La infusión intracerebroventricular prolongada de líquido cefalorraquídeo procedente de pacientes con esclerosis lateral amiotrófica provoca cambios histológicos en el cerebro y la médula espinal de la rata similares a los hallados en la enfermedad / Histological changes in the rat brain and spinal cord following prolonged intracerebroventricular infusion of cerebrospinal fluid from amyotrophic lateral sclerosis patients are similar to those caused by the disease

INTRODUCCIÓN: La exposición de líquido cefalorraquídeo (LCR) de pacientes con esclerosis lateral amiotrófica (ELA) induce efectos citotóxicos en cultivos celulares de neuronas motoras in vitro. MATERIAL Y MÉTODOS: Se seleccionó LCR de 32 pacientes con ELA que previamente habían demostrado efectos citotóxicos. Se implantaron con minibombas osmóticas intracerebroventriculares (ICV) en 28 ratas macho adultas y se dividieron en 3 grupos: 9 ratas de LCR de pacientes no-ELA, 15 ratas de ELA-LCR citotóxico y 4 ratas de una solución salina fisiológica. El LCR se administró por vía ICV de forma continua durante periodos de 20 o 43 días. Se realizó la evaluación clínica, electromiográfica y análisis de tejidos después de sacrificio a los 20, 45 y 82 días tras la cirugía. RESULTADOS: Los estudios inmunohistoquímicos muestran daño en los tejidos con características similares a las encontradas en formas esporádicas de ELA, tales como sobre expresión de cistatina C, transferrina y la proteína en el TDP-43 citoplasmática. Los primeros cambios observados parecían jugar un papel protector por la sobreexpresión de periferina, panAKT, fosfoAKT y metalotioneínas; esta expresión habría disminuido al momento de analizar las ratas que se sacrificaron al día 82, en el que hay un aumento de apoptosis. Los primeros cambios celulares identificados fueron la constatación de activación de la microglía seguido por astrogliosis con sobreexpresión de GFAP y proteína S100B. CONCLUSIONES: Nuestros datos parecen indicar que la ELA podría propagarse a través del LCR, y que la administración ICV de ELA-LCR citotóxico produce cambios similares a los encontrados en las formas esporádicas de la enfermedad

INTRODUCTION: Cerebrospinal fluid (CSF) from amyotrophic lateral sclerosis (ALS) patients induces cytotoxic effects in in vitro cultured motor neurons. MATERIAL AND METHODS: We selected CSF with previously reported cytotoxic effects from 32 ALS patients. Twenty-eight adult male rats were intracerebroventricularly implanted with osmotic mini-pumps and divided into 3 groups: 9 rats injected with CSF from non-ALS patients, 15 rats injected with cytotoxic ALS-CSF, and 4 rats injected with a physiological saline solution. CSF was intracerebroventricularly and continuously infused for periods of 20 or 43days after implantation. We conducted clinical assessments and electromyographic examinations, and histological analyses were conducted in rats euthanised 20, 45, and 82days after surgery. RESULTS: Immunohistochemical studies revealed tissue damage with similar characteristics to those found in the sporadic forms of ALS, such as overexpression of cystatin C, transferrin, and TDP-43 protein in the cytoplasm. The earliest changes observed seemed to play a protective role due to the overexpression of peripherin, AKTpan, AKTphospho, and metallothioneins; this expression had diminished by the time we analysed rats euthanised on day 82, when an increase in apoptosis was observed. The first cellular changes identified were activated microglia followed by astrogliosis and overexpression of GFAP and S100B proteins. CONCLUSION: Our data suggest that ALS could spread through CSF and that intracerebroventricular administration of cytotoxic ALS-CSF provokes changes similar to those found in sporadic forms of the disease

Histological changes in the rat brain and spinal cord following prolonged intracerebroventricular infusion of cerebrospinal fluid from amyotrophic lateral sclerosis patients are similar to those caused by the disease. / La infusión intracerebroventricular prolongada de líquido cefalorraquídeo procedente de pacientes con esclerosis lateral amiotrófica provoca cambios histológicos en el cerebro y la médula espinal de la rata similares a los hallados en la enfermedad.

