BACKGROUND Cerebral malaria (CM) is a severe immunovasculopathy caused for Plasmodium falciparum infection, which is characterised by the sequestration of parasitised red blood cells (pRBCs) in brain microvessels. Previous studies have shown that some terpenes, such as perillyl alcohol (POH), exhibit a marked efficacy in preventing cerebrovascular inflammation, breakdown of the brain-blood barrier (BBB) and brain leucocyte accumulation in experimental CM models. OBJECTIVE To analyse the effects of POH on the endothelium using human brain endothelial cell (HBEC) monolayers co-cultured with pRBCs. METHODOLOGY The loss of tight junction proteins (TJPs) and features of endothelial activation, such as ICAM-1 and VCAM-1 expression were evaluated by quantitative immunofluorescence. Microvesicle (MV) release by HBEC upon stimulation by P. falciparum was evaluated by flow cytometry. Finally, the capacity of POH to revert P. falciparum-induced HBEC monolayer permeability was examined by monitoring trans-endothelial electrical resistance (TEER). FINDINGS POH significantly prevented pRBCs-induced endothelial adhesion molecule (ICAM-1, VCAM-1) upregulation and MV release by HBEC, improved their trans-endothelial resistance, and restored their distribution of TJPs such as VE-cadherin, Occludin, and JAM-A. CONCLUSIONS POH is a potent monoterpene that is efficient in preventing P. falciparum-pRBCs-induced changes in HBEC, namely their activation, increased permeability and alterations of integrity, all parameters of relevance to CM pathogenesis.

Abstract The influences of 3-N-butyphthalide (NBP) on early brain injury (EBI) induced via mild subarachnoid hemorrhage (SAH) and its mechanism were explored. Establishment of SAH model was via autologous blood injection. The protection of NBP on EBI in SAH model mice was evaluated. Determination of neuronal apoptosis was conducted. Detection of blood brain barrier (BBB), ZO-1, claudin-5, occludin and MMP-9 was manifested. The effects of NBP on oxidative stress, inflammation, and the SIRT1/NF-κB and the LKB-1/AMP-activated protein kinase (AMPK) pathways were investigated. NBP could alleviate neurological deficits and BBB dysfunction, repress cerebral edema and mitigate brain histomorphology. NBP repressed apoptosis in brain tissues, oxidative stress, inflammation, NF-κB activity but facilitated SIRT1. Finally, NBP activated the LKB-1/AMPK pathway. NBP may lighten BBB dysfunction, oxidative stress, inflammation and apoptosis after SAH via activating the LKB-1/AMPK pathway, thereby mitigating EBI.

BACKGROUND Cerebral malaria is a lethal complication of Plasmodium falciparum infections in need of better therapies. Previous work in murine experimental cerebral malaria (ECM) indicated that the combination of artemether plus intraperitoneal whole blood improved vascular integrity and increased survival compared to artemether alone. However, the effects of blood or plasma transfusion administered via the intravenous route have not previously been evaluated in ECM. OBJECTIVES To evaluate the effects of intravenous whole blood compared to intravenous plasma on hematological parameters, vascular integrity, and survival in artemether-treated ECM. METHODS Mice with late-stage ECM received artemether alone or in combination with whole blood or plasma administered via the jugular vein. The outcome measures were hematocrit and platelets; plasma angiopoietin 1, angiopoietin 2, and haptoglobin; blood-brain barrier permeability; and survival. FINDINGS Survival increased from 54% with artemether alone to 90% with the combination of artemether and intravenous whole blood. Intravenous plasma lowered survival to 18%. Intravenous transfusion provided fast and pronounced recoveries of hematocrit, platelets, angiopoietins levels and blood brain barrier integrity. MAIN CONCLUSIONS The outcome of artemether-treated ECM was improved by intravenous whole blood but worsened by intravenous plasma. Compared to prior studies of transfusion via the intraperitoneal route, intravenous administration was more efficacious.

