NDLI: Inhibition of the NMDA receptor protects the rat sciatic nerve against ischemia/reperfusion injury

Content Provider	PubMed Central
Author	Tie, Ke Li, Renbin Chen, Wenchang
Copyright Year	2016
Abstract	Inhibition of the N-methyl-D-aspartate (NMDA) receptor by MK-801 reduces ischemia/reperfusion (I/R) injury in the central nervous system. However, few previous studies have evaluated the neuroprotective effects of MK-801 against peripheral I/R injury. The present study aimed to investigate the protective effects of MK-801 pretreatment against I/R injury in the rat sciatic nerve (SN). Sprague-Dawley rats were subjected to a sham surgery (n=8) or to a 5-h ischemic insult by femoral artery clamping (I/R and I/R+MK-801 groups; n=48 per group). I/R+MK-801 rats were intraperitoneally injected with MK-801 (0.5 ml or 1 mg/kg) at 15 min prior to reperfusion. The rats were sacrificed at 0, 6, 12, 24, 72 h, or 7 days following reperfusion. Plasma malondialdehyde (MDA) and nitric oxide (NO) concentrations, and SN inducible NO synthase (iNOS) protein expression levels, were measured using colorimetry. In addition, the protein expression levels of tumor necrosis factor-α (TNF-α) were measured using immunohistochemistry, and histological analyses of the rat SN were conducted using light and electron microscopy. Alterations in the mRNA expression levels of TNF-α and TNF-α converting enzyme (TACE) in the rat SN were detected using reverse transcription-quantitative polymerase chain reaction. In the I/R group, plasma concentrations of NO (175.3±4.2 µmol/l) and MDA (16.2±1.9 mmol/l), and the levels of iNOS (2.5±0.3) in the SN, peaked at 24 h post-reperfusion. At 24 h, pretreatment with MK-801 significantly reduced plasma NO (107.3±3.6 µmol/l) and MDA (11.8±1.6 mmol/l), and SN iNOS (1.65±0.2) levels (all P<0.01). The mRNA expression levels of TNF-α and TACE in the SN were significantly reduced in the I/R+MK-801 group, as compared with the I/R group (P<0.05). Furthermore, MK-801 pretreatment was shown to have alleviated histological signs of I/R injury, including immune cell infiltration and axon demyelination. The results of the present study suggested that pretreatment with MK-801 may alleviate I/R injury of the SN by inhibiting the activation of TNF-α and reducing the levels of iNOS in the SN.
Related Links	http://dx.doi.org/10.3892/etm.2016.3148
Ending Page	1572
Page Count	10
Starting Page	1563
File Format	PDF
ISSN	17920981
e-ISSN	17921015
Journal	Experimental and Therapeutic Medicine
Issue Number	5
Volume Number	11
Language	English
Publisher	D.A. Spandidos
Publisher Date	2016-03-01
Access Restriction	Open
Rights Holder	D.A. Spandidos
Subject Keyword	Immunology and Microbiology (miscellaneous) Cancer Research Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research 2400/2401

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