Aripiprazole Improves Spinal Cord Injury in Rats: Involvement of Inflammatory Pathways
Abstract
Macrophages and glial activation contribute to the pathophysiology of spinal cord injury (SCI). Some preclinical studies have shown the anti-inflammatory effects of aripiprazole (ARP). In the current study, we evaluated the anti-inflammatory effects of ARP in a rat SCI model. Forty male Wistar rats underwent either T9 vertebra laminectomy or were used as a sham-operated group without laminectomy. There were four major groups in this study: a sham-operated, three treatments (normal saline [vehicle] control versus ARP 10 and 20 mg/kg/day for three days after surgery, first dose 30 minutes post-surgery) SCI groups. We evaluated locomotor scaling and neuropathic pain behavioral tests over 28 days. On Day 28, tissue samples were investigated for neuroinflammatory and histopathology changes through flow cytometry and ELISA. ARP (10 and 20 mg/kg/day, 3 days) treatment significantly reduced locomotors disability (P<0.01) and mechanical (P<0.01) and thermal allodynia (P<0.001) scores. Additionally, Levels of tumor necrosis factor (TNF)-α level and interleukin (IL)-10 were significantly altered in ARP-treated spinal cord tissues 28 days after SCI (P<0.01). Moreover, spinal cord tissue expression of M1 and M2 macrophages, as well as M1/M2 ratio, were reduced in ARP-treated SCI animals, concurrent with decreased M1 and increased M2 and M1/M2 in dorsal root ganglion (P<0.001). Our study indicates that ARP has therapeutic effects on SCI via the reduction of neuroinflammation and SCI sensory and locomotor abnormalities.
1. Lynch J, Cahalan R. The impact of spinal cord injury on the quality of life of primary family caregivers: a literature review. Spinal cord 2017; 55(11): 964-78.
2. Furlan JC, Sakakibara BM, Miller WC, Krassioukov AV. Global incidence and prevalence of traumatic spinal cord injury. The Canadian journal of neurological sciences Le journal canadien des sciences neurologiques 2013; 40(4): 456-64.
3. Badhiwala JH, Wilson JR, Fehlings MG. Global burden of traumatic brain and spinal cord injury. The Lancet Neurology 2019; 18(1): 24-25.
4. Eckert MJ, Martin MJ. Trauma: Spinal Cord Injury. The Surgical clinics of North America 2017; 97(5): 1031-45.
5. Witiw CD, Fehlings MG. Acute Spinal Cord Injury. Journal of spinal disorders & techniques 2015; 28(6): 202-10.
6. David G, Mohammadi S, Martin AR, Cohen-Adad J, Weiskopf N, Thompson A, Freund P. Traumatic and nontraumatic spinal cord injury: pathological insights from neuroimaging. Nature reviews Neurology 2019.
7. Fan B, Wei Z, Yao X, Shi G, Cheng X, Zhou X, Zhou H, Ning G, Kong X, Feng S. Microenvironment Imbalance of Spinal Cord Injury. Cell transplantation 2018; 27(6): 853-66.
8. Inoue K. A state-of-the-art perspective on microgliopathic pain. Open biology 2018; 8(11).
9. Milich LM, Ryan CB, Lee JK. The origin, fate, and contribution of macrophages to spinal cord injury pathology. Acta neuropathologica 2019; 137(5): 785-97.
10. Akhmetzyanova E, Kletenkov K, Mukhamedshina Y, Rizvanov A. Different Approaches to Modulation of Microglia Phenotypes After Spinal Cord Injury. Frontiers in systems neuroscience 2019; 13: 37.
11. Kopper TJ, Gensel JC. Myelin as an inflammatory mediator: Myelin interactions with complement, macrophages, and microglia in spinal cord injury. Journal of neuroscience research 2018; 96(6): 969-77.
12. Kroner A, Rosas Almanza J. Role of microglia in spinal cord injury. Neuroscience letters 2019; 709: 134370.
13. Orr MB, Gensel JC. Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 2018; 15(3): 541-53.
14. Tsuda M. Microglia in the CNS and Neuropathic Pain. Advances in experimental medicine and biology 2018; 1099: 77-91.
15. Anwar MA, Al Shehabi TS, Eid AH. Inflammogenesis of Secondary Spinal Cord Injury. Frontiers in cellular neuroscience 2016; 10: 98.
16. Di Sciascio G, Riva MA. Aripiprazole: from pharmacological profile to clinical use. Neuropsychiatr Dis Treat 2015; 11: 2635-47.
17. Muneer A. The Treatment of Adult Bipolar Disorder with Aripiprazole: A Systematic Review. Cureus 2016; 8(4): e562-e62.
18. Shapiro DA, Renock S, Arrington E, Chiodo LA, Liu L-X, Sibley DR, Roth BL, Mailman R. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology 2003; 28(8): 1400-11.
19. Yoo S, Kim M-Y, Cho JY. Syk and Src-targeted anti-inflammatory activity of aripiprazole, an atypical antipsychotic. Biochem Pharmacol 2018; 148: 1-12.
