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Modulation of Triggering receptor expressed in myeloid cells 2 by gene transfer as novel neuroprotective estrategy for neonatal hypoxic ischemic brain injury using behavioural outcome as readout (Neonatal HI injury)
Start date: Jun 16, 2011, End date: Jun 15, 2013 PROJECT  FINISHED 

Insults during the perinatal stage of brain development lead to major causes of neurological disability throughout life, ranging from motor deficits, cognitive limitations, learning difficulties and even severe disabilities, such as cerebral palsy. In term newborn infants, hypoxic-ischemic (HI) brain injury is the most common cause of encephalopathy and seizures. Despite major improvements in neonatal care, there are no established therapeutic procedures successful for the prevention or treatment of perinatal brain lesions. In contrast to the adult, the immature brain displays distinct physiological and morphological features as a consequence of its ongoing postnatal development. Furthermore, experimental evidences also suggest that the inflammatory response associated to a CNS injury is exacerbated during immaturity. As brain development substantially influences the progression and hallmarks of brain injury, it is not possible to apply the results of medical research obtained in adults reliably to babies. The neonatal brain damage is poorly characterized, in this sense, studies performed in several laboratories have shown that the production of inflammatory molecules and inducers of oxidative stress by inflammatory cell types contribute to extension of neuronal damage and tissue injury induced by neurodegeneration. The field of endogenous regulatory receptors modulating inflammatory cell activation is largely unknown in the brain and no studies have yet focused on the damaged neonatal brain. In consequence, reaching a detailed knowledge of the endogenous inflammatory regulation the CNS during the early postnatal stage is essential for the proper development of neuroprotective therapies specific for this period. The modulation of TREM2 by gene transfer accompanied by the determination of the behavioural analysis will help to understand the mechanism regulating inflammatory response in neonatal injured brain and to reach a potential target for treatment.

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