Aspek Imunologi Peran Homosistein Dalam Patogenesis Gangguan Kognitif Pasca Stroke Iskemik
DOI:
https://doi.org/10.29303/jku.v9i3.423Keywords:
hyperhomocysteinemia, ischemic stroke, neuroinflammation, neurodegenerative processes, cognitive impairmentAbstract
Approximately 70% of acute ischemic stroke patients suffered from cognitive impairment that can be a direct insult of the ischemic stroke itself or as a consequence of the interaction between ischemic stroke event and its associated risk factors. Hyperhomocysteinemia is one of the vascular risk factors which can contribute to the pathophysiology of cognitive impairment after ischemic stroke. This condition can be due to an increase in the SAM / SAH ratio associated with a high methionine-containing diet, genetic predisposition, and deficiency of vitamin B6 and folic acid. The role of homocysteine ??in the pathogenesis of post-stroke cognitive impairment has not yet been studied extensively. Homocysteine ??is toxic and can induce systemic inflammatory responses, disruption of the blood-brain barrier, neuroinflamation, and neuronal death that lead to neurodegenerative processes. Neurodegenerative processes in particular brain structures that carry out certain function of cognitive domains will disrupt the function of those cognitive domains. Understanding the immunological aspects of the role of homocysteine ??in the occurrence of cognitive impairment among ischemic stroke patients is beneficial in providing an opportunity for development of interventions against homocysteine ??and its immunological responses consequences as the part of optimal management of post-ischemic cognitive impairment.
References
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31. Beard RS, Reynolds JJ, Bearden SE. Hyperhomocysteinemia increases permeability of the blood-brain barrier by NMDA receptor-dependent regulation of adherens and tight junctions. Blood. 2011;118(7):2007–14.
32. Chen S, Dong Z, Cheng M, Zhao Y, Wang M, Sai N, et al. Homocysteine exaggerates microglia activation and neuroinflammation through microglia localized STAT3 overactivation following ischemic stroke. Jounal of Neuroinflammation. 2017;14:187.
33. Weekman EM, Woolums AE, Sudduth TL, Wilcock DM. Hyperhomocysteinemia-Induced Gene Expression Changes in the Cell Types of the Brain. Am Soc Neurochem. 2017;9(6):1759091417742296.
34. Zhang J, Yan R, Tang Y, Guo Y, Chang Y, Jing L, et al. Hyperhomocysteinemia-induced autophagy and apoptosis with downregulation of hairy enhancer of split 1 / 5 in cortical neurons in mice. Int J Immunopathol Pharmacol. 2017;30(4):371–82.
35. Kamat PK, Vacek JC, Kalani A, Tyagi N. Homocysteine Induced Cerebrovascular Dysfunction: A Link to Alzheimer’s Disease Etiology. Open Neurol J. 2015;9:9–14.
36. Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett. 2006;580:2994–3005.
37. Swardfager W, Winer DA, Herrmann N, Winer S, Lanctot KL. Interleukin-17 in post-stroke neurodegeneration. Neurosci Biobehav Rev. 2013;37(3):436–47.
38. Choe YM, Sohn BK, Choi HJ, Byun MS, Seo EH, Han JY, et al. Neurobiology of Aging Association of homocysteine with hippocampal volume independent of cerebral amyloid and vascular burden. Neurobiol Aging [Internet]. 2014;35(7):1519–25. Available from: http://dx.doi.org/10.1016/j.neurobiolaging.2014.01.013
2. Lesniak M, Bak T, Czepiel W, Seniow J, Czlonkowska A. Frequency and Prognostic Value of Cognitive Disorders in Stroke Patients. Dement Geriatr Cogn Disord. 2008;26:356–63.
3. Renjen PN, Gauba C, Chaudhari D. Cognitive Impairment After Stroke. Cureus. 2015;7(9):e335.
4. Kalaria RN, Akinyemi R, Ihara M. Stroke injury, cognitive impairment and vascular dementia. Biochim Biophys Acta - Mol Basis Dis [Internet]. 2016;1862(5):915–25. Available from: http://dx.doi.org/10.1016/j.bbadis.2016.01.015
5. Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015;14:6.
