Correlatos neurobiológicos y consecuencias clínicas de las experiencias adversas tempranas: un enfoque sistémico / Neurobiological Correlates and Clinical Consequences of Early Adverse Expriencies: A Systemic Approach

En este artículo se ofrece una perspectiva y un panorama general acerca de los efectos y consecuencias de un amplio grupo de experiencias traumáticas tempranas, organizadas bajo el concepto abarcador de experiencias adversas tempranas y trauma de apego: abuso sexual, maltrato físico y verbal, abandono parental temprano e interacción en un ambiente familiar caótico, entre otras. Se considera un mecanismo general por el cual, las experiencias adversas generan estrés agudo o crónico que se evidencia por alterciones en la regulación del eje hipotálamo-hipófisis-suprarrenal actuando el estrés así generado como una carga alostática que genera alteraciones mente/cuerpo. Las dificultades para regular la respuesta al estrés o factores que actúan en forma independiente pueden conducir a desorganización parcial de la estructura cortical cerebral especialmente en los sistemas neuronales que procesan las emociones (sistema límbico), la memoria (hipocampo) y la capacidad de reconocer estados mentales en el propio individuo y en las personas con las cuales interactúa (teoría de la mente). Se analizan los mecanismos moleculares de resiliencia que permiten recuperarse o resistir dichas experiencias. Se menciona la importancia de reconocer un período crítico basado en el desarrollo cerebral, que podría generar una latencia en los efectos de los acontecimientos trumáticos generando vulnerabilidad y daño tanto en la infancia como durante la adolescencia o adultez joven bajo la forma de depresión, ansiedad, trsatornos de la personalidad o abuso de sustancias. El reconocimiento e investigación del trauma temprano resulta fundmental para evitar la repetición intergeneracional de las adversidades y para el desarrollo de tratamientos efectivos...

This article offers an insight and an overview of the effects and consequences of a wide range of early traumatic experiences organized within the encompassing concept of early adverse experiences and attachment trauma: sexual abuse, physical and verbal harassment, early parental abandonment and interaction in a chaotic family environment. It is considered a general mechanism by which adverse experiences generate chronic or acute stress evidenced by alterations in the regulation of the hippocampal-hypophiseal-suprarenal axis; the generated stress thus acts as an allostatic load that generates mind/body alterations. Difficulties to regulate the response to stress or factors that act independently may lead to a partial disorganization of the cerebral, cortical structure, particularly in the neuronal systems that process emotions (limbic system), memory (hippocampus) and the ability to recognize mental states within the same individual and the interacting people (theory of the mind). The author analyzes the molecular mechanisms of resilience that enable to recover from or resist to such experiences, higlighting the importance of recognizing a critical period bases on brain development, which might generate a latency in the effects of traumatic events, generating vulnerability and abuse both in the childhood as well as in the adolescence or young adulthood in the shape of depression, anxiety, personality disorders or drug abuse. The recognition and research of early trauma is key to avoid the intergenerational repetition of advesities and for the develpment of effective treatments...

Psychiatric comorbidities in temporal lobe epilepsy: possible relationships between psychotic disorders and involvement of limbic circuits / Comorbidades psiquiátricas na epilepsia do lobo temporal: possíveis relações entre desordens psicóticas e comprometimento de circuitos límbicos

OBJECTIVE: Mounting evidence suggests that the limbic system is pathologically involved in cases of psychiatric comorbidities in temporal lobe epilepsy (TLE) patients. Our objective was to develop a conceptual framework describing how neuropathological and connectivity changes might contribute to the development of psychosis and to the potential neurobiological mechanisms that cause schizophrenia-like psychosis in TLE patients. METHODS: In this review, clinical and neuropathological findings, especially brain circuitry of the limbic system, were examined together to enhance our understanding of the association between TLE and psychosis. Finally, the importance of animal models in epilepsy and psychiatric disorders was discussed. CONCLUSIONS: TLE and psychiatric symptoms coexist more frequently than chance would predict. Damage and deregulation among critical anatomical regions, such as the hippocampus, amygdala, thalamus, and the temporal, frontal and cingulate cortices, might predispose TLE brains to psychosis. Studies of the effects of kindling and injection of neuroactive substances on behavior and electrophysiological patterns may offer a model of how limbic seizures in humans increase the vulnerability of TLE patients to psychiatric symptoms.

OBJETIVO: Existem cada vez mais evidências de que o sistema límbico está envolvido na patologia das comorbidades psiquiátricas em pacientes com epilepsia do lobo temporal (ELT). Nosso objetivo foi elaborar um desenho conceitual descrevendo como aspectos neuropatológicos e de conectividade podem contribuir para o desenvolvimento de psicose em pacientes com ELT. MÉTODOS: Nesta revisão, achados clínicos e neuropatológicos, e especialmente os aspectos da circuitaria límbica, foram examinados em conjunto para auxiliar nossa compreensão sobre a associação entre ELT e psicose. Achados em modelos animais de epilepsia e esquizofrenia também foram levados em consideração. CONCLUSÕES: ELT e comorbidades psiquiátricas coexistem com maior frequência que o predito pela associação ao acaso. Dano e desregulação entre estruturas anatômicas críticas, como hipocampo, amígdala, tálamo, e córtices temporal, frontal e cingulado podem predispor o cérebro com ELT à psicose. Estudos sobre efeitos comportamentais e eletrofisiológicos do abrasamento elétrico e injeções de substâncias neuroativas em modelos animais podem oferecer pistas sobre como crises límbicas em humanos aumentam a vulnerabilidade de pacientes com ELT a sintomas psiquiátricos.