INTRODUCTION: Cerebrospinal fluid (CSF) from amyotrophic lateral sclerosis (ALS) patients induces cytotoxic effects in in vitro cultured motor neurons. MATERIAL AND METHODS: We selected CSF with previously reported cytotoxic effects from 32 ALS patients. Twenty-eight adult male rats were intracerebroventricularly implanted with osmotic mini-pumps and divided into 3 groups: 9 rats injected with CSF from non-ALS patients, 15 rats injected with cytotoxic ALS-CSF, and 4 rats injected with a physiological saline solution. CSF was intracerebroventricularly and continuously infused for periods of 20 or 43days after implantation. We conducted clinical assessments and electromyographic examinations, and histological analyses were conducted in rats euthanised 20, 45, and 82days after surgery. RESULTS: Immunohistochemical studies revealed tissue damage with similar characteristics to those found in the sporadic forms of ALS, such as overexpression of cystatinC, transferrin, and TDP-43 protein in the cytoplasm. The earliest changes observed seemed to play a protective role due to the overexpression of peripherin, AKTpan, AKTphospho, and metallothioneins; this expression had diminished by the time we analysed rats euthanised on day 82, when an increase in apoptosis was observed. The first cellular changes identified were activated microglia followed by astrogliosis and overexpression of GFAP and S100B proteins. CONCLUSION: Our data suggest that ALS could spread through CSF and that intracerebroventricular administration of cytotoxic ALS-CSF provokes changes similar to those found in sporadic forms of the disease.

Astrocitos en las enfermedades neurodegenerativas (I): función y caracterización molecular / Astrocytes in neurodegenerative diseases (I): Function and molecular description

Introducción: Los astrocitos han sido considerados como células de sostén en el SNC. Sin embargo, hoy día se sabe que participan de forma activa en muchas de las funciones del SNC y que pueden tener un papel destacado en las enfermedades neurodegenerativas. Desarrollo: Se revisan las funciones del astrocito en el desarrollo y plasticidad del SNC, en el control sináptico, regulación del flujo sanguíneo, energía y metabolismo, en la barrera hematoencefálica, regulación de los ritmos circadianos, metabolismo lipídico y secreción de lipoproteínas y en la neurogénesis. Asimismo, se revisan sus marcadores y el papel de la astrogliosis. Conclusión: Los astrocitos tienen un papel activo en el SNC. Su conocimiento parece esencial para comprender los mecanismos de las enfermedades neurodegenerativas

Introduction: Astrocytes have been considered mere supporting cells in the CNS. However, we now know that astrocytes are actively involved in many of the functions of the CNS and may play an important role in neurodegenerative diseases. Development: This article reviews the roles astrocytes play in CNS development and plasticity; control of synaptic transmission; regulation of blood flow, energy, and metabolism; formation of the blood-brain barrier; regulation of the circadian rhythms, lipid metabolism and secretion of lipoproteins; and in neurogenesis. Astrocyte markers and the functions of astrogliosis are also described. Conclusion: Astrocytes play an active role in the CNS. A good knowledge of astrocytes is essential to understanding the mechanisms of neurodegenerative diseases

Astrocytes in neurodegenerative diseases (I): function and molecular description.

INTRODUCTION: Astrocytes have been considered mere supporting cells in the CNS. However, we now know that astrocytes are actively involved in many of the functions of the CNS and may play an important role in neurodegenerative diseases. DEVELOPMENT: This article reviews the roles astrocytes play in CNS development and plasticity; control of synaptic transmission; regulation of blood flow, energy, and metabolism; formation of the blood-brain barrier; regulation of the circadian rhythms, lipid metabolism and secretion of lipoproteins; and in neurogenesis. Astrocyte markers and the functions of astrogliosis are also described. CONCLUSION: Astrocytes play an active role in the CNS. A good knowledge of astrocytes is essential to understanding the mechanisms of neurodegenerative diseases.