6. Lan L, Ali Z. Homocysteine level in stroke patients in the rehabilitation setting?: a prospective observational study. Hosp Palliat Med Int J. 2018;2(3):204–8.
7. Hainsworth AH, Yeo NE, Weekman EM, Wilcock DM, Sciences C. Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID). Biochem J. 2016;1862(5):1008–17.
8. Ashrafi G, Wu Z, Farrell RJ, Ryan TA. GLUT4 Mobilization Supports Energetic Demands of Active Synapses. Neuron [Internet]. 2017;93(3):606–15. Available from: http://dx.doi.org/10.1016/j.neuron.2016.12.020
9. Oikonomidi A, Lewczuk P, Kornhuber J, Smulders Y, Linnebank M, Semmler A, et al. Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble amyloid precursor protein and amyloid beta. J Neurochem. 2016;139:324–32.
10. Li J-G, Pratico D. High Levels of Homocysteine Results in Cerebral Amyloid Angiopathy in Mice. J Alzheimer’s Dis. 2015;43(1):29–35.
11. Mijajlovic MD, Pavlovic A, Brainin M, Heiss W, Quinn TJ, Ihle-hansen HB, et al. Post-stroke dementia – a comprehensive review. BMC Med. 2017;15(1):11.
12. Danovska M, Stamenov B, Alexandrova M, Peychinska D. POST-STROKE COGNITIVE IMPAIRMENT - PHENOMENOLOGY AND PROGNOSTIC. J IMAB. 2012;18:290–7.
13. del Ser T, Barba R, Morin MM, Domingo J, Cemillan C, Pondal M, et al. Evolution of Cognitive Impairment After Stroke and Risk Factors for Delayed Progression. Stroke. 2005;36:2670–5.
14. Cumming TB, Marshall RS, Lazar RM. Stroke , cognitive deficits , and rehabilitation?: still an incomplete picture. Int J Stroke. 2013;8:38–45.
15. Barroso M, Handy DE, Castro R. The Link Between Hyperhomocysteinemia and Hypomethylation?: Implications for Cardiovascular Disease. J Inborn Errors Metab Screen. 2017;5:1–15.
16. Cacciapuoti F. Poor re-Methylation of Homocysteine and Trans- Methylation of Methionine: Cause and Effect of Hyper- Homocysteinemia?: Which Role for Folic Acid and Vitamins B- 6-12 Supplementation?? Ann Clin Exp Metab. 2018;3(1):1026.
17. Škovierová H, Mahmood S, Blahovcová E, Hatok J, Lehotský J, Murín R. Effect of Homocysteine on Survival of Human Glial Cells. Physiol Res. 2015;64:747–54.
18. Keung W, Lai C, Kan MY. Homocysteine-Induced Endothelial Dysfunction. Ann Nutr Metab. 2015;67:1–12.
19. Li A, Shi Y, Xu L, Zhang Y, Zhao H, Li Q, et al. A possible synergistic effect of MTHFR C677T polymorphism on homocysteine level variations increased risk for ischemic stroke. Medicine (Baltimore). 2017;96(51):e9300.
20. Jiang B, Chen Y, Yao G, Yao C, Zhao H, Jia X, et al. Effects of differences in serum total homocysteine , folate , and vitamin B 12 on cognitive impairment in stroke patients. BMC Neurol. 2014;14:217.
21. Meng S, Ciment S, Jan M, Tran T, Pham H, Cueto R, et al. Homocysteine induces inflammatory transcriptional signaling in monocytes. Front Biosci. 2013;18:685–95.
22. Wang G, Siow YL, Karmin O. Homocysteine stimulates nuclear factor jB activity and monocyte chemoattractant protein-1 expression in vascular smooth-muscle cells?: a possible role for protein kinase C. Biochem J. 2000;352:817–25.
23. Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. Ninth. Philadelphia: Elsevier Inc.; 2018. 80-81.
