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 Table of Contents  
INVITED REVIEW
Year : 2017  |  Volume : 12  |  Issue : 7  |  Page : 1044-1047

Spinal cord injury drives chronic brain changes


1 Laboratorio de Bioquímica Neuroendocrina, Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina
2 Laboratorio de Bioquímica Neuroendocrina, Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires; Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

Date of Acceptance19-Jun-2017
Date of Web Publication1-Aug-2017

Correspondence Address:
Florencia Labombarda
Laboratorio de Bioquímica Neuroendocrina, Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires; Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires
Argentina
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1673-5374.211177

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  Abstract 

Only a few studies have considered changes in brain structures other than sensory and motor cortex after spinal cord injury, although cognitive impairments have been reported in these patients. Spinal cord injury results in chronic brain neuroinflammation with consequent neurodegeneration and cognitive decline in rodents. Regarding the hippocampus, neurogenesis is reduced and reactive gliosis increased. These long-term abnormalities could explain behavioral impairments exhibited in humans patients suffering from spinal cord trauma.

Keywords: spinal cord injury; brain neurodegeneration; neuroinflammation


How to cite this article:
Jure I, Labombarda F. Spinal cord injury drives chronic brain changes. Neural Regen Res 2017;12:1044-7

How to cite this URL:
Jure I, Labombarda F. Spinal cord injury drives chronic brain changes. Neural Regen Res [serial online] 2017 [cited 2019 May 22];12:1044-7. Available from: http://www.nrronline.org/text.asp?2017/12/7/1044/211177


  Introduction Top


Spinal cord injury (SCI) produces an extensive brain reorganization of the sensorimotor cortex due to cortical circuit deafferentation (Nardone et al., 2013). Concomitantly with the cortical plastic changes SCI leads to the atrophy not only of spinal cord (Lundell et al., 2011) but also of the sensorimotor cortex and corticospinal tract (CST) (Jurkiewicz et al., 2006; Wrigley et al., 2009). In particular, human magnetic resonance imaging (MRI) studies using voxel-based morphometry and diffusion tensor imaging have revealed that grey matter volume decreases in primary somatosensory (S1) and motor cortex (M1) in chronic SCI, which is consistent with atrophy and/or neuronal loss (Jurkiewicz et al., 2006; Wrigley et al., 2009; Freund et al., 2011, 2013a, b). In addition, these studies have demonstrated that axonal and myelin integrity of CST is reduced following spinal cord trauma (Wrigley et al., 2009; Freund et al., 2012, 2013b). Concerning the survival of cortical axotomized motoneurons there is no uniform consensus. A number of reports on SCI animal models have shown apoptotic neurons on Lamina V of primary motor cortex (Hains et al., 2003; Lee et al., 2004) while others have demonstrated that the number of large pyramidal neurons remains invariable (Wannier et al., 2005; Brock et al., 2010; Nielson et al., 2011). Despite this controversy regarding the survival of the upper-motoneuron both positions agree with the fact that those neurons suffer changes as atrophy and shrinkage following SCI (Tseng and Prince, 1996; Wannier et al., 2005; Brock et al., 2010; Nielson et al., 2011).

Crucially, the decrease of CST integrity and cortical grey matter volume is directly correlated with spinal cord atrophy in humans (Freund et al., 2012, 2013a) suggesting that trauma-induced spinal degenerative process spreads towards the brain.

According to human MRI studies SCI can cause progressive reduction in grey matter volume not only in the sensorimotor cortex but also in regions not directly connected to the injury site, such as insular, cerebellar, medial prefrontal, anterior cingulate and temporal cortices, which are crucial for the processing of emotional information and the modulation of attentional states (Nicotra et al., 2006; Wrigley et al., 2009).

In this regard there have been several reports about long-term cognitive impairments in humans after SCI. Standardized neuropsychological tests have identified performance impairments in span memory, executive functioning, memory function, concentration ability, attention, processing speed, and learning (Roth et al., 1989; Murray et al., 2007; Lazzaro et al., 2013; Craig et al., 2015). As comorbid traumatic brain injury (TBI) can result in cognitive impairments, it is worth mentioning that the stated reports exclude people with concomitant TBI. Sixty percent of spinal cord injured patients suffer not only from cognitive impairment but also from depression (Shin et al., 2012) and anxiety (Post and van Leeuwen, 2012) conditions which result in a general decrease in quality of life (Boakye et al., 2012). A prospective longitudinal neuropsychological study has shown that cognitive impairment in spinal cord injured patients was associated with elevated depressive mood, anxiety and fatigue only when patients returned to society, where there is less support and substantial challenges (Craig et al., 2015).

