P R E F A C E 17th international conference on Brain Edema and Cellular Injury

International audienceBrain edema is frequently observed in various cerebral and non-cerebral disorders, including traumatic brain injury (TBI), cerebral ischemia, brain tumors, cardiac arrest, altitude sickness, and liver failure. Brain edema is acutely life threatening and part of the patho-physiology of brain insults. The development of new neuroimaging tools, as well as new molecular tools, has provided a new way to examine the process by which edema develops longitudinally and in real time both in preclinical models and in patients. The recent work in this field of research was presented at the 17th international conference on Brain Edema (2017), held on December 8-10, 2017 in the beautiful city of Guangzhou, China. Professor Anding Xu, a Neurologist from Jinnan University hospital, chaired the meeting. It was a unique occasion to gather many leading brain edema researchers from Asia, Europe, and North America for a 2-day meeting. The present special issue is a compilation of articles illustrating the scientific presentations during these 2 days of meetings. This special issue, comprising 19 articles, including reviews and original clinical and preclinical studies, presents the latest developments in the cellular and molecular complexity of brain edema and cellular injuries. In the first part, we present a collection of papers reviewing recent developments in molecular and cellular mechanisms of edema, neuroinflammation as well as the role of immune cells in various acute brain injuries. The second part of the special issue is a collection of original studies presenting new therapeutic approaches in addition to the molecular mechanisms of the secondary injuries in preclinical models. Three papers present the use of neuroimaging for prognostic factor and the quality of care for patient with subarachnoid hemorrhage (SAH)

Matemática,1º ano, 5ª edição, 1934.

O livro possui dimensões 220 mm X 160 mm, 394 páginas. O exemplar pertence ao acervo do GHEMAT na cidade de Osasco- SP. Doado pela professora Circe Dynnikov.O livro destina-se ao uso de professores e traz considerações teóricas e práticas de abordagens de conteúdos de matemática para o ensino primário. São temas tratados: numeração, adição subtração, multiplicação, divisão, potencia de número, múltiplo e divisor, números primos, frações, álgebra etc

Aquaporins in the brain: from aqueduct to "multi-duct”

The aquaporin channel family was first considered as a family of water channels, however it is now clear that some of these channels are also permeable to small solutes such glycerol, urea and monocarboxylates. In this review, we will consider AQP4 and AQP9 expressed in the rodent brain. AQP4 is present on astrocytic end-feet in contact with brain vessels and could be involved in ionic homeostasis. However, AQP4 may also be involved in cell adhesion. AQP4 expression is highly modified in several brain disorders and it can play a key role in the cerebral edema formation. However, the exact role of AQP4 in edema formation is still debated. Recently, AQP4 has been shown to be also involved in astrocyte migration during glial scar formation. AQP9 is expressed in astrocytes and in catecholaminergic neurons. Two isoforms of AQP9 are expressed in brain cells, the shortest isoform is localized in the inner membrane of mitochondria and the longest in the cell membrane. The level of expression of AQP9 is negatively regulated by high concentrations of insulin. Taken together, these results suggest that AQP9 could be involved in brain energy metabolism. The induction of AQP9 in astrocytes is observed with time after stroke onset suggesting participation in the clearance of excess lactate in the extracellular space. These recent exciting results suggest that AQPs may not only be involved in water homeostasis in the brain but could also participate in other important physiological function

Rôles des aquaporines dans le cerveau

Il y a maintenant plus d’une dizaine d’années que l’aquaporine 1 (AQP1) a été mise en évidence et clonée à partir des globules rouges. Cette découverte majeure pour le monde du vivant a été récompensée en 2003 par le Prix Nobel de Chimie décerné au Professeur Peter Agre. Les aquaporines (AQP) sont des canaux à eau. Cette famille de protéines est composée actuellement de onze sous-types différents exprimés chez les mammifères. Les trois AQP principales caractérisées dans le cerveau des mammifères sont l’AQP1, l’AQP4 et l’AQP9. Les travaux récents montrent que ces canaux sont impliqués dans différentes fonctions physiologiques. L’AQP1 serait importante dans la formation du liquide céphalorachidien, tandis que l’AQP4 aurait un rôle dans l’homéostasie de l’eau et de la pression osmotique du tissu nerveux. L’AQP9 serait impliquée dans le métabolisme énergétique. En condition physiologique, le niveau d’expression de ces AQP est finement régulé. Dans différentes maladies du système nerveux, le niveau d’expression de ces canaux est modifié, ce qui peut avoir des conséquences sur la formation de l’oedème cérébral en modifiant la perméabilité à l’eau. Actuellement, le rôle de chacune de ces AQP dans ce phénomène n’est pas encore compris. L’AQP4 semble avoir un rôle très important dans le développement de l’oedème après un traumatisme crânien, une lésion ou un accident vasculaire cérébral. Une meilleure compréhension des mécanismes de régulation des AQP permettra d’envisager de nouvelles stratégies thérapeutiques pour prévenir la formation de l’oedème cérébral. La découverte récente de l’AQP9 dans les neurones catécholaminergiques a modifié la vision du rôle des AQP dans le système nerveux, avec une implication possible de cette dernière dans le métabolisme énergétique cérébral.It is now over 10 years ago that aquaporin 1 (AQP1) was discovered and cloned from the red blood cells, and in 2003 the Nobel price in Chemistry was awarded to Pr. Peter Agre for his work on AQPs, highlighting the importance of these proteins in life sciences. AQPs are water channels. To date this protein family is composed of 11 sub-types in mammalians. Three main AQPs described in the mammalian brain are AQP1, AQP4 and AQP9. Several recent studies have shown that these channels are implicated in numerous physiological functions. AQP1 has a role in cerebrospinal fluid formation, whereas AQP4 is involved in water homeostasis and extracellular osmotic pressure in brain parenchyma. AQP4 seems also to have an important function in oedema formation after brain trauma or brain ischemia. AQP9 is implicated in brain energy metabolism. The level of expression of each AQP is highly regulated. After a trauma or an ischemia perturbation of the central nervous system, the level of expression of each AQP is differentially modified, resulting in facilitating oedema formation. At present, the exact role of each AQP is not yet determined. A better understanding of the mechanisms of AQP regulation should permit the development of new pharmacological strategies to prevent oedema formation. AQP9 has been recently specifically detected in the catecholaminergic neurons of the brain. This new result strengthens the hypothesis that the AQPs are not only water channels, but that some AQPs may play a role in energy metabolism as metabolite channels

