Zytokinexpression in der ischämischen Penumbra nach transientem Verschluß der A. cerebri media in der Ratte
The present study examined dynamic processes within the ischemic penumbra at various times after transient (3h) ischemia. We chose the intraluminal suture method to produce an occlusion of the middle cerebral artery (MCA-O) in rats. The animals were killed at 1, 3, 7 or 14 days following operation. Coronal brain sections were processed for astroglial (GFAP), microglial (OX 42), cytokin (IL-1-beta, IL-6, TNF-alpha), and apoptotic (TUNEL) markers, for i-NOS and n-NOS activity, and NISSL-staining. The MCA-O led to a reproducible cell death in the lateral and medial part of the striatum and in the adjacent cortex. In this study it was possible to show a long lasting inflammation up to day 14 after the focal cerebral ischemia by immunohistochemistry. These inflammatory processes could be related to neuronal cell death. The cytokines IL-1-beta, IL-6, and TNF-alpha were expressed up to day 14 inthe ischemic penumbra. According to the shape of these cells they seemed to be glia or neurons. At the same time an expression of the inducible nitric oxide synthase took place which led to the production of the gas NO und at least to the formation of the heavily zytotoxic agent peroxinitrite. The expression of i-NOS remained raised up to day 14 after ischemia, too. With the help of TUNEL-staining ("TdT-mediated dUTP nick end labeling") which detects necrosis and apoptosis a degeneration of cells was found in this study. A decline of intact neurons was indicated by the neuronal marker n-NOS which was expressed by a small group of neurons. Even two weeks after the ischemic infarct indications for neuronal cell degeneration in the penumbral zone could be found. The results of the present study reflect that dynamic processes in the ischemic penumbra hold on even until day 14 after ischemia. This knowledge has to be taken into consideration for future research which will include the development of pharmaceuticals suitable for neuroprotection.
info:eu-repo/classification/ddc/610, Medizin
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