NgR1 pathway expression in cerebral ischemic Sprague-Dawley rats with cognitive impairment

Document Type : Original Article

Authors

1 Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China

2 Department of Rehabilitation Medicine, Guangzhou Panyu Central Hospital, No.8 Fuyu east Road, Guangzhou 511400, Guangdong Province, China

3 Kerry Rehabilitation Medicine Research Institute, Shenzhen 518048, Guangdong Province, China

4 Shenzhen Dapeng New District Nan’ao People’s Hospital Shenzhen 518048, Guangdong Province, China

5 Stroke Biological Recovery Laboratory, Spaulding Rehabilitation Hospital, The Teaching Affiliate of Harvard Medical School,96 13th Street, Charlestown, MA 02129

Abstract

Objective(s): This study aimed to determine the effect of ischemic occlusion duration and recovery time course on motor and cognitive function, identify optimal conditions for assessing cognitive function with minimal interference from motor deficits, and elucidate the underlying mechanism of axonal inhibitors.
Materials and Methods: Sprague-Dawley (SD) rats were randomly allocated to the transient middle cerebral artery occlusion (tMCAO) 60-min (tMCAO60min), tMCAO90min, tMCAO120min, and sham groups. We conducted forelimb grip strength, two-way shuttle avoidance task, and novel object recognition task (NORT)tests at three time points (14, 21, and 28 days). Expression of Nogo receptor-1 (NgR1), the endogenous antagonist lateral olfactory tract usher substance, ras homolog family member A (Rho-A), and RhoA-activated Rho kinase (ROCK) was examined in the ipsilateral thalamus.
Results: There was no difference in grip strength between sham and tMCAO90min rats at 28 days. tMCAO90min and tMCAO120min rats showed lower discrimination indices in the NORT than sham rats on day 28. Compared with that in sham rats, the active avoidance response rate was lower in tMCAO90min rats on days 14, 21, and 28 and in tMCAO120min rats on days 14 and 21. Furthermore, 50-54% of rats in the tMCAO90min group developed significant cognitive impairment on day 28, and thalamic NgR1, RhoA, and ROCK expression were greater in tMCAO90min rats than in sham rats.
Conclusion: Employing 90-min tMCAO in SD rats and assessing cognitive function 28 days post-stroke could minimize motor dysfunction effects in cognitive function assessments. Axonal inhibitor deregulation could be involved in poststroke cognitive impairment.