Abstract The ovulation mechanism is one of the fascinating physiological processes in reproductive biology in mammals. From the reproductive point of view, the species have been classified as spontaneous or induced ovulators. Although the release of GnRH followed by the preovulatory LH surge is shared between both types of ovulation, the stimulus to initiate GnRH release varies between both categories. In spontaneous ovulators, ovulation depends on the systemic concentration of ovarian steroids, however, in induced ovulators, different stimuli such as copulation, environmental, and social cues can facilitate or induce ovulation regardless of the increases in systemic estradiol concentration. In this review, we document evidence that a male-derived protein is the main factor responsible for inducing ovulation and also modulating the ovarian function in the domestic South American camelid, the llama. The neurotrophin beta-Nerve Growth Factor (β-NGF) is the principal factor present in the semen of llamas responsible for inducing ovulation in this species. After the intrauterine deposit of semen during mating, β-NGF is absorbed through the endometrium to reach the circulatory system, where it reaches the hypothalamus and stimulates GnRH release. The potential site of action of this neurotrophin at the brain has not been elucidated, however, hypotheses are raised that the factor may cross the blood-brain barrier and stimulate upstream neuronal networks that lead to the stimulation of GnRH-secreting neurons. It is possible that β-NGF could be sensed at the median eminence without crossing the blood-brain barrier. Finally, it has been observed that this factor is not only a powerful stimulator of ovulation but also has a luteotrophic effect, resulting in the development of a corpus luteum capable of secreting more progesterone when compared to other ovulation-stimulating analogues. mammals view ovulators categories steroids however copulation environmental review malederived male derived camelid llama betaNerve beta Nerve βNGF β NGF (β-NGF mating system elucidated bloodbrain blood GnRHsecreting neurons Finally effect ovulationstimulating stimulating analogues

Resumen La infección por enterobacterias desencadena usualmente síntomas gastrointestinales caracterizados por vómito, diarrea y dolor abdominal, de severidad y curso variable. El compromiso extraintestinal esta descrito, inclusive sin las manifestaciones gastrointestinales clásicas lo que favorece diagnósticos y tratamientos tardíos pudiendo llegar a ser incapacitantes y letales. El síndrome de Ekiri, también denominado síndrome de encefalopatía letal tóxico, se caracteriza por una disfunción aguda del sistema nervioso central secundaria a infección por enterobacterias las cuales favorecen el desarrollo de microtrombos a nivel cerebral con inflamación mediada por el factor de necrosis tumoral α e IL- 1β y disfunción de la barrera hematoencefálica con una alta tasa de mortalidad. Dentro de nuestro conocimiento, presentamos el primer caso reportado en Colombia sobre el síndrome de Ekiri.

Abstract Gastrointestinal infection usually manifests with nausea, vomit and abdominal pain, all of them wit course and variable severity. Extrainstestinal compromise is described, even without gastrointestinal symptoms, what causes a delay on diagnosis and treatment, worsening the prognosis. Ekiri syndrome, also known as lethal toxic encephalopathy is characterized by an acute neurological dysfunction secondary to enterobacterial infection which favor thrombi development and local inflammation mediated by tumor necrosis factor alpha and IL-1β with blood brain barrier dysfunction and high mortality. As we know, we present the first Ekiri syndrome case reported in Colombia.

ABSTRACT Introduction: MASP-2 is a mannose blinding lectin associate to serine protease in cerebrospinal fluid and its dynamics through the blood brain barrier is unknown. Objective: To describe MASP-2 diffusion pattern from blood to cerebrospinal fluid. Methods: A transversal observational prospective study was performed 56 control samples of cerebrospinal fluid and serum were employed. ELISA measured MASP-2. Two groups were made: control patients without organic brain disease with normal cerebrospinal fluid and normal barrier function and patients without inflammatory diseases with a blood cerebrospinal fluid barrier dysfunction. Results: MASP-2 concentration in cerebrospinal fluid increase with augment the Q Albumin. QMASP-2 vs. Q Albumin saturation curve indicates that MASP-2 is interacting with other molecules in the subarachnoid environment. The higher inter-individual variation of cerebrospinal fluid MASP-2 of the control compared to the serum MASP-2 indicates that MASP-2 is a protein derived from blood. Conclusions: MASP-2 in CSF is predominantly blood-derived. The saturation curve demonstrates that MASP-2 interacts with the starters of the lectin pathway like mannose binding lectin, ficolins and collectin LK.

