Present address: Institute for Cell Engineering, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Insulin-like growth factor-1 is an endogenous mediator of focal ischemia-induced neural progenitor proliferation
Article first published online: 11 JUL 2006
European Journal of Neuroscience
Volume 24, Issue 1, pages 45–54, July 2006
How to Cite
Yan, Y.-P., Sailor, K. A., Vemuganti, R. and Dempsey, R. J. (2006), Insulin-like growth factor-1 is an endogenous mediator of focal ischemia-induced neural progenitor proliferation. European Journal of Neuroscience, 24: 45–54. doi: 10.1111/j.1460-9568.2006.04872.x
- Issue published online: 11 JUL 2006
- Article first published online: 11 JUL 2006
- Received 10 January 2006, revised 4 April 2006, accepted 12 April 2006
- dentate gyrus;
- spontaneously hypertensive rat;
- subventricular zone
The adult mammalian brain contains resident neural progenitors in the subgranular zone of the dentate gyrus (DG) and the subventricular zone (SVZ) of the lateral ventricles. The proliferation of neural progenitors increases after focal cerebral ischemia in both of these regions, but the mechanisms that promote ischemia-induced neural progenitor proliferation are not yet understood. We hypothesize that diffusible factors from the ischemic area play a role in this process as the DG is remote from the area of infarction. In this study, we observed that the peak of neural progenitor proliferation in the ipsilateral DG was between day 2 and day 4 of reperfusion after transient middle cerebral artery occlusion in adult spontaneously hypertensive rats. GeneChip and real-time PCR analysis showed a three- to 102-fold increase in the expression of 15 diffusible, mitogenic factors in the ischemic cortex at 3 days of reperfusion. Of these, insulin-like growth factor-1 (IGF-1) showed increased protein expression in the activated astrocytes in the ischemic penumbra. In addition, the progenitors in both the SVZ and DG showed IGF-1 receptor expression. Inhibiting IGF-1 activity by introcerebroventricular infusion of IGF-1 antibody significantly prevented the ischemia-induced neural progenitor proliferation. These results indicate that IGF-1 formed in the ischemic penumbra might be one of the diffusible factors that mediate post-ischemic neural progenitor proliferation.