20. Stapel B, Sieve I, Falk CS, Bleich S, Hilfiker-Kleiner D, Kahl KG. Second generation atypical antipsychotics olanzapine and aripiprazole reduce expression and secretion of inflammatory cytokines in human immune cells. J Psychiatr Res 2018; 105: 95-102.
21. Juncal-Ruiz M, Riesco-Dávila L, Ortiz-García de la Foz V, Martínez-Garcia O, Ramírez-Bonilla M, Ocejo-Viñals JG, Leza JC, López-Hoyos M, Crespo-Facorro B. Comparison of the anti-inflammatory effect of aripiprazole and risperidone in 75 drug-naïve first episode psychosis individuals: A 3 months randomized study. Schizophr Res 2018; 202: 226-33.
22. Zargar S, Al-Majed A-RA, Wani TA. Potentiating and synergistic effect of grapefruit juice on the antioxidant and anti-inflammatory activity of aripiprazole against hydrogen peroxide induced oxidative stress in mice. BMC Complement Altern Med 2018; 18(1): 106-06.
23. Sato-Kasai M, Kato TA, Ohgidani M, Mizoguchi Y, Sagata N, Inamine S, Horikawa H, Hayakawa K, Shimokawa N, Kyuragi S, Seki Y, Monji A, Kanba S. Aripiprazole inhibits polyI:C-induced microglial activation possibly via TRPM7. Schizophr Res 2016; 178(1-3): 35-43.
24. Sobiś J, Rykaczewska-Czerwińska M, Świętochowska E, Gorczyca P. Therapeutic effect of aripiprazole in chronic schizophrenia is accompanied by anti-inflammatory activity. Pharmacol Rep 2015; 67(2): 353-59.
25. Kato T, Mizoguchi Y, Monji A, Horikawa H, Suzuki SO, Seki Y, Iwaki T, Hashioka S, Kanba S. Inhibitory effects of aripiprazole on interferon-gamma-induced microglial activation via intracellular Ca2+ regulation in vitro. J Neurochem 2008; 106(2): 815-25.
26. Wang J-S, Zhu H-J, Donovan JL, Yuan H-J, Markowitz JS, Geesey ME, Devane CL. Aripiprazole brain concentration is altered in P-glycoprotein deficient mice. Schizophr Res 2009; 110(1-3): 90-94.
27. Baek K-S, Ahn S, Lee J, Kim JH, Kim HG, Kim E, Kim JH, Sung NY, Yang S, Kim MS, Hong S, Kim J-H, Cho JY. Immunotoxicological Effects of Aripiprazole: In vivo and In vitro Studies. Korean J Physiol Pharmacol 2015; 19(4): 365-72.
28. Kowalchuk C, Kanagasundaram P, Belsham DD, Hahn MK. Antipsychotics differentially regulate insulin, energy sensing, and inflammation pathways in hypothalamic rat neurons. Psychoneuroendocrinology 2019; 104: 42-48.
29. Arias-Salgado EG, Lizano S, Sarkar S, Brugge JS, Ginsberg MH, Shattil SJ. Src kinase activation by direct interaction with the integrin beta cytoplasmic domain. Proc Natl Acad Sci U S A 2003; 100(23): 13298-302.
30. Rowley RB, Burkhardt AL, Chao HG, Matsueda GR, Bolen JB. Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation motif binding and autophosphorylation. J Biol Chem 1995; 270(19): 11590-94.
31. Gil CH, Kim YR, Lee HJ, Jung DH, Shin HK, Choi BT. Aripiprazole exerts a neuroprotective effect in mouse focal cerebral ischemia. Exp Ther Med 2018; 15(1): 745-50.
32. Gholampour H, Moezi L, Shafaroodi H. Aripiprazole prevents renal ischemia/reperfusion injury in rats, probably through nitric oxide involvement. Eur J Pharmacol 2017; 813: 17-23.
33. Afshari K, Dehdashtian A, Haddadi NS, Haj-Mirzaian A, Iranmehr A, Ebrahimi MA, Tavangar SM, Faghir-Ghanesefat H, Mohammadi F, Rahimi N, Javidan AN, Dehpour AR. Anti-inflammatory effects of Metformin improve the neuropathic pain and locomotor activity in spinal cord injured rats: introduction of an alternative therapy. Spinal cord 2018; 56(11): 1032-41.
34. Zakeri M, Afshari K, Gharedaghi MH, Shahsiah R, Rahimian R, Maleki F, Dehpour AR, Javidan AN. Lithium protects against spinal cord injury in rats: role of nitric oxide. Journal of neurological surgery Part A, Central European neurosurgery 2014; 75(6): 427-33.
35. Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. Journal of neurotrauma 1995; 12(1): 1-21.
36. Singh P, Kongara K, Harding D, Ward N, Dukkipati VSR, Johnson C, Chambers P. Comparison of electroencephalographic changes in response to acute electrical and thermal stimuli with the tail flick and hot plate test in rats administered with opiorphin. BMC neurology 2018; 18(1): 43.
