Mitochondria-targeted protective strategies for limiting injury in the developing brain. (360G-Wellcome-094823_Z_10_Z)

£1,096,179

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