¿Cómo reparar el daño cerebral isquémico? Utilidad de los modelos experimentales en la búsqueda de respuestas / How to repair an ischemic brain injury? Value of experimental models in search of answers

El objetivo principal de los modelos experimentales de isquemia cerebral es el estudio del daño isquémico cerebral en condiciones fisiológicamente controladas y reproducibles. Los estudios realizados han sido esenciales para establecer nuevos conceptos sobre los mecanismos subyacentes al daño cerebral isquémico tales como la penumbra isquémica, el daño por reperfusión, los mecanismos de muerte celular o la importancia del daño sufrido por las mitocondrias, las células gliales y la sustancia blanca. Sin embargo, debido a la discrepancia entre los estudios experimentales y clínicos respecto a la eficacia de las terapias que tratan de aminorar o revertir el daño isquémico cerebral, existe una polémica creciente en torno a la utilidad clínica de los modelos experimentales de isquemia cerebral. Uno de los principales motivos del fracaso de las diversas estrategias terapéuticas ensayadas en el ámbito clínico es el enfoque teórico reduccionista de la mayoría de los ensayos farmacológicos, que analizan el efecto de una molécula con un mecanismo de acción conocido dentro de una ruta concreta de progresión del daño isquémico. Este abordaje contrasta con la complejidad estructural y funcional del tejido cerebral y la intricada fisiopatología de las alteraciones celulares y moleculares inducidas por la isquemia. Creemos que el objetivo fundamental de los estudios realizados en modelos experimentales de isquemia cerebral debe ser la obtención de conocimientos básicos acerca de los procesos patobiológicos subyacentes al daño isquémico y que los ensayos clínicos no deberían iniciarse con agentes terapéuticos cuyos beneficios hayan sido escasos o inconsistentes en los estudios experimentales (AU)

The major aim of experimental models of cerebral ischemia is to study the cerebral ischemic damage under controlled and reproducible conditions. Experimental studies have been fundamental in the establishment of new concepts regarding the mechanisms underlying the ischemic brain injury, such as the ischemic penumbra, the reperfusion injury, the cell death or the importance of the damage induced on mitochondria, glial cells and white matter. Disagreement between experimental and clinical studies regarding the benefit of drugs to reduce or restore the cerebral ischemic damage has created a growing controversy about the clinical value of the experimental models of cerebral ischemia. One of the major explanations for the failure of the clinical trials is the reductionist approach of most therapies, which are focused on the known effect of a single molecule within a specific pathway of ischemic damage. This philosophy contrasts to the complex morphological design of the cerebral tissue and the complex cellular and molecular physiopathology underlying the ischemic brain injury. We believe that the main objective of studies carried out in experimental models of cerebral ischemic injury must be a better understanding of the fundamental mechanisms underlying progression of the ischemic injury. Clinical trials should not be considered if the benefit obtained in experimental studies is limited or weak (AU)

How to repair an ischemic brain injury? Value of experimental models in search of answers.

The major aim of experimental models of cerebral ischemia is to study the cerebral ischemic damage under controlled and reproducible conditions. Experimental studies have been fundamental in the establishment of new concepts regarding the mechanisms underlying the ischemic brain injury, such as the ischemic penumbra, the reperfusion injury, the cell death or the importance of the damage induced on mitochondria, glial cells and white matter. Disagreement between experimental and clinical studies regarding the benefit of drugs to reduce or restore the cerebral ischemic damage has created a growing controversy about the clinical value of the experimental models of cerebral ischemia. One of the major explanations for the failure of the clinical trials is the reductionist approach of most therapies, which are focused on the known effect of a single molecule within a specific pathway of ischemic damage. This philosophy contrasts to the complex morphological design of the cerebral tissue and the complex cellular and molecular physiopathology underlying the ischemic brain injury. We believe that the main objective of studies carried out in experimental models of cerebral ischemic injury must be a better understanding of the fundamental mechanisms underlying progression of the ischemic injury. Clinical trials should not be considered if the benefit obtained in experimental studies is limited or weak.

