Project name: AGE-RELATED DETERIORATION OF BIOLOGICAL PATHWAYS AND THEIR SIGNIFICANCE FOR BRAIN TISSUE REGENERATION AND FUNCTIONAL RECUPERATION AFTER STROKE.
Contracting authority: UEFISCDI
Cod Proiect: PN-II-ID-PCE-2011-3-0848
ProJect name: 314/2011
Starting date: 05.10.2011
Term: 36 months
Abstract: Ischemic stroke is the second leading cause of death and the primary cause for sustained disability worldwide for which no cure exists. Currently, there is much interest in harnessing the potential of stem cells in the brain for therapeutic purposes. However, data regarding the ability of antidepressants to potentiate ischemia-induced neurogenesis and enhance post-stroke recovery in aged animals is missing. Therefore the major aim of this proposal is to exploit the endogenous potential of brain self-repair to improve recovery of tissue and function after stroke.Using a systemic approach in a mouse model suitable to study the therapeutic potential of adult neurogenesis the major objectives of this proposal are: (i) develop novel strategies to repair the brain and restore function after stroke in aged mice by stimulation of endogenous neurogenesis; (ii) assess the capacity of the aged post-stroke rodent brain environment to support the migration and neuronal differentiation of newly generated post-stroke neurons; (iii) identify age-related changes in regulatory networks involved in healthy aging and post-stroke recovery at transcriptional level by prediction and informatical work bench. By this measure we expect to develop a pre-clinical protocol of improved post-stroke recovery based on enhancement of the endogeneous neurogenesis in aged animal models.
Abstract (ROM): Accidentul vascular ischemic este a doua cauza de deces si cauza primara de disabilitate pe termen lung, pentru care nu exista nici o terapie specifica. Astazi, exista un efort sustinut in ceea ce priveste valorificarea potentialului celulelor stem de la nivelul creierului in scop terapeutic. Cu toate acestea, lipsesc inca dovezi legate de abilitatea antidepresivelor de crestere a neurogenezei indusa de leziunea ischemica si de a imbunatati recuperarea dupa ischemia cerebrala. Din aceste motive obiectivul major al acestui proiect este acela de a exploata potentialul endogen de auto-reparare al creierului in scopul imbunatatirii recuperarii tisulare si functionale dupa accidentele vasculare ischemice. Folosind o abordare sistemica a potentialului terapeutic al neurogenezei adulte in cadrul modelului de ischemie cerebrala la soarece obiectivele majore ale acestui proiect sunt: i) dezvoltarea unor strategii de reparare a creierului si de restaurare a functiilor dupa ischemia cerebrala la soarecii batrani prin stimularea neurogeneyei endogene, ii) aprecierea capacitatii creierului imbatranit de a sustine si a asigura un mediu propice migrarii si diferentierii noilor celule neuronale formate, iii) identificarea schimbarilor legate de varsta in reglarea cailor implicate in imbatranire si recuperarea post/accident vascular la nivel transcriptional folosind metode informatice predictive. prin aceste masuratori ne asteptam sa dezvoltam un protocol preclinic de imbunatatire a recuperarii bazate pe stimularea neurogenezei endogene pe modele de animale batrane.