Since human behavior is very complex, factors other than TBI might also contribute to lower cognitive performance such as chronic pain, taking multiple medication and alcohol and substance abuse. In this context, Faden and colleagues´ work is very significant as it reveals that SCI in both mouse and rat causes impairment of spatial and retention memory and depressive-like behavior as demonstrated by diminished performance in the Morris water maze, Y-maze, novel objective recognition, sucrose preference and tail suspension tests (Wu et al., 2014a, b). One recent report has provided evidence for a relationship between the up-regulation of peripheral and hippocampal cytokine levels and the increase of depression or anxiety-like signs following rodent spinal cord contusion (Maldonado-Bouchard et al., 2016).

There is compelling evidence suggesting that chronic SCI results in a widespread brain neuroinflammation (Felix et al., 2012; Wu et al., 2014a, b; Maldonado-Bouchard et al., 2016; Jure et al., 2017). Indeed, trauma to spinal cord frequently causes neuropathic pain associated with chronic inflammation in both the dorsal horn and spinothalamic projection sites in the thalamus (Hulsebosch et al., 2009; Zhao et al., 2007). Microglial cells and astrocytes under pathological conditions (chronic stress, injury, neurodegenerative diseases, diabetes, aging, infection, etc.) become reactive and develop a neuroinflammatory response leading to functional consequences for learning and memory (Sierra et al., 2014). In this regard, Faden's group have demonstrated that microglia is activated in cerebral cortex, thalamus and hippocampus in a rodent model of SCI (Wu et al., 2014a, b, 2016). The authors have described that there is a significant decrease in the number of resting microglia displaying ramified cellular morphology and an increase in the number of activated microglia displaying a bushy and hypertrophy cellular morphology. The latter changes in microglia morphology are associated with M1 pro-inflammatory cytokine profile expression and are observed both in the acute and chronic phases post trauma (Wu et al., 2014a, b). Pro-inflammatory cytokines (TNFα, IL-6) and cell cycle genes (cyclin A1, A2, D1, PCNA) are chronically increased in the hippocampus after severe SCI (Wu et al., 2014a, b). In line with these findings, our results have shown a chronic increase of hyperthophic and bushy microglia in the molecular layer, subgranular zone (SGZ) and hilus of the hippocampal dentate gyrus (DG) after severe SCI (Jure et al., 2017). In the same report we have provided the first evidence for astrocyte activation in all the DG sub-regions mentioned, suggesting that astrocytes could articulate and develop the neuroinflammatory response alongside microglial cells (Jure et al., 2017)

Interestingly, glia reactivity is related to SCI intensity. Severe lesions induce reactive microglia and astrogliosis in all DG sub-regions. However, reactive microglia and astrogliosis develop only in the hilus and in the molecular layer respectively after moderate SCI while no changes are observed in the mildly injured rats (Jure et al., 2017). In accordance with our result, a recent report has shown microglia activation only after moderate and severe SCI and not in mildly injured mice in the cerebral cortex and hippocampus (Wu et al., 2016). Widespread brain neuroinflammation could lead to remote neurodegeneration after SCI. Indeed, neuroinflammation and microglia activation are common landmarks following normal aging, neurodegenerative diseases, chronic stress, and brain ischemia (Sierra et al., 2014). In this regard isolated thoracic SCI in both rat and mouse models has resulted in significant neuronal loss in the hippocampus, cortex, and thalamus only in the chronic phase but not at early time points (Wu et al., 2014a, b). Stereological analyses have demonstrated that moderate and severe - but not mild- SCI reduces neuronal survival and increases neuronal endoplasmic reticulum stress in important brain regions associated with cognitive decline and depression (Wu et al., 2016). In summary it could be stated that on the one hand there are no signs of either neuronal loss or neuroinflammation in mildly injured rats and on the other hand, neuroinflammation arises both in the acute and chronic phases preceding neurodegeneration which appears only at late time points, suggesting that inflammation leads to SCI-induced brain neurodegeneration.