Comentario al trabajo, Variaciones del sector anterior del polígono de Willis. Correlación anatomo-angiográfica y su implicancia en la cirugía de aneurismas intracraneanos. (Arterias, ácigos cerebral anterior, mediana del cuerpo calloso y cerebral media accesoria) de Martínez y cols / No disponible

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Intraventricular craniopharyngiomas: topographical classification and surgical approach selection based on an extensive overview.

BACKGROUND: This retrospective study analyzes the clinical, neuroradiological, pathological and surgical characteristics of well-described intraventricular craniopharyngiomas with the aims of: (i) critically to review the criteria used to affirm the diagnosis of an intraventricular location (ii) defining more accurately this topographical diagnosis preoperatively, and (iii) to investigate factors influencing the surgical outcome. METHOD: Clinical, neuroradiological, pathological and surgical objective data of 104 well-described intraventricular craniopharyngiomas (IVC) reported in the literature, in addition to a new case, were analyzed. On the basis of the proofs provided for third ventricle intactness, a new topographical classification for IVC was developed, distinguishing between: (i) strict IVC, with a proved third ventricle floor integrity and (ii) non-strict IVC, without any reliable proof confirming the intactness of the third ventricle floor. Following this classification, clinical features, pathology and surgical outcome for strictly and non-strictly IVC were compared. FINDINGS: For 105 IVC compiled, 36 belonged to the strictly group and 69 to the non-strictly group. Two pathological features were associated with the non-strictly IVC group: a preferentially adamantinomatous pattern (p=0.106) and wider and tighter adherences to third ventricle margins (p=0.01). The non-strict topography was also associated with a worse postoperative outcome (p=0.046). There was a significant relationship between the surgical approach and the final outcome (p=0.05), being the translamina terminalis approach associated with the best outcome. CONCLUSIONS: Two different topographies might be considered among IVC: strict and non-strict intraventricular location. Non-strictly IVC have wider and tighter adhesions to third ventricle boundaries and this subtype is associated with a worse outcome.

[Blood brain barrier: development of a structure which supports the functional heterogeneity of the central nervous system]. / La barrera hematoencefalica: desarrollo de una estructura que permite la heterogeneidad funcional del sistema nervioso central.

AIMS: To analyze the functional reasons justifying the existence of the blood brain barrier with an emphasis on its fundamental role supporting neuroglial coupling. DEVELOPMENT: We review in an integrated manner the contributions of different research areas in physiology and metabolism of the central nervous system which allow to understand the functional need for the existence of the blood brain barrier. In particular, we describe the physiological basis of the metabolic functional coupling and the metabolic interactions between neurons and glial cells, two properties directly derived from the presence of the blood brain barrier. Likewise the blood brain barrier is presented as an important determinant of the heterogeneous activation of cerebral tissue as detected by neuroimaging technologies as positron emission tomography and functional magnetic resonance imaging. CONCLUSIONS: The main function of the blood brain barrier is to maintain a stable composition of the extracellular milieu in nervous tissue. This allows the changes in ionic composition and neurotransmitter concentration in the extracellular milieu, to reflect indirectly the generation of action potentials and the state of neurotransmission of neuronal circuits. Glial cells induce the development of the blood brain barrier and are the main sensors of neuronal function, due to their important take up capacity for extracellular potassium and neurotransmitters. Glial homeostasis of the extracellular milieu is circuit specific, limiting the functional metabolic coupling to discrete regions of the brain and generating the classical pattern of heterogeneous activity in the different modules of the nervous tissue.

