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EGF amplifies the replacement of parvalbumin-expressing striatal interneurons after ischemia
Tetsuyuki Teramoto, … , Jean-Christophe Plumier, Michael A. Moskowitz
Tetsuyuki Teramoto, … , Jean-Christophe Plumier, Michael A. Moskowitz
Published April 15, 2003
Citation Information: J Clin Invest. 2003;111(8):1125-1132. https://doi.org/10.1172/JCI17170.
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Article Neuroscience

EGF amplifies the replacement of parvalbumin-expressing striatal interneurons after ischemia

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Abstract

EGF promotes proliferation and migration of stem/progenitor cells in the normal adult brain. The effect of epidermal growth factor on neurogenesis in ischemic brain is unknown, however. Here we show that intraventricular administration of EGF and albumin augments 100-fold neuronal replacement in the injured adult mouse striatum after cerebral ischemia. Newly born immature neurons migrate into the ischemic lesion and differentiate into mature parvalbumin-expressing neurons, replacing more than 20% of the interneurons lost by 13 weeks after ischemia and representing 2% of the total BrdU-labeled cells. These data suggest that administration of EGF and albumin could be used to manipulate endogenous neurogenesis in the injured brain and to promote brain self-repair.

Authors

Tetsuyuki Teramoto, Jianhua Qiu, Jean-Christophe Plumier, Michael A. Moskowitz

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Figure 1

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EGF-enhanced proliferation after ischemia. (a) Ischemia reperfusion caus...
EGF-enhanced proliferation after ischemia. (a) Ischemia reperfusion caused a marked loss of NeuN+ neurons (outlined area) confined to the striatum (ST). SVZ, subventricular zone. Scale bar is 200 μm. (b–e) Without ischemia (b), few nestin+ cells (green) expressing EGF receptors (red) surrounded the lateral ventricle (V). After ischemia, the intensity of EGF receptor immunoreactivity in nestin+ SVZ cells (arrowheads) and the number of nestin+ cells expressing EGF receptor increased at 1 day (c), reached maximum at 3 days (d), and returned to basal levels at 21 days (e). The dotted line delineates lateral ventricle. Scale bar is 20 μm (n = 3–4/time-point). (f–i) BrdU+ cells at 9 days after sham or ischemia in an area corresponding to the box (a). After vehicle, the number of BrdU+ cells was higher after ischemia (g) than sham (f) (quantification in j). Ischemia followed by EGF (I-E; 400 ng/day) increased BrdU+ cells and was greater when EGF infusion started 2 days (h) rather than 21 days (i) after ischemia. (f) Scale bar is 100 μm. Bregma, 0.8 mm. (j) Quantification. S-V, sham-operated; I-V, ischemic group with vehicle; I-E (2d), ischemic groups with EGF (400 ng/day) initiated at day 2; I-E (21d), day 21 after ischemia. The effects of EGF (40 and 400 ng/day) initiated at day 2 were compared. +Significant difference between S-V and I-V; *between vehicle- and EGF-treated ischemic groups; #between groups treated with EGF 2 days or 21 days; §between medial and lateral striatum within the same group; n = 3–4/group, unpaired Student t test, P < 0.05.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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