The hippocampus is involved in the formation of memory and learning, processes that require extensive neuroplasticity (O´Keefe, 2007). In this regard, the incorporation of newborn neurons into the mature circuit enhances hippocampal-dependent learning performances in the DG (Kempermann and Gage, 1999). Microglia and astrocytes are important components of the neurogenic niche and a growing number of reports relate the activation of both cells to decreased neurogenesis (Belarbi and Rosi, 2013; Sierra et al., 2014). Indeed, a significant long-term neurogenesis reduction has been reported after chronic cervical and thoracic SCI that could be associated with microglia activation in the hippocampus (Felix et al., 2012; Wu et al., 2014a). In this regard, we have recently demonstrated that severe and moderate SCI down-regulates the production of newborn neurons in the same manner (Jure et al., 2017). However, neurogenesis in the mildly injured rats has remained unchanged suggesting that neurogenesis reduction could be an all-or-none response from a certain threshold. Notably, in line with these findings it has been shown that injured animals with moderate and severe SCI show the same outcome in cognitive tests and development of depression-like symptoms (Maldonado-Bouchard et al., 2016; Wu et al., 2016). In addition, neurogenesis appears to be more sensitive to SCI than astrocytes and microglial morphological responses, since moderately injured rats show a sharp newborn neuron decrease associated with no glial changes in the SGZ (Jure et al., 2017).

Convincing work has demonstrated that the brain is affected by SCI. However, exact mechanisms underlying those changes are completely unknown. On the one hand, the systemic immune function is markedly altered after SCI and this mechanism could affect the brain (Popovich and McTigue, 2009; Schwab et al., 2014) and on the other hand, corticosterone released in the acute phase after SCI could model the brain producing long-term alterations. It is well documented that the hippocampus and cerebral cortex are vulnerable to glucocorticoid actions (Lucassen et al., 2015). Finally, BDNF and other molecules that participate in neuron-glia communication as chemokines (Cardona et al., 2006; Wu et al., 2014b; Gundersen et al., 2015) could be involved in brain changes following SCI. In this regard, BDNF is known to regulate adult neurogenesis at the SGZ (Lee et al., 2002; Scharfman et al., 2005; Fumagalli et al., 2009) and it has been shown that reduced hippocampal neurogenesis is correlated with the decrease of BDNF protein levels (Felix et al., 2012). However, other reports found that this factor remains unchanged after 4 and 12 weeks of injury (Fumagalli et al., 2009).

Regarding chemokines, CCL21 is produced by spinal cord neurons after nerve damage or glutamate exposure (Hulsebosch et al., 2009) and is delivered at more distant sites resulting in microglia activation and neuropathic pain generation (Zhao et al., 2007). In addition, CCL21 is up-regulated in neurons both in the acute and chronic phases after SCI in the thalamus, hippocampus and cerebral cortex (Wu et al., 2014a, 2016). Consistent with these results, the microglia activator CCL2 (Zhang et al., 2017) and its receptor CCR2 are chronically expressed in neurons after severe spinal contusion in the thalamus, hippocampus and periaqueductal gray matter, brain circuits associated with pain and emotional or memory functions (Knerlich-Lukoschus et al., 2011).

In conclusion, SCI results in chronic brain neuroinflammation that is remarkably similar to that reported after TBI producing a progressive delayed neurodegeneration and functional deficits as cognitive impairment and depressive-like behavior (Faden et al., 2016). Those long-term brain abnormalities and the reported diffuse neuroinflammation associated could explain behavioral impairments exhibited in patients suffering from spinal cord trauma (Davidoff et al., 1992; Dowler et al., 1997; Lazzaro et al., 2013). Future rehabilitation strategies should be oriented to improving not only sensorimotor skills but also cognitive function. Given that SCI drives chronic brain changes, it will be necessary to consider cognitive and emotional patient impairments as a consequence of SCI per se and not as a consequence of the lifestyle resulting from the disability. Therefore, future therapies should include the inhibition of post-traumatic brain inflammatory response to avoid cognitive and emotional deficits. [47]

 
  References Top

1.
Belarbi K, Rosi S (2013) Modulation of adult-born neurons in the inflamed hippocampus. Front Cell Neurosci 7:145.  Back to cited text no. 1
    