La barrera hematoencefálica: desarrollo de una estructura que permite la heterogeneidad funcional del sistema nervioso central / Blood-brain barrier: development of a structure which supports the functional heterogeneity of the central nervous system

Objetivo. Analizar las razones funcionales que justifican la existencia de la barrera hematoencefálica (BHE), con énfasis en su papel crucial como soporte de la unidad funcional neurona-glía.Desarrollo. Se revisan en detalle y de manera integrada las aportaciones de diversas áreas de investigación en fisiología y metabolismo del sistema nervioso central que permiten comprender la necesidad funcional de la existencia de la BHE. En especial, se describen las bases fisiológicas del acoplamiento metabólico-funcional en el tejido nervioso y las interacciones metabólicas entre las neuronas y las células gliales, dos propiedades derivadas directamente de la presencia de la BHE. Se presenta la barrera como un importante determinante de la activación heterogénea del tejido cerebral, detectable mediante tecnologías de neuroimagen funcional, como la tomografía de emisión de positrones y la imagen de resonancia magnética funcional. Conclusiones. La función principal de la BHE es mantener una composición estable del medio extracelular en el tejido nervioso. Esto permite que los cambios de composición iónica y de concentración de neurotransmisores del medio extracelular sean el reflejo indirecto de la generación de potenciales de acción y del estado de neurotransmisión de los circuitos neuronales. Las células gliales inducen el desarrollo de la barrera y son los principales sensores de la función neuronal, debido a su capacidad de recaptación del exceso extracelular de potasio y de neurotransmisores. La homeostasis glial del medio extracelular es específica de circuito, limita el acoplamiento metabólico-funcional a regiones discretas del cerebro y genera el patrón de actividad heterogénea en los diversos módulos del tejido nervioso (AU)

Aims. To analyze the functional reasons justifying the existence of the blood-brain barrier with an emphasis on its fundamental role supporting neuroglial coupling. Development. We review in an integrated manner the contributions of different research areas in physiology and metabolism of the central nervous system which allow to understand the functional need for the existence of the blood-brain barrier. In particular, we describe the physiological basis of the metabolic-functional coupling and the metabolic interactions between neurons and glial cells, two properties directly derived from the presence of the blood-brain barrier. Likewise the blood-brain barrier is presented as an important determinant of the heterogeneous activation of cerebral tissue as detected by neuroimaging technologies as positron emission tomography and functional magnetic resonance imaging. Conclusions. The main function of the blood-brain barrier is to maintain a stable composition of the extracellular milieu in nervous tissue. This allows the changes in ionic composition and neurotransmitter concentration in the extracellular milieu, to reflect indirectly the generation of action potentials and the state of neurotransmission of neuronal circuits. Glial cells induce the development of the blood-brain barrier and are the main sensors of neuronal function, due to their important take up capacity for extracellular potassium and neurotransmitters. Glial homeostasis of the extracellular milieu is circuit-specific, limiting the functional-metabolic coupling to discrete regions of the brain and generating the classical pattern of heterogeneous activity in the different modules of the nervous tissue (AU)

[The role of the extra-intracranial anastomosis and interventionist endovascular therapy in the treatment of complex cerebral aneurysms]. / Papel de la anastomosis extra-intracraneal y de la terapia endovascular intervencionista en el tratamiento de aneurismas complejos cerebrales.

Cerebral revascularization is an useful tool in the treatment of giant or complex cerebral aneurysms that can not be clipped directly by different causes. In turn, interventionist endovascular therapy, an emergent technique with very good results in the treatment of cerebral aneurysms during the last five years, is a new complementary tool to cerebral revascularization for the treatment of complex aneurysms. In the present manuscript we emphasize the beneficial effect of revascularization, followed in a short period of time by the endovascular technique in order to either occlude the parent vessel or to exclude the aneurysm from cerebral circulation. Advantages of this form of therapy, as well as the selection of patients and the present revascularization procedures, are commented.

[Anatomic and hemodynamic study of anterior communicating artery complex]. / Bases anatómicas y hemodinámicas del complejo de la arteria comunicante anterior.

