Studying Injury Mechanisms of TBI and Possible Pharmacologic Interventions
TBI is the signature injury of the wars in Iraq and Afghanistan, with up to 20 percent of veterans sustaining TBIs during deployments. TBIs due to blasts exposure frequently go undiagnosed and untreated, leading to long-term cognitive and behavioral deficits. We have been studying TBI injury pathways to find out how secondary injury might be mitigated and neuroregeneration promoted following injury.
Last year we experimented with NgR1 knockout mice, and targeted multiple injury pathways with Protein S, which showed lower cell death and smaller lesions one day after injury compared to controls. This study led us to our current focus of examining the mechanisms of cerebral edema following TBI. Edema leading to increased intracranial pressure is a significant factor behind cell death and axonal injury. A study of ours showed increased aquaporin-4 signaling in astrocytes following injury, and our future work points toward the role of electroneutral ion transportation in TBI-induced edema. We have also been testing various approved drugs, including antidepressants and NMDA receptor antagonists, that we predict might serve as a preventative measure.
Axon Stretch Growth of DRG Neurons for Peripheral Nerve Injury Repair
Neurons demonstrate tremendous stretch capacity during growth, and dorsal root ganglia (DRG) axons can extend up to 10 cm at a peak rate of 1 cm/day. Previous work has shown that these neurons, once transplanted, have tremendous long-term survival and integration in rats, bringing hope that one day such repairs can be made in humans who suffer from nerve crush or transection injuries.
Currently, the gold standard for these injuries is using autologous nerve grafts, sections of nerves transplanted from one area of the body, to another. This has the disadvantage of creating a second injury to remedy the first. To overcome this, tissue-engineered nerve grafts have been developed that would allow for allogeneic transplantations. However, there are challenges to be overcome in such PNI repair. First, there is immunogenicity, and second, allogeneic grafts lack the appropriate microstructure of autologous grafts. On top of stretching DRG neurons, we have been experimenting with grafts seeded with Schwann cells and signaling factors.
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Algattas H; Huang JH. "Traumatic Brain Injury pathophysiology and treatments: early, intermediate, and late phases post-injury." International journal of molecular sciences. 2014; 15(1):309-41. Epub 2013 Dec 30.
Liu X; Tian W; Kolar B; Hu R; Huang Y; Huang J; Ekholm S. "Advanced MR diffusion tensor imaging and perfusion weighted imaging of intramedullary tumors and tumor like lesions in the cervicomedullary junction region and the cervical spinal cord." Journal of neuro-oncology.. 2014; 116(3):559-66. Epub 2013 Dec 30.