scholarly journals Serum CCL21 as a Potential Biomarker for Cognitive Impairment in Spinal Cord Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Yuanzhen Chen ◽  
Liangke Liang ◽  
Shengnan Cao ◽  
Guangjian Hou ◽  
Qian Zhang ◽  
...  

Objective. Cognitive impairment is considered to be an important complication of spinal cord injury (SCI), but its underlying mechanism remains unclear. The purpose of this study is to explore whether serum CCL21 can be used as a potential biomarker of cognitive impairment in SCI. Methods. In Neck-Shoulder and Lumbocrural Pain Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, hospitalized or treated acute SCI patients were included in the study as the SCI group (SCI). At the same time, a normal control group (NC) matching the age and sex of the SCI group was recruited in the outpatient clinic. Once the two groups were enrolled, their demographics and clinical characteristics were collected immediately. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum CCL21 levels within 24 hours of admission. Three months later, the Montreal Cognitive Assessment (MoCA) was used to test the cognitive function of the population. Results. A total of 84 SCI patients and 49 NC populations were eligible for inclusion in the study. There was no significant statistical difference in the demographics and clinical characteristics (age, gender, BMI, TG, LDL-C, FBG, SBP, and DBP) between the two groups ( p > 0.05 ). Compared with the NC group, the SCI group had a higher serum CCL21 level ( p < 0.001 ) and a lower MoCA score ( p < 0.001 ). Serum CCL21 level in SCI was negatively correlated with MoCA score ( p = 0.023 ). Multivariable analyses showed that serum CCL21 level is an independent prognostic factor of cognitive impairment in SCI. Conclusions. MoCA score has a linear relationship with serum CCL21 quartile, and SCI cognitive function has a negative correlation with serum CCL21. Serum CCL21 is an independent risk factor for cognitive impairment after SCI.

Neurology ◽  
2018 ◽  
Vol 91 (13) ◽  
pp. 611-621 ◽  
Author(s):  
Rahul Sachdeva ◽  
Feng Gao ◽  
Chetwyn C.H. Chan ◽  
Andrei V. Krassioukov

ObjectiveTo systematically examine the incidence of cognitive impairment in individuals with spinal cord injury (SCI), as well as identify potential contributing and confounding factors.MethodsStudies quantitatively reporting cognitive ability after spinal cord injury were searched electronically via Medline, CINAHL, Embase, and PsycINFO. Manual screening for references within articles was also performed. A total of 2,481 studies were screened and a total of 70 were included in this review, 21 reporting cognitive function after SCI compared to an able-bodied control group and 49 with no able-bodied controls. Studies were analyzed for the incidence of impairment and the interactions with concomitant traumatic brain injury, psychological or somatic complaints, decentralized cardiovascular control, sleep apnea, neurologic level of injury, and age.ResultsThere is a high volume of evidence reporting substantial cognitive impairment in individuals with SCI. Potential co-contributors include concomitant brain injury, psychological or somatic comorbidities, decentralized cardiovascular control, and sleep apnea. Cognitive functioning was negatively correlated with age. No clear agreement was found for the incidence of cognitive impairment or its association with level of injury.ConclusionCurrent evidence suggests that individuals with SCI should be examined and addressed for cognitive impairment. Future studies aimed at identifying potential secondary causative factors should employ stringent controls for co-occurring brain trauma since it appears to be a major contributor and confounder to impaired cognition.


2014 ◽  
Vol 34 (5) ◽  
pp. 794-801 ◽  
Author(s):  
Aaron A Phillips ◽  
Darren ER Warburton ◽  
Philip N Ainslie ◽  
Andrei V Krassioukov

Individuals with high-level spinal cord injury (SCI) experience low blood pressure (BP) and cognitive impairments. Such dysfunction may be mediated in part by impaired neurovascular coupling (NVC) (i.e., cerebral blood flow responses to neurologic demand). Ten individuals with SCI > T6 spinal segment, and 10 age- and sex-matched controls were assessed for beat-by-beat BP, as well as middle and posterior cerebral artery blood flow velocity (MCAv, PCAv) in response to a NVC test. Tests were repeated in SCI after 10 mg midodrine (alpha1-agonist). Verbal fluency was measured before and after midodrine in SCI, and in the control group as an index of cognitive function. At rest, mean BP was lower in SCI (70 ± 10 versus 92 ± 14 mm Hg; P<0.05); however, PCAv conductance was higher (0.56 ± 0.13 versus 0.39 ± 0.15 cm/second/mm Hg; P<0.05). Controls exhibited a 20% increase in PCAv during cognition; however, the response in SCI was completely absent ( P<0.01). When BP was increased with midodrine, NVC was improved 70% in SCI, which was reflected by a 13% improved cognitive function ( P<0.05). Improvements in BP were related to improved cognitive function in those with SCI ( r2 = 0.52; P<0.05). Impaired NVC, secondary to low BP, may partially mediate reduced cognitive function in individuals with high-level SCI.


