Document Type : Research articles

Authors

1 Department of Biology and Anatomical Sciences, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

2 Department of Physiology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Abstract

Background: Curcumin is a natural antioxidant known for its neuroprotective properties against cerebral ischemic reperfusion injury. Stroke has the greatest impact on the hippocampus cornu ammonis (CA1) region and leads to cognitive impairment.
Objectives: This study aimed to investigate the effect of pretreatment with turmeric extracts before the induction of cerebral ischemia on the structure of the hippocampus CA1 region, learning, and spatial memory.
Methods: A total of 32 adult male Wistar rats were randomly divided into four groups: 1) control group, 2) sham group (received dimethyl sulfoxide), 3) ischemia group (15 min bilateral carotid artery), and 4) curcumin group (received 100 mg/kg of curcumin daily for five days before the induction of ischemia). The Morris water maze test was performed to evaluate memory impairment in mice 48 h after ischemia induction. The animals were then anesthetized, and their blood samples were taken for malondialdehyde measurement. Subsequently, the animals brains were removed, and the number of neurons, as well as the volume of the layers, were examined using cresyl violet staining.
Results: The results of the stereology showed a significant increase in the volume of the CA1 region and its substrates in the curcumin treatment group, compared to the ischemia group. In addition, the number of pyramidal neurons in the treatment group showed a significant increase, in comparison with the ischemia group. Moreover, curcumin administration reduced the spatial memory impairment in the treatment group, compared to the ischemia group.
Conclusion: These findings suggest that pretreatment with curcumin can improve memory and learning disorders, as well as hippocampal neuron damage, following ischemia.

