Chemokine expression in the white matter spinal cord precursor niche after force-defined spinal cord contusion injuries in adult rats.
Inflammatory cascades induced by spinal cord injuries (SCI) are localized in the white matter, a recognized neural stem- and progenitor-cell (NSPC) niche of the adult spinal cord. Chemokines, as integrators of these processes, might also be important determinants of this NSPC niche. CCL3/CCR1, CCL2/CCR2, and SDF-1alpha/CXCR4 were analyzed in the ventrolateral white matter after force defined thoracic SCI: Immunoreactivity (IR) density levels were measured 2 d, 7 d, 14 d, and 42 d on cervical (C 5), thoracic (T 5), and lumbar (L 5) levels. On day post operation (DPO) 42, chemokine inductions were further evaluated by real-time RT-PCR and Western blot analyses. Cellular phenotypes were confirmed by double labeling with markers for major cell types and NSPCs (nestin, Musashi-1, NG2, 3CB2, BLBP). Mitotic profiles were investigated in parallel by BrdU labeling. After lesion, chemokines were induced in the ventrolateral white matter on IR-, mRNA-, and protein-level. IR was generally more pronounced after severe lesions, with soaring increases of CCL2/CCR2 and continuous elevations of CCL3/CCR1. SDF-1alpha and CXCR4 IR induction was focused on thoracic levels. Chemokines/-receptors were co-expressed with astroglial, oligodendroglial markers, nestin, 3CB2 and BLBP by cells morphologically resembling radial glia on DPO 7 to DPO 42, and NG2 or Musashi-1 on DPO 2 and 7. In the white matter BrdU positive cells were significantly elevated after lesion compared with sham controls on all investigated time points peaking in the early time course on thoracic level: Here, chemokines were co-expressed by subsets of BrdU-labeled cells. These findings suggest an important role of chemokines/-receptors in the subpial white matter NSPC niche after SCI.
Department of Neurosurgery, University of Schleswig-Holstein Medical Center, Kiel D43 TW001035, Germany.
Friederike
F
Knerlich-Lukoschus
Beata
B
von der Ropp-Brenner
Ralph
R
Lucius
Hubertus Maximilian
HM
Mehdorn
Janka
J
Held-Feindt
D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D018925:Chemokines / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D007211:Indoles; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D019707:Receptors, Chemokine / Q000145:classification / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology*; D055153:Stem Cell Niche / Q000378:metabolism*; D013997:Time Factors
D018925:Chemokines; D007211:Indoles; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine; C007293:DAPI; D001973:Bromodeoxyuridine