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

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 4

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Neuronal replacement in the ischemic striatum. (a) Confocal 3D reconstru...
Neuronal replacement in the ischemic striatum. (a) Confocal 3D reconstruction revealed newborn PV+ neurons (arrowhead) triple-labeled with BrdU, NeuN, and PV in the medial striatum of EGF-treated mice at 13 weeks after ischemia. (b–e) The triple-labeling with BrdU, PV, and DARPP-32 revealed that newborn PV+ neurons (e, arrowhead) were located in the boundary zone of the ischemic lesion. White solid line delineates the lesion area. Scale bars are 20 μm. (f) Numbers of BrdU+NeuN+PV+ cells in the medial striatum at 13 weeks after ischemia. Ud, undetected in VAS-V and S-E groups. (g) NRI (see text) indicates ratio between newborn neurons and the neurons lost after injury. (h) Progressive repopulation of PV+ neurons in the ischemic striatum measured as a percentage of PV+ neurons in ischemic striatum relative to the number in the nonischemic contralateral striatum. *Significant difference between ischemic group administered with vehicle (I-V) or EGF (I-E) (P < 0.01); n = 5-6/group, unpaired Student t test.