Research Mitochondrial damage and increased oxidative stress are key in many neurodegenerative diseases, such as Parkinson's disease and in acute brain injury after ischemia. In order to protect the brain, we need to understand where the damaging free radicals are generated and develop therapies to reduce free radical levels while increasing the cell's anti-oxidant capacity.
Currently my lab is testing three potential neuroprotective therapies.
- 1. Control of oxygen levels after ischemia to reduce reactive oxygen species generation.
- 2. Activation of the cell's intrinsic anti-oxidant defense systems by activation of the Nrf-2 system.
- 3. Treatment with the nerve growth factor brain-derived neurotrophic factor (BDNF) to protect cells from both acute and chronic insults.
The Nrf2 pathway induces antioxidant gene expression | 
Complex I-mediated respiration is defective in Ts16 |
Lab Techniques To address these questions we use primary cultures of neurons. Injury is induced by oxygen-glucose deprivation to model ischemia or by using mice with a genetic defect in Complex I of the mitochondrial electron transport chain. Mitochondrial function, intracellular calcium and oxidative stress are followed in live cells using fluorescence microscopy. These studies are complemented by measurements of cell survival and mitochondrial bioenergetics using a range of techniques including immunocytochemistry, spectrophotometry and oxygen respiration.
PublicationsSelected Recent Publications:
1. Bambrick L.L*, Mehrayban Z, Chandrasekaran K, Wright C and Fiskum G (2006) Calcium-induced mitochondrial dysfunction in cortical astrocytes and cerebellar granule neurons Journal of Bioenergetics and Biomembranes 38: 43-47.
2. Dorsey SG, Renn C, Carim-Todd L, Barrick CA, Bambrick LL, Krueger BK, Ward CW, Tessarollo L (2006) In vivo restoration of physiological levels of truncated TrkB.T1 receptor rescues neuronal cell death in a trisomic mouse model. Neuron 51: 21-28.
3. Hilton GD, Nunez JL, Bambrick LL, Thompson SM, McCarthy MM (2006) Glutamate-mediated excitotoxicity in neonatal hippocampal neurons is mediated by mGluR-induced release of Ca++ from intracellular stores and is prevented by estradiol. European Journal of Neuroscience 24:3008-1.
4. Kingsbury TK, Bambrick LL, Roby C, Krueger BK. (2007) Calcineurin activity is required for CREB-mediated gene transcription in cortical neurons. Journal of Neurochemistry 103: 761-770.
5. Bambrick LL*, Fiskum G (2008) Mitochondrial dysfunction in trisomy 16 mouse cortex. Brain Research 1188: 9-16.
6. Fiskum G, Mehrabian Z, Bambrick LL, Danilov C, McKenna MC, Hopkins I, Richards EM, Rosenthal RE, Postischemic hyperoxia promotes mitochondrial metabolic failure in neurons and astrocytes. Annals of the New York Academy of Sciences, in press.
7. Bambrick LL (2007) Complex I defect impairs mitochondrial function in mouse Ts16 brain. Abstract, Society for Neurosciences.
Laboratory PersonnelOther Resources Neuroprotection Research in the Department of Anesthesiology
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