Long-Term Impairment of Subependymal Repopulation Following Damage by Ionizing Irradiation

Tada, Eiji; Yang, Cindy F.; Gobbel, Glenn T.; Lamborn, Kathleen R.; Fike, John R.

doi:10.1006/exnr.1999.7172

Cited by 109 publications

(80 citation statements)

References 35 publications

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“…Low levels of focused gamma irradiation (1-3 Gy) have been shown to result in a transient increase in mitotic cell activity in the SEZ, with levels eventually diminishing in the weeks following in a dose-dependent fashion compared with untreated controls [27,31]. Contrary to the results after LI, we observed no decrease in the overall number of β-III tubulin-positive migratory neuroblasts in the RMS of irradiated animals 3 weeks after whole-body exposure to 450 rad (a dose equivalent to 4.5 Gy).…”

Section: Analysis Of Rms Neuroblast Migration and Quantification Of Smentioning

confidence: 99%

“…Depletion of the NSC niche has been previously achieved with antimitotic agents [26] and both ionizing and x-irradiation [27][28][29][30][31][32], yielding transient and long-term depletion of neurogenesis in the hippocampus and SEZ. Neurogenesis in the hippocampus can be attenuated by exposure to varying levels of x-irradiation, as seen by a decrease in the number of migrating granular neurons out of the subgranular layer [28][29][30]32].…”

Section: Introductionmentioning

confidence: 99%

“…Neurogenesis in the hippocampus can be attenuated by exposure to varying levels of x-irradiation, as seen by a decrease in the number of migrating granular neurons out of the subgranular layer [28][29][30]32]. Previous studies investigating the effects of focused exposure of x-irradiation to the brain of adult rats on SEZ neurogenesis have reported ablation of NSCs in the SEZ immediately after irradiation [27,31]. A dose-dependent recovery of NSCs occurred within 2 months of exposure, with recovery never reaching basal levels in all but the lowest doses.…”

Section: Introductionmentioning

confidence: 99%

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Ionizing Radiation Enhances the Engraftment of Transplanted In Vitro–Derived Multipotent Astrocytic Stem Cells

et al. 2005

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The subependymal zone (SEZ) is a region of persistent neurogenesis in the adult mammalian brain containing a neural stem cell (NSC) pool that continuously generates migratory neuroblasts that travel in chains through the rostral migratory stream (RMS) to the olfactory bulb (OB), where they differentiate and functionally integrate into existing neural circuitry. NSCs can be isolated from the SEZ and cultured to generate either neurospheres (NSs) or multipotent astrocytic stem cells (MASCs), with both possessing the stem cell characteristics of multipotency and self-renewal. NSs and MASCs home to the SEZ after transplantation into the lateral ventricle (LV) and contribute to neuroblast migration, with minimal engraftment into the OB observed in the adult mouse. Recent studies have compared the relatively uncharacterized NSC with the more established hematopoietic stem cell (HSC) in an effort to determine the level of stemness possessed by the NSC. Depletion of native HSCs in the bone marrow by lethal irradiation (LI) is necessary to maximize functional engraftment of donor HSCs. Our data show that the NSC pool and neuroblasts in the SEZ can be significantly and permanently depleted by exposure to LI. Attenuation of donor-derived migratory neuroblast engraftment into the OB is observed after transplantation of gfp + MASCs into the LV of LI animals, whereas engraftment is significantly enhanced after transplantation into animals exposed to sublethal levels of ionizing radiation. By increasing receptiveness of the NSC niche through depletion of indigenous cells, the adult SEZ-RMS-OB can be used as a model to further characterize the NSC. Stem Cells 2005;23:1276-1285

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Section: Analysis Of Rms Neuroblast Migration and Quantification Of Smentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ionizing Radiation Enhances the Engraftment of Transplanted In Vitro–Derived Multipotent Astrocytic Stem Cells

et al. 2005

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“…Studies have shown that cells from this area have selfrenewal capacity, differentiate into neurons or glia, migrate over longer distances throughout the brain and may be essential for repair processes after brain toxicity (Doetsch et al, 1999). Irradiation with doses of 2 Gy induces apoptosis in the subependyma of young rats (Hopewell and Cavanagh, 1972) (Bellinzona et al, 1996) and in proliferating cells of the hippocampus (Peissner et al, 1999) leading to a prolonged impairment of the repopulative capacity (Tada et al, 1999).…”

Section: Toxicity To Defined Structural Compartments Of the Brainmentioning

confidence: 99%

Radiation induced CNS toxicity – molecular and cellular mechanisms

et al. 2001

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Radiotherapy of tumours proximal to normal CNS structures is limited by the sensitivity of the normal tissue. Prior to the development of prophylactic strategies or treatment protocols a detailed understanding of the mechanisms of radiation induced CNS toxicity is mandatory. Histological analysis of irradiated CNS specimens defines possible target structures prior to a delineation of cellular and molecular mechanisms. Several lesions can be distinguished: Demyelination, proliferative and degenerative glial reactions, endothelial cell loss and capillary occlusion. All changes are likely to result from complex alterations within several functional CNS compartments. Thus, a single mechanism responsible cannot be separated. At least four factors contribute to the development of CNS toxicity: (1) damage to vessel structures; (2) deletion of oligodendrocyte-2 astrocyte progenitors (O-2A) and mature oligodendrocytes; (3) deletion of neural stem cell populations in the hippocampus, cerebellum and cortex; (4) generalized alterations of cytokine expression. Several underlying cellular and molecular mechanisms involved in radiation induced CNS toxicity have been identified. The article reviews the currently available data on the cellular and molecular basis of radiation induced CNS side effects. http://www.bjcancer.com © 2001 Cancer Research Campaign

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“…In the absence of NSC/NPC-depleted transgenic animals, methodologies such as whole brain irradiation or anti-mitotic agent administration have exploited the mitotic activity of these cells to deplete them from the CNS (Shors et al, 2002;Tada et al, 1999Tada et al, , 2000. While such investigations have provided some insight into the contribution of NSC/ NPCs to cognition, injury repair processes and brain homeostasis, both methodologies are limited in their ability to target region-specific stem/progenitor cell populations.…”

Section: Introductionmentioning

confidence: 99%

Utilizing X-irradiation to selectively eliminate neural stem/progenitor cells from neurogenic regions of the mammalian brain

McGinn¹,

Sun²,

Colello³

2008

Journal of Neuroscience Methods

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Long-Term Impairment of Subependymal Repopulation Following Damage by Ionizing Irradiation

Cited by 109 publications

References 35 publications

Ionizing Radiation Enhances the Engraftment of Transplanted In Vitro–Derived Multipotent Astrocytic Stem Cells

Ionizing Radiation Enhances the Engraftment of Transplanted In Vitro–Derived Multipotent Astrocytic Stem Cells

Radiation induced CNS toxicity – molecular and cellular mechanisms

Utilizing X-irradiation to selectively eliminate neural stem/progenitor cells from neurogenic regions of the mammalian brain

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