Dr. Robertson’s research is focused on identifying interventions that could minimize the neurological deficits that can persist after traumatic brain injury (TBI) in children. Following TBI, multiple pathologic intracellular cascades ensue, many of which involve mitochondrial dysfunction, which can lead to metabolic failure and cell death.
Dr. Robertson and her team are using a preclinical model to study potential disruption of mitochondrial function and alterations in cerebral metabolism. After the brain mitochondria are isolated, they measure mitochondrial respiration, calcium uptake, production of reactive oxygen species, membrane potential and the activity levels of key enzymes.
She has found that a substantial amount of mitochondrial dysfunction is present in the first six hours after TBI. Mitochondria isolated from the peri-trauma region show alterations in both active, phosphorylating respiration (State 3) and in resting (State 4) rates of respiration. In addition, she has shown a decrease in the activity of the mitochondrial enzyme pyruvate dehydrogenase, the enzyme that converts pyruvate to acetyl-Co A, the first substrate in the energy-producing Krebs cycle.
In a related study, Dr. Robertson is collaborating with investigators at the University of Pennsylvania to compare mitochondrial function after head injury in different clinically relevant models. They are testing whether the FDA-approved drug cyclosporin A is capable of mitochondrial rescue and improving histologic and neurologic outcomes after TBI. She is hopeful that treatments like these, targeted at mitochondrial rescue, will ultimately lead to the development of clinically useful neuroprotective strategies for the developing brain.
Dr. Courtney Robertson's Lab
- Casey PA, McKenna MC, Fiskum G, Saraswati M, and Robertson CL. "Early and sustained alterations in cerebral metabolism after traumatic brain injury in immature rats." J Neurotrauma. 2008 Jun;25(6):603-14. doi: 10.1089/neu.2007.0481.
- Ahn ES, Robertson CL, Vereczki V, Hoffman GE and Fiskum G. "Normoxic ventilatory resuscitation after controlled cortical impact reduces peroxynitrite-mediated protein nitration in the hippocampus." J Neurosurg. 2008 Jan;108(1):124-31. doi: 10.3171/JNS/2008/108/01/0124.
- Robertson CL, Saraswati M, and Fiskum G. "Mitochondrial dysfunction early after traumatic brain injury in immature rats." J Neurochem. 2007 Jun;101(5):1248-57. Epub 2007 Apr 2.
- Robertson CL, Soane L, Siegel ZT, Fiskum G. "The potential role of mitochondria in pediatric traumatic brain injury." Dev Neurosci. 2007. 101: 1248-57.
- Robertson CL, Puskar A, Hoffman GE, Murphy AZ, Saraswati M, Fiskum G. "Physiologic progesterone reduces mitochondrial dysfunction and hippocampal cell loss after traumatic brain injury in female rats." Exp Neurol. 2006. 197:235-43.
- Robertson C, Bucci C, Fiskum G. "Mitochondrial response to calcium in the developing brain." Res Brain Dev Brain Res. 2004. 151:141-8.
- Robertson CL, Bell M, Kochanek P, Adelson P, Ruppel R, Wisniewski S, Mi Z, Janesko K, Clark R, Jackson E. "Increased adenosine in cerebrospinal fluid after severe traumatic brain injury in infants and children: association with severity of injury and excitoxicity." Crit Care Med. 2001. 29:2287-93.