MIF functional polymorphisms (-794 CATT5-8 and -173 G>C) are associated with MIF serum levels, severity and progression in male multiple sclerosis from western Mexican population.

Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue damage in multiple autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis. The role of MIF in multiple sclerosis (MS) and the contribution of its polymorphisms are unknown in our population. Therefore, we decided to investigate the genetic association of -794 CATT5-8 (rs5844572) and -173 G>C (rs755622) MIF polymorphisms with MS, clinical variables and MIF serum levels in the population of western Mexico. 230 MS patients diagnosed according to McDonald criteria and 248 control subjects (CS) were recruited for this study, both polymorphisms were genotyped by PCR and PCR-RFLP and MIF serum levels were measured by ELISA kit. Severity and progression of MS were evaluated by EDSS and MSSS scores, respectively. Genotypes carrying the 5 repeats alleles of -794 CATT5-8MIF polymorphism present higher MIF serum levels in comparison with no carriers, and the presence of 5,7 heterozygous genotype contribute to the increase of disease severity and damage progression in MS patients. Notably when we stratified by sex, an effect of risk alleles (7 repeats and -173*C) of both MIF polymorphisms on EDSS and MSSS scores on males was found (p < 0.01). This study suggests that polymorphic alleles of MIF polymorphisms could act as sex-specific disease modifiers that increase the severity and progression of MS in male Mexican-Mestizo western population.

Immunological regulation of neurogenic niches in the adult brain.

In mammals, neurogenesis and oligodendrogenesis are germinal processes that occur in the adult brain throughout life. The subventricular zone (SVZ) and subgranular zone (SGZ) are the main neurogenic regions in the adult brain. Therein, resides a subpopulation of astrocytes that act as neural stem cells (NSCs). Increasing evidence indicates that pro-inflammatory and other immunological mediators are important regulators of neural precursors into the SVZ and the SGZ. There are a number of inflammatory cytokines that regulate the function of NSCs. Some of the most studied include: interleukin-1, interleukin-6, tumor necrosis factor alpha, insulin-like growth factor-1, growth-regulated oncogene-alpha, leukemia inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, interferon-gamma, monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha. This plethora of immunological mediators can control the migration, proliferation, quiescence, cell-fate choices and survival of NSCs and their progeny. Thus, systemic or local inflammatory processes represent important regulators of germinal niches in the adult brain. In this review, we summarized the current evidence regarding the effects of pro-inflammatory cytokines involved in the regulation of adult NSCs under in vitro and in vivo conditions. Additionally, we described the role of proinflammatory cytokines in neurodegenerative diseases and some therapeutical approaches for the immunomodulation of neural progenitor cells.

Responses of glial cells to stress and glucocorticoids.

A growing body of evidence suggests that glial cells are involved in practically all aspects of neural function. Glial cells regulate the homeostasis of the brain, influence the development of the nervous system, modulate synaptic activity, and carry out the immune response inside the brain. In addition, they play an important role in the restoration of the nervous system after damage, and they also participate in various neurodegenerative disorders. In a similar way, the importance of stress and glucocorticoids (GCs) on brain function is being increasingly recognized. Within the brain, stress hormones target both neurons and glial cells. Through their actions on these cells, glucocorticoids exert organizational functions on various processes of the developing brain and contribute to neuronal plasticity in the adult brain. Moreover, stress and glucocorticoids have become especially attractive in the study of a number of neurodegenerative disorders. However, studies on the mechanisms behind glucocorticoid-induced regulation of brain function have been classically focused on their effects on neurons. In this review, we start by describing the main functions of glial cells and then proceed to present data highlighting the effects of stress and GCs on brain function. We conclude the review by presenting recent evidence linking stress and glucocorticoids to glial cell function.

Beneficial effects of alpha-lipoic acid plus vitamin E on neurological deficit, reactive gliosis and neuronal remodeling in the penumbra of the ischemic rat brain.