Keywords

References

1. Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380:2197-2223.
2. Farokhi-Sisakht F, Farhoudi M, Sadigh-Eteghad S, Mahmoudi J, Mohaddes G. Cognitive rehabilitation improves ischemic stroke-induced cognitive impairment: Role of growth factors. J Stroke Cerebrovasc Dis 2019; 28:104299.
3. Tatemichi TK, Desmond DW, Mayeux R, Paik M, Stern Y, Sano M, et al. Dementia after stroke: Baseline frequency, risks, and clinical features in a hospitalized cohort. Neurology 1992;42:1185-1193.
4. Tatemichi TK, Paik M, Bagiella E, Desmond DW, Stern Y, Sano M, et al. Risk of dementia after stroke in a hospitalized cohort: results of a longitudinal study. Neurology 1994;44:1885-1891.
5. Mijajlovic MD, Pavlovic A, Brainin M, Heiss WD, Quinn TJ, Ihle-Hansen HB, et al. Post-stroke dementia - a comprehensive review. BMC Med 2017; 15:11-44.
6. World Health Organization. Towards a dementia plan: A WHO guide. 2018; Available from: http://apps.who.int/iris/bitstream/handle/10665/272642/9789241514132-eng.pdf?ua=1.
7. Cao JY, Lin Y, Han YF, Ding SH, Fan YL, Pan YH, et al. Expression of nerve growth factor carried by pseudotyped lentivirus improves neuron survival and cognitive functional recovery of post-ischemia in rats. CNS NeurosciTher 2018; 24:508-518.
8. Sun H, Li A, Hou T, Tao X, Chen M, Wu C, et al. Neurogenesis promoted by the CD200/CD200R signaling pathway following treadmill exercise enhances post-stroke functional recovery in rats. Brain Behav Immun 2019; 82:354-371.
9. Bingham D, Martin SJ, Macrae IM, Carswell HV. Watermaze performance after middle cerebral artery occlusion in the rat: The role of sensorimotor versus memory impairments. J Cereb Blood Flow Metab 2012; 32:989-999.
10. Gupta YK, Sinha K, Chaudhary G. Transient focal ischemia induces motor deficit but does not impair the cognitive function in middle cerebral artery occlusion model of stroke in rats. J Neurol Sci 2002; 203-204:267-271.
11. Schwab ME, Strittmatter SM. Nogo limits neural plasticity and recovery from injury. Curr Opin Neurobiol. 2014; 27:53-60.
12. Delekate A, Zagrebelsky M, Kramer S, Schwab ME, Korte M. NogoA restricts synaptic plasticity in the adult hippocampus on a fast time scale. Proc Natl Acad Sci U S A 2011; 108:2569-2574.
13. Li C, Wen H, Wang Q, Zhang C, Jiang L, Dou Z, et al. Exercise training inhibits the Nogo-A/NgR1/Rho-A signals in the cortical peri-infarct area in hypertensive stroke rats. Am J Phys Med Rehabil 2015; 94:1083-1094.
14. Tong J, Liu W, Wang X, Han X, Hyrien O, Samadani U, et al. Inhibition of Nogo-66 receptor 1 enhances recovery of cognitive function after traumatic brain injury in mice. J Neurotrauma 2013; 30:247-258.
15. VanGuilder Starkey HD, Sonntag WE, Freeman WM. Increased hippocampal NgR1 signaling machinery in aged rats with deficits of spatial cognition. Eur J Neurosci 2013; 37:1643-1658.
16. Lovero KL, Fukata Y, Granger AJ, Fukata M, Nicoll RA. The LGI1-ADAM22 protein complex directs synapse maturation through regulation of PSD-95 function. Proc Natl Acad Sci U S A 2015; 112:E4129-E4137.
17. Sato Y, Iketani M, Kurihara Y, Yamaguchi M, Yamashita N, Nakamura F, et al. Cartilage acidic protein-1B (LOTUS), an endogenous Nogo receptor antagonist for axon tract formation. Science 2011; 333:769-773.
18. Takase H, Kurihara Y, Yokoyama TA, Kawahara N, Takei K. LOTUS overexpression accelerates neuronal plasticity after focal brain ischemia in mice. PLoS One 2017; 12:e0184258.
19. VanGuilder Starkey HD, Bixler GV, Sonntag WE, Freeman WM. Expression of NgR1-antagonizing proteins decreases with aging and cognitive decline in rat hippocampus. Cell Mol Neurobiol 2013; 33:483-488.
20. Cong HM, Gao QP, Song GQ, Ye YX, Li XL, Zhang LS, et al. Hydrogen-rich saline ameliorates hippocampal neuron apoptosis through up-regulating the expression of cystathionine beta-synthase (CBS) after cerebral ischemia- reperfusion in rats. Iran J Basic Med Sci 2020; 23:494-499.
21. Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 1986;17:472-476.
22. Chen J, Sanberg PR, Li Y, Wang L, Lu M, Willing AE, et al. Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke 2001; 32:2682-2688.
23. Zhang C, Zou Y, Li K, Li C, Jiang Y, Sun J, et al. Different effects of running wheel exercise and skilled reaching training on corticofugal tract plasticity in hypertensive rats with cortical infarctions. Behav Brain Res 2018; 336:166-172.
24. Ma J, Xiong JY, Hou WW, Yan HJ, Sun Y, Huang SW, et al. Protective effect of carnosine on subcortical ischemic vascular dementia in mice. CNS NeurosciTher 2012; 18:745-753.
25. Happel MF, Deliano M, Ohl FW. Combined shuttle-box training with electrophysiological cortex recording and stimulation as a tool to study perception and learning. J Vis Exp 2015:e53002.
