Effect of Electro-acupuncture on the Expression of Slit2 and HSPGs in Rats with Focal Cerebral Infarction

LONG Fei, LI Xue-zhi, GONG Biao. et al

Abstract

To determine the expression of Slit2 and heparan sulfate proteoglycans (HSPGs) in cortex of rats with focal cerebral infarction and the effect of acupuncture (EA) on the expression of Slit2 and HSPGs. Methods 40 male Sprague Dawley (SD) rats were equally randomized into four groups：Control group，model group，non-acupoint EA group，and EA group. Thread-tying method was used in the model group, non-acupoint EA group and EA group to clog arteries and then open up after 1.5 h. Morphology changes of tissues around the infarction area were observed 14 days later by Nissl staining. The expressions of Slit2 and HSPGs in the ischemic brain tissues were detected by indirect immunofluorescence staining (IF) and Western blot (WB). Results Modified neurologicalseverity scores (mNSS) showed zero in the control group, lower than the score of EA group. The EA group had lower mNSS score than the non-acupoint group. The highest mNSS score appeared in the model group. Paired comparisons showed statistical differences （ P<0.01）. Nissl’s staining showed that EA group had increased Nissl bodies in alignment; non-acupoint EA group had increased and disordered Nissl bodies; model group had decreased and disordered Nissl bodies with edema in the brain. IF and WB showed that non-acupoint EA group had higher levels of Slit2 and HSPGs than model group ( P<0.05); EA group had higher levels of Slit2 and HSPGs than non-acupoint EA group ( P<0.05); model group had higher levels of Slit2 and HSPGs than control group ( P<0.05). The results of Nissl’s staining, IF and WB were consistent. Conclusion EA can enhance the expressions of Slit2 and HSPGs. This may be one of the mechanisms of EA promoting recovery of neural functions after cerebral infarction.

 

Keywords: Cerebral ischemia-reperfusion, Electroacupunture, Slit2-Robo, HSPGs 

 

Full Text:

PDF


References


Tessier Lavigne M. Goodman CS. The molecular biology of axon guidance. Science, 1996 ;274(5290); 1123-1133.

Wu W, Wong K,Chen J ,et al. Directi onal guidance of neuronal migration in the olfactory system by the protein slit. Nature, 1999;400(6742);331-336.

Pircher A, Wellbrock J, Fiedler W, et al. New antiangiogenic strategies beyond inhibition of vascular endothelial growth factor with special focus on axon guidance molecules. Oncology»2014 ;86( 1):46-52.

Refai O, Rohs P, Mains PE. et al. Extension of the Caenorhabditis elegans Pharyngeal Ml neuron axon is regulated by multiple mechanisms. G3 ( Bethesda) , 2013; 3(11): 2015- 2029.

Yaron A,Zheng B. Navigating their way to the clinic; emerging roles for axon guidance molecules in neuroles in neurological disorders and injury .Dev Neurobiol, 2007; 6 7 (9); 1216-1231.

Campbell DS, Holt CE. Apoptotic pathway and MAPKs different tially regulate chemotropic responses of retinal growth cones. Neuron, 2003 ; 37(6); 939-952.

Brose K. Bland KS, Wang KH, et al. Slit proteins bind Robo receptors and have an evolutionary conserved role in repulsive axon guidance. Cell ,1999 ; 96(6); 795-806.

Hu H. Chemorepulsion of neuronal migration by Slit2 in the developing mammalian forebrain. Neuron, 1999; 23 ( 4 ); 703- 711.

Ozdinler PH, Erzurumlu RS. Slit2, a branching-arborization factor for sensory axons in the mammalian CNS. Neurosci, 2002;22(11): 4540-4549.

James G, Foster SR. Key B, et al. The expression pattern of EVA1C» a novel slit receptor, is consistent with an axon guidance role in the mouse nervous system. PLos One, 2013; 8 (9) :e74115. doi: 10. 1371/journal, pone. 0074115.

Kimberley F, Guadagnoli M, van Eenennaam H, et al. A proliferation-inducing ligand (APRIL); the development of antagonistic agents as potential therapeutics anddeciphering the role of heparan sulphate proteoglycans (HSPGs) in APRIL Signalling. Adv Exp Med Biol, 2011; 691; 501-506. doi; 10.1007/978-1-4419-6612-4_52.

Wang B, Xiao Y. Ding BB, et al. Induction of tumor angiogenesis by Slit-Robo signaling andinhibition of cancer growth by blocking Robo activity. Cancer Cell, 2003 ;4( 1): 19- 29.

Thompson H, Camand O, Barker D, et al. Slit proteins regulate distinct aspects of retinal ganglion cell axon guidance within dorsal and ventral retina. J Neurosci, 2006; 26 (31 ); 8082-8091.

Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral atery occlusion without craniectomy in rats. Stroke, 1989; 20(1) s 184-191. 213 ]JO

Schwab ME. Repairing the injured spinal cord. Science.2002; 295(5557):1029-1031.

Marillat V, Cases O, Nguyen-Ba-Charvet KT, et al. Spatiotemporal expression patterns of slit and robo genes in the rat brain. J Comp Neurol,2002;442(2); 110-155.

Seeger M. Tear G, Ferres-Marco D, et al. Mutations affecting growth cone guidance in Drosophila; genes neces-sary for guidance toward or away from the midline. Neuron. 1993; 10 <3);409-426.

Kaneko S, Iwanami A, Nakamura M, et al .A selective SemalA inhibitor enhances regenerative responses and functional recovery of the injured spinal cord. Nat Med,2006; 12(12):1380-1389.

Zheng B, Lee JK, Xie F. Genetic mouse models for studying inhibitors of spinal axon regeneration. Trends Neurosci, 2006; 29(11):640-646.

Whitford KL. Marillai V. Stein E. et al. Regulation of cortical dendrite development by Slit-Robo interactions. Neuron. 2002; 33(1) : 4 7-61.

Andrews W. Liapi A, Plachez C, et al. Robol regulates the development of major axon tracts and interneuron migration in the forebrain. Development ,2006; 133(11);2243-2252.

Johnson KG, Tenney AP, Ghose A, et al. The HSPGs Syndecan and Dallylike bind the receptor phosphatase LAR and exert distinct effects on synaptic development. Neuron,2006;49 (4)j517-531.

Walz A, McFarlane S, Brickman YG, et al. Essential role of heparan sulfates in axon navigation andtargeting in the developing visual system. Development, 1997; 124 ( 12): 2421- 2430.

Paveliev M,Hienola A.Jokitalo Y.et al. Sensory neurons from N-syndecan-deficient mice are defective in survival. Neuroreport.2008; 19( 14 ): 1397-1400.


Refbacks

  • There are currently no refbacks.