RESUMEN Introducción: MASP2 es una proteína de unión a manosa asociada a una proteasa de serina encontrada en la periferia, pero puede pasar a líquido cefalorraquídeo. Sin embargo, su dinámica a través de la barrera sangre-líquido cefalorraquídeo es aún desconocida. Objetivo: Describir la difusión del MASP-2 desde la sangre al líquido cefalorraquídeo. Métodos: Se realiza estudio observacional prospectivo de corte transversal donde se emplearon 56 muestras de suero y líquido cefalorraquídeo. Fue seleccionado un grupo control con pacientes sin enfermedad orgánica del cerebro, con líquido cefalorraquídeo y función de barrera normal y otro grupo de pacientes sin enfermedades inflamatorias del cerebro con disfunción de barrera sangre-líquido cefalorraquídeo. Resultados: La concentración de MASP-2 en líquido cefalorraquídeo aumentó con el incremento de la Q Albúmina. La curva de saturación de Q MASP-2 contra la Q Albúmina indicó que el MASP-2 se encuentra interactuando con otras moléculas en el espacio subaracnoideo. El aumento del coeficiente de variación individual de MASP-2 en líquido cefalorraquídeo de los controles comparado con el MASP-2 en suero indicó que el MASP-2 es una proteína derivada de la sangre. Conclusiones: La producción de MASP-2 en líquido cefalorraquídeo es predominantemente derivada de la sangre. La curva de saturación demostró que el MASP-2 interactúa con los iniciadores de la vía de las lectinas como lectina unida a manosa, las ficolinas y la colectina LK.

Abstract Purpose To investigate the role of Rosmarinic acid (RA) in the prevention of traumatic brain injury and the immunohistochemical analysis of IBA-1 and GFAP expressions. Methods Healthy male rats were randomly divided into 3 groups consisting of 10 rats. Groups were as follows; control group, traumatic brain injury (TBI) group, and TBI+RA group. After traumatic brain injury, blood samples were taken from the animals and analyzed with various biochemical markers. And then IBA-1 and GFAP expressions were evaluated immunohistochemically. Results Significant results were obtained in all biochemical parameters between groups. Immunohistochemical sections showed IBA-1 not only in microglia and macrophage activity but also in degenerative neurons in blood vessel endothelial cells. However, GFAP reaction and post-traumatic rosmarinic acid administration showed positive expression in astrocytes with regular structure around the blood vessel. Conclusion Rosmarinic acid in blood vessel endothelial cells showed that preserving the integrity of astrocytic structure in the blood brain barrier may be an important antioxidant.

Cryptococcus neoformans is an opportunistic pathogenic yeast that causes serious infections, most commonly of the central nervous system (CNS). C. neoformans is mainly found in the environment and acquired by inhalation. It could be metaphorically imagined that cryptococcal disease is a “journey” for the microorganism that starts in the environment, where this yeast loads its suitcase with virulence traits. C. neoformans first encounters the infected mammalian host in the lungs, a site in which it must choose the right elements from its “virulence suitcase” to survive the pulmonary immune response. However, the lung is often only the first stop in this journey, and in some individuals the fungal trip continues to the brain. To enter the brain, C. neoformans must “open” the main barrier that protects this organ, the blood brain barrier (BBB). Once in the brain, C. neoformans expresses a distinct set of protective attributes that confers a strong neurotropism and the ability to cause brain colonisation. In summary, C. neoformans is a unique fungal pathogen as shown in its ability to survive in the face of multiple stress factors and to express virulence factors that contribute to the development of disease.