Anterior communicating artery complex accounts for the most frequent site of cerebral aneurysms and it is characterized by its great anatomical variability. The development of aneurysms in this complex has been associated with the asymmetry of its afferent vessels. An anatomical and hemodynamic study of the anterior communicating artery was performed. Twenty brain samples obtained from adult necropsies were studied by means of microsurgical dissection. Additionally; 118 cerebral angiographies from patients with spontaneous subarachnoid hemorrhage were studied. A high number of perforanting vessels originated at the anterior communicating artery complex was a relevant finding. The number, distribution and size of these vessels is reported accurately. Analysis of the angiographies showed the association between the existence of an anterior communicating artery aneurysm and the presence of a blood flow predominance through one of the two proximal anterior cerebral arterias.

Primary hypothalamic-third ventricle lymphoma. Case report and review of the literature.

Primary central nervous system lymphomas (PCNSL) are infrequent tumors and their presentation as a solitary hypothalamic-third ventricle mass can be considered exceptional. We report the case of a 57-year-old woman with progressive visual deterioration, diabetes insipidus and mental confusion. She had a diffuse and homogeneous tumoral lesion involving the third ventricle and the adjacent hypothalamic area with marked enhancement after contrast administration on both, competed tomography scan and magnetic resonance images. It was approached and partially resected by the translamina terminalis route. Histological diagnosis proved to be a diffuse non-Hodgkin lymphoma and the patient subsequently was treated with adjuvant radiotherapy and chemotherapy. Followup examination showed visual acuity recover but persistent confessional state. Eight similar well described cases reported in the literature are reviewed with a description of the major diffenciating features of this neurological entity. Treatment of PCNSL remains a challenge, and the topographical location within the hypothalamic-third ventricle area is even more complex.

Linfoma primitivo de hipotálamo. Caso clínico y revisión de la literatura / Primary hypothalamic-third ventricle lymphoma. Case report and review of the literature

Los linfomas primarios del sistema nervioso central son tumores infrecuentes cuya presentación clínica como una lesión aislada a nivel del tercer ventrículo y área hipotalámica puede considerarse excepcional. En este trabajo describimos el caso de una paciente de 57 años que presentaba un cuadro clínico de pérdida de visión, junto a diabetes insípida y Neurocirugía 2002; 13: 305-310 confusión mental y que fue diagnosticada mediante tomografia computerizada y resonancia magnética cerebral de una lesión tumoral situada en el tercer ventrículo y área hipotalámica adyacente. En ambas pruebas diagnósticas la tumoración captaba contraste de forma intensa y homogénea. Esta lesión se abordó quirúrgicamente a través de una vía translámina terminalis y fue extirpada parcialmente. El estudio anatomopatológico confirmó el diagnóstico de un finfoma no Hodgkin de tipo difuso y la paciente recibió un tratamiento complementario con quimioterapia y radioterapia. Durante la evolución postquirúrgica la paciente recuperó su agudeza visual pero mantuvo su estado de confusión mental. La revisión exhaustiva de la literatura ha evidenciado la existencia de tan sólo 8 casos similares descritos previamente. El tratamiento de los finfomas primarios del sistema nervioso central sigue constituyendo un desafio médico y quirúrgico, incrementándose en los casos con una localización topográfica en el área hipotalámica y del tercer ventrículo (AU)

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Bases anatómicas y hemodinámicas del complejo de la arteria comunicante anterior / Anatomic and hemodinamic, study of the anterior communicating artery complex

El complejo de la arteria comunicante anterior constituye la localización más frecuente de aneurismas cerebrales y se caracteriza por su gran número de variantes anatómicas. La presencia de aneurismas de la arteria comunicante anterior se ha asociado a la existencia de una asimetría de este complejo. El objetivo de este trabajo ha sido estudiar anatómica y hemodinámicamente el complejo de la arteria comunicante anterior. Se han estudiado 20 cerebros de cadáver adulto mediante disección microquirúrgica así como 118 angiografías cerebrales de pacientes diagnosticados de hemorragia subaracnoidea aneurismática. Uno de los hallazgos más relevantes del estudio microanatómico ha sido la observación de un elevado número de arterias perforantes con origen en el complejo de la arteria comunicante anterior. Se describe detalladamente el número, distribución y tamaño de cada uno de los vasos del complejo. Del análisis de las angiografías se destaca la asociación de aneurismas del complejo de la arteria comunicante anterior a la presencia de dominancia de flujo sanguíneo a través de una de las dos arterias cerebrales anteriores proximales (AU)