2.
Boakye M, Leigh BC, Skelly AC (2012) Quality of life in persons with spinal cord injury: comparisons with other populations. J Neurosurg Spine 17:29-37.  Back to cited text no. 2
    
3.
Brock JH, Rosenzweig ES, Blesch A, Moseanko R, Havton LA, Edgerton VR, Tuszynski MH (2010) Local and remote growth factor effects after primate spinal cord injury. J Neurosci 30:9728-9737.  Back to cited text no. 3
    
4.
Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, Huang D, Kidd G, Dombrowski S, Dutta R, Lee JC, Cook DN, Jung S, Lira SA, Littman DR, Ransohoff RM (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9:917-924.  Back to cited text no. 4
    
5.
Craig A, Nicholson Perry K, Guest R, Tran Y, Dezarnaulds A, Hales A, Ephraums C, Middleton J (2015) Prospective study of the occurrence of psychological disorders and comorbidities after spinal cord injury. Arch Phys Med Rehabil 96:1426-1434.  Back to cited text no. 5
    
6.
Davidoff GN, Roth EJ, Richards JS (1992) Cognitive deficits in spinal cord injury: epidemiology and outcome. Arch Phys Med Rehabil 73:275-284.  Back to cited text no. 6
    
7.
Dowler RN, Harrington DL, Haaland KY, Swanda RM, Fee F, Fiedler K (1997) Profiles of cognitive functioning in chronic spinal cord injury and the role of moderating variables. J Int Neuropsychol Soc 3:464-472.  Back to cited text no. 7
    
8.
Faden AI, Wu J, Stoica BA, Loane DJ (2016) Progressive inflammation-mediated neurodegeneration after traumatic brain or spinal cord injury. Br J Pharmacol 173:681-691.  Back to cited text no. 8
    
9.
Felix MS, Popa N, Djelloul M, Boucraut J, Gauthier P, Bauer S, Matarazzo VA (2012) Alteration of forebrain neurogenesis after cervical spinal cord injury in the adult rat. Front Neurosci 6:45.  Back to cited text no. 9
    
10.
Freund P, Curt A, Friston K, Thompson A (2013a) Tracking changes following spinal cord injury: insights from neuroimaging. Neuroscientist 19:116-128.  Back to cited text no. 10
    
11.
Freund P, Wheeler-Kingshott CA, Nagy Z, Gorgoraptis N, Weiskopf N, Friston K, Thompson AJ, Hutton C (2012) Axonal integrity predicts cortical reorganisation following cervical injury. J Neurol Neurosurg Psychiatry 83:629-637.  Back to cited text no. 11
    
12.
Freund P, Weiskopf N, Ward NS, Hutton C, Gall A, Ciccarelli O, Craggs M, Friston K, Thompson AJ (2011) Disability, atrophy and cortical reorganization following spinal cord injury. Brain 134:1610-1622.  Back to cited text no. 12
    
13.
Freund P, Weiskopf N, Ashburner J, Wolf K, Sutter R, Altmann DR, Friston K, Thompson A, Curt A (2013b) MRI investigation of the sensorimotor cortex and the corticospinal tract after acute spinal cord injury: a prospective longitudinal study. Lancet Neurol 12:873-881.  Back to cited text no. 13
    
14.
Fumagalli F, Madaschi L, Caffino L, Marfia G, Di Giulio AM, Racagni G, Gorio A (2009) Acute spinal cord injury reduces brain derived neurotrohic factor expression in rat hippocampus. Neuroscience 159:936-939.  Back to cited text no. 14
    
15.
Gundersen V, Storm-Mathisen J, Bergersen LH (2015) Neuroglial transmission. Physiol Rev 95:695-726.  Back to cited text no. 15
    
16.
Hains BC, Black JA, Waxman SG (2003) Primary cortical motor neurons undergo apoptosis after axotomizing spinal cord injury. J Comp Neurol 462:328-341.  Back to cited text no. 16
    
17.
Hulsebosch CE, Hains BC, Crown ED, Carlton SM (2009) Mechanisms of chronic central neuropathic pain after spinal cord injury. Brain Res Rev 60:202-213.  Back to cited text no. 17
    
