Temporal profile of MicroRNA expression in contused cortex after traumatic brain injury in mice

MicroRNAs (miRNAs) were recently identified as important regulators of gene expression under a wide range of physiological and pathophysiological conditions. Thus, they may represent a novel class of molecular targets for the management of traumatic brain injury (TBI). In this study, we investigated the temporal profile of miRNA expression during the development of secondary brain damage after experimental TBI. For this purpose, we used a controlled cortical impact model in C57Bl/6 mice (n = 6) to induce a cortical contusion and analyzed miRNA expression in the traumatized cortex by microarray analysis during the development of secondary contusion expansion-i.e., at 1, 6, and 12 h after TBI. Of a total 780 mature miRNA sequences analyzed, 410 were detected in all experimental groups. Of these, 158 miRNAs were significantly upregulated or downregulated in TBI compared with sham-operated animals, and 52 miRNAs increased more than twofold. We validated the upregulation of five of the most differentially expressed miRNAs (miR-21*, miR-144, miR-184, miR-451, miR-2137) and the downregulation of four of the most differentially expressed miRNAs (miR-107, miR-137, miR-190, miR-541) by quantitative polymerase chain reaction (qPCR). miR-2137, the most differentially expressed miRNA after TBI, was further investigated by in situ hybridization and was found to be upregulated in neurons within the traumatic penumbra. This study gives a comprehensive picture of miRNA expression levels during secondary contusion expansion after TBI and may pave the way for the identification of novel targets for the management of brain trauma

The choroid plexus is a key cerebral invasion route for T cells after stroke.

Neuroinflammation contributes substantially to stroke pathophysiology. Cerebral invasion of peripheral leukocytes-particularly T cells-has been shown to be a key event promoting inflammatory tissue damage after stroke. While previous research has focused on the vascular invasion of T cells into the ischemic brain, the choroid plexus (ChP) as an alternative cerebral T-cell invasion route after stroke has not been investigated. We here report specific accumulation of T cells in the peri-infarct cortex and detection of T cells as the predominant population in the ipsilateral ChP in mice as well as in human post-stroke autopsy samples. T-cell migration from the ChP to the peri-infarct cortex was confirmed by in vivo cell tracking of photoactivated T cells. In turn, significantly less T cells invaded the ischemic brain after photothrombotic lesion of the ipsilateral ChP and in a stroke model encompassing ChP ischemia. We detected a gradient of CCR2 ligands as the potential driving force and characterized the neuroanatomical pathway for the intracerebral migration. In summary, our study demonstrates that the ChP is a key invasion route for post-stroke cerebral T-cell invasion and describes a CCR2-ligand gradient between cortex and ChP as the potential driving mechanism for this invasion route

Perioperative Strategien zur Regulierung des Sympathikotonus

Obwohl für verschiedene therapeutische Konzepte zur Verminderung der kardialen perioperativen Morbidität und Mortalität zunehmend Evidenz vorliegt, bleibt die tatsächliche Umsetzung solcher Konzepte im klinischen Alltag oft aus. Zwar ist einem großen Teil der klinisch tätigen Ärzte die wachsende Literatur bekannt; dieses Wissen wird aber nur in einem Teil der Fälle angewendet, selbst wenn allgemein akzeptierte Indikationen bestehen. Die vorliegende Übersichtsarbeit hat deshalb zum Ziel, die Gründe für die mangelnde Umsetzung aufzuzeigen und nochmals die wesentlichen Grundlagen sowie die klinische Bedeutung einzelner Strategien einschließlich des α2-Agonismus, der β-adrenergen Blockade und der Regionalanästhesien zusammenzufassen. Dies insbesondere im Hinblick auf die klinische Anwendung dieser Konzepte in einem allgemeinanästhesiologischen Umfeld. Zudem wird ein Ausblick in die auf "gene profiling" basierende individualisierte Pharmakotherapie der perioperativen Medizin von morgen gegebe