title: Proof-of Concept that an Acute Trophic Factors Intervention After Spinal Cord Injury Provides an Adequate Niche for Neuroprotection, Recruitment of Nestin-Expressing Progenitors and Regeneration.
abstract: Trophic factor treatment has been shown to improve the recovery of brain and spinal cord injury (SCI). In this study, we examined the effects of TSC1 (a combination of insulin-like growth factor 1 and transferrin) 4 and 8 h after SCI at the thoracic segment level (T12) in nestin-GFP transgenic mice. TSC1 treatment for 4 and 8 h increased the number of nestin-expressing cells around the lesion site and prevented Wallerian degeneration. Treatment with TSC1 for 4 h significantly increased heat shock protein (HSP)-32 and HSP-70 expression 1 and 2 mm from lesion site (both, caudal and rostral). Conversely, the number of HSP-32 positive cells decreased after an 8-h TSC1 treatment, although it was still higher than in both, non-treated SCI and intact spinal cord animals. Furthermore, TSC1 increased NG2 expressing cell numbers and preserved most axons intact, facilitating remyelination and repair. These results support our hypothesis that TSC1 is an effective treatment for cell and tissue neuroprotection after SCI. An early intervention is crucial to prevent secondary damage of the injured SC and, in particular, to prevent Wallerian degeneration.
authors.affiliation: Departments of Neurobiology, Psychiatry and Biobehavioral Sciences, Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, 635 Charles E. Young Drive South, Suite 375E, Los Angeles, CA, 90095-7332, USA. warink@swu.ac.th.|Division of Physiotherapy, Faculty of Health Science, Srinakharinwirot University, Bangkok, Thailand. warink@swu.ac.th.
authors.forename: Warin
authors.initials: W
authors.lastname: Krityakiarana
authors.affiliation: Departments of Neurobiology, Psychiatry and Biobehavioral Sciences, Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, 635 Charles E. Young Drive South, Suite 375E, Los Angeles, CA, 90095-7332, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Zhao
authors.affiliation: Departments of Neurobiology, Psychiatry and Biobehavioral Sciences, Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, 635 Charles E. Young Drive South, Suite 375E, Los Angeles, CA, 90095-7332, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Nguyen
authors.affiliation: Department of Physiological Sciences and Department of Neurosurgery, University of California at Los Angeles, Los Angeles, CA, USA.|Department of Physiology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomez-Pinilla
authors.affiliation: Neuro-Behavioural Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, 999 Phutthamonthol 4 Road, Salaya, Phutthamonthol, Nakornpathom, 73170, Thailand.
authors.forename: Naiphinich
authors.initials: N
authors.lastname: Kotchabhakdi
authors.affiliation: Departments of Neurobiology, Psychiatry and Biobehavioral Sciences, Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, 635 Charles E. Young Drive South, Suite 375E, Los Angeles, CA, 90095-7332, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: de Vellis
authors.affiliation: Departments of Neurobiology, Psychiatry and Biobehavioral Sciences, Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, 635 Charles E. Young Drive South, Suite 375E, Los Angeles, CA, 90095-7332, USA. aespinosa@mednet.ucla.edu.
authors.forename: Araceli
authors.initials: A
authors.lastname: Espinosa-Jeffrey
mesh_terms: D000818:Animals; D051379:Mice; D008822:Mice, Transgenic; D064231:Nestin / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology*; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D064231:Nestin; D018696:Neuroprotective Agents
keywords: Heat shock proteins; IGF-1; Myelin; Oligodendrocytes; Transferrin; Wallerian degeneration