Show simple item record

dc.contributor.authorAngus, Ruth
dc.identifier.citationAngus, R. 2017. In vivo and in vitro studies on docosahexaenoic acid in traumatic brain injury. Queen Mary University of Londonen_US
dc.description.abstractTraumatic brain injury (TBI) is a devastating disease causing disability and death, and currently there are no effective treatments available. Therefore, there is an utmost need to improve our understanding of the pathophysiology of TBI and to identify potential therapies that can provide neuroprotection after injury. The aims of this thesis were to develop an in vivo and in vitro model of TBI, in which to assess the potential neuroprotective effects of an omega-3 polyunsaturated fatty acid (PUFAs), docosahexaenoic acid (DHA). Method The controlled cortical impact (CCI) in vivo model of TBI was optimized and performed in mice. Both a behavioural (Morris water maze (MWM) for cognitive deficits) and histological endpoints (astrogliosis, lesion size and activated microglia) were used to assess severity and neuroprotective effects of DHA. An in vitro model of mechanical TBI was also set up and optimized. This model employed 3D astrocyte cultures obtained from GFP positive rat pups. The CCI impactor from the in vivo studies was used to damage the cultures, and at 24 hours, 5 days and 10 days the astrogliosis and cell number was measured. Results The optimization of the in vivo studies demonstrated that at impaction depth of 2.2 mm produced an injury that was significantly different to the sham injury, in MWM performance and increased astrogliosis. Interestingly, there was an increase in the amount of astrogliosis on the contralateral side of the brain. A second study performed using the 2.2 mm injury parameters was performed, where an injection of DHA was administered via the tail vein 30 min after injury. The DHA-treated group did not demonstrate any neuroprotection compared to the injury-only group. However, there was an increase in the amount of astrogliosis in the contralateral hippocampus of the DHA-treat group. In the fat-1 studies it was shown that older male mice performed worse in the MWM, that the fat-1 gene did not confer neuroprotection but did lead to increased astrogliosis. The in vitro study revealed that astrocytes in the lesioned gels demonstrated an increase in astrogliosis, there was also an increase in the number of cell in the cultures following the lesion. Conclusion In conclusion, the in vivo model of CCI replicated components of the human TBI including a behavioural deficit and pathophysiological changes. Omega-3 PUFAs failed to demonstrate functional neuroprotection in this model, but histologically, promoted an increase in reactive astrogliosis. The development of a novel in vitro model of focal injury in a 3D culture system, that elicits reactive astrogliosis, could be used to support further studies of the astrocytic responses to mechanical injury.en_US
dc.description.sponsorshipMedical Research Councilen_US
dc.publisherQueen Mary University of Londonen_US
dc.rightsThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author
dc.subjectNeuroscience and Traumaen_US
dc.subjecttraumatic brain injuryen_US
dc.titleIn vivo and in vitro studies on docosahexaenoic acid in traumatic brain injuryen_US

Files in this item


This item appears in the following Collection(s)

Show simple item record

Return to top