During cerebral ischemia-reperfusion, the enhanced production of oxygen-derived free radicals contributes to neuronal death. The antioxidants alpha-lipoic acid and vitamin E have shown synergistic effects against lipid peroxidation by oxidant radicals in several pathological conditions. A thromboembolic stroke model in rats was used to analyze the effects of this mixture under two oral treatments: intensive and prophylactic. Neurological functions, glial reactivity and neuronal remodeling were assessed after experimental infarction. Neurological recovery was only found in the prophylactic group, and both antioxidant schemes produced down-regulation of astrocytic and microglial reactivity, as well as higher neuronal remodeling in the penumbra area, as compared with controls. The beneficial effects of this antioxidant mixture suggest that it may be valuable for the treatment of cerebral ischemia in humans.

Utilización de prótesis de quitosana y silicona en la regeneración del nervio ciático axotomizado de ratas / Quitosan and silicon protesis of the axiotomized cyatic nerve in rats

Para la tubulización de nervios lesionados se ha utilizado silicona con buenos resultados en defectos menores de 3 cm. La silicona es considerada como un material inerte, pero tiene como inconveniente que no es absorbible y es necesaria una segunda cirugía para retirarla. Recientemente, se ha centrado el interés en la utilización de compuestos bioactivos, tales como, la quitosana, homopolímero de estructura lineal con enlaces1-4, N acetilglucosamina, obtenida de la desacetilación de la quitina. La quitosana es absorbible, hipoalergénica, inmunoestimulante y puede actuar como vehículo para liberación prolongada de compuestos. En este trabajo, fue usada para tubulizar el nervio ciático de ratas, para ello se compararon los efectos de ambas prótesis (silicona y quitosana), se analizó la supervivencia neuronal en el dominio medular del nervio ciático y la recuperación locomotriz por medio del índice funcional del nervio ciático. En ninguno de los grupos de animales tubulizados con quitosana o silicona se encontraron indicios de degeneración neuronal en el dominio medular correspondiente. Los animales tubulizados con prótesis de quitosana presentaron una mejor recuperación funcional, esto indica que las prótesis de quitosana produjeron efectos similares a los que resultaron con silicona. Una de las ventajas inmediatas por el uso de quitosana fue evitar una segunda cirugía para retirar la prótesis; sin embargo, este biomaterial posee muchas otras cualidades que facilitan la recuperación de nervios seccionados, mismas que deberán estudiarse utilizando otras técnicas.

Prednisone induces anxiety and glial cerebral changes in rats.

OBJECTIVE: To assess whether prednisone (PDN) produces anxiety and/or cerebral glial changes in rats. METHODS: Male Wistar rats were studied and 3 groups were formed (8 rats per group). The moderate-dose group received 5 mg/kg/day PDN released from a subcutaneous implant. In the high-dose group, implants containing PDN equivalent to 60 mg/kg/day were applied. In the control group implants contained no PDN. Anxiety was assessed using an open field and elevated plus-maze devices. The number of cells and cytoplasmic transformation of astrocytes and microglia cells were assessed by immunohistochemical analyses. RESULTS: Anxiety was documented in both groups of PDN treated rats compared with controls. The magnitude of transformation of the microglia assessed by the number of intersections was significantly higher in the PDN groups than in controls in the prefrontal cortex (moderate-dose, 24.1; high-dose, 23.6; controls 18.7; p < 0.01) and striatum (moderate-dose 25.6; high-dose 26.3; controls 18.9; p < 0.01), but not in hippocampus. The number of stained microglia cells was significantly higher in the PDN treated groups in the prefrontal cortex than in controls (moderate-dose, 29.1; high-dose, 28.4; control, 17.7 cells per field; p < 0.01). Stained microglia cells were significantly more numerous striatum and hippocampus in the high-dose group compared to controls. CONCLUSION: Subacute exposure to PDN induced anxiety and reactivity of microglia. The relevance of these features for patients using PDN remains to be elucidated.