Abstract
Spinal cord injury (SCI) results in complex posttraumatic sequelae affecting the whole neuraxis. Due to its involvement in varied neuromodulatory processes, the chemokine-ligand/receptor-network is a key element of secondary lesion cascades induced by SCI. This review will provide a synopsis of chemokine-ligand/receptor-expression along the whole neuraxis after traumatic spinal cord (sc) insults on basis of recent in vivo and in vitro findings in a SCI paradigm of thoracic force-defined impact lesions (Infinite Horizon Impactor) in adult rats. Analyses of chemokine-ligand/receptor-expression at defined time points after sc lesion of different severity grades or sham operation revealed that these inflammatory mediators are induced in distinct anatomical sc regions and in thalamic nuclei, periaqueductal grey, and hippocampal structures in the brain. Cellular and anatomical expression profiles together with colocalization/expression of neural stem/progenitor cell markers in adult sc stem cells niches or with pain-related receptors and mediators in dorsal horns, dorsal columns, and pain-processing brain areas support the notion that chemokines are involved in distinct cascades underlying clinical posttraumatic impairments and syndromes. These aspects and their implication in concepts of tailored SCI treatment are reviewed in the context of the recent literature on chemokine-ligand/receptor involvement in complex secondary lesion cascades.
Highlights
Spinal cord injury (SCI) continues to pose serious clinical and socioeconomic problems given that affected individuals often face a multifaceted spectrum of complex long-term sequelae including loss of motor function, vegetative dysfunction, development of central pain syndromes, and even cognitive impairment [1, 2]
CXCL12/ CXCR4 especially was identified as an essential factor regulating secretion of neurotrophic factors, differentiation, and correct migration of neural stem/progenitor cells [20,21,22]
Hassanshahi et al recently reported increased CXCL1 and CXCL12 expression levels immediately after SCI, elevated CXCL12, CXCL1, CXCL9, and CXCL10 levels at 7 days, and prolonged CXCL12 expression up to 28 days after SCI [28]. This mirrors findings reported in animal SCI paradigms, which over all demonstrated that chemokines and cytokines are induced after different neurological trauma modalities [29] and are involved in secondary lesion cascades at different stages and central nervous system (CNS) regions after SCI ([30, 31], and own investigations)
Summary
Spinal cord injury (SCI) continues to pose serious clinical and socioeconomic problems given that affected individuals often face a multifaceted spectrum of complex long-term sequelae including loss of motor function, vegetative dysfunction, development of central pain syndromes, and even cognitive impairment [1, 2]. One prerequisite for developing tailored mechanismdriven therapies is a detailed understanding of pathological cascades and cellular changes that are induced by the initial trauma. These cascades, which are subsumed under the umbrella term “secondary lesion,” have been subject of intense research over the last decades. In terms of factors mediating inflammatory reactions after SCI, the chemokine-ligand/receptor-system is of particular interest. Due to their widespread induction after SCI and their versatility, one can assume that these chemotactic cytokines and their receptors bear promising potential for future mechanism-driven trials
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