2021 ◽  
Vol 12 ◽  
Author(s):  
Feng Zhang ◽  
Guangshun Hou ◽  
Guangjian Hou ◽  
Congan Wang ◽  
Bin Shi ◽  
...  

Background: Irisin, a new exercise-related myokine, has been shown to be associated with a variety of diseases including serious neurological disorders. However, whether irisin is involved in the pathogenesis of vascular dementia (VD) has not yet been reported. Our aim is to determine the serum irisin level in patients with VD and investigate its relationship with cognitive function.Methods: The subjects of the study were VD patients and controls with normal cognitive function who were hospitalized in the Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University from July 2018 to June 2020. Upon admission, a cognitive function assessment was performed. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of irisin in serum.Results: During the study period, 187 subjects (82 controls and 105 VD patients) were included in the analysis. The serum irisin level of VD patients was significantly lower than that of the control group (p &lt; 0.001). Spearman analysis showed that irisin was positively correlated with HLD-C and MoCA, and negatively correlated with all clinical characteristics except for HCY. Logistic regression analysis showed that after adjusting for all clinical characteristics, the serum irisin of VD patients still had a significant correlation with MoCA (β = 0.304, p = 0.029). According to receiver operating characteristic (ROC) curve analysis, the diagnostic accuracy for serum irisin levels on VD was 76% with the sensitivity and 71% with specificity respectively.Conclusions: These data indicate that a decrease in serum irisin levels is a powerful biological marker for cognitive decline in patients with VD, even after adjustment for risk factors. Further multi-center studies need to confirm this connection, which may pave the way for new treatment options.


2020 ◽  
Vol 10 (3) ◽  
pp. 323-328
Author(s):  
Zhigang Zhou ◽  
Kai Cao ◽  
Jianping Liao ◽  
Song Zhou ◽  
Liangliang Zhou ◽  
...  

The incidence of spinal cord injury (SCI) increases year by year. SCI is characterized as high disability rate and poor prognosis. BMP/Smads signaling participates in the formation of osteoblasts and renal failure. This article will explore the regulation of BMP/Smads signaling pathway in SCI. Wistar rats were divided into control group; SCI group; and BMP-2 treatment group that were treated by tail vein injection of BMP-2 antisense oligonucleotide BMP-2 phosphorothioate AODN at 30 min after modeling. Real-time PCR and Western blot were used to detect BMP-2, Smad1, and Smad5 expressions. Hematoxylin-eosin (HE) staining was applied to analyze the change of SCI in each group. Immunohistochemistry (IHC) was selected to test BMPR Ia expression. Basso, Beattie Bresnahan-cocomotor rating scale (BBB) scale and Reuter score were compared. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect TNF-α and Interleukin-2 (IL-2) expressions. Compared with the control group, BMP-2, Smad1, and Smad5 mRNA and protein expressions increased, BBB score declined, Reuter score elevated, and TNF-α and IL-2 secretion enhanced in the SCI group (P < 0.05). HE staining showed spinal cord injury, and IHC exhibited increased expression of BMPR Ia. The TGF-β treatment group significantly reduced the expressions of BMP-2, Smad1, and Smad5 mRNA and protein, increased BBB score, reduced Reuter score, and weakened the secretions of TNF-α and IL-2 (P < 0.05). HE staining demonstrated decreased reduction of spinal cord tissue and declined expression of BMPR Ia. SCI activated BMP/Smads signaling pathway, up-regulated BMPR Ia expression, and promoted inflammation. Regulation of BMP/Smads signaling pathway can downregulate BMPR Ia expression and inhibit inflammation to effectively relieve SCI.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 143
Author(s):  
Ganchimeg Davaa ◽  
Jin Young Hong ◽  
Tae Uk Kim ◽  
Seong Jae Lee ◽  
Seo Young Kim ◽  
...  

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.


2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Sipin Zhu ◽  
Yibo Ying ◽  
Jiahui Ye ◽  
Min Chen ◽  
Qiuji Wu ◽  
...  

