MD, University of Toronto
Effects of Ionizing Radiation on the Central Nervous System
Radiation therapy is a major cancer treatment modality. Radiation injury of the brain and spinal cord has devastating and sometimes fatal consequences. The overall goal of my laboratory research program is to understand the mechanisms of radiation injury in the central nervous system (CNS), and to develop neuroprotective strategies against this injury.
The underlying mechanisms of this injury remain unclear. There is an increasing body of data including those from our laboratory that suggests that the radiation response in the CNS is a continuous, dynamic, and interacting process. It is recognized that clonogenic cell death is not the only mode of radiation-induced cell death. Certain glial, neuronal and endothelial cells including neural progenitor cells in the CNS undergo apoptosis within a few hours after irradiation. There is also component of secondary injury and cell death that is mediated by neuro-inflammation, oxidative stress and microenvironmental alterations. Disruption of the vasculature and microenvironment after irradiation may influence cell fate and lead to inhibition of neurogenesis and neurocognitive deficits.
We are currently studying these effects at the tissue, cell and molecular level. Our work is focused on potentially reversible components of cell death and damage since targeting these damage pathways provide the best opportunities for neuroprotection. Current work includes characterizing apoptosis, neuroinflammation and perturbations of the vascular/neural progenitor cell niche and cell fate determination after irradiation. Our studies are performed in vivo using transgenic mouse models of radiation- induced neurobehavioral damage and myelopathy, and in vitro using glial and neural progenitors cultured from the CNS of these animals.
- Li YQ, Chen P, Haimovitz-Friedman A, Reilly RM, Wong CS: Endothelial apoptosis initiates acute blood-brain barrier disruption after ionizing radiation. Cancer Res 2003; 63:5950-5956.
- Nordal RA, Nagy A, Pintilie M, Wong CS. Hypoxia and hypoxiainducible Factor-1 target genes in central nervous system radiation injury: A role for vascular endothelial growth factor. Clin Cancer Res 10(10):3342-3353, 2004.
- Lu F, Wong CS. Time-dependent neurosphere-forming ability of adult rat spinal cord after irradiation. Radiat Res 168: 453-461, 2007.