26. Stark H, Rothe T, Deliano M, Scheich H. Dynamics of cortical theta activity correlates with stages of auditory avoidance strategy formation in a shuttle-box. Neuroscience 2008; 151:467-475.
27. He Q, Li S, Li L, Hu F, Weng N, Fan X, et al. Total flavonoids in caragana (TFC) promotes angiogenesis and enhances cerebral perfusion in a rat model of ischemic stroke. Front Neurosci 2018; 12:635.
28. YuKH, Cho SJ, Oh MS, Jung S, Lee JH, Shin JH, et al. Cognitive impairment evaluated with Vascular Cognitive Impairment Harmonization Standards in a multicenter prospective stroke cohort in Korea. Stroke 2013; 44:786-788.
29. Sexton E, McLoughlin A, Williams DJ, Merriman NA, Donnelly N, Rohde D, et al. Systematic review and meta-analysis of the prevalence of cognitive impairment no dementia in the first year post-stroke. Eur Stroke J 2019; 4:160-171.
30. Iadecola C, Duering M, Hachinski V, Joutel A, Pendlebury ST, Schneider JA, et al. Vascular cognitive impairment and dementia: Jacc scientific expert. Panel J Am Coll Cardiol 2019; 73:3326-3344.
31. HowellsDW, Porritt MJ, Rewell SS, O’Collins V, Sena ES, van der Worp HB, et al. Different strokes for different folks: the rich diversity of animal models of focal cerebral ischemia. J Cereb Blood Flow Metab 2010; 30:1412-1431.
32. Fluri F, Schuhmann MK, Kleinschnitz C. Animal models of ischemic stroke and their application in clinical research. Drug Des DevelTher 2015; 9:3445-3454.
33. Zvejniece L, Svalbe B, Liepinsh E, Pulks E, Dambrova M. The sensorimotor and cognitive deficits in rats following 90- and 120-min transient occlusion of the middle cerebral artery. J Neurosci Methods 2012; 208:197-204.
34. Encarnacion A, Horie N, Keren-Gill H, Bliss TM, Steinberg GK, Shamloo M. Long-term behavioral assessment of function in an experimental model for ischemic stroke. J Neurosci Methods 2011; 196:247-257.
35. Karhunen H, Pitkanen A, Virtanen T, Gureviciene I, Pussinen R, Ylinen A, et al. Long-term functional consequences of transient occlusion of the middle cerebral artery in rats: a 1-year follow-up of the development of epileptogenesis and memory impairment in relation to sensorimotor deficits. Epilepsy Res 2003; 54:1-10.
36. Mathiasen JR, DiCamillo A. Novel object recognition in the
rat: a facile assay for cognitive function. Curr Protoc Pharmacol
2010; Chapter 5:Unit 5.59.
37. Xu F, Zhang G, Yin J, Zhang Q, Ge MY, Peng L, et al. Fluoxetine mitigating late-stage cognition and neurobehavior impairment induced by cerebral ischemia reperfusion injury through inhibiting ERS-mediated neurons apoptosis in the hippocampus. Behav Brain Res 2019; 370:111952.
38. Li W, Huang R, Shetty RA, Thangthaeng N, Liu R, Chen Z, et al. Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model. Neurobiol Dis 2013; 59:18-25.
39. Nakajima M, Suda S, Sowa K, Sakamoto Y, Nito C, Nishiyama Y, et al. AMPA receptor antagonist perampanel ameliorates post-stroke functional and cognitive impairments. Neuroscience 2018; 386:256-264.
40. Liu Y, Li C, Wang J, Fang Y, Sun H, Tao X, et al. NafamostatMesilate improves neurological outcome and axonal regeneration after stroke in rats. Mol Neurobiol 2017; 54:4217-4231.
41. Andrews MMM, Peruzzaro S, Raupp S, Wilks J, Rossignol J, Dunbar GL. Using the behavioral flexibility operant task to detect long-term deficits in rats following middle cerebral artery occlusion. Behav Brain Res 2019; 356:1-7.
42. Tatu L, Vuillier F. Structure and vascularization of the human hippocampus. Front Neurol Neurosci 2014; 34:18-25.
43.Hata R, Mies G, Wiessner C, Fritze K, Hesselbarth D, Brinker G, et al. A reproducible model of middle cerebral artery occlusion in mice: Hemodynamic, biochemical, and magnetic resonance imaging. J Cereb Blood Flow Metab 1998; 18:367-375.
44. El Amki M, Clavier T, Perzo N, Bernard R, Guichet PO, Castel H. Hypothalamic, thalamic and hippocampal lesions in the mouse MCAO model: Potential involvement of deep cerebral arteries? J Neurosci Methods 2015; 254:80-85.
45. Baumgartner P, El Amki M, Bracko O, Luft AR, Wegener S. Sensorimotor stroke alters hippocampo-thalamic network activity. Sci Rep 2018; 8:15770.
46. Dhawan J, Benveniste H, Nawrocky M, Smith SD, Biegon A. Transient focal ischemia results in persistent and widespread neuroinflammation and loss of glutamate NMDA receptors. Neuroimage 2010; 51:599-605.
47. Mulherkar S, ToliasKF. RhoA-ROCK Signaling as a Therapeutic Target in Traumatic Brain Injury. Cells 2020; 9:245.
48. Mulherkar S, Firozi K, Huang W, Uddin MD, Grill RJ, Costa-Mattioli M, et al. RhoA-ROCK inhibition reverses synaptic remodeling and motor and cognitive deficits caused by traumatic brain injury. Sci Rep 2017; 7:1-12.
Iranian Journal of Basic Medical Sciences
Volume 24, Issue 6
June 2021
Pages 767-775

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