ABSTRACT To study what kind of role uric acid play on the relationship between oxidative Stress and inflammation in peripheral and cerebral system of oxonate-induced hyperuricemic rats. Twenty-six eight male Wistar rats were divided into two groups randomly. Potassium oxonate was used to establish hyperuricemic model for four weeks. In 2nd and 4th week, uric acid (UA) level, total superoxide dismutase (T-SOD), Gu,Zn-SOD activity and interleukin-1beta (IL-1β) concentration in serum were determined respectively. In 4th week, one hour after last PO treatment, five rats of every group were given Evans Blue to test blood-brain barrier (BBB) permeability. Other brains were obtained to analysis T-SOD, Gu,Zn-SOD activity and IL-1β concentration in cerebral system. Meanwhile, brain and kidney were stained with hematoxylin and eosin (H&E) to observe pathological change. In 2nd week, both of T-SOD and Gu,Zn-SOD activity in serum increased obviously (P<0.05) in hyperuricemia rats. However, IL-1β content didn’t change remarkably. In the 4th week, T-SOD activity in model group had become similar with control group, and at the same time IL-1β content in serum increased significantly (P<0.05). Pathological section showed the structural and functional unit of the kidney had been damaged. On the contrary, both of T-SOD and Gu,Zn-SOD activity in brain increased obviously (P<0.05), but IL-1β concentration was no significant difference between two groups. In addition, the results of Evans Blue and H&E suggested the integrity of BBB and structure of brain were not changed after PO treatment. The permeability of BBB and form of UA would be potential factors to decide what kind role UA play on keeping balance between anti-oxidative stress and induction of inflammatory response.

Esta revisión comprende una descripción de los mecanismos propuestos para explicar el desarrollo de la enfermedad de Alzheimer (EA) y de las estrategias para su tratamiento a la luz de estos mecanismos, enfatizando la utilización de compuestos polifenólicos como agentes terapéuticos. Se analizan los efectos de especies reactivas de oxígeno ROS y presencia de metales redox en el desarrollo de EA y las estrategias de tratamiento, basadas en la actividad antioxidante y quelante de un medicamento y en sus alcances a través de vías de señalización. Dada la importancia de los polifenoles tipo flavonoides para el tratamiento de EA, se tienen en cuenta ejemplos con el flavonoide (-)-epigalocatequin-3-galato (EGCG), perteneciente a la familia de las catequinas. Es importante estudiar como intervienen los polifenoles a nivel celular (rol de su estructura química en la interacción con la célula y en su actividad biológica) con el fin de modular la interacción y las vías de señalización para lograr los efectos neurotróficos esperados. Los efectos in vitro, frecuentemente no corresponden a aquellos in vivo, dado que diferencias en concentraciones y condiciones de estudio hacen que las actividades química y biológica de un medicamento varíen. Esto puede ser debido en parte a la necesidad de un ajuste en concentraciones y tiempo entre los estudios pre clínicos y clínicos. Por otra parte, métodos de liberación eficientes deben ser investigados, teniendo en cuenta que un agente terapéutico para enfermedades neurológicas debería cruzar la barrera sanguínea-cerebral. La nanotecnología basada en sistemas de liberación controlada de medicamentos puede superar estas limitaciones.

This review includes a description of the proposed mechanisms to explain the development of Alzheimer's disease (AD) and strategies for treatment in the light of these mechanisms, with emphasis on the use of polyphenolic compounds as therapeutic agents. The effects of reactive oxygen species ROS and presence of metal redox in the development of AD and treatment strategies with a drug or active substance, based on antioxidant and chelating activity and in its potentiality through signaling pathways are analyzed. Given the importance of polyphenolic compounds as natural antioxidants for treating of AD, in special the flavonoids family, this review takes into account examples of this family, with emphasis on the catechin type flavonoid (-)-epigalocatechin-3-gallate (EGCG). Understanding of how polyphenols are involved at the cellular level (role of its chemical structure in the interaction with the cell and therefore its biological activity) is required in order to modulate the interaction and signaling pathways to achieve the desired neurotrophic effects. Effects in vitro often do not correspond to those in vivo. Differences in concentrations and study conditions make that chemical and biological activities of a drug vary. This may be due in part to the need for an adjustment in concentration and time between preclinical and clinical studies. Furthermore, efficient release methods should be investigated, particularly considering that a therapeutic agent for neurological diseases should cross the blood - brain - barrier (BBB). Nanotechnology based on controlled release systems of drugs may overcome these limitations.

