Nitroxidative Stress Induced Neurodegeneration In Intracerebral Hemorrhagic Stroke-a Nanomedical Approach
The aim of this work was to study an imbalance between nitric oxide (NO) bioavailability and nitroxidative stress during intracerebral hemorrhage stroke (ICH). Microliters of blood, platelets and leucocytes were injected directly into the caudate putamen of Sprague-Dawley Kyoto rats. Nitric oxide, superoxide (O 2 . -),and peroxynitrite (ONOO -) were measured with nanosensors implanted into the caudate putamen. After injection of 5-50 microliters of blood, significant decrease in NO concentration was recorded at 6 hour post stroke and resulted in excessive clot formation. The concentrations of both O 2 . -and ONOO -reached their maxima 12 hours after ICH. A main sources of O 2 . -and ONOO -were uncoupled endothelial (eNOS) and neuronal (nNOS) nitric oxide synthases. As a consequence, endothelial dysfunction as well as defective circulation of platelet and leucocytes were observed. ICH modeling performed with the injection of platelet, resulted in a larger infarct size than that observed after the injection of the whole blood or leucocytes. ICH induced nitroxidative stress caused differences in enzymatic expression. Maximal expression of eNOS and nNOS were shifted in time (1 hour and 3 hour post-stroke, respectively). Expression of MnSOD was the highest at 12 hour post-stroke, and correlated positively with a highest concentration of ONOO -and protein nitration. L-arginine treatment before ICH resulted in decrease of ONOO -concentration, increase in bioavailable NO and improved the locomotor function in post-stroke animals. The increase in NO bioavailability by exogenous L-arginine and decrease in ONOO -associated with improved coupling of constitutive (eNOS and nNOS) nitric oxide synthases. Therefore, a supplementation of L-arginine may be of significance in treatment of ICH.
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:intracerebral hemorrhage stroke nitric oxide synthase superoxide peroxynitrite l arginine
Date of Publication:01/01/2007