Papel de la anastomosis extra-intracraneal y de la terapia endovascular intervencionista en el tratamiento de aneurismas complejos cerebrales / The role of the extra-intracraneal anastomosis and interventionist endovascular therapy in the treatment of complex cerebral aneurysms

La revascularización cerebral es una herramienta muy útil en el caso de aneurismas gigantes o complejos que no pueden ser abordados directamente por diversos motivos. A su vez, la terapia endovascular intervencionista, técnica emergente con muy buenos resultados en aneurismas cerebrales en los últimos cinco años, constituye una nueva ruta complementaria a la cirugía revascularizadora en el tratamiento de estos aneurismas de difícil resolución. En el presente trabajo se destaca el beneficio de la realización de revascularización cerebral, seguida, en un corto espacio de tiempo, de terapia endovascular intervencionista. Ésta hará posible la oclusión del vaso proximal al aneurisma o excluirá a la malformación vascular de la circulación cerebral. Se resaltan las ventajas de dicha terapia frente a la cirugía directa, se discute la forma de seleccionar a los pacientes y se enumeran las técnicas de revascularización más actuales (AU)

Periosteal glomus tumor of the femur: a case report.

Osseous abnormalities produced by glomus tumors located in soft tissues of the periungual region have been described. More rare is the location of a glomus tumor within bone, which usually is located in the phalanx of the fingers. However, to the authors' knowledge, there is no previous description of a glomus tumor located in a periosteal location of a long bone. A 50-year-old man with a glomus tumor in a periosteal location of the lower metaphysis of the femur without neoplastic erosion of the cortical surface is reported. Magnetic resonance imaging and intraoperative ultrasonography were needed to locate the lesion.

Nonhistological diagnosis of human cerebral tumors by 1H magnetic resonance spectroscopy and amino acid analysis.

We describe a multivariate analysis procedure to classify human cerebral tumors nonhistologically in vitro, combining the use of 1H magnetic resonance spectroscopy (MRS) with automatic amino acid analysis of biopsy extracts. Eighty-one biopsies were obtained surgically and classified histologically in eight classes: high-grade astrocytomas (class 1, n = 19), low-grade astrocytomas (class 2, n = 10), normal brain (class 3, n = 9), medulloblastomas (class 4, n = 4), meningiomas (class 5, n = 18), metastases (class 6, n = 8), neurinomas (class 7, n = 9), and oligodendrogliomas (class 8, n = 4). Perchloric acid extracts were prepared from every biopsy and analyzed by high resolution 1H MRS and automatic amino acid analysis by ionic exchange chromatography. Intensities of 27 resonances and ratios of resonances were measured in the 1H MRS spectra, and 17 amino acid concentrations were determined in the chromatograms. Linear discriminant analysis provided the most adequate combination of these variables for binary classifications of a biopsy between any two possible classes and in multiple choice comparisons, involving the eight possible classes considered. Correct diagnosis was obtained when the class selected by the computer matched the histological diagnosis. In binary comparisons, consideration of the amino acid profile increased the percentage of correct classifications, being always higher than 75% and reaching 100% in many cases. In multilateral comparisons, scores were: high-grade astrocytomas, 80%; low-grade astrocytomas, 74%; normal brain, 100%; medulloblastomas, 100%; meningiomas, 94.5%; metastases, 86%; neurinomas, 100%; and oligodendrogliomas, 75%. These results indicate that statistical multivariate procedures, combining 1H MRS and amino acid analysis of tissue extracts, provide a valuable classifier for the nonhistological diagnosis of biopsies from brain tumors in vitro.