This Article Full Text Full Text (PDF) All Versions of this Article: 39/10/2837    most recent STROKEAHA.107.510982v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hou, S.-W. Articles by Sun, F.-Y. Search for Related Content PubMed PubMed Citation Articles by Hou, S.-W. Articles by Sun, F.-Y.

(Stroke. 2008;39:2837.)
© 2008 American Heart Association, Inc.

Original Contributions

Functional Integration of Newly Generated Neurons Into Striatum After Cerebral Ischemia in the Adult Rat Brain

Shang-Wei Hou, MD, PhD; Yong-Quan Wang, MD, PhD; Ming Xu, MD; Di-Han Shen, MS; Ji-Jiang Wang, MD, PhD; Fang Huang, PhD; Zhang Yu, MD Feng-Yan Sun, MD, PhD

From the Department of Neurobiology and State Key Laboratory of Medical Neurobiology (S.-W.H., Y.-Q.W., M.X., D.-H.S., J.-J.W., F.H., F.-Y.S.), the Electron Microscopy Core Laboratory (Z.Y.), and the Institutes for Biomedical Sciences (F.-Y.S.), Shanghai Medical College of Fudan University, Shanghai, PR China.

Correspondence to Feng-Yan Sun, MD, PhD, Department of Neurobiology, Shanghai Medical College of Fudan University, 138 Yi-Xue-Yuan Road, Shanghai 200032, PR China. E-mail fysun{at}shmu.edu.cn

Background and Purpose— Ischemic injury can induce neurogenesis in the striatum. Those newborn neurons can express glutamic acid decarboxylase and choline acetyltransferase, markers of GABAergic and cholinergic neurons, respectively. The present study investigated whether these GABAergic and cholinergic new neurons could differentiate into functional cells.

Methods— Retrovirus containing the EGFP gene was used to label dividing cells in striatal slices prepared from adult rat brains after middle cerebral artery occlusion. EGFP-targeted immunostaining and immunoelectron microscopy were performed to detect whether newborn neurons could anatomically form neuronal polarity and synapses with pre-existent neurons. Patch clamp recording on acute striatal slices of brains at 6 to 8 weeks after middle cerebral artery occlusion was used to determine whether the newborn neurons could display functional electrophysiological properties.

Results— EGFP-expressing (EGFP⁺) signals could be detected mainly in the cell body in the first 2 weeks. From the fourth to thirteenth weeks after their birth, EGFP⁺ neurons gradually formed neuronal polarity and showed a time-dependent increase in dendrite length and branch formation. EGFP⁺ cells were copositive for NeuN and glutamic acid decarboxylase (EGFP⁺-NeuN⁺-GAD₆₇⁺), MAP-2, and choline acetyltransferase (EGFP⁺-MAP-2⁺-ChAT⁺). They also expressed phosphorylated synapsin I (EGFP⁺-p-SYN⁺) and showed typical synaptic structures comprising dendrites and spines. Both GABAergic and cholinergic newborn neurons could fire action potentials and received excitatory and inhibitory synaptic inputs because they displayed spontaneous postsynaptic currents in picrotoxin- and CNQX-inhibited manners.

Conclusion— Ischemia-induced newly formed striatal GABAergic and cholinergic neurons could become functionally integrated into neural networks in the brain of adult rats after stroke.

Key Words: functional neurogenesis • neural network • nonneurogenic regions • striatum • stroke

This article has been cited by other articles:

				C. Darian-Smith Synaptic Plasticity, Neurogenesis, and Functional Recovery after Spinal Cord Injury Neuroscientist, April 1, 2009; 15(2): 149 - 165. [Abstract] [PDF]