Aspek Imunologi Peran Homosistein Dalam Patogenesis Gangguan Kognitif Pasca Stroke Iskemik
DOI:
https://doi.org/10.29303/jku.v9i3.423Kata Kunci:
hiperhomosisteinemia, stroke iskemik, neuroinflamasi, proses neurodegeneratif, gangguan kognitifAbstrak
Sekitar 70% pasien stroke iskemik akut mengalami gangguan kognitif dapat terjadi akibat langsung dari stroke iskemik itu sendiri atau merupakan interaksi dari stroke iskemik dan faktor-faktor risiko yang menyertainya. Kondisi hiperhomosisteinemia merupakan salah satu faktor risiko vaskuler yang secara patofisiologik dapat menyebabkan terjadinya gangguan kognitif pasca stroke iskemik. Kondisi tersebut dapat terjadi karena peningkatan rasio SAM/SAH akibat diet tinggi kadar methionin, predisposisi genetik berupa mutasi gen pengkode enzim, dan defisiensi vitamin B6 dan asam folat. Peran homosistein dalam patogenesis terjadinya gangguan kognitif pasca stroke saat ini belum banyak diteliti. Homosistein bersifat toksik dan dapat menginduksi terjadinya respon inflamasi sistemik, disrupsi sawar darah otak, neuroinflamasi, dan kematian sel-sel neuronal yang mengarah pada proses neurodegeneratif. Proses neurodegeneratif pada struktur otak yang mengemban fungsi domain kognitif tertentu akan menyebabkan terganggunya fungsi dari domain kognitif tersebut. Pemahaman aspek imunologi peran homosistein dalam terjadinya gangguan fungsi kognitif pada pasien stroke iskemik tersebut dapat memberikan celah kemungkinan intervensi terhadap homosistein dan respon imunologis yang ditimbulkannya sebagai bagian dari tatalaksana optimal terhadap gangguan kognitif pasca stroke iskemik.
Referensi
1. Nys GMS, van Zandvoort M, de Kort P, Jansen B, de Haan E, Kappelle L. Cognitive Disorders in Acute Stroke?: Prevalence and Clinical Determinants. Cerebrovasc Dis. 2007;23:408–16.
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
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
Unduhan
Diterbitkan
2020-10-17
Cara Mengutip
Harahap, H. S. (2020). Aspek Imunologi Peran Homosistein Dalam Patogenesis Gangguan Kognitif Pasca Stroke Iskemik. Baphomet University : Situs Slot Online Gacor Terbaik Hari Ini Server Thailand Gampang Maxwin 2024, 9(3), 175–183. https://doi.org/10.29303/jku.v9i3.423
Terbitan
Bagian
Tinjauan Pustaka
