scholarly journals Folic Acid Modulates Matrix Metalloproteinase-2 Expression, Alleviates Neuropathic Pain, and Improves Functional Recovery in Spinal Cord-Injured Rats

2017 ◽  
Vol 24 (2) ◽  
pp. 74-81 ◽  
Author(s):  
Gurwattan S. Miranpuri ◽  
Sivan Vadakkadath Meethal ◽  
Emmanuel Sampene ◽  
Abhishek Chopra ◽  
Seah Buttar ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Folic Acid ◽  
Matrix Metalloproteinase ◽  
Functional Recovery ◽  
Matrix Metalloproteinase 2 ◽  
Spinal Cord Injured

scholarly journals Nitrous Oxide Impairs Axon Regeneration after Nervous System Injury in Male Rats

2019 ◽  
Vol 131 (5) ◽  
pp. 1063-1076
Author(s):  
Krista J. Stewart ◽  
Bermans J. Iskandar ◽  
Brenton M. Meier ◽  
Elias B. Rizk ◽  
Nithya Hariharan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Nitrous Oxide ◽  
Folic Acid ◽  
Functional Recovery ◽  
Axon Regeneration ◽  
Retinal Ganglion ◽  
Cord Injury

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Nitrous oxide can induce neurotoxicity. The authors hypothesized that exposure to nitrous oxide impairs axonal regeneration and functional recovery after central nervous system injury. Methods The consequences of single and serial in vivo nitrous oxide exposures on axon regeneration in four experimental male rat models of nervous system injury were measured: in vitro axon regeneration in cell culture after in vivo nitrous oxide administration, in vivo axon regeneration after sharp spinal cord injury, in vivo axon regeneration after sharp optic nerve injury, and in vivo functional recovery after blunt contusion spinal cord injury. Results In vitro axon regeneration 48 h after a single in vivo 70% N2O exposure is less than half that in the absence of nitrous oxide (mean ± SD, 478 ± 275 um; n = 48) versus 210 ± 152 um (n = 48; P < 0.0001). A single exposure to 80% N2O inhibits the beneficial effects of folic acid on in vivo axonal regeneration after sharp spinal cord injury (13.4 ± 7.1% regenerating neurons [n = 12] vs. 0.6 ± 0.7% regenerating neurons [n = 4], P = 0.004). Serial 80% N2O administration reverses the benefit of folic acid on in vivo retinal ganglion cell axon regeneration after sharp optic nerve injury (1277 ± 180 regenerating retinal ganglion cells [n = 7] vs. 895 ± 164 regenerating retinal ganglion cells [n = 7], P = 0.005). Serial 80% N2O exposures reverses the benefit of folic acid on in vivo functional recovery after blunt spinal cord contusion (estimate for fixed effects ± standard error of the estimate: folic acid 5.60 ± 0.54 [n = 9] vs. folic acid + 80% N2O 5.19 ± 0.62 [n = 7], P < 0.0001). Conclusions These data indicate that nitrous oxide can impair the ability of central nervous system neurons to regenerate axons after sharp and blunt trauma.

scholarly journals Promotion of astrocytoma cell invasion by micro RNA–22 targeting of tissue inhibitor of matrix metalloproteinase–2

2017 ◽  
Vol 26 (3) ◽  
pp. 396-403 ◽  
Author(s):  
Yu-ichiro Ohnishi ◽  
Koichi Iwatsuki ◽  
Masahiro Ishihara ◽  
Toshika Ohkawa ◽  
Manabu Kinoshita ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Matrix Metalloproteinase ◽  
Cell Lines ◽  
Matrix Metalloproteinase 2 ◽  
Luciferase Reporter ◽  
Tissue Inhibitor ◽  
Thoracic Spinal Cord ◽  
Diffuse Infiltration ◽  
Astrocytoma Cells ◽  
1321N1 Astrocytoma

OBJECTIVE Diffuse astrocytomas (DAs) have a high recurrence rate due to diffuse infiltration into the brain and spinal cord. Micro RNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to complementary sequences of target messenger RNA (mRNA). It has been reported that miRNA-22 (miR-22) is involved in the invasion of some cancer cell lines. The aim of this study was to identify the biological effects of miR-22 in regard to the invasion of human DAs. METHODS The authors evaluated whether the level of miR-22 is elevated in human spinal DAs by using miRNA chips. Next, the role of miR-22 in 1321N1 human astrocytoma cells was investigated. Finally, to elucidate whether miR-22 promotes invasion by astrocytoma cells in vivo, the authors transplanted miR-22 overexpressed astrocytoma cells into mouse thoracic spinal cord. RESULTS The miR-22 significantly upregulated the invasion capacity of 1321N1 cells. Computational in silico analysis predicted that tissue inhibitor of matrix metalloproteinase–2 (TIMP2) is a target gene of miR-22. This was confirmed by quantitative reverse transcription polymerase chain reaction and Western blotting, which showed that miR-22 inhibited TIMP2 mRNA and protein expression, respectively. Luciferase reporter assays demonstrated that miR-22 directly bound the 3′-untranslated regions of TIMP2. The authors further showed that miR-22 promoted invasiveness in 1321N1 astrocytoma cells when transplanted into mouse spinal cord. CONCLUSIONS These data suggest that miR-22 acts to regulate invasion of 1321N1 astrocytoma cells by targeting TIMP2 expression. Additional studies with more cases and cell lines are required to elucidate the findings of this study for a novel treatment target for spinal DAs.

scholarly journals Assessment of Nogo-66 Receptor 1 Function In Vivo After Spinal Cord Injury

Neurosurgery ◽  
2014 ◽  
Vol 75 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Jing Tong ◽  
Yi Ren ◽  
Xiaowei Wang ◽  
Vassilios G. Dimopoulos ◽  
Henry N. Kesler ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Matrix Metalloproteinase ◽  
Functional Recovery ◽  
Axon Regeneration ◽  
Matrix Metalloproteinase 9 ◽  
Mutant Mice ◽  
Locomotor Function ◽  
Cord Injury ◽  
Metalloproteinase 9

Abstract BACKGROUND: Neuronal Nogo-66 receptor 1 (NgR1) has attracted attention as a converging point for mediating the effects of myelin-associate inhibitory ligands in the central nervous system, establishing the growth-restrictive environment, and limiting axon regeneration after traumatic injury. OBJECTIVE: To investigate the factors that may be contributing to the discrepancy in the importance of NgR1, which has been undermined by several studies that have shown the lack of substantial axon regeneration after spinal cord injury (SCI) in NgR1-knockout or -knockdown animal models. METHODS: We used mice carrying either a homozygous or heterozygous null mutation in the NgR1 gene and subjected them to either a moderate or severe SCI. RESULTS: Locomotor function assessments revealed that the level of functional recovery is affected by the degree of injury suffered. NgR1 ablation enhanced local collateral sprouting in the mutant mice. Reactive astrocytes and chondroitin sulfate proteoglycans (CSPGs) are upregulated surrounding the injury site. Matrix metalloproteinase-9, which has been shown to degrade CSPGs, was significantly upregulated in the homozygous mutant mice compared with the heterozygous or wild-type mice. However, CSPG levels remained higher in the homozygous compared with the heterozygous mice, suggesting that CSPG-degrading activity of matrix metalloproteinase-9 may require the presence of NgR1. CONCLUSION: Genetic ablation of NgR1 may lead to significant recovery in locomotor function after SCI. The difference in locomotor recovery we observed between the groups that suffered various degrees of injury suggests that injury severity may be a confounding factor in functional recovery after SCI.

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