Although radiosurgery has been used widely to treat primary brain tumor and brain metastases, its biological effect on the surrounding normal tissues is unclear. Damage from localized irradiation in different regions of brain may not be restricted to just these areas, but could eventually spread to other regions of the brain producing more diffuse brain injury. Understanding the process and mechanism(s) associated with the spread of normal tissue damage from localized brain irradiation is critical for the development of interventions aimed at preventing or ameliorating the long term effects of radiation-induced brain injury. Our study will provide preclinical data to help clinicians estimate the risk/benefit ratio of using radiosurgery and institute more effective ways of treating brain tumor patients with radiosurgery.
Stem cell loss and reduced neurogenesis in the hippocampus may play an important role in the development of radiation-induced late brain injury, specially, cognitive impairment. We hypothesize that transplantation of neuronal stem cells or GDNF-engineered neuronal stem cells will mitigate radiation-induced decline in neurogenesis by restoring the progressive cell lose and providing neuronal trophic factors to support endogenous cell survival. Currently, we are testing the effect of irradiated microenvironment on the migration and differentiation of neuronal stem cells in vitro and in vivo.
Several lines of evidence suggest a pathogenic link between the nAChR-α7 and brain disordersincluding schizophrenia, Alzheimer’s disease, and traumaticbrain injury. Activation of nAChR-α7can improve cognitive performance in rats, rabbits, and monkeys, whereas blockade ofthose receptors impairs performance. We are using molecular and cellular techniques and rodent model to exploit whether activation of nAChR-α7 will ameliorate the development and progression of radiation-induced brain injury, including inflammation and cognitive dysfunction.