Mientras que las neuronas juegan un papel fundamental en la neurotransmisión en el sistema nervioso central de los animales, las células gliales son cruciales para dar sostén a las neuronas y por lo tanto, para el funcionamiento del cerebro. Estudios recientes han puesto de manifiesto que las células gliales regulan la liberación y reciclaje de neurotransmisores, el metabolismo del piruvato y del glutatión, sirviendo de tampón para diferentes iones, participando en la organización de la barrera hematoencefálica y en la producción de mielina y del líquido cefalorraquídeo. La actividad de las células gliales se encuentra estrechamente coordinada por la comunicación entre las neuronas y la glía. Entre la señalización celular del cerebro, la vía Sonic Hedgehog (SHH) juega un papel importante al regular el desarrollo y patrón del sistema nervioso central. En el cerebro adulto, la proteína SHH es secretada por las neuronas y por los astrocitos y media de esa manera las interacciones neuro-gliales. Cuando ocurre un daño en el cerebro, la vía de señalización SHH es (re)-activada en el cerebro adulto. Las células gliales y particularmente los astrocitos, son células esenciales para la respuesta del cerebro frente a un daño y para su reparación. La respuesta de los astrocitos se encuentra mediada por la activación de la vía SHH en estas células. En este artículo se revisa la importancia de las células gliales y específicamente de los astrocitos en la fisiología del cerebro, la implicación de la vía de señalización SHH en la organización y funcionamiento del cerebro, y cómo la señalización SHH regula la re-activación de los astrocitos y la respuesta celular frente al daño tisular y a la reparación del cerebro en el organismo adulto.

While neurons play a key role in neurotransmission in the nervous central system (CNS) of animals, glial cells are crucial for neuron support and brain maintenance. Recent studies reveal that glial cells regulate the release and reuptake of neurotransmitters, pyruvate and glutathione metabolism, ion buffering, the organization of blood brain barrier and ensures the production of myelin and cerebrospinal fluid. The activity of glial cells is coordinated by the communication between neurons and the glia. Among cell signals in the brain, Sonic Hedgehog (SHH) pathway plays a key role regulating the development and the patterning of the central nervous system. In the adult brain, SHH has been found to be secreted by neurons and astrocytes, and to regulate in this manner, neuro-glial interactions. Upon brain injury, SHH signaling appears to be (re)- activated in the adult brain and may be related with tissue regeneration. The glial cells and more particularly astrocytes are key cells responding to brain injury and participating in brain repair. Interestingly, astrocyte response is mediated by SHH activation in these cells that elicits diverse cell reactions in the brain leading to neuroprotection and reinforcement of the blood brain barrier upon injury. This review highlights the important role of glial cells and more specifically of astrocytes in brain physiology, the implication of SHH signaling in brain organization and function, and finally, how SHH signaling regulates astrocyte re-activation and cell response to tissue injury and repair in the brain in the adult organism.

Bone damage and accidents, traumas can alter people's normal life, and damage the soft tissues. In this study, we aimed to investigate in calvarial defects in rats depending on the severity of cerebral contusion injury occurring in the temporal region. The rats were randomly divided into two groups: group 1 (control group), critical size cranial model with no treatment (n= 10); group 2 (14-day synthetic graft group given 7th day DEXA), critical size cranial model treated with Dexamethasone (0.05 mg/kg intramuscular injection) +Synthetic graft (n= 10) One calvarium defect of 7 mm was made in the parietal bone of each animal under general anesthesia. Calvarial defect results in dilatation of blood vessels, hemorrhage and deterioration was observed in glial fibrillary structures. Additionally, the increase in vascular endothelial growth factor expression showed a positive reaction with glial fibrillary acid protein astrocytes extensions. Apoptotic glial cells stained positive with Bcl-2. Calvarial defects caused by mild brain injury, to be induced by inflammatory cytokines, interrupting glial fibrillary degeneration by affecting the blood brain barrier is thought to promote apoptotic changes.

