Aşağıda yer alan makalede beyindeki serebral palsinin nedenlerinden biri olan ve emar bulgularında görülebilen periventrikuler lökomolazi periventricular leukomalacia (PVL)
bulgusu rastlanan fareler üzerinde yapılan hücre bazlı araştırmalarda mikroglial hücrelerde aktivasyon artışı görülmüş bu bu aktivasyon artışının önlenebildiği durumlarda serebral palsiye bağlı dejeneratif hücre kaybının azaltılabileceğine ışık tutulmuştur. Microglial hücrelerin aktivasyonunun hızlanmasına sebeb olabilecek iltihabi durumlar oksijensiz yada kansız kalma gibi hallerdir. Microglial hücrelerdeki bu aktivasyon artışı bir beyin hasarına yada akmadde (white matter) hasarına perinatal dönemde sbebeiyet vermektedir. PET bulguları ile de ilgili veriler ispat edilmiştir.
Bu bulgular ışığında tedavi edici etkileri özellikle insanlar üzerinde başarıyla uygulanmakta olan cerebrolysin in Microglial hücrelerdeki bu aktivasyon artışını azaltarak nörodejeneratif hastalıklarda başarıyla kullanılabilmektedir. Bu tedavi edici özelliği ile serebral palsi hastalığının önlenmesinde ve tedavisinde vojta ve bobath neurodevolepment yöntemleri ile bir arada başarı ile kullanılabilmektedir. Aşağıda yer alan makalelerin tıbbi terimler içeren karmaşık birerbir tercümesine yer verilmemiştir. Bu makaleler 2007 senesine ait çok güncel araçtırma sonuçları olup amerika ve ispanyada alanında otorite bilim grupları tarafından yayınlanmışlardır.
Microglial Activation in Perinatal Rabbit Brain Induced by Intrauterine Inflammation: Detection with 11C-(R)-PK11195 and Small-Animal PET
Sujatha Kannan 1*, Fadoua Saadani-Makki 1, Otto Muzik 2, Pulak Chakraborty 3, Thomas J. Mangner 3, James Janisse 4, Roberto Romero 5, and Diane C. Chugani 2
1 Carman and Ann Adams Department of Pediatrics, Wayne State University, Detroit, Michigan
2 Carman and Ann Adams Department of Pediatrics, Wayne State University, Detroit, Michigan; Department of Radiology, Wayne State University School of Medicine, Detroit, Michigan
3 Department of Radiology, Wayne State University School of Medicine, Detroit, Michigan
4 Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan
5 Perinatology Research Branch, NICHD, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland and Detroit, Michigan; Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan
* To whom correspondence should be addressed. E-mail: skannan@med.wayne.edu.
Abstract
Intrauterine infection can lead to a fetal inflammatory response syndrome that has been implicated as one of the causes of perinatal brain injury leading to periventricular leukomalacia (PVL) and cerebral palsy. The presence of activated microglial cells has been noted in autopsy specimens of patients with PVL and in models of neonatal hypoxia and ischemia. Activated microglial cells can cause oligodendrocyte damage and white matter injury by release of inflammatory cytokines and production of excitotoxic metabolites. We hypothesized that exposure to endotoxin in utero leads to microglial activation in the fetal brain that can be monitored in vivo by 11C-(R)-PK11195 (1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide)--a positron-emitting ligand that binds peripheral benzodiazepine receptor sites in activated microglia--using small-animal PET. Methods: Pregnant New Zealand White rabbits underwent laparotomy and were injected with 20 and 30 µg/kg of Escherichia coli lipopolysaccharide along the length of the uterus on day 28 of gestation. The pups were born spontaneously at term (31 d) and were scanned using small-animal PET after intravenous administration of 11C-(R)-PK11195 and by MRI on postnatal day 1. The standard uptake values (SUVs) of the tracer were calculated for the whole brain at 10-min intervals for 60 min after tracer injection. The pups were euthanized after the scan, and brains were fixed, sectioned, and stained for microglial cells using biotinylated tomato lectin. Results: There was increased brain retention of 11C-(R)-PK11195--as determined by a significant difference in the slope of the SUV over time--in the endotoxin-treated pups when compared with that of age-matched controls. Immunohistochemical staining showed dose-dependent changes in activated microglia (increased number and morphologic changes) in the periventricular region and hippocampus of the brain of newborn rabbit pups exposed to endotoxin in utero. Conclusion: Intrauterine inflammation leads to activation of microglial cells that may be responsible for the development of brain injury and white matter damage in the perinatal period. PET with the tracer 11C-(R)-PK11195 can be used as a noninvasive, sensitive tool for determining the presence and progress of neuroinflammation due to perinatal insults in newborns.
Cerebrolysin reduces microglial activation in vivo and in vitro: a potential mechanism of neuroprotection
All Words Any Words
Neurotrophins, such as NGF, BDNF and NT-3 play a regulatory role on the function of microglial cells in vivo and in vitro, and the identification of new compounds with neurotrophic properties is becoming a new strategy for the prevention and/or treatment of neurodegenerative disorders. In this study we describe the use of two different models to demonstrate the ability of Cerebrolysin to reduce microglial activation. The results of these in vitro and in vivo studies indicate that Cerebrolysin might exert a neuroimmunotrophic activity reducing the extent of inflammation and accelerated neuronal death under pathological conditions such as those observed in neurodegenerative diseases.
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Authored by Alvarez XA, Lombardi VR, Fernandez-Novoa L, Garcia M, Sampedro C, Cagiao A, Cacabelos R, Windisch M. Department of Neuropharmacology, EuroEspes Biomedical Research Center, Santa Marta de Babio, Bergondo, A Coruna, Spain.