Chronic spinal cord compression associated with intervertebral disc degeneration in SPARC-null mice

Chronic spinal cord compression(CSCC)is induced by disc herniation and other reasons,leading to movement and sensation dysfunction,with a serious impact on quality of life.Spontaneous disc herniation rarely occurs in rodents,and therefore establishing a chronic spinal cord compression(CSCC)animal model is of crucial importance to explore the pathogenesis and treatment of CSCC.The absence of secreted protein,acidic,and rich in cysteine(SPARC)leads to spontaneous intervertebral disc degeneration in mice,which resembles human disc degeneration.In this study,we evaluated whether SPARC-null mice may serve as an animal model for CSCC.We performed rod rotation test,pain threshold test,gait analysis,and Basso Mouse Scale score.Our results showed that the motor function of SPARC-null mice was weakened,and magnetic resonance images revealed compression at different spinal cord levels,particularly in the lumbar segments.Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes,activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype;it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway.Notably,these findings are characteristics of CSCC.Therefore,we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.

Effect of docosahexaenoic acid on the recovery of motor function in rats with spinal cord injury: a meta-analysis

Objective:Studies have shown that docosahexaenoic acid(DHA)has a beneficial effect in the treatment of spinal cord injury.A meta-analysis was used to study the effect of DHA on the neurological recovery in the rat spinal cord injury model,and the relationship between the recovery of motor function after spinal cord injury and the time and method of administration and the dose of DHA.Data source:Published studies on the effect of DHA on spinal cord injury animal models from seven databases were searched from their inception to January 2019,including PubMed,MEDLINE,EMBASE,the China National Knowledge Infrastructure,Wanfang,VIP,and SinoMed databases.The search terms included“spinal cord injury”“docosahexaenoic acid”,and“rats”.Data selection:Studies that evaluated the influence of DHA in rat models of spinal cord injury for locomotor functional recovery were included.The intervention group included any form of DHA treatment and the control group included treatment with normal saline,vehicle solution or no treatment.The Systematic Review Centre for Laboratory animal Experimentation’s risk of bias assessment tool was used for the quality assessment of the included studies.Literature inclusion,quality evaluation and data extraction were performed by two researchers.Meta-analysis was then conducted on all studies that met the inclusion criteria.Statistical analysis was performed on the data using RevMan 5.1.2.software.Outcome measures:The primary outcome measure was the score on the Basso,Beattie,and Bresnahan scale.Secondary outcome measures were the sloping plate test,balance beam test,stair test and grid exploration test.Results:A total of 12 related studies were included,3 of which were of higher quality and the remaining 9 were of lower quality.The highest mean Basso,Beattie,and Bresnahan scale score occurred at 42 days after DHA treatment in spinal cord injury rats.At 21 days after treatment,the mean difference in Basso,Beattie,Bresnahan scores between the DHA group and the control group was the most significant(pooled MD=4.14;95%CI=3.58–4.70;P<0.00001).In the subgroup analysis,improvement in the Basso,Beattie,and Bresnahan scale score was more significant in rats administered DHA intravenously(pooled MD=2.74;95%CI=1.41–4.07;P<0.0001)and subcutaneously(pooled MD=2.99;95%CI=2.29–3.69;P<0.00001)than in the groups administered DHA orally(pooled MD=3.04;95%CI=–1.01 to 7.09;P=0.14).Intravenous injection of DHA at 250 nmol/kg(pooled MD=2.94;95%CI=2.47–3.41;P<0.00001]and 1000 nmol/kg[pooled MD=3.60;95%CI=2.66–4.54;P<0.00001)significantly improved the Basso,Beattie,and Bresnahan scale score in rats and promoted the recovery of motor function.Conclusion:DHA can promote motor functional recovery after spinal cord injury in rats.The administration of DHA by intravenous or subcutaneous injection is more effective than oral administration of DHA.Intravenous injection of DHA at doses of 250 nmol/kg or 1000 nmol/kg is beneficial.Because of the small number and the low quality of the included studies,more high-quality research is needed in future to substantiate the results.

MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis

OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.DATA SOURCES: Key terms were "stroke","brain diseases","brain injuries","brain hemorrhage, traumatic","acute brain injury","dizocilpine maleate","dizocilpine","MK-801","MK801","rat","rats","rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform(VJIP) and SinoMed databases were searched from their inception dates to March 2018.DATA SELECTION: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments.OUTCOME MEASURES: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury.RESULTS: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P < 0.00001) and degree of cerebral edema(5 studies, n = 75, MD =-1.21, 95% CI:-1.50 to-0.91;P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test(2 studies, n = 60, MD =-10.88, 95% CI:-20.75 to-1.00;P = 0.03) and neurological function 24 hours after brain injury(11 studies, n = 335, MD =-1.04, 95% CI:-1.47 to-0.60;P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P = 0.004). Further network analysis showed that 0–1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model.CONCLUSION: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.