TY  - THES
A1  - Raslan, Furat
T1  - Pathomechanismen und Therapie der Kallikrein-Kinin-System vermittelten Hirnödembildung nach Neurotrauma
T1  - Blockade of bradykinin receptor B1 reduces brain injury in a mouse model of neurotrauma
N2  - In einem experimentellen Schädel-Hirn-Trauma-Modell der fokalen Kälteläsion bei der Maus wurde die Effektivität der B1R-Blockade untersucht. Die Ergebnisse dieser Untersuchung dokumentierten auf der Suche nach einer grundlegenden spezifischen Therapie des vasogenen traumatischen Hirnödems die B1R-Blockade als einen potentiellen Ansatz zu Reduktion der sekundären Hirn-schäden. Zum Einen konnte durch die selektive Blockade von B1R mit dem Präparat R-715 nach einer fokalen Kälteläsion im Mausmodell die Hirnschädigung um etwa 75 % gegenüber den Tieren der Kontrollgruppen reduziert werden. Zum Anderen lässt sich nach der B1R-Blockade u. a. eine signifikante Abschwächung des vasogenen Hirnödems um etwa 50 % im Vergleich zu den Tieren der Kontrollgruppen feststellen. Die Reduktion der sekundären Hirnschädigung durch die B1R-Blockade 24 Stunden nach der Läsionsinduktion macht die selektive B1R-Blockade als kausaler Therapie-ansatz eine interessante Behandlungsoption des posttraumatischen vasogenen Hirnödems.
N2  - B1R knockout mice showed less neuronal damage and developed significantly smaller brain lesions compared to wild-type controls (2.5±2.6 mm3 vs 11.5±3.9 mm3, mean±SD respectively; n=7; p=0.0008). Pharmacological blockade of B1R with the selective antagonist R-175 likewise salvaged lesioned tissue (2.6±1.4 mm3 vs 12.2±6.1 mm3, mean±SD respectively; n=7; p=0.0034), reduced vasogenic edema and gene expression of vasoactive and proinflammatory cytokines in the lesioned cortex. In contrast, B2R inhibition with Hoe-140 was less effective (p=0.0667). Inhibition of B1R attenuates brain damage in mice and may open new avenues for the management of clinical head injuries.
KW  - Schädel-Hirn-Trauma
KW  - Blut-Hirn-Schranke
KW  - Bradykininantagonist
KW  - Neuroprotektion
KW  - Hirnödem
KW  - Traumatic brain injury
KW  - brain edema
KW  - blood brain barier
KW  - bradykinin antagonist
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-71407
ER  - 
TY  - JOUR
A1  - Westermaier, Thomas
A1  - Stetter, Christian
A1  - Kunze, Ekkehard
A1  - Willner, Nadine
A1  - Raslan, Furat
A1  - Vince, Giles H.
A1  - Ernestus, Ralf-Ingo
T1  - Magnesium treatment for neuroprotection in ischemic diseases of the brain
JF  - Experimental and Translational Stroke Medicine
N2  - This article reviews experimental and clinical data on the use of magnesium as a neuroprotective agent in various conditions of cerebral ischemia. Whereas magnesium has shown neuroprotective properties in animal models of global and focal cerebral ischemia, this effect could not be reproduced in a large human stroke trial. These conflicting results may be explained by the timing of treatment. While treatment can be started before or early after ischemia in experimental studies, there is an inevitable delay of treatment in human stroke. Magnesium administration to women at risk for preterm birth has been investigated in several randomized controlled trials and was found to reduce the risk of neurological deficits for the premature infant. Postnatal administration of magnesium to babies after perinatal asphyxia has been studied in a number of controlled clinical trials. The results are promising but the trials have, so far, been underpowered. In aneurysmal subarachnoid hemorrhage (SAH), cerebral ischemia arises with the onset of delayed cerebral vasospasm several days after aneurysm rupture. Similar to perinatal asphyxia in impending preterm delivery, treatment can be started prior to ischemia. The results of clinical trials are conflicting. Several clinical trials did not show an additive effect of magnesium with nimodipine, another calcium antagonist which is routinely administered to SAH patients in many centers. Other trials found a protective effect after magnesium therapy. Thus, it may still be a promising substance in the treatment of secondary cerebral ischemia after aneurysmal SAH. Future prospects of magnesium therapy are discussed.
KW  - Medizin
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96729
UR  - http://www.etsmjournal.com/content/5/1/6
ER  -