Research Article| Volume 306, ISSUE 1-2, P129-137, July 15, 2011

Neurobiological responses to stereotactic focal irradiation of the adult rodent hippocampus

  • Matthew K. Schindler
    Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC, USA
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  • J. Daniel Bourland
    Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Brain Tumor Center of Excellence, Wake Forest University School of Medicine, Winston-Salem, NC, USA
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  • M. Elizabeth Forbes
    Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC, USA
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  • Kun Hua
    Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC, USA
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  • David R. Riddle
    Corresponding author at: Department of Neurobiology, Wake Forest University School of Medicine, Medical Center Blvd., Winston Salem, NC 27157, USA. Tel.: +1 336 716 4677; fax: +1 336 716 4534.
    Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Brain Tumor Center of Excellence, Wake Forest University School of Medicine, Winston-Salem, NC, USA
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Published:April 11, 2011DOI:


      Radiation effectively treats brain tumors and other pathologies but dose and treatment plans are limited by normal tissue injury, a major cause of morbidity in survivors. Clinically significant normal tissue injury can occur even with therapies that target pathological tissue and limit out-of-target irradiation. Elucidating the mechanisms underlying normal tissue injury is facilitated by studying the effects of focal irradiation and comparing irradiated and un-irradiated tissue in experimental animals. Young adult rats were irradiated using the Leksell Gamma Knife® with a 10 Gy maximum dose directed at the left hippocampus and shaped to minimize irradiation contralaterally. At least 95% of targeted hippocampus received ≥3 Gy, while all points in the contralateral hippocampus received <0.3 Gy. Neuronal and microglial markers of damage were assessed in the targeted and contralateral hemispheres of Gamma Knife®-treated rats and compared to non-irradiated controls. Acute cell death and sustained changes in neurogenesis and in microglia occurred in the dentate gyrus of the targeted, but not the contralateral, hippocampus, providing experimental evidence that focal irradiation at doses received by peri-target regions during targeted radiation therapy produces robust normal tissue responses. Additional studies using this approach will facilitate assessment of in vivo dose responses and the cellular and molecular mechanisms of radiation-induced brain injury.


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