AbstractNeural stem cell (NSCs) transplantation has been one of the hot topics in the repair of spinal cord injury (SCI). Fibroblast growth factor (FGF) is considered a promising nerve injury therapy after SCI. However, owing to a hostile hypoxia condition in SCI, there remains a challenging issue in implementing these tactics to repair SCI. In this report, we used adeno-associated virus 2 (AAV2), a prototype AAV used in clinical trials for human neuron disorders, basic FGF (bFGF) gene under the regulation of hypoxia response element (HRE) was constructed and transduced into NSCs to yield AAV2-5HRE-bFGF-NSCs. Our results showed that its treatment yielded temporally increased expression of bFGF in SCI, and improved scores of functional recovery after SCI compared to vehicle control (AAV2-5HRE-NSCs) based on the analyses of the inclined plane test, Basso–Beattie–Bresnahan (BBB) scale and footprint analysis. Mechanistic studies showed that AAV2-5HRE-bFGF-NSCs treatment increased the expression of neuron-specific neuronal nuclei protein (NeuN), neuromodulin GAP43, and neurofilament protein NF200 while decreased the expression of glial fibrillary acidic protein (GFAP) as compared to the control group. Further, the expressions of autophagy-associated proteins LC3-II and Beclin 1 were decreased, whereas the expression of P62 protein was increased in AAV2-5HRE-bFGF-NSCs treatment group. Taken together, our data indicate that AAV2-5HRE-bFGF-NSCs treatment improved the recovery of SCI rats, which is accompanied by evidence of nerve regeneration, and inhibition of SCI-induced glial scar formation and cell autophagy. Thus, this study represents a step forward towards the potential use of AAV2-5HRE-bFGF-NSCs for future clinical trials of SCI repair.


Spinal Cord ◽  
2021 ◽  
Author(s):  
Helge Kasch ◽  
Uffe Schou Løve ◽  
Anette Bach Jønsson ◽  
Kaare Eg Severinsen ◽  
Marc Possover ◽  
...  

Abstract Study design 1-year prospective RCT. Objective Examine the effect of implantable pulse generator and low-frequency stimulation of the pelvic nerves using laparoscopic implantation of neuroprosthesis (LION) compared with neuromuscular electrical stimulation (NMES) in SCI. Methods Inclusion criteria: traumatic spinal cord injury (SCI), age 18–55 years, neurological level-of-injury Th4–L1, time-since-injury >1 year, and AIS-grades A–B. Participants were randomized to (A) LION procedure or (B) control group receiving NMES. Primary outcome measure: Walking Index for Spinal Cord Injury (WISCI-II), which is a SCI specific outcome measure assessing ability to ambulate. Secondary outcome measures: Spinal Cord Independence Measure III (SCIM III), Patient Global Impression of Change (PGIC), Penn Spasm Frequency Scale (PSFS), severity of spasticity measured by Numeric Rating Scale (NRS-11); International Spinal Cord Injury data sets-Quality of Life Basic Data Set (QoLBDS), and Brief Pain Inventory (BPI). Results Seventeen SCI individuals, AIS grade A, neurological level ranging from Th4–L1, were randomized to the study. One individual was excluded prior to intervention. Eight participants (7 males) with a mean age (SD) of 35.5 (12.4) years were allocated to the LION procedure, 8 participants (7 males) with age of 38.8 (15.1) years were allocated to NMES. Significantly, 5 LION group participants gained 1 point on the WISCI II scale, (p < 0.013; Fisher´s exact test). WISCI II scale score did not change in controls. No significant changes were observed in the secondary outcome measures. Conclusion The LION procedure is a promising new treatment for individuals with SCI with significant one-year improvement in walking ability.


2014 ◽  
Vol 23 (11) ◽  
pp. 1451-1464 ◽  
Author(s):  
Hiroki Iwai ◽  
Satoshi Nori ◽  
Soraya Nishimura ◽  
Akimasa Yasuda ◽  
Morito Takano ◽  
...  

