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Project
Interactions between estrogens and the insulin-likegrowth factor IGF-I in neuroprotection in focal cerebralischemia (FWOKN250)
Project summary in layman's terms
Ischemic stroke is the most common cause of disability in adults and the 3rd cause of death. It is brought about by a blocked blood vessel in the brain leading to neuronal death. Restoration of circulation via resolution of the blood clot in the vessel by treatment with tissue-type plasminogen activator is the only approved treatment. However, the majority of patients cannot be treated this way. In these patients, restoration of blood supply usually takes much longer and new treatments are needed in order to protect neurons before restoration of circulation. Brain ischemia leads to a cascade of pathological events (e.g. membrane depolarization, oxidative stress, inflammation, cell death) and it is the current concept that different levels of this cascade need to be targetted for effective treatment, for example by using a combination of neuroprotective factors. We have observed that insulin-like growth factor-I (IGF-I) and estradiol both are neuroprotective when given separately after induction of ischemic stroke. Moreover, these factors are even more effective when administered together. The current study is aiming at finding out how the two hormones work together in order to able to optimize the treatment protocol. We will use a relevant preclinical rat model of ischemic stroke to determine: 1) for each of the two hormones whether it influences the efficacy of the other one by using specific antagonists for estrogen and IGF-I receptors; 2) the working mechanism of IGF-I with special focus on modulation of neuroinflammation and cytokine expression.
Ischemic stroke is the most common cause of disability in adults and the 3rd cause of death. It is brought about by a blocked blood vessel in the brain leading to neuronal death. Restoration of circulation via resolution of the blood clot in the vessel by treatment with tissue-type plasminogen activator is the only approved treatment. However, the majority of patients cannot be treated this way. In these patients, restoration of blood supply usually takes much longer and new treatments are needed in order to protect neurons before restoration of circulation. Brain ischemia leads to a cascade of pathological events (e.g. membrane depolarization, oxidative stress, inflammation, cell death) and it is the current concept that different levels of this cascade need to be targetted for effective treatment, for example by using a combination of neuroprotective factors. We have observed that insulin-like growth factor-I (IGF-I) and estradiol both are neuroprotective when given separately after induction of ischemic stroke. Moreover, these factors are even more effective when administered together. The current study is aiming at finding out how the two hormones work together in order to able to optimize the treatment protocol. We will use a relevant preclinical rat model of ischemic stroke to determine: 1) for each of the two hormones whether it influences the efficacy of the other one by using specific antagonists for estrogen and IGF-I receptors; 2) the working mechanism of IGF-I with special focus on modulation of neuroinflammation and cytokine expression.
Date:1 Jan 2013 → 31 Dec 2013
Keywords:Pituitary Tumors, Gene Regulation, IGF-1, Hypophyse, Prolactin, PRL-R signalling pathways, In Situ Hybridization, Lymphohemopoietic System, Dopamine, PRL isoforms, Endocrinology, PRL gene regulation, termination of signalling, CIS and SOCS molecules, PRL, PRL-R pathways, Growth Hormone
Disciplines:Basic sciences, Biological sciences