Culture & characterisation of limbal epithelial cells & oral mucosal cells.

Background & objectives: Sources of autologous tissue that can functionally replace the corneal epithelium have been considered as an alternative to allogenous limbal transplants for limbal stem cells deficiency (LSCD). The aim of the present study was to compare the characterization of oral mucosa with limbal epithelial cells by markers using reverse transcriptase polymerase chain reaction (RT-PCR). Methods: Experiments were performed using oral tissue (n=6) obtained from patients who underwent oral mucosal graft for LSCD. Confluent cultures of limbus and oral mucosa epithelial cells were characterized by the pututative stem cell markers using RT-PCR. The morphological characteristics of cultivated epithelial cells were analyzed by haematoxylin and eosin staining and phase contrast microscopy. Results: Confluent sheets of epithelial cells were seen at the end of 14th day resembling the morphological features of limbal epithelia. RT–PCR analysis showed that cultured oral epithelial cells expressed markers such as ABCG2, p63, delta Np63, isoforms of p63, Keratin 3 (K3), membrane protein – Mucin (MUC 1, 4 and 16) and Antimicrobial Peptide - AMP (Human β Defensin – hBD 1, 2 and 3). Interpretation & conclusions: Oral epithelial cultures have morphological features resembling corneal and limbal epithelial cells by expressing similar marker genes. Thus, feasibility of clinical use of oral epithelial cells need be evaluated for allogenous limbal transplants.

Assessment of the progressive nature of cell damage in the pilocarpine model of epilepsy

Pilocarpine-induced (320 mg/kg, ip) status epilepticus (SE) in adult (2-3 months) male Wistar rats results in extensive neuronal damage in limbic structures. Here we investigated whether the induction of a second SE (N = 6) would generate damage and cell loss similar to that seen after a first SE (N = 9). Counts of silver-stained (indicative of cell damage) cells, using the Gallyas argyrophil III method, revealed a markedly lower neuronal injury in animals submitted to re-induction of SE compared to rats exposed to a single episode of pilocarpine-induced SE. This effect could be explained as follows: 1) the first SE removes the vulnerable cells, leaving behind resistant cells that are not affected by the second SE; 2) the first SE confers increased resistance to the remaining cells, analogous to the process of ischemic tolerance. Counting of Nissl-stained cells was performed to differentiate between these alternative mechanisms. Our data indicate that different neuronal populations react differently to SE induction. For some brain areas most, if not all, of the vulnerable cells are lost after an initial insult leaving only relatively resistant cells and little space for further damage or cell loss. For some other brain areas, in contrast, our data support the hypothesis that surviving cells might be modified by the initial insult which would confer a sort of excitotoxic tolerance. As a consequence of both mechanisms, subsequent insults after an initial insult result in very little damage regardless of their intensity.

Aspectos psicobiológicos de la conducta delictiva / Psychobiological aspects of criminal behavior

Desde los estudios clásicos de Lombroso sobre la biotipología del delincuente, se han realizado estudios relacionados con los aspectos biológicos de la conducta delictiva, que recaen fundamentalmente sobre aspectos neurofisiológicos, hormonales, genéticos, y más recientemente, etológicos. Entre los primeros se destaca la relación entre la conducta delictiva y la actividad anormal de las estructuras nerviosas que constituyen en Sistema Límbico, su relación con la conducta agresiva y la incidencia de la Epilepsia Temporal en reos. La relación entre las alteraciones premenstruales y la conducta anormal, incluyendo la conducta delictiva en mujeres, es la mas destacada en estudios sobre la función hormonal y la conducta delictiva. La existencia de anormalidades cromosómicas, tales como un cromosoma Y exstra, ha sido el principal enfoque en el aspecto genético de los delincuentes, asociado con anormalidades en el metabolismo de la testosterona en éstos. Los aspectos de territorialidad y dominancia, han sido algunos de los aspectos etológicos estudiados en los índices de criminalidad en grandes masas de población y en las macrópolis. No existen conclusiones definitivas sobre el papel de estas variables en la conducta social anormal, aunque constituyen algunos aspectos relevantes dentro del estudio de la conducta compleja, tal como ocurre en la conducta delictiva. Las teorías contemporáneas contemplan la interrelación de estas variables psicobiológicas, con factores económicos y geopolíticos, habilidades sociales, etc.

Alteraçöes neuroanatômicas na esquizofrenia: Parte 1 - Estudos anatomopatológicos / Neuroanatomical changes in schizophrenia: Part I - Anatomopathological studies

Os autores fazem uma revisäo da literatura atual sobre as alteraçöes anatomopatológicas na esquizofrenia. Os estudos apontam para alteraçöes principalmente nas regiöes límbicas, gânglios da base e regiöes corticais frontais. Os resultados säo discutidos à luz das hipóteses atuais sobre as possíveis causas da esquizofrenia: predisposiçäo genética associada ou näo a fatores ambientais, ocorrendo principalmente no período pré e perinatal do desenvolvimento do sistema nervoso central. Limitaçöes metodológicas inerentes a esses estudos säo também consideradas