18.
Jure I, Pietranera L, De Nicola AF, Labombarda F (2017) Spinal cord injury impairs neurogenesis and induces glial reactivity in the hippocampus. Neurochem Res doi:10.1007/s11064-017-2225-9.  Back to cited text no. 18
    
19.
Jurkiewicz MT, Crawley AP, Verrier MC, Fehlings MG, Mikulis DJ (2006) Somatosensory cortical atrophy after spinal cord injury: a voxel-based morphometry study. Neurology 66:762-764.  Back to cited text no. 19
    
20.
Kempermann G, Gage FH (1999) Experience-dependent regulation of adult hippocampal neurogenesis: effects of long-term stimulation and stimulus withdrawal. Hippocampus 9:321-332.  Back to cited text no. 20
    
21.
Knerlich-Lukoschus F, Noack M, von der Ropp-Brenner B, Lucius R, Mehdorn HM, Held-Feindt J (2011) Spinal cord injuries induce changes in CB1 cannabinoid receptor and C-C chemokine expression in brain areas underlying circuitry of chronic pain conditions. J Neurotrauma 28:619-634.  Back to cited text no. 21
    
22.
Lazzaro I, Tran Y, Wijesuriya N, Craig A (2013) Central correlates of impaired information processing in people with spinal cord injury. J Clin Neurophysiol 30:59-65.  Back to cited text no. 22
    
23.
Lee BH, Lee KH, Kim UJ, Yoon DH, Sohn JH, Choi SS, Yi IG, Park YG (2004) Injury in the spinal cord may produce cell death in the brain. Brain Res 1020:37-44.  Back to cited text no. 23
    
24.
Lee J, Duan W, Mattson MP (2002) Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem 82:1367-1375.  Back to cited text no. 24
    
25.
Lucassen PJ, Oomen CA, Naninck EF, Fitzsimons CP, van Dam AM, Czeh B, Korosi A (2015) Regulation of Adult Neurogenesis and Plasticity by (Early) Stress, Glucocorticoids, and Inflammation. Cold Spring Harb Perspect Biol 7:a021303.  Back to cited text no. 25
    
26.
Lundell H, Christensen MS, Barthelemy D, Willerslev-Olsen M, Biering-Sorensen F, Nielsen JB (2011) Cerebral activation is correlated to regional atrophy of the spinal cord and functional motor disability in spinal cord injured individuals. NeuroImage 54:1254-1261.  Back to cited text no. 26
    
27.
Maldonado-Bouchard S, Peters K, Woller SA, Madahian B, Faghihi U, Patel S, Bake S, Hook MA (2016) Inflammation is increased with anxiety- and depression-like signs in a rat model of spinal cord injury. Brain Behav Immun 51:176-195.  Back to cited text no. 27
    
28.
Murray RF, Asghari A, Egorov DD, Rutkowski SB, Siddall PJ, Soden RJ, Ruff R (2007) Impact of spinal cord injury on self-perceived pre- and postmorbid cognitive, emotional and physical functioning. Spinal Cord 45:429-436.  Back to cited text no. 28
    
29.
Nardone R, Holler Y, Brigo F, Seidl M, Christova M, Bergmann J, Golaszewski S, Trinka E (2013) Functional brain reorganization after spinal cord injury: systematic review of animal and human studies. Brain Res 1504:58-73.  Back to cited text no. 29
    
30.
Nicotra A, Critchley HD, Mathias CJ, Dolan RJ (2006) Emotional and autonomic consequences of spinal cord injury explored using functional brain imaging. Brain 129:718-728.  Back to cited text no. 30
    
31.
Nielson JL, Strong MK, Steward O (2011) A reassessment of whether cortical motor neurons die following spinal cord injury. J Comp Neurol 519:2852-2869.  Back to cited text no. 31
    
32.
O´Keefe J (2007) Hippocampal neurophysiology in the behaving animal. In: The Hippocampus Book (Andersen PMR, Amaral D, Bliss T, O´Keefe J eds), pp475-548. Oxford Oxford: University press.  Back to cited text no. 32
    
33.
Popovich P, McTigue D (2009) Damage control in the nervous system: beware the immune system in spinal cord injury. Nat Med 15:736-737.  Back to cited text no. 33
    
34.
Post MW, van Leeuwen CM (2012) Psychosocial issues in spinal cord injury: a review. Spinal Cord 50:382-389.  Back to cited text no. 34
    