Transplantation of neural stem/progenitor cells (NS/PCs) promotes functional recovery after spinal cord injury (SCI); however, few studies have examined the optimal site of NS/PC transplantation in the spinal cord. The purpose of this study was to determine the optimal transplantation site of NS/PCs for the treatment of SCI. Wild-type mice were generated with contusive SCI at the T10 level, and NS/PCs were derived from fetal transgenic mice. These NS/PCs ubiquitously expressed ffLuc-cp156 protein (Venus and luciferase fusion protein) and so could be detected by in vivo bioluminescence imaging 9 days postinjury. NS/PCs (low: 250,000 cells per mouse; high: 1 million cells per mouse) were grafted into the spinal cord at the lesion epicenter (E) or at rostral and caudal (RC) sites. Phosphate-buffered saline was injected into E as a control. Motor functional recovery was better in each of the transplantation groups (E-Low, E-High, RC-Low, and RC-High) than in the control group. The photon counts of the grafted NS/PCs were similar in each of the four transplantation groups, suggesting that the survival of NS/PCs was fairly uniform when more than a certain threshold number of cells were transplanted. Quantitative RT-PCR analyses demonstrated that brain-derived neurotropic factor expression was higher in the RC segment than in the E segment, and this may underlie why NS/PCs more readily differentiated into neurons than into astrocytes in the RC group. The location of the transplantation site did not affect the area of spared fibers, angiogenesis, or the expression of any other mediators. These findings indicated that the microenvironments of the E and RC sites are able to support NS/PCs transplanted during the subacute phase of SCI similarly. Optimally, a certain threshold number of NS/PCs should be grafted into the E segment to avoid damaging sites adjacent to the lesion during the injection procedure.


2021 ◽  
Vol 37 (2) ◽  
Author(s):  
Huan-xia Li ◽  
Jing Cui ◽  
Jing-shi Fan ◽  
Jian-zhou Tong

Objective: To examine the clinical efficacy of combining Riluzole with mannitol and hyperbaric oxygen therapy in treating thoracolumbar vertebral fracture-induced acute spinal cord injury (ASCI). Methods: From June 2015 to May 2018, 80 patients with thoracolumbar fractures and ASCI who were treated at Baoding First Central Hospital were selected. All patients underwent posterior laminectomy and screw fixation, and they were randomly divided into two groups using a random number table method. The control group received conventional postoperative treatment, while the experimental group was treated with riluzole combined with mannitol and hyperbaric oxygen on the basis of conventional treatment. The recovery of nerve function which included motor function and sensory function, and the changes of serum IL-6, CRP, BDNF, BFGF and other factors before treatment and four weeks after treatment of the two groups of patients were observed and evaluated. Results: After treatment, the motor function scores and sensory function scores of the two groups of patients were improved compared with those before treatment (p<0.05). Compared with the control group, the experimental group improved significantly, and the difference was statistically significant (p<0.05). The levels of IL-6, BDNF and NFGF in the experimental group were significantly lower than those in the control group (p<0.05). Conclusions: For patients with thoracolumbar fractures and ASCI undergoing laminar decompression and fixation, the comprehensive treatment plan of riluzole combined with mannitol and hyperbaric oxygen has certain advantages. Compared with the conventional therapy, it may significantly improve the movement and sensory functions of patients, relieve the inflammatory response of spinal cord, and promote recovery from the injury. doi: https://doi.org/10.12669/pjms.37.2.3418 How to cite this:Li H, Cui J, Fan J, Tong J. An observation of the clinical efficacy of combining Riluzole with mannitol and hyperbaric oxygen in treating acute spinal cord injury. Pak J Med Sci. 2021;37(2):---------. doi: https://doi.org/10.12669/pjms.37.2.3418 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


2020 ◽  
Vol 3 (1) ◽  
pp. 1-4
Author(s):  
Lin JM ◽  
◽  
Hui Chen ◽  
Liu QL ◽  
Huang MP ◽  
...  

Objective: To evaluate the d the safety and efficacy of 200 U vs. 300 U botulinum toxin A (BTX-A) injections for patients with neurogenic detrusor overactivity (NDO) secondary to spinal cord injury (SCI). Methods: We retrieved the data for the patients who receive a single dose into the detrusor of BTX-A (300 U or 200 U). The clinical outcome included maximum detrusor pressure (Pdetmax) during cystometry, voiding volume, urinary incontinence (UI) episodes between CICs per 24 hour, and complete dryness. Related adverse events were recorded. Results: From July 2015 to June 2017, 28 cases received 300 U BTX-A injections (experiment group) while 19 cases received 200U BTX-A injections (control group). There were no significant differences in baseline evaluation items (gender, age, duration of spinal cord injury, level of neurological injury, AIS scores) between the two groups. There were significant improvement in Pdetmax, UI and I-QoL from baseline in the two groups. Patients in experiment group had statistically greater improvement than those in the control group for Pdetmax (-32.09 cm H2O vs. -28.02 cm H2O, P = 0.016), mean urinary incontinence episodes (-6.18/d vs. -5.01/d, P = 0.042), complete dryness (11 vs. 2, P = 0.031), mean voiding volume (160.52 ml vs. 133.66 ml, P <0.001), and I-QoL (28.53 vs. 20.41, P <0.001). Conclusion: Preliminary results indicate that 300 U BTX-A is more effective than 200 U BTX-A for SCI patients with NDO.


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