Daños óseos, accidentes y traumas pueden alterar la vida normal de las personas y dañar los tejidos blandos. Este estudio tuvo como objetivo investigar los defectos de calota en ratas en función de la gravedad de la lesión cerebral que ocurre en una contusión de la región temporal. Las ratas fueron divididas aleatoriamente en dos grupos: al grupo 1 (control), se le realizó un modelo de defecto craneal de tamaño crítico sin tratamiento (n= 10) y al grupo 2, se le realizó un modelo de defecto craneal de tamaño crítico que fue tratado con dexametasona (0,05 mg/kg vía i.m.) + injerto sintético (n= 10) (14 d con injerto sintético y el día 7 se le administró dexametasona). El modelo generó un defecto de 7 mm en el hueso parietal en cada animal, bajo anestesia general. Los defectos craneales produjeron dilatación de los vasos sanguíneos, hemorragias y deterioro en las estructuras gliales fibrilares. Además, el aumento de la expresión del factor de crecimiento vascular endotelial mostró una reacción con las positiva con la proteína ácida fibrilar de la glía el las extensiones de los astrocitos. Las células gliales apoptóticas se tiñeron positivas con Bcl-2. Los defectos de calota causan una lesión cerebral leve, inducidas por citoquinas inflamatorias, las que interrumpen la degeneración glial fibrilar al afectar la barrera hematoencefálica, induciendo cambios apoptóticos.

Microglial cells play a major role in the innate immunity of the central nervous system. Alterations in the normal cross-talks between microglia and brain neuronal cells may lead to serious disturbances and neurodegenerative diseases. We have postulated that neuroinflammatory processes are a critical factor triggering the pathological cascade leading to neuronal degeneration. In our neuroimmunomodulation theory, external or internal damage signals activate microglial cells, producing cytotoxic factors that induce neuronal degeneration. These factors activate protein-kinases, that lead to tau hyperphosphorylation, and its consequent oligomerization. The tau aggregates released into the extracellular medium favor a positive feedback mechanism that determines neurodegeneration. Nowadays, natural components with a string anti-inflammatory activity and that cross the blood brain barrier appears as candidates for prevention and treatment of degenerative brain disorders such as Alzheimers'disease.

Las células microgliales juegan un papel importante en la inmunidad innata del sistema nervioso central. Las alteraciones en la normal diafonía celular, entre microglias y células neuronales cerebrales, pueden conducir a graves disturbios y enfermedades neurodegenerativas. En este contexto, hemos postulado que los procesos neuroinflamatorios son un factor crítico a desencadenar la cascada patológica que conduce a la degeneración neuronal. En nuestra teoría Neuroinmunomoduladora, señales de daños externos o internos activan las células microgliales, favoreciendo la producción de factores citotóxicos que inducen la degeneración neuronal. Estos factores activan la proteína-quinasas, que conducen a la hiperfosforilación de la proteína tau, y su consecuente oligomerización. Estos agregados de tau liberados al medio extracelular, al activar a la célula microglial, provocarían un mecanismo de retroalimentación positiva favoreciendo la neurodegeneración. Hoy en día, compuestos de origen natural con una fuerte actividad anti-inflamatoria, capaces de cruzar la barrera hematoencefálica del cerebro, aparecen como candidatos para la prevención y el tratamiento de trastornos neurodegenerativos tales como la enfermedad de Alzheimer.

Abstract Multiple sclerosis (MS) is a chronic inflammatory and immune-degenerative disease that affects young people and has a high social impact due to direct and indirect costs. Objective: Regulate neurodegenerative process through a suitable modulation of inflammatory factors by using methylprednisolone and evaluation with Magnetic Resonance studies. Patients and methods: Female patients between the 1st and 5th decade of life, with diagnosis of Multiple Sclerosis, were included in the study if they met the criteria of McDonal 2010 (specially space and time monitoring) methylprednisolone boluses were administered regularly, even when the patient had no relapses, and the patients were then evaluated with Magnetic Resonance per annum, with a follow-up of up to 15 years. Results: There is a marked decrease of lesion in function of time and the bolus administration of methylprednisolone, and lesions disappeared entirely after 3 to 10 years of administration. Conclusions: The regular bolus administration of methylprednisolone attenuates the inflammatory process and the damage to the blood brain barrier and thus contributes in preventing neurodegeneration and is coadyuvant in remyelination.

