Recent research on changes in genomic regulation and protein expression in intracerebral haemorrhage

Intracerebral haemorrhage (ICH) is a devastating form of stroke that accounts for roughly 10% of all strokes and the effects on those that survive are often debilitating. To date, no suitable therapy exists. Recent work has examined alterations in gene and protein expression after ICH. The focus of this review is to outline the current knowledge of changes in genetic and protein expression after ICH and how those changes may affect the course of brain injury. Both animal and human data are reviewed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73607/1/j.1747-4949.2007.00160.x.pd

COMPARISON OF SELECTIVE AND NON SELECTIVE CYCLO-OXYGENASE 2 INHIBITORS IN EXPERIMENTAL COLITIS EXACERBATION: role of leukotriene B4 and superoxide dismutase

Context Nonsteroidal anti-inflammatory drugs are considered one of the most important causes of reactivation of inflammatory bowel disease. With regard to selective cyclo-oxygenase 2 inhibitors, the results are controversial in experimental colitis as well as in human studies. Objectives The aim this study is to compare nonsteroidal anti-inflammatory drugs effects, selective and non selective cyclo-oxygenase 2 inhibitors, in experimental colitis and contribute to the understanding of the mechanisms which nonsteroidal anti-inflammatory drugs provoke colitis exacerbation. Methods Six groups of rats: without colitis, with colitis, and colitis treated with celecoxib, ketoprofen, indometacin or diclofenac. Survival rates, hemoglobin, plasmatic albumin, colonic tissue of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, prostaglandin E2, catalase, superoxide dismutase, thiobarbituric acid-reactive substances, chemiluminescence induced by tert-butil hydroperoxides, and tissue and plasmatic leukotriene B4 were determined. Results The groups treated with diclofenac or indometacin presented lower survival rates, hemoglobin and albumin, higher tissue and plasmatic leukotriene B4 and tissue superoxide dismutase than the group treated with celecoxib. Ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib, concerning to survival rate and albumin. The groups without colitis, with colitis and with colitis treated with celecoxib showed leukotriene B4 and superoxide dismutase lower levels than the groups treated with nonselective cyclo-oxygenase 2 inhibitors. Conclusions Diclofenac and indometacin presented the highest degree of induced colitis exacerbation with nonsteroidal anti-inflammatory drugs, celecoxib did not show colitis exacerbation, and ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib. These results suggest that leukotriene B4 and superoxide dismutase can be involved in the exacerbation of experimental colitis by nonselective nonsteroidal anti-inflammatory drugs.Contexto Os anti-inflamatórios não-esteróides são considerados uma das mais importantes causas de reativação da doença inflamatória intestinal. Em relação aos inibidores seletivos da ciclo-oxigenase 2, os resultados são controversos tanto em estudos envolvendo humanos como na colite experimental. Objetivos Comparar os efeitos dos anti-inflamatórios não-esteróides, seletivos e não seletivos da ciclo-oxigenase 2, na colite experimental e, contribuir para o entendimento do mecanismo no qual os anti-inflamatórios não-esteróides provocam a exacerbação da colite. Métodos Seis grupos de ratos foram estudados: sem colite, com colite e com colite e tratados com celecoxib, cetoprofeno, indometacina ou diclofenaco. Foram determinadas a taxa de sobrevida, as concentrações de hemoglobina e albumina plasmática, as concentrações teciduais na mucosa colônica de interleucina-1ß, interleucina-6, fator de necrose tumoral alfa, prostaglandina E2, catalase, superóxido dismutase, substâncias reativas ao ácido tiobarbitúrico e quimiluminescência estimulada por hidroperóxido de tert-butil, e as concentraçãos plasmática e tecidual de leucotrieno B4. Resultados O grupo tratado com diclofenaco ou indometacina apresentaram as menores taxas de sobrevida, concentrações de hemoglobina e albumina, e as maiores concentrações plasmática e tecidual de leucotrieno B4 e tecidual de superóxido dismutase do que os groupos tratados com celecoxib. O grupo tratado com cetoprofeno apresentou um comportamento intermediário entre diclofenaco/indometacina e celecoxib, em relação a taxa de sobrevida e albumina. Os grupos sem colite, colite e colite tratado com celecoxib apresentaram menores concentrações de leucotrieno B4 e superóxido dismutase do que os grupos tratados com inibidores não seletivos ciclo-oxigenase 2. Conclusões Diclofenaco e indometacina apresentaram os maiores graus de exacerbação da colite entre os anti-inflamatórios não-esteróides, o celecoxib não apresentou exacerbação e o cetoprofeno apresenteou um comportamento intermediario entre diclofenaco/indometacina e celecoxib. Estes resultados sugerem que o leucotrieno B4 e superóxido dismutase estão envolvidos na exacerbação da colite experimental pelo anti-inflamatórios não-esteróides não seletivos ciclo-oxigenase 2.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade de Londrina Análises Clínicas e Toxicológicas Departamento de PatologiaUniversidade de Londrina Departamento de Medicina InternaUniversidade Estadual de São Paulo Faculdade de Medicina Departamento de PatologiaUniversidade de Londrina Laboratorio de Fisiopatologia de Radicais Livre

Src Family Kinases in Brain Edema After Acute Brain Injury

Brain edema, the first stage of intracranial hypertension, has been associated with poor prognosis and increased mortality after acute brain injury, such as ischemic stroke, intracranial hemorrhage (ICH), and traumatic brain injury (TBI). The acute brain injury often initiates release of many molecules, including glutamate, adenosine, thrombin, oxyhemoglobin, cytokines, reactive oxygen species (ROS), damage associated molecular pattern molecules (DAMPs), and others. Most of those molecules activate Src family kinases (SFKs), a family of proto-oncogenic non-receptor tyrosine kinases, resulting in blood-brain barrier (BBB) disruption and brain edema at the acute stage after brain injury. However, SFKs also contributes to BBB self-repair and brain edema resolution in the chronic stage that follows brain injury. In this review we summarize possible pathways through which SFKs are implicated in both brain edema formation and its eventual resolution