and the controls were found. We conclude that spinal motoneuron excitability is not reduced in iron deficiency anaemia. A decreased tissue oxygenation leading to a change in the brain neurotransmitters may have a role to play.

Potencial evocado miogênico vestibular: novas perspectivas diagnósticas em esclerose múltipla / Vestibular evoked myogenic potential: new perspectives in multiple sclerosis

OBJETIVO: Avaliar o potencial evocado miogênico vestibular em pacientes com esclerose múltipla, como método de auxílio diagnóstico. FORMA DE ESTUDO: Caso-controle. MATERIAL E MÉTODO: Estudamos um grupo-controle (n=15) de indivíduos normais e um grupo experimental (n=15) que foi composto por pacientes com diagnóstico de esclerose múltipla. Ambos os grupos foram submetidos ao exame de potencial evocado miogênico vestibular. Em cada orelha foram aplicados 200 estímulos na forma de cliques e repetidos por 2 ciclos consecutivos com objetivo de avaliar a reprodutibilidade. Os eletrodos ativos de superfície foram colocados no Scsuperior do músculo esternocleidomastoideo e de referência na borda anterior da clavícula ipsilateral. Os indivíduos foram instruídos à rotacão lateral da cabeca em direcão contralateral à orelha estimulada. RESULTADOS: Obtivemos no potencial evocado miogênico vestibular respostas rápidas, reprodutíveis e bifásicas. A latência das ondas P1 e N2 e amplitude P1-N2 apresentaram um maior valor no grupo experimental quando comparada com o grupo-controle. Não observamos diferenca significativa nas respostas das ondas P1 e N2 e amplitude P1-N2 quando comparamos as orelhas. Verificamos que os indivíduos com esclerose múltipla apresentaram ausência de respostas em 30 por cento dos casos. Ao avaliarmos os indivíduos do grupo experimental com sintomas otoneurológicos e compararmos com os pacientes sem sintomas, observamos que a latência da onda P1, N2 e amplitude P1-N2 estiveram maiores nos casos sintomáticos. CONCLUSAO: O potencial evocado miogênico vestibular foi considerado um bom método de auxílio diagnóstico da via vestíbulo-espinal nos casos de esclerose múltipla.

Differential depression of spinal synaptic transmission in vitro by different hypoxic insults.

The effects of hypoxia (O2-free), aglycemia (glucose-free), ischemia (O2- and glucose-free) and chemical anoxia (by 3-nitropropionic acid; 3-NPA) were evaluated on the synaptic transmission in vitro. Stimulation of a dorsal root in hemisected spinal cord from neonatal rat, evoked monosynaptic (MSR) and polysynaptic reflexes (PSR) in the segmental ventral root. In all the hypoxic conditions, the reflexes were depressed in a time-dependent manner. Hypoxia took longer time (> 240 min) to abolish the reflexes where as, aglycemia and ischemia abolished them within 35 min. Recovery after wash was complete in hypoxia, 60-70% in aglycemia and 20-25% in ischemia. The time required for 50% depression of reflexes (T-50) was also in the same order (100, 23 and 13 min). The elimination of O2 in hypoxic or ischemic solution by N2 bubbling abolished the reflexes within 16 min. The T-50 values in both the conditions were between 5-8 min. Superfusion of 3-NPA (an irreversible inhibitor of succinate dehydrogenase) depressed the reflexes. The abolition time and T-50 values were shorter with the increasing concentrations of 3-NPA. The present results reveal that the energy production in hypoxic condition with normal glucose level can sustain the synaptic activity for a longer time while the glucose deficiency even in normoxic conditions drastically impair the synaptic activity. Further, aglycemia depressed the reflexes almost in a similar time as seen with ischemia.

Ventricular nociception induced vesicular motility and urine flow: their relationship.

Heart acts as an important reflexogenic organ. Reflex urination and defaecation are two of the most important visceral symptoms observed in patients with myocardial ischaemia, infarction etc. In experimental animals also ventricular nociceptor stimulation by left anterior descending coronary artery (LAD) occlusion and nicotine application causes biphasic changes in urinary bladder movement and urine flow. Aim of the present study is to elucidate if there is any correlation between urine formation by the kidneys and movement of the urinary ladder under such experimental conditions. The experiments performed on intact cats show apparent coincidence of the two events. But, subsequent experiments following denervation of vagi and inferior cardiac nerve (ICN), spinal transaction and decerebration experiments indicate that these two are separate events. Further, experiments with different neurotransmitter blockers indicate that ventricular nocieptor induced urine formation and urinary bladder movements are two separate reflex responses and not dependent on each other.

