Liggins Institute seminar: Preterm brain injury and Toll-receptors: Harnessing endogenous mechanisms for neuroprotection and Glutamate and its receptors in a model of infection related pre-oligodendrocyte injury Event as iCalendar

27 November 2013

4 - 5pm

Venue: Seminar Room 505-003, Building 505, 85 Park Road, Grafton

Preterm brain injury and Toll-receptors: Harnessing endogenous mechanisms for neuroprotection

Exposure to infection and secondary inflammation both before and after birth is highly associated with premature birth. Although infection has been commonly associated with neural injury, pre-clinical evidence suggests that whereas acute exposure to infection can trigger injury, longer exposure leads to both self-tolerance and variably either protection or sensitisation to injury from other insults. The molecular mechanisms of this variability have not been elucidated. While studies in fetal and newborn animals have highlighted a strong relationship between the Toll-like receptor (TLR) 4 agonist, lipopolysaccharide (LPS), and brain injury, very little is known regarding the involvement of other TLRs and which specific TLR signalling attenuates responses to subsequent acute injury. The objective of this study was to determine the effect of LPS and subsequent HI on key inflammatory genes within the fetal brain and to target relevant TLR receptors in order to mimic the neuroprotective effect of LPS preconditioning.

Presented by: Dr Mhoyra Fraser

Glutamate and its receptors in a model of infection related pre-oligodendrocyte injury.

Glutamate toxicity is thought to contribute to the pathogenesis of neonatal brain injury, however, its role in infection/inflammation-induced preterm brain injury, in particular the injury to developing oligodendrocytes, is not known. To examine this we used primary cultures of fetal ovine (day 90 of gestation; term gestation = 145) glial cells and firstly assessed the expression of AMPA and NMDA-type glutamate receptor subunits, as well as glutamate levels following 24-96h of exposure to TNF-α (100ng/mL) or LPS (1 ug/mL). We then examined the extent of developing oligodendrocyte death within a TNF-α and prostaglandin dependent pathway after glial inflammation. Results of these studies suggest a potential role for the involvement of a TNF-α-Cox-2-glutamate pathway in the damage of immature white matter associated with infection/inflammation.

Presented by: Luke Weaver-Mikaere


For more information, please contact: Elise Donovan , PhD Clint Gray , PhD Email: e.donovan@auckland.ac.nz Email: c.gray@auckland.ac.nz Phone: +64 9 923 4776                                           Phone: +64 9 923 4785