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Radiation
injury and neurogenesis
Monje
ML, Palmer T
Department
of Neurosurgery, MSLS P309, MC-5487, Stanford, CA, USA.
Purpose of review. For many cancers, survival depends on
aggressive combined therapies, but treatment comes at a price.
Children
and adults who receive radiotherapy involving the brain frequently
experience a progressive cognitive decline.
The
overt pathologies of radiation injury such as white matter necrosis or
vasculopathy are the obvious "smoking guns" of
dysfunction.
However,
many patients exhibit severe learning and memory deficits with no
overt pathologic changes.
This
is especially true when the radiation field involves the temporal
lobes.
The
cause of this debilitating dysfunction is currently unknown and
untreatable.
Recent
findings.
Within the temporal lobe, the hippocampal formation plays a central
role in short-term learning and memory--the functions most notably
affected by radiation.
Recent
work has also shown that hippocampus-dependent learning and memory are
strongly influenced by the activity of neural stem cells and their
proliferative progeny.
The
hippocampal granule cell layer undergoes continuous renewal and
restructuring by the addition of new neurons.
Radiation
at much lower doses than that needed to injure the more resistant
post-mitotic neurons and glia of the brain has been found to affect
these highly proliferative progenitors severely.
The
stem/progenitor cell is so sensitive to radiation that a single low
dose to the cranium of a mature rat is sufficient to ablate
hippocampal neurogenesis.
Summary.
Progressive learning and memory deficits following irradiation may be
caused by the accumulating hippocampal dysfunction that results from a
long-term absence of normal stem/progenitor activity.
Here,
the authors describe the nature of this stem cell dysfunction and
contemplate how restoration of stem/progenitor cell activity might be
approached in experimental models and, eventually, the clinic.
PMID:
12644738 [PubMed - indexed for MEDLINE]
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