Mitochondria-targeted protective strategies for limiting injury in the developing brain. (360G-Wellcome-094823_Z_10_Z)
We have established a Strategic Initiative to combat cerebral palsy, focussing on the mechanisms and treatment of perinatal brain damage. Brain injury evolves over many hours after the insult, and interventions (hypothermia) administered after hypoxia-ischaemia improves outcome. However, hypothermia only saves one baby in eight and we need to obtain a better understanding of the pathophysiology to improve things further. Our hypothesis is that mitochondrial membrane permeabilization (MP) trigge red by the pro-apototic protein Bax is a key event in secondary brain injury. More specifically the research objectives are to explore (i) the role of Bax/Bak dependent permeabilization in hypoxia-ischemia; (ii) to what extent the up-stream regulation of MP involves cytosolic p53 and caspase-2 and (iii) how these mechanisms are modulated by inflammation. As injury in both white and grey matter is common in preterm and term infants, we will investigate mechanisms in neurons and oligodendrocyte pr ecursors (OPCs) using in vivo (transgenic mice, siRNA) and in vitro (cell lines, primary cultures, and isolated mitochondria) models. This work will increase understanding of the mechanisms of perinatal brain injury and result in development of cerebroprotective strategies to reduce the severe adverse consequences of injury in the immature brain.
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Grant Details
Amount Awarded | 1096179 |
Applicant Surname | Hagberg |
Approval Committee | Neurosciences And Mental Health |
Award Date | 2011-03-03T00:00:00+00:00 |
Financial Year | 2010/11 |
Grant Programme: Title | Programme Grant |
Internal ID | 094823/Z/10/Z |
Lead Applicant | Prof Henrik Hagberg |
Other Applicant(s) | Dr Etienne Jacotot, Prof Anthony Edwards, Prof Pierre Gressens |
Partnership Value | 1096179 |
Planned Dates: End Date | 2012-08-31T00:00:00+00:00 |
Planned Dates: Start Date | 2011-09-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |