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Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13360-5. doi: 10.1073/pnas.1510176112. Epub 2015 Oct 12.

Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury.

Author information

1
Department of Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China;
2
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095;
3
Beijing Friendship Hospital, Capital Medical University, Beijing 100068, China;
4
Department of Biochemistry and Molecular Biology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China;
5
Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China;
6
Department of Computer Engineering, University of California Santa Barbara, Santa Barbara, CA 93106;
7
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095;
8
Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095;
9
Department of Spine Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China;
10
Department of Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; Department of Neurobiology, School of Basic Medical Sciences, Captial Medical University, Beijing 100069, China wack_lily@163.com ysun@mednet.ucla.edu lxgchina@sina.com.
11
Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095; wack_lily@163.com ysun@mednet.ucla.edu lxgchina@sina.com.

Abstract

Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration.

KEYWORDS:

NT3; WGCNA; chitosan; spinal cord injury; transcriptome

PMID:
26460053
PMCID:
PMC4629389
DOI:
10.1073/pnas.1510176112
[Indexed for MEDLINE]
Free PMC Article

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