Adrian M. Corbett

Biography

Ph.D., University of Miami (Florida), 1984 Associate Professor, Neuroscience Cell Biology & Physiology , works in  Biological Sciences Bldg II 247, 3640 Colonel Glenn Hwy., Dayton, OH 45435-0001

Research Interest

Since 2008, she have worked on the pharmacological increase of adult neurogenesis in middle aged rats (generally post-menopausal in female rats). Her basic premise was that many disease states and brain injuries are often worse (show less recovery) when patients are older: if they can make an older brain behave like a younger brain, then functional recovery from any form of brain injury in an older animal should be improved. She have focused on manipulating adult neurogenesis, since increases in neurogenesis are tied to increases in nerve growth factors. Increased nerve growth factors should help an injured nerve survive, reducing injury, and would also help to rewire cortical circuits through increased plasticity in the surviving neurons if some neurons die. They have evaluated this drug treatment as a post-stroke treatment in middle aged rats, showing some amazing functional recovery in grasping after they have targeted the forelimb motor cortex for the ischemic stroke. Interestingly, this treatment, using a combination of Fluoxetine, simvastatin and ascorbic acid, works by a number of different pathways. They believe that the fluoxetine in the injured brain is changing the M1 inflammatory type of microglia into the M2 type, which releases BDNF (see picture). Further evidence to support this comes from our most recent paper (submitted), where they see that ischemic stroke animals treated with our drug combination do not show evidence of extensive infiltrating macrophages and leukocytes and have reduced blood brain barrier permeability, resulting in a smaller infarct volume as well as reducing possible brain edema. Much of the neuronal injury in the infarct is believed to be due to damage caused by M1 type microglia releasing inducible nitric oxide (NOS2) and other inflammatory cytokines, damage that is missing in our treated animals (see 2015 Journal of Neurology and Neuroscience article). They have confirmed in control versus drug combination treated stroked rat brains, using real time PCR custom microarrays with cDNA reversed transcribed from the mRNA in the peri-infarct region, that our drug treatment reliably reduces Nos2, Il1, Tnfa, Fas, Il6, Mmp9 and other proinflammatory cytokines, while increasing Bdnf, Npy, Hpcrt or its receptors (males versus females), Fgf9, Sox2, Camk2g, which supports neuronal survival and plasticity. The simvastatin, they believe, is increasing BDNF through the vascular endothelial nitric oxide synthase. They believe it is also capable of cleaving any microglia released pro-BDNF to BDNF using the plasmin pathway, which results in more beneficial neurotrophins and less antagonizing neurotrophins. The ascorbic acid in our treatment is working to keep the highly oxidizable serotonin and endothial nitric oxide synthase in their non-oxidized forms. These mechanisms have implications for other forms of brain injury, such as Alzheimer’s disease, traumatic brain injury, Parkinson’s disease, as well as chronic neuropathic pain, and she look forward to being able to test the drug combination of animal models of those diseases for an effect.