24. Li T, Chen Y, Li J, Yang X, Zhang H. Serum Homocysteine Concentration Is Significantly Associated with Inflammatory / Immune Factors. PLoS One. 2015;10(9):e0138099.
25. Salomão RG, Carvalho LM De, Izumi C, Czernisz ÉS, Rosa JC, Roberto S, et al. Homocysteine, folate, hs-C-reactive protein, tumor necrosis factor alpha and inflammatory proteins: are these biomarkers related to nutritional status and cardiovascular risk in childhood-onset systemic lupus erythematosus? Pediatr Rheumatol. 2018;16(1):4.
26. Fefelova E V, Tereshkov PP, Dutov AA, Tsybikov NN. Lymphocyte Subpopulations and Cytokine Levels in Experimental Hyperhomocysteinemia. Bull Exp Biol Med. 2015;159(3):358–60.
27. Zhang Q, Zeng X, Guo J, Wang X. Effects of homocysteine on murine splenic B lymphocyte proliferation and its signal transduction mechanism. Cardiovasc Res. 2001;52:328–36.
28. Chang L, Zhang Z, Li W, Dai J, Guan Y, Wang X. Liver-X-receptor activator prevents homocysteine-induced production of IgG antibodies from murine B lymphocytes via the ROS – NF-kB pathway. Biochem Biophys Res Commun. 2007;357:772–8.
29. Chamorro Á, Meisel A, Planas AM, Urra X, Beek D Van De, Veltkamp R. The immunology of acute stroke. Nat Rev Neurol [Internet]. 2012;8(7):401–10. Available from: http://dx.doi.org/10.1038/nrneurol.2012.98
30. Kamath AF, Chauhan AK, Kisucka J, Dole VS, Loscalzo J, Handy DE, et al. Brief report Elevated levels of homocysteine compromise blood-brain barrier integrity in mice. Blood. 2006;107(2):591–4.
31. Beard RS, Reynolds JJ, Bearden SE. Hyperhomocysteinemia increases permeability of the blood-brain barrier by NMDA receptor-dependent regulation of adherens and tight junctions. Blood. 2011;118(7):2007–14.
32. Chen S, Dong Z, Cheng M, Zhao Y, Wang M, Sai N, et al. Homocysteine exaggerates microglia activation and neuroinflammation through microglia localized STAT3 overactivation following ischemic stroke. Jounal of Neuroinflammation. 2017;14:187.
33. Weekman EM, Woolums AE, Sudduth TL, Wilcock DM. Hyperhomocysteinemia-Induced Gene Expression Changes in the Cell Types of the Brain. Am Soc Neurochem. 2017;9(6):1759091417742296.
34. Zhang J, Yan R, Tang Y, Guo Y, Chang Y, Jing L, et al. Hyperhomocysteinemia-induced autophagy and apoptosis with downregulation of hairy enhancer of split 1 / 5 in cortical neurons in mice. Int J Immunopathol Pharmacol. 2017;30(4):371–82.
35. Kamat PK, Vacek JC, Kalani A, Tyagi N. Homocysteine Induced Cerebrovascular Dysfunction: A Link to Alzheimer’s Disease Etiology. Open Neurol J. 2015;9:9–14.
36. Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett. 2006;580:2994–3005.
37. Swardfager W, Winer DA, Herrmann N, Winer S, Lanctot KL. Interleukin-17 in post-stroke neurodegeneration. Neurosci Biobehav Rev. 2013;37(3):436–47.
38. Choe YM, Sohn BK, Choi HJ, Byun MS, Seo EH, Han JY, et al. Neurobiology of Aging Association of homocysteine with hippocampal volume independent of cerebral amyloid and vascular burden. Neurobiol Aging [Internet]. 2014;35(7):1519–25. Available from: http://dx.doi.org/10.1016/j.neurobiolaging.2014.01.013
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2020-10-17
How to Cite
Harahap, H. S. (2020). Aspek Imunologi Peran Homosistein Dalam Patogenesis Gangguan Kognitif Pasca Stroke Iskemik. Jurnal Kedokteran, 9(3), 175–183. https://doi.org/10.29303/jku.v9i3.423
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