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Stem Cell Transplantation Strategies for the Restoration of Cognitive Dysfunction Caused by Cranial Radiotherapy
Published on: October 18, 2011
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Defining functional changes in the brain caused by targeted stereotaxic radiosurgery
Vipan K Parihar1, Munjal M Acharya1, Dante E Roa1
1Department of Radiation Oncology, University of California Irvine, Irvine, CA 92697, USA.
Translational Cancer Research
|June 7, 2014
Summary
Cranial radiotherapy can cause cognitive dysfunction. This study used stereotaxic radiosurgery (SRS) in rats to show targeted brain irradiation impacts neurogenesis and cognition, with potential compensatory mechanisms in the opposite hemisphere.
Area of Science:
- Neuroscience
- Oncology
- Radiology
Background:
- Cranial radiotherapy for brain tumors often leads to cognitive dysfunction, a significant clinical challenge with no current solutions.
- Understanding the specific effects of different irradiation methods on cognitive performance and cellular mechanisms is crucial for developing better treatments.
- Current research lacks detailed insights into how focused radiation impacts distinct brain regions and their associated cognitive functions.
Purpose of the Study:
- To investigate the cognitive and cellular consequences of targeted hippocampal irradiation versus whole-brain irradiation using a novel stereotaxic radiosurgery (SRS) technique in rats.
- To compare the effects of unilateral and bilateral hippocampal SRS on cognitive performance and neurogenesis.
- To elucidate the underlying cellular mechanisms, including neurogenesis and neuroinflammation, affected by focused brain irradiation.
Main Methods:
- Developed and utilized a stereotaxic radiosurgery (SRS) technique to deliver focused X-ray beams to precise brain volumes in athymic rats.
- Evaluated cognitive functions, including novel place recognition and fear conditioning, after targeted irradiation of the hippocampus (unilateral and bilateral) and whole-brain irradiation.
- Assessed neurogenesis by immunohistochemically staining for immature (doublecortin positive) and mature (NeuN positive) neurons, and measured neuroinflammation using ED1 positive cell staining for activated microglia.
Main Results:
- Whole-brain irradiation caused significant deficits in novel place recognition and fear conditioning.
- Bilateral hippocampal SRS led to deficits in fear conditioning, while unilateral hippocampal SRS showed less pronounced cognitive decrements.
- SRS of one hippocampus significantly reduced neurogenesis (80% decrease in doublecortin positive neurons) and mature neurons (27% decrease) in the targeted area, but upregulated neurogenesis (22% increase in doublecortin, 36% increase in NeuN) in the contralateral hemisphere, accompanied by increased neuroinflammation.
Conclusions:
- Targeted stereotaxic radiosurgery (SRS) induces distinct cognitive and neurogenic consequences compared to whole-brain irradiation.
- Cognitive deficits are linked to alterations in neurogenesis, with compensatory neurogenesis in the contralateral hemisphere potentially mitigating effects under specific conditions.
- Regional differences in neuroinflammation may play a role in regulating the neurogenic response to unilateral irradiation, suggesting potential therapeutic targets.