Effects of iontophoretically applied substance P, calcitonin gene-related peptide on excitability of dorsal horn neurones in rats

Spontaneous pain, allodynia and hyperalgesia are well known phenomena following peripheral nerve or tissue injury, and it is speculated that secondary hyperalgesia and allodynia, are generally thought to depend on a hyperexcitability (sensitization) of neurons in the dorsal horn. It is supposed that the sensitization may be due to various actions of neurotransmitters (SP, CGRP, excitatory amino acids) released from the primary afferent fibers. In this study, we examined effects of the iontophoretically applied SP and CGRP on the response to EAA receptor agonists (NMDA and non-NMDA) in the WDR dorsal horn neurones and see if the effects of SP or CGRP mimic the characteristic response pattern known in various pain models. The main results are summarized as follows: 1) SP specifically potentiated NMDA response. 2) CGRP non-specifically potentiated both NMDA and AMPA responses. Potentiation of NMDA response, however, was significantly greater than that of AMPA response. 3) 50% of SP applied cells and 15.8% of CGRP applied cells showed reciprocal changes(potentiation of NMDA response and suppression of AMPA response). These results are generally consistent with the sensitization characteristics in diverse pain models and suggests that the modulatory effects of SP and CGRP on NMDA and non-NMDA (AMPA) response are, at least in part, contribute to the development of sensitization in various pain models.

Can regeneration be promoted within the spinal cord

Although regeneration in the peripheral nervous system (PNS) after injury is robust, regeneration in the central nervous system (CNS) is abortive. The results from differences in the balance of regeneration inhibiting and promoting factors, which in the CNS is skewed toward inhibition while in the PNS it is skewed towards promotion of nerve growth. In addition to lacking regeneration promoting factor the CNS has the ubiquitous distribution of factors that inhibit regeneration. PNS Schwann cells release a number of characterized and uncharacterized neurotrophic factors that exert powerful regeneration promoting influences on axons in the PNS. Thus it has been hypothesize that implantation of Schwann cells, or infusion of factors they release into the lesioned spinal cord should lead to CNS regeneration. However, Schwann cell implants alone are not very successful in promoting CNS regeneration Although still limited, improved regeneration takes place when there is the simultaneously inhibition of CNS regeneration blocking factors and the presence of Schwann cell-released factors. To further improve the extent of CNS regeneration we must determine the best combination of neurotrophic factors to infuse into the site of a CNS lesion, as well as be able to characterize and block all CNS regeneration inhibiting factors. This review examines what is known about promoting and inhibiting regeneration in both the PNS and CNS, and the approaches that may allow us to change the cellular environment of the CNS to one that is permissive to and promotes regeneration.

An update on the physiology of two- and three-toed sloths

Physiological and pharmacological research undertaken on sloths during the past 30 years is comprehensively reviewed. This includes the numerous studies carried out upon the respiratory and cardiovascular systems, anesthesia, blood chemistry, neuromuscular responses, the brain and spinal cord, vision, sleeping and waking, water balance and kidney function and reproduction. Similarities and differences between the physiology of sloths and that of other mammals are discussed in detail

Morfología de la medula espinal y del tallo encefálico: neuroanatomía / Morphology of the spinal cord and of the stem encephalic: neuroanatomy

La neuroanatomía es ciertamente espectacular y considerada como un conjunto sugerente de múltiples secretos y entre ellos el más destacado, la vida. Dió origen a la más aventuradas especulaciones, como aquella de la ubicación de sus actividades en la epífisis; desde entonces privó la meta de la localización de funciones, con la mira de establecer relaciones con las enfermedades, prevalentemente las de tipo mental. El tiempo no anuló esa tendencia porque la principal característica de la anatomía del sistema nervioso es su integración permanente con la fisiología, la patología y con todas las otras ciencias de la medicina, cuyos límites sobrepasa para asociarse con la filosofía. Su expansión no tiene límites y la física o la química ofrece su aporte para su progreso en el avance de su instrumentación o en la utilización de los isótopos para perseguir al contraste en la imagenología. Sus límites son así imponderables y es la Neurociencia la verdadera acepción para establecer su calificación, que la extrae de la simple morfología para asignar un contorno cada vez más invasivo. Razetti fue el iniciador del estudio de la neuroanatomía en nuestro medio. Decia en su clase, en enero de 1990: "De acuerdo con el programa de ésta Cátedra hoy principiamos el estudio de la anatomía del sistema nervioso. Los trabajos modernos, que han realizado una verdadera y transcendental revolución en nuestros conocimientos acerca de éste maravilloso aparato, me obligan a dar a esta parte de la anatomía del hombre una extensión mucho mayor de la que generalmente se ha acostumbrado en esta aula". El maestro estaba entusiasmado con los conceptos de Cajal, expresados en la teoría de la neurona, y la individualidad que ella le concedía, desde entonces sometida a la ley de la polarización dinámica de la corriente nerviosa. La concepción neurológica complementaba así a las deducciones del método de Flechsig, afirmando en la embriología para sustentar al concepto de la descendencia; su fundamento era el estudio de la complejidad creciente de las vainas de mielina en la filogenia, para permitir el establecimiento de la hermosa teoría de los centros sensoriales e intelectuales del cerebro, desde entonces consideramos por Claudio Bernard como los órganos de la inteligencia, tal como el corazón es el factor principal de la circulación o "La laringe como producto de la voz". se había llegado a la exposición de los elementos basales de la vida y la filosofía positiva aseveraba