Keywords

  1. Hankey GJ. Stroke. Lancet. 2017;389(10069):641-54. doi: 10.1016/S0140-6736(16)30962-X. [PubMed: 27637676].
  2. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38-360. doi: 10.1161/CIR.0000000000000350. [PubMed: 26673558].
  3. Fisher M. The spectrum of translational stroke research. Neurol Res. 2013;35(5):443-7. doi: 10.1179/1743132813Y.0000000214. [PubMed: 23594388].
  4. Nadia Sharifi Z, Abolhassani F, Hassanzadeh G, Zarrindast MR, Movassaghi S. Neuroprotective treatment with FK506 reduces hippocampal damage and prevents learning and memory deficits after transient global ischemia in rat. Arch Neurosci. 2014;1(1):35-40. doi: 10.5812/archneurosci.9163.
  5. Chen YW, Sung SF, Chen CH, Tang SC, Tsai LK, Lin HJ, et al. Intravenous thrombolysis administration 3–4.5 h after acute ischemic stroke: A retrospective, multicenter study. Front Neurol. 2019;10:1038. doi: 10.3389/fneur.2019.01038. [PubMed: 31681138].
  6. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):344-418. doi: 10.1161/STR.0000000000000211. [PubMed: 31662037].
  7. Qureshi AI, Singh B, Huang W, Du Z, Lobanova I, Liaqat J, et al. Mechanical thrombectomy in acute ischemic stroke patients performed within and outside clinical trials in the United States. Neurosurgery. 2020;86(1):2-8. doi: 10.1093/neuros/nyz359. [PubMed: 31670379].
  8. Wang Z, Ye Z, Huang G, Wang N, Wang E, Guo Q. Sevoflurane post-conditioning enhanced hippocampal neuron resistance to global cerebral ischemia induced by cardiac arrest in rats through PI3K/Akt survival pathway. Front Cell Neurosci. 2016;10:271. doi: 10.3389/fncel.2016.00271. [PubMed: 27965539].
  9. Chen CH, Hsieh CL. Effect of acupuncture on oxidative stress induced by cerebral ischemia-reperfusion injury. Antioxidants. 2020;9(3):248. doi: 10.3390/antiox9030248. [PubMed: 32204376].
  10. Khandelwal P, Yavagal DR, Sacco RL. Acute ischemic stroke intervention. J Am Coll Cardiol. 2016;67(22):2631-44. doi: 10.1016/j.jacc.2016.03.555. [PubMed: 27256835].
  11. Wu L, Xiong X, Wu X, Ye Y, Jian Z, Zhi Z, et al. Targeting oxidative stress and inflammation to prevent ischemia-reperfusion injury. Front Mol Neurosci. 2020;13:28. doi: 10.3389/fnmol.2020.00028. [PubMed: 32194375].
  12. Singleton RH, Yan HQ, Fellows-Mayle W, Dixon CE. Resveratrol attenuates behavioral impairments and reduces cortical and hippocampal loss in a rat controlled cortical impact model of traumatic brain injury. J Neurotrauma. 2010;27(6):1091-9. doi: 10.1089/neu.2010.1291.[PubMed: 20560755].
  13. Zhang Y, Zhang Y, Jin Xf, Zhou Xh, Dong Xh, Yu WT, et al. The role of astragaloside IV against cerebral ischemia/reperfusion injury: suppression of apoptosis via promotion of P62-LC3-autophagy. Molecules. 2019;24(9):1838. doi: 10.3390/molecules24091838.[PubMed: 31086091].
  14. Li H, Sureda A, Devkota HP, Pittalà V, Barreca D, Silva AS, et al. Curcumin, the golden spice in treating cardiovascular diseases. Biotechnol Adv. 2020;38:107343. doi: 10.1016/j.biotechadv.2019.01.010. [PubMed: 30716389].
  15. Khurana S, Jain S, Mediratta PK, Banerjee BD, Sharma KK. Protective role of curcumin on colchicine-induced cognitive dysfunction and oxidative stress in rats. Hum Exp Toxicol. 2012;31(7):686-97. doi: 10.1177/0960327111433897.
  16. Merrell JG, McLaughlin SW, Tie L, Laurencin CT, Chen AF, Nair LS. Curcumin loaded poly (ε-caprolactone) nanofibers: diabetic wound dressing with antioxidant and anti-inflammatory properties. Clin Exp Pharmacol Physiol. 2009;36(12):1149-56. doi: 10.1111/j.1440-1681.2009.05216.x. [PubMed: 19473187].
  17. Wang Y, Yin H, Wang L, Shuboy A, Lou J, Han B, et al. Curcumin as a potential treatment for Alzheimer's disease: a study of the effects of curcumin on hippocampal expression of glial fibrillary acidic protein. Am J Chinese Med AM J . 2013;41(01):59-70. doi: 10.1142/S0192415X13500055.
  18. Wu L, Jiang C, Kang Y, Dai Y, Fang W, Huang P. Curcumin exerts protective effects against hypoxia‑reoxygenation injury via the enhancement of apurinic/apyrimidinic endonuclease 1 in SH‑SY5Y cells: Involvement of the PI3K/AKT pathway. Int J Med. 2020;45(4):993-1004. doi: 10.3892/ijmm.2020.4483. [PubMed: 32124937].
  19. Liu L, Zhang W, Wang L, Li Y, Tan B, Lu X, et al. Curcumin prevents cerebral ischemia reperfusion injury via increase of mitochondrial biogenesis. Neurochem Res. 2014;39(7):1322-31. doi: 10.1007/s11064-014-1315-1. [PubMed: 24777807].
  20. Kakkar V, Muppu SK, Chopra K, Kaur IP. Curcumin loaded solid lipid nanoparticles: an efficient formulation approach for cerebral ischemic reperfusion injury in rats. Eur J Pharm Biopharm. 2013;85(3):339-45. doi: 10.1016/j.ejpb.2013.02.005. [PubMed: 23454202].
  21. Huang S, Wang B, Zhang Z, Meng Z, Cao H, Lian Q, et al. Effect of curcumin on the expression of high mobility group box 1 and apoptotic neurons in hippocampus after global cerebral ischemia reperfusion in rats. Zhonghua Yi Xue Za Zhi. 2011;91(19):1340-3. [PubMed: 21756762].
  22. Hassanpour A, Hassanpour A, Rezvani ME, Sharifabad MH, Basiri M. The Effect of Intermittent Fasting Diet on the Hippocampus of Adult Male Mouse After Inducing Demyelination by Ethidium Bromide Injection. Int J Morphol. 2019;37(3):805-14.
