Bipolar disorder (BD), previously known as manic depressive disorder, is associated with recurring episodes of depression and mania/hypomania. Currently, no definitive biological mechanisms have been pinpointed with regards to the origin and progression of BD, however, inflammation and oxidative stress have been shown to present in the brains of individuals with BD. Notably, other neurodegenerative disorders which also contain an inflammatory component including Alzheimer’s disease and Multiple Sclerosis display with disruption of the brain blood barrier (BBB). We thus propose a model of BD wherein BBB disruption facilitates inflammation and oxidative stress induced neural damage.
This study looked to utilize amphetamine (AMPH) induced mania model and lipopolysaccharide (LPS) induced inflammatory model to represent BD like conditions in rats and to assess BBB permeability. We observed elevated locomotor data in response to AMPH administration and a trend of increased BBB permeability across regions following low dose chronic AMPH injections. In the LPS induced BBB permeability model, we did not detect any elevated serum C-reactive protein (CRP) or tumour necrosis factor alpha (TNF-α) levels but did see significantly elevated BBB permeability in the LPS group and lithium pre-treatment providing some protection against BBB permeability in one of our cohorts. These trends were further corroborated by a follow-up study and thus
warrant further investigation into the mechanistic nature of BBB breakdown in this model. This may provide a breakthrough in understanding the pathophysiology of BD and the underlying mechanistic effects of lithium, paving the way for new more target therapeutic remedies to combat this debilitating disorder. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/20438 |
| Date | January 2016 |
| Creators | Patel, Jay P. |
| Contributors | Frey, Benicio N., Neuroscience |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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