ABSTRACT
Introducción: El cerebro es un órgano extraordinariamente dinßmico, su fisiología es sorprendente especialmente por la respuesta concertada del tejido nervioso en su conjunto ante situaciones patológicas. Estas respuestas incluyen no solo aquellas desencadenadas por la estimulación de receptores o cambios en el metabolismo celular sino los complejos cambios genéticos y las modificaciones continuas de los fenotipos celulares y la conectividad que se reflejan en el conjunto del cerebro incluyendo los procesos de neurogénesis, neuritogénesis y en general de plasticidad neuronal. Los aspectos relacionados con la neuroplasticidad han sido planteados como el fundamento de la fisiopatología de la isquemia cerebral y los fenómenos exofocales relacionados. El progreso en el entendimiento de la fisiopatología de la lesión cerebral ha requerido de la implementación de modelos experimentales contrastables que permiten evaluar los fenómenos celulares inmediatos y a largo plazo, asociar los hallazgos a la clínica y plantear posibles intervenciones farmacológicas. Objetivo: Revisar los avances en los fenómenos de plasticidad después de lesión desde el punto de vista experimental haciendo énfasis en los sectores alejados del foco de injuria.Discusión y conclusiones: En el presente trabajo se exponen los avances recientes en el entendimiento de los fenómenos de neuroplasticidad desde la óptica de un modelo experimental, así como también se exponen los hallazgos preclínicos relacionados con los fenómenos exofocales isquémicos: las alteraciones en ßreas en las cuales la isquemia no es completa, las alteraciones en areas no isquémicas ocasionadas por señales químicas o eléctricas emanadas del foco isquémico, las alteraciones de los patrones de conectividad y los cambios adaptativos en estructuras cerebrales remotas al foco. Se finaliza con un recuento de los aspectos clínicos asociados con estos cambios y las estrategias experimentales y clínicas de intervención farmacológica.
Introduction: The brain is an extraordinarily dynamic structure specially its physiology in response to pathological events. This response include several mechanisms such as changes in cell metabolism, genes expression and possible modifications in cell phenotype and in connectivity that reflect activation of processes like neurogenesis, neuritogenesis and synaptogenesis. Several aspects related with neuroplasticity has been proposed as part of the pathophysiological bases to understand brain ischemia and its exofocal phenomena. Progress in understanding of the pathophysiology of brain lesion has required the use of experimental models to evaluate cellular events that occur immediately after the lesion or later, to associate this changes with clinical observations and to propose pharmacological neuroprotection therapies.Objective: The purpose of the present work is to compile the advances in understanding of plasticity after brain lesion, mainly related with exofocal areas to a core lesion. Discussion and conclusions: The present work shows recent advances in neuroplasticity based on experimental approaches, and preclinical findings related with the exofocal ischemic phenomena: changes in areas not completely ischemic, changes in no ischemic areas affected by chemical or electrical signals, changes in the pattern of connectivity and adaptative changes in remote areas to the ischemic core. Finally, we discuss clinical aspects associated with this changes, experimental strategies and clinical pharmacological interventions.
Subject(s)
Apoptosis , Brain Ischemia , Cerebrum , Ischemia , Necrosis , Neurogenesis , Neuronal PlasticityABSTRACT
To understand the changes in expression of calcium binding proteins(CaBP) during the experimental focal ischemia, expression of two kinds of CaBP, paralvumin(PV) and calbindin D-28K(Calbindin), immunocytochemically, and activities of cytochrome oxidase(CO) and acetylcholinesterase(AchE), histochemically, in focal ischemic brain of the rat were investigated. Two groups of focal ischemic infarction were produced in Sprague Dawley rats(200-350 mg):Group I, Clip compression of left middle cerebral artery(MCA) for 5-10 mins and release;Group II, Electric coagulation of left MCA for 2-24 hrs. In the group I, CO activity and PV- and Calbindin-immunoreactivity(IR) were decreased in the left MCA territory, and decreased in number of PV- and Calbindin-IR neurons and degree of IR, but AchE activity was nearly same as that of control cortex. In the group II, decrease of CO and AchE activities, and marked increase of PV- and Calbindin IRs were noted on neuropil in the layers I through VI of ischemic region. Characteristically pyramidal cells, which did not express the both CaBPs in the control cortex, of layer V of ischemic cortex showed PV- and Calbindin Irs in the cell body and apical dendrite. These findings suggest that 1) PV- and Calbindin-IR neurons, mainly non-pyramidal cells, are more vulnerable than pyramidal cell to ischemic injury, 2) CaBP may have some roles in hypoxic neuronal injury, and 3) PV and Calbindin-immunocytochemistry can be used as useful technique in evaluation of experimental ischemia.