Biochemical events related to glial response in spinal cord injury / Eventos bioquímicos de respuesta glial en la fisiopatología de la lesión de médula espinal

Abstract Introduction: Spinal cord injury (SCI) is a devastating event with physical, psychological and socioeconomic implications. Morphophysiological changes are observed in the tissue close to the injury, which allow determining the functional recovery of the medullary segment and the effector organs that depend on the injured axonal tracts. Objective: To describe the most relevant sequential biochemical events of glial cells response after SCI. Materials and methods: A search of scientific publications released in the past 18 years was carried out in PubMed and Science Direct databases, with the terms spinal cord injury (SCI), SCI pathophysiology, SCI inflammation, microglia in SCI, glial scar and chondroitin sulfate proteoglycans (CSPG). Results: The pathophysiological processes resulting from SCI are determinant for the neurological recovery of patients. Activation of glial cells plays an important role in promoting bioactive molecules and the formation of physical barriers that inhibit neural regeneration. Conclusion: Knowledge of neurobiological changes after SCI allows a greater understanding of the pathophysiology and favors the search for new therapeutic alternatives that limit the progression of the primary injury and minimize secondary damage, responsible for neurological dysfunction.

Resumen Introducción. La lesión de la médula espinal (LME) es un evento devastador con implicaciones físicas, psicológicas y socioeconómicas. En el tejido cercano a la lesión se instauran cambios morfofisiológicos que determinan la recuperación funcional del segmento medular y de los órganos efectores dependientes de los tractos axonales lesionados. Objetivo. Describir los eventos bioquímicos secuenciales más relevantes de la respuesta de las células gliales posterior a la LME. Materiales y métodos. Se realizó una búsqueda de publicaciones científicas de los últimos 18 años en las bases de datos PubMed y ScienceDirect, bajo los términos en inglés spinal cord injury (SCI), SCI pathophysiology, SCI inflammation, microglia in SCI, glial scar y chondroitin sulfate proteoglycans (CSPG). Resultados. Los procesos fisiopatológicos que se producen después de la LME determinan la recuperación neurológica de los pacientes. La activación de las células gliales juega un papel importante, ya que promueve la producción de moléculas bioactivas y la formación de barreras físicas que inhiben la regeneración neural. Conclusión. El conocimiento de los cambios neurobiológicos ocurridos tras la LME permite una mayor comprensión de la fisiopatología y favorece la búsqueda de nuevas alternativas terapéuticas que limiten la progresión de la lesión primaria y que minimicen el daño secundario responsable de la disfunción neurológica.

Sex steroid hormones as neuroprotective elements in ischemia models.

Among sex steroid hormones, progesterone and estradiol have a wide diversity of physiological activities that target the nervous system. Not only are they carried by the blood stream, but also they are locally synthesized in the brain and for this reason, estradiol and progesterone are considered 'neurosteroids'. The physiological actions of both hormones range from brain development and neurotransmission to aging, illustrating the importance of a deep understanding of their mechanisms of action. In this review, we summarize key roles that estradiol and progesterone play in the brain. As numerous reports have confirmed a substantial neuroprotective role for estradiol in models of neurodegenerative disease, we focus this review on traumatic brain injury and stroke models. We describe updated data from receptor and signaling events triggered by both hormones, with an emphasis on the mechanisms that have been reported as 'rapid' or 'cytoplasmic actions'. Data showing the therapeutic effects of the hormones, used alone or in combination, are also summarized, with a focus on rodent models of middle cerebral artery occlusion (MCAO). Finally, we draw attention to evidence that neuroprotection by both hormones might be due to a combination of 'cytoplasmic' and 'nuclear' signaling.

Regulatory effect of Dimethyl Sulfoxide (DMSO) on astrocytic reactivity in a murine model of cerebral infarction by arterial embolization.

INTRODUCTION: The pathophysiology of cerebral ischemia is essential for early diagnosis, neurologic recovery, the early onset of drug treatment and the prognosis of ischemic events. Experimental models of cerebral ischemia can be used to evaluate the cellular response phenomena and possible neurological protection by drugs. OBJECTIVE: To characterize the cellular changes in the neuronal population and astrocytic response by the effect of Dimethyl Sulfoxide (DMSO) on a model of ischemia caused by cerebral embolism. METHODS: Twenty Wistar rats were divided into four groups (n= 5). The infarct was induced with α-bovine thrombin (40 NIH/Unit.). The treated group received 90 mg (100 µL) of DMSO in saline (1:1 v/v) intraperitoneally for 5 days; ischemic controls received only NaCl (placebo) and two non-ischemic groups (simulated) received NaCl and DMSO respectively. We evaluated the neuronal (anti-NeuN) and astrocytic immune-reactivity (anti-GFAP). The results were analyzed by densitometry (NIH Image J-Fiji 1.45 software) and analysis of variance (ANOVA) with the Graph pad software (Prism 5). RESULTS: Cerebral embolism induced reproducible and reliable lesions in the cortex and hippocampus (CA1)., similar to those of focal models. DMSO did not reverse the loss of post-ischemia neuronal immune-reactivity, but prevented the morphological damage of neurons, and significantly reduced astrocytic hyperactivity in the somato-sensory cortex and CA1 (p <0.001). CONCLUSIONS: The regulatory effect of DMSO on astrocyte hyperreactivity and neuronal-astroglial cytoarchitecture , gives it potential neuroprotective properties for the treatment of thromboembolic cerebral ischemia in the acute phase.

INTRODUCCIÓN: La fisiopatolog ía de la isquemia cerebral es fundamental para el diagnóstico oportuno, la recuperación neurológica, la instauración temprana del tratamiento y el pronóstico del evento isquémico. Los modelos experimentales de isquemia cerebral, permiten evaluar los fenómenos de respuesta celular y la posible neuroprotección por fármacos. OBJETIVO: caracterizar los cambios celulares en la población neuronal y la respuesta astrocitaria por efecto del dimetilsulfóxido (DMSO) en un modelo de isquemia por embolia cerebral. Métodos: Se utilizaron 20 ratas Wistar distribuidas en cuatro grupos (n =5). Se indujo embolia cerebral con α- trombina bovina (40 NIH/Unit.) y el grupo tratado recibió 90 mg (100 µL) de DMSO en NaCl (1:1 v/v) intraperitoneal por 5 días; el control isquémico, recibió solamente NaCl (placebo) y los dos grupos no isqu émicos (simulados) recibieron NaCl y DMSO respectivamente. Se evaluó la inmunoreactividad neuronal (anti-NeuN) y astrocitaria (anti-GFAP). Los resultados fueron analizados por densitometría (Fiji-Image J NIH 1.45 software) y análisis de varianza (ANOVA) con el programa Graph pad Prism 5. RESULTADOS: La embolia cerebral produjo lesiones reproducibles y confiables en corteza e hipocampo (CA1), similares a las de los modelos focales. El DMSO no revirtió la pérdida de la inmunoreactividad neuronal postisquemia, pero previno el daño morfológico neuronal y redujo significativamente la hiperreactividad astrocitaria en CA1 y corteza somatosensoria (p <0.001). CONCLUSIONES: El efecto regulatorio del DMSO sobre la hiperreactividad astrocitaria y la citoarquitectura neuronal - astroglial, le confiere características potencialmente neuroprotectivas para el tratamiento de la isquemia cerebral tromboembólica en fase aguda.