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Ischemic brain injury: molecular mechanisms for protection and prevention.

Applicant Hirt Lorenz
Number 68306
Funding scheme Project funding
Research institution Service de Neurologie Département des Neurosciences Cliniques CHUV
Institution of higher education University of Lausanne - LA
Main discipline Pathophysiology
Start/End 01.11.2002 - 31.12.2006
Approved amount 260'000.00
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Keywords (5)

PROTHROMBIN; TRANSIENT FOCAL CEREBRAL; ISCHEMIA; MOUSE; NEUROPROTECTION

Lay Summary (English)

Lead
Lay summary
Stroke is a major cause of death and disability throughout the world. Most strokes are ischemic, which means that they arise from a lack of blood supply to a part of the brain. Understanding the mechanisms of cell death and survival is important to try and develop strategies to protect the brain in cerebral ischemia.
This project was aimed at studying molecular mechanisms underlying cell death or survival in cerebral ischemia. We have studied the role of the serine protease thrombin in cerebral ischemia, and have shown that it mediates ischemic neuronal death in an in vitro ischemia model (Exp Neurol 2006;198:199-203; Brain Research 2005;1051:117-22). We have also shown that thrombin can induce tolerance to cerebral ischemia, both in vitro and in vivo. The ischemic tolerance induced by thrombin is prevented by selective inhibition of the c-jun N-terminal kinase (manuscript submitted).
We have studied the role of aquaporins in cerebral ischemia and in ischemia associated oedema. We observed that there is a strong induction of aquaporin 4 on astrocytic end-feet 1 hour after ischemia onset, correlating with a very early hemispheric swelling (J Neurosci Res.2006;83:1231-40).
Using a novel protease resistant and cell penetrating peptide (D-JNKI1-XG102), we have shown that a selective inhibition of the c-jun N-terminal kinase after cerebral ischemia induces a strong neuroprotection with an extended therapeutic window (Nature Med, 2003;9:1180-6; Stroke 2004;35:1738-43). This work was awarded the Pfizer Price for fundamental neuroscience in 2005, and was thereafter supported by a KTI-CTI grant.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
112484 Investigation of the role of the serine protease thrombin in cerebral ischemia 01.01.2007 Project funding

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