Noninvasive magnetic resonance imaging stratifies injury severity in a rodent model of male juvenile traumatic brain injury

International audienc

Aquaporins and Their Regulation after Spinal Cord Injury

After injury to the spinal cord, edema contributes to the underlying detrimental pathophysiological outcomes that lead to worsening of function. Several related membrane proteins called aquaporins (AQPs) regulate water movement in fluid transporting tissues including the spinal cord. Within the cord, AQP1, 4 and 9 contribute to spinal cord injury (SCI)-induced edema. AQP1, 4 and 9 are expressed in a variety of cells including astrocytes, neurons, ependymal cells, and endothelial cells. This review discusses some of the recent findings of the involvement of AQP in SCI and highlights the need for further study of these proteins to develop effective therapies to counteract the negative effects of SCI-induced edema

Aquaporins in neurological disorders

Aquaporins (AQPs) are water channel molecules that allow the passage of water through the lipid bilayers of cell membranes. AQP1, AQP4 and AQP9 are expressed in the central nervous system and AQP4 is well known as the target of auto-antibodies in Devic’s neuromyelitis optica. The role of AQPs in facilitating water movements suggests a link with oedema formation and resolution in the brain. Furthermore, AQPs are also involved in process formation in glial cells with a close link to neuroinflammation. This mini-review gives an overview of what is currently known about the role of AQPs in different neurological disorders

Caveolin expression changes in the neurovascular unit after juvenile traumatic brain injury: signs of blood-brain barrier healing?

Traumatic brain injury (TBI) is one of the major causes of death and disability in pediatrics, and results in a complex cascade of events including the disruption of the blood-brain barrier (BBB). A controlled-cortical impact on post-natal 17-day-old rats induced BBB disruption by IgG extravasation from 1 to 3 days after injury and returned to normal at day 7. In parallel, we characterized the expression of three caveolin isoforms, caveolin 1 (cav-1), caveolin 2 (cav-2) and caveolin 3 (cav-3). While cav-1 and cav-2 are expressed on endothelial cells, both cav-1 and cav-3 were found to be present on reactive astrocytes, in vivo and in vitro. Following TBI, cav-1 expression was increased in blood vessels at 1 and 7 days in the perilesional cortex. An increase of vascular cav-2 expression was observed 7 days after TBI. In contrast, astrocytic cav-3 expression decreased 3 and 7 days after TBI. Activation of endothelial nitric oxide synthase (eNOS) (via its phosphorylation) was detected 1 day after TBI and phospho-eNOS was detected both in association with blood vessels and with astrocytes. The molecular changes involving caveolins occurring in endothelial cells following juvenile-TBI might participate, independently of eNOS activation, to a mechanism of BBB repair while, they might subserve other undefined roles in astrocytes

Small Interference RNA Targeting Connexin-43 Improves Motor Function and Limits Astrogliosis After Juvenile Traumatic Brain Injury

International audienceJuvenile traumatic brain injury (jTBI) is the leading cause of death and disability for children and adolescents worldwide, but there are no pharmacological treatments available. Aquaporin 4 (AQP4), an astrocytic perivascular protein, is increased after jTBI, and inhibition of its expression with small interference RNA mitigates edema formation and reduces the number of reactive astrocytes after jTBI. Due to the physical proximity of AQP4 and gap junctions, coregulation of AQP4 and connexin 43 (Cx43) expressions, and the possibility of water diffusion via gap junctions, we decided to address the potential role of astrocytic gap junctions in jTBI pathophysiology. We evaluated the role of Cx43 in the spread of the secondary injuries via the astrocyte network, such as edema formation associated with blood-brain barrier dysfunctions, astrogliosis, and behavioral outcome. We observed that Cx43 was altered after jTBI with increased expression in the perilesional cortex and in the hippocampus at several days post injury. In a second set of experiments, cortical injection of small interference RNA against Cx43 decreased Cx43 protein expression, improved motor function recovery, and decreased astrogliosis but did not result in differences in edema formation as measured via T2-weighted imaging or diffusion-weighted imaging at 1 day or 3 days. Based on our findings, we can speculate that while decreasing Cx43 has beneficial roles, it likely does not contribute to the spread of edema early after jTBI