  23. Baluchnejadmojarad T, Roghani M. Coenzyme q10 ameliorates neurodegeneration, mossy fiber sprouting, and oxidative stress in intrahippocampal kainate model of temporal lobe epilepsy in rat. J Mol Neurosci. 2013;49(1):194-201. doi: 10.1007/s12031-012-9886-2. [PubMed: 23008120].
  24. Amini E, Golpich M, Farjam AS, Kamalidehghan B, Mohamed Z, Ibrahim NM, et al. Brain lipopolysaccharide preconditioning-induced gene reprogramming mediates a tolerance state in electroconvulsive shock model of epilepsy. Front Pharmacol. 2018;9:416. doi: 10.3389/fphar.2018.00416. [PubMed: 29765321].
  25. Faiq MA, Universitas GM, Achmad B, Partadiredja G. Implementation of unbiased stereology method for organ volume estimation using image processing. EECSI. 2017;1-6. doi: 10.1109/EECSI.2017.8239093.
  26. Altindağ F, Rağbetli MÇ. The effect of maternal treatment with diclofenac sodium and thymoquinone on testicular parameters in rat offspring. Rev Int Androl. 2021;19(1):34-40. doi: 10.1016/j.androl.2019.07.001. [PubMed: 31628026].
  27. Akbari F, Ansari Samani R, Karimi A, Mortazaei S, Shahinfard N, Rafieian-Kopaei M. Effect of turnip on glucose and lipid profiles of alloxan-induced diabetic rats. Iran J. Endocrinol Metab. 2013;14(5):492-97.
  28. Zamani M, Hassanshahi J, Soleimani M, Zamani F, Chubin K. Effects of olive oil consumption on stroke complications, particularly in the hippocampal region, in mice. Iranian J Nutr Sci Food Technol . 2012;7(2):1-8.
  29. Al-Omar FA, Nagi MN, Abdulgadir MM, Al Joni KS, Al-Majed AA. Immediate and delayed treatments with curcumin prevents forebrain ischemia-induced neuronal damage and oxidative insult in the rat hippocampus. Neurochem Res. 2006;31(5):611-8. doi: 10.1007/s11064-006-9059-1. [PubMed: 16770732].
  30. Li W, Suwanwela NC, Patumraj S. Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R. Microvasc Res. 2016;106:117-27. doi: 10.1016/j.mvr.2015.12.008. [PubMed: 26686249].
  31. Ahmad N, Umar S, Ashafaq M, Akhtar M, Iqbal Z, Samim M, et al. A comparative study of PNIPAM nanoparticles of curcumin, demethoxycurcumin, and bisdemethoxycurcumin and their effects on oxidative stress markers in experimental stroke. Protoplasma. 2013;250(6):1327-38. doi: 10.1007/s00709-013-0516-9. [PubMed: 23784381].
  32. Jia G, Tan B, Ma J, Zhang L, Jin X, Li C. Prdx6 upregulation by curcumin attenuates ischemic oxidative damage via SP1 in rats after stroke. BioMed Res Int. 2017;2017: 6597401. doi: 10.1155/2017/6597401. [PubMed: 28596967].
  33. Wu J-x, Zhang L-y, Chen YL, Yu SS, Zhao Y, Zhao J. Curcumin pretreatment and post-treatment both improve the antioxidative ability of neurons with oxygen-glucose deprivation. Neural Regen Res. 2015;10(3):481-9. doi: 10.4103/1673-5374.153700. [PubMed: 25878600].
  34. Miao Y, Zhao S, Gao Y, Wang R, Wu Q, Wu H, et al. Curcumin pretreatment attenuates inflammation and mitochondrial dysfunction in experimental stroke: The possible role of Sirt1 signaling. Brain Res Bull. 2016;121:9-15. doi: 10.1016/j.brainresbull.2015.11.019. [PubMed: 26639783].
  35. Liu Z, Ran Y, Huang S, Wen S, Zhang W, Liu X, et al. Curcumin protects against ischemic stroke by titrating microglia/macrophage polarization. Front Aging Neurosci. 2017;9:233. doi: 10.3389/fnagi.2017.00233. [PubMed: 28785217].
  36. Samini F, Samarghandian S, Borji A, Mohammadi G, bakaian M. Curcumin pretreatment attenuates brain lesion size and improves neurological function following traumatic brain injury in the rat. Pharmacol Biochem Behav. 2013;110:238-44. doi: 10.1016/j.pbb.2013.07.019. [PubMed: 23932920].
  37. Xie CJ, Gu AP, Cai J, Wu Y, Chen RC. Curcumin protects neural cells against ischemic injury in N2a cells and mouse brain with ischemic stroke. Brain Behav. 2018;8(2):00921. doi: 10.1002/brb3.921. [PubMed: 29484272].
  38. Tian M, Zhang X, Wang L, Li Y. Curcumin induces ABCA1 expression and apolipoprotein AI-mediated cholesterol transmembrane in the chronic cerebral hypoperfusion aging rats.  Am J Chin Med. 2013;41(05):1027-42. doi: 10.1142/S0192415X13500699. [PubMed: 24117066].
  39. Dolatabadi LK, Emamghoreishi M, Namavar MR, Sarkala HB. Curcumin effects on memory impairment and restoration of irregular neuronal distribution in the hippocampal CA1 region after global cerebral ischemia in male rats. Basic Clin Neurosci. 2019;10(5):527-39. doi: 10.32598/bcn.9.10.365. [PubMed: 32284841].
  40. Mukherjee A, Sarkar S, Jana S, Swarnakar S, Das N. Neuro-protective role of nanocapsulated curcumin against cerebral ischemia-reperfusion induced oxidative injury. Brain Res. 2019;1704:164-73. doi: 10.1016/j.brainres.2018.10.016. [PubMed: 30326199].
  41. Ghezzi A, Baroncini D, Zaffaroni M, Comi G. Pediatric versus adult MS: similar or different? Mult Scler Demyelinating Disord. 2017;2(1):1-14. doi: 10.1186/s40893-017-0022-6.
  42. Wu A, Noble EE, Tyagi E, Ying Z, Zhuang Y, Gomez-Pinilla F. Curcumin boosts DHA in the brain: Implications for the prevention of anxiety disorders. Biochim Biophys Acta. 2015;1852(5):951-61. doi: 10.1016/j.bbadis.2014.12.005. [PubMed: 25550171].
  43. Ji B, Han Y, Liu Q, Liu X, Yang F, Zhou R, et al. Curcumin improves the impaired working memory in cerebral ischemia-reperfusion rats by inhibiting proinflammatory cytokines. Zhonghua Yi Xue Za Zhi. 2014;94(13):1029-33. [PubMed: 24851695].