Neural Stem Cells Block Brain RT Memory Effects


Cognitive function improved significantly after human neural stem cell transplantation in a preclinical model of radiation-induced cognitive impairment, researchers reported.

One month after stem-cell implantation, irradiated rats' performance on standardized tasks was similar to that of control animals not exposed to cranial irradiation. In contrast, irradiated animals that did not receive neural stem cells performed significantly worse than either treated animals or the control group.

Four months after engraftment, the treated irradiated animals continued to perform significantly better than the untreated irradiated animals, as reported July 15 in Cancer Research.

The improved performance by treated animals was associated with engraftment-cell survival and migration.

"Engrafted cells migrated extensively, differentiated along glial and neuronal lineages, and expressed the activity-regulated cytoskeleton-associated protein (Arc), suggesting their capability to functionally integrate into the hippocampus," Munjal M. Acharya, PhD, of the University of California Irvine, and co-authors wrote in conclusion.

"These data show that human neural stem cells afford a promising strategy for functionally restoring cognition in irradiated animals."

Cranial radiotherapy for brain malignancies can cause progressive, debilitating cognitive impairment. Although the mechanisms of the impairment are unclear, loss of neural stem cells in the hippocampus is one plausible explanation, the authors noted in their introduction.

Neural stem cells that survive irradiation exhibit a stress response that leads to altered proliferation, metabolism, survival, and differentiation, as well as altered expression of certain genes, such as Arc.

To determine the potential of neural stem cell transplantation to reverse radiation-induced cognitive impairment, the authors conducted a study involving three groups of laboratory rats. Two groups of animals underwent cranial irradiation, followed by human neural stem cell transplantation into the hippocampus or a sham transplant procedure. A control group consisted of animals that were not irradiated but underwent sham transplantation.

One and four months after transplantation, investigators assessed stem-cell survival and phenotypic fate, as well as the rats' cognitive function.

The authors found that 23% of the transplanted cells survived at one month and 12% at four months. The patterns of proliferation, migration, and differentiation, as well as Arc expression, suggested the transplanted cells had the potential to integrate into the hippocampus.

Assessment of cognitive function, primarily by tasks involving memory and retention, showed that irradiated animals engrafted with human neural stem cells were indistinguishable from the control animals but performed significantly better than the irradiated animals that had sham transplants (P<0.001 to P<0.0001).

"Our current studies have now clearly shown the benefits of engrafted stem cells for reversing cognitive impairment following cranial irradiation," the authors wrote.

"The capability to minimize the adverse cognitive sequelae associated with cranial radiotherapy is encouraging and points to the promise of using stem-cell-based strategies or minimizing normal tissue damage," they added.

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    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined Medpage Today in 2007. Follow


The study was supported by the California Institute for Regenerative Medicine, NIH, and the Department of Energy.

The authors had no relevant disclosures.