Resumen La esclerosis múltiple (EM) es una enfermedad inmune-inflamatoria y crónico-degenerativa, que afecta a personas jóvenes y tiene un alto impacto social por los costos directos e indirectos. Objetivo: Regular el proceso neurodegenerativo a través de una adecuada modulación de los factores inflamatorios mediante el uso de metilprednisolona y la evaluación con estudios de resonancia magnética. Pacientes y métodos: Pacientes mujeres que se encuentran entre la 1ª y 5ª década de la vida, con diagnóstico de EM, que se incluyeron por cumplir con los criterios diagnósticos de McDonald 2010 (sobre todo la diseminación en tiempo y espacio). Se les administraron bolos de metilprednisolona de manera regular, aun cuando no presentaran recaídas y se evaluaron con estudios de resonancia magnética (RM) anual, con un seguimiento de hasta 15 años. Resultados: Se observa una marcada disminución de las lesiones en función del tiempo y la administración de los bolos de metilprednisolona, y entre los 3 y 10 años las lesiones desaparecen en su totalidad. Conclusiones: La administración de bolos de metilprednisolona de manera regular atenúa el proceso inflamatorio y el daño a la barrera hematoencefálica, y por lo tanto, coadyuva en la remielinización y previene la neurodegeneración.

OBJETIVO: Revelar a expressão e os possíveis papéis da aquaporina 9 (AQP9) no cérebro de ratos após lesão cerebral traumática (LCT) grave. MÉTODOS: Foram utilizados: determinação do conteúdo cerebral de água, corante cloreto de tetrazólio, corante azul de Evans, imunoistoquímica (IHQ), imunofluorescência (IF), western blot e PCR em tempo real. RESULTADOS: O conteúdo cerebral de água alcançou o primeiro e o segundo (o mais alto) picos após 6 e 72 horas. A função da barreira hematoencefálica se mostrou muito prejudicada após 6 horas da LCT. A pior isquemia cerebral ocorreu após 72 horas da LCT. Astrócitos AQP9 positivos e neurônios no hipotálamo foram detectados difusamente pela IHQ e IF após LCT. A abundância de AQP9 e de sua mRNA aumentou após LCT e alcançou dois picos após 6 e 72 horas, respectivamente, da LCT. CONCLUSÕES: AQP9 aumentada pode contribuir para a eliminação de água e lactato em excesso na fase precoce da LCT. Astrócitos difusamente localizados AQP9 positivos podem ajudar a entrada do lactato nos neurônios, promovendo edema cerebral celular na fase tardia da LCT. Neurônios AQP9 positivos sugerem que AQP9 tem um papel no equilíbrio energético após LCT.

OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9) in rat brain, after severe traumatic brain injury (TBI). METHODS: Brain water content (BWC), tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC), immunofluorescence (IF), western blot, and real-time polymerase chain reaction were used. RESULTS: The BWC reached the first and second (highest) peaks at 6 and 72 hours, and the blood brain barrier (BBB) was severely destroyed at six hours after the TBI. The worst brain ischemia occurred at 72 hours after TBI. Widespread AQP9-positive astrocytes and neurons in the hypothalamus were detected by means of IHC and IF after TBI. The abundance of AQP9 and its mRNA increased after TBI and reached two peaks at 6 and 72 hours, respectively, after TBI. CONCLUSIONS: Increased AQP9 might contribute to clearance of excess water and lactate in the early stage of TBI. Widespread AQP9-positive astrocytes might help lactate move into neurons and result in cellular brain edema in the later stage of TBI. AQP9-positive neurons suggest that AQP9 plays a role in energy balance after TBI.