35.
Roth E, Davidoff G, Thomas P, Doljanac R, Dijkers M, Berent S, Morris J, Yarkony G (1989) A controlled study of neuropsychological deficits in acute spinal cord injury patients. Paraplegia 27:480-489.  Back to cited text no. 35
    
36.
Scharfman H, Goodman J, Macleod A, Phani S, Antonelli C, Croll S (2005) Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats. Exp Neurol 192:348-356.  Back to cited text no. 36
    
37.
Schwab JM, Zhang Y, Kopp MA, Brommer B, Popovich PG (2014) The paradox of chronic neuroinflammation, systemic immune suppression, autoimmunity after traumatic chronic spinal cord injury. Exp Neurol 258:121-129.  Back to cited text no. 37
    
38.
Shin JC, Goo HR, Yu SJ, Kim DH, Yoon SY (2012) Depression and Quality of Life in Patients within the First 6 Months after the Spinal Cord Injury. Ann Rehabil Med 36:119-125.  Back to cited text no. 38
    
39.
Sierra A, Beccari S, Diaz-Aparicio I, Encinas JM, Comeau S, Tremblay ME (2014) Surveillance, phagocytosis, and inflammation: how never-resting microglia influence adult hippocampal neurogenesis. Neural Plast 2014:610343.  Back to cited text no. 39
    
40.
Tseng GF, Prince DA (1996) Structural and functional alterations in rat corticospinal neurons after axotomy. J Neurophysiol 75:248-267.  Back to cited text no. 40
    
41.
Wannier T, Schmidlin E, Bloch J, Rouiller EM (2005) A unilateral section of the corticospinal tract at cervical level in primate does not lead to measurable cell loss in motor cortex. J Neurotrauma 22:703-717.  Back to cited text no. 41
    
42.
Wrigley PJ, Gustin SM, Macey PM, Nash PG, Gandevia SC, Macefield VG, Siddall PJ, Henderson LA (2009) Anatomical changes in human motor cortex and motor pathways following complete thoracic spinal cord injury. Cereb Cortex 19:224-232.  Back to cited text no. 42
    
43.
Wu J, Zhao Z, Kumar A, Lipinski MM, Loane DJ, Stoica BA, Faden AI (2016) Endoplasmic reticulum stress and disrupted neurogenesis in the brain are associated with cognitive impairment and depressive-like behavior after spinal cord injury. J Neurotrauma 33:1919-1935.  Back to cited text no. 43
    
44.
Wu J, Zhao Z, Sabirzhanov B, Stoica BA, Kumar A, Luo T, Skovira J, Faden AI (2014a) Spinal cord injury causes brain inflammation associated with cognitive and affective changes: role of cell cycle pathways. J Neurosci 34:10989-11006.  Back to cited text no. 44
    
45.
Wu J, Stoica BA, Luo T, Sabirzhanov B, Zhao Z, Guanciale K, Nayar SK, Foss CA, Pomper MG, Faden AI (2014b) Isolated spinal cord contusion in rats induces chronic brain neuroinflammation, neurodegeneration, and cognitive impairment. Involvement of cell cycle activation. Cell Cycle 13:2446-2458.  Back to cited text no. 45
    
46.
Zhang ZJ, Jiang BC, Gao YJ (2017) Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain. Cell Mol Life Sci doi:10.1007/s00018-017-2513-1.  Back to cited text no. 46
    
47.
Zhao P, Waxman SG, Hains BC (2007) Modulation of thalamic nociceptive processing after spinal cord injury through remote activation of thalamic microglia by cysteine cysteine chemokine ligand 21. J Neurosci 27:8893-8902.  Back to cited text no. 47
    

Author contributions: IJ and FL have conceived and participated in article preparation.
Conflicts of interest: None declared.
Contributor agreement: A statement of “Publishing Agreement” has been signed by an authorized author on behalf of all authors prior to publication.
Plagiarism check: This paper has been checked twice with duplication-checking software iThenticate.
Peer review: A double-blind and stringent peer review process has been performed to ensure the integrity, quality and significance of this paper.
Open peer reviewers: Michele Fornaro, Midwestern University, USA; Gregory Hawryluk, The University of Utah, USA.



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