Cerebral ischemia/Experimental stroke

The main types stroke are ischemic (85 %), due to an embolic thrombus, and hemorrhagic (15 %). The causes behind stroke are multifactorial where both genetics and associated life style factors, risk factors, such as hypertension, diabetes, dyslipidemia and smoking contributes strongly. However, despite 3 decades of intense research and the major investments into more than 1000 different molecules and principles, we are today practically at early treatment in selected cases (treatment before 3 hrs with thrombolysis) or cooling of the brain. There is a need for novel ways of treatment.

We have observed that cerebral ischemia, both forms, are associated with up regulation of endothelin and angiotensin receptors in smooth muscle cells of the ischemic brain vessels. The treatment with direct G-protein receptor inhibition towards these receptor subtypes, combined treatment, results experimentally in reduced infarct volume. Since the group of up regulated GPCR is not limited to these two, we are currently analysing the underlying signal-transduction mechanisms using the latest molecular biology experiments. With specific inhibition of protein kinases involved we observed markedly attenuated cerebral infarct volume, better neurology score and cerebral blood flow improvements.



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