37. Arroz M, Came N, Lin P, Chen W, Yuan C, Lagoo A, Monreal M, de Tute R, Vergilio JA, Rawstron AC, Paiva B. Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting. Cytometry Part B, Clinical cytometry 2016; 90(1): 31-9.
38. Zhang HW, Ding JD, Zhang ZS, Zhao SS, Duan KY, Zhu BQ, Zhao WF, Chai ZT, Liu XW. Critical Role of p38 in Spinal Cord Injury by Regulating Inflammation and Apoptosis in a Rat Model. Spine 2019.
39. Fei L, Abrardi L, Mediati RD. Unexpected effect of aripiprazole on nociceptive pain. Ther Adv Psychopharmacol 2012; 2(5): 211-12.
40. Almeida-Santos AF, Ferreira RC, Duarte ID, Aguiar DC, Romero TR, Moreira FA. The antipsychotic aripiprazole induces antinociceptive effects: Possible role of peripheral dopamine D2 and serotonin 5-HT1A receptors. Eur J Pharmacol 2015; 765: 300-6.
41. Ferreira RCM, Almeida-Santos AF, Duarte IDG, Aguiar DC, Moreira FA, Romero TRL. Peripheral Antinociception Induced by Aripiprazole Is Mediated by the Opioid System. BioMed research international 2017; 2017: 8109205.
42. Zhao Q-L, Ito H, Kondo T, Uehara T, Ikeda M, Abe H, Saitoh J-I, Noguchi K, Suzuki M, Kurachi M. Antipsychotic drugs scavenge radiation-induced hydroxyl radicals and intracellular ROS formation, and protect apoptosis in human lymphoma U937 cells. Free Radic Res 2019; 53(3): 304-12.
43. Liu J, Li K, Zhou J, Sun T, Yang C, Wei J, Xie K, Luo Q, Tang Y. Bisperoxovanadium induces M2-type macrophages and promotes functional recovery after spinal cord injury. Molecular immunology 2019; 116: 56-62.
44. Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. The Journal of neuroscience : the official journal of the Society for Neuroscience 2009; 29(43): 13435-44.
45. Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F, Seifi B, Mohammadi A, Afshari JT, Sahebkar A. Macrophage plasticity, polarization, and function in health and disease. Journal of cellular physiology 2018; 233(9): 6425-40.
46. Francos-Quijorna I, Amo-Aparicio J, Martinez-Muriana A, Lopez-Vales R. IL-4 drives microglia and macrophages toward a phenotype conducive for tissue repair and functional recovery after spinal cord injury. Glia 2016; 64(12): 2079-92.
47. Orecchioni M, Ghosheh Y, Pramod AB, Ley K. Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively Activated Macrophages. Frontiers in immunology 2019; 10: 1084.
48. Silveira LS, Antunes Bde M, Minari AL, Dos Santos RV, Neto JC, Lira FS. Macrophage Polarization: Implications on Metabolic Diseases and the Role of Exercise. Critical reviews in eukaryotic gene expression 2016; 26(2): 115-32.
49. Guo Y-F, Fu H-B, Liu Z-Y, Lu W, Luo K-Y, Zhu H-R, Ning W-D, Chen F, Yang L-Y, Zhou X-D. Effects of the modified electric convulsive treatment (MECT) on cell factors of schizophrenia. Exp Ther Med 2017; 13(3): 873-76.
50. Wang X, Cao K, Sun X, Chen Y, Duan Z, Sun L, Guo L, Bai P, Sun D, Fan J, He X, Young W, Ren Y. Macrophages in spinal cord injury: phenotypic and functional change from exposure to myelin debris. Glia 2015; 63(4): 635-51.
51. Xie C, Liu C, Wu B, Lin Y, Ma T, Xiong H, Wang Q, Li Z, Ma C, Tu Z. Effects of IRF1 and IFN-beta interaction on the M1 polarization of macrophages and its antitumor function. International journal of molecular medicine 2016; 38(1): 148-60.
52. Orihuela R, McPherson CA, Harry GJ. Microglial M1/M2 polarization and metabolic states. British journal of pharmacology 2016; 173(4): 649-65.
53. Yang HC, Park HC, Quan H, Kim Y. Immunomodulation of Biomaterials by Controlling Macrophage Polarization. Advances in experimental medicine and biology 2018; 1064: 197-206.
54. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, Gordon S, Hamilton JA, Ivashkiv LB, Lawrence T, Locati M, Mantovani A, Martinez FO, Mege JL, Mosser DM, Natoli G, Saeij JP, Schultze JL, Shirey KA, Sica A, Suttles J, Udalova I, van Ginderachter JA, Vogel SN, Wynn TA. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014; 41(1): 14-20.
55. Gensel JC, Kopper TJ, Zhang B, Orr MB, Bailey WM. Predictive screening of M1 and M2 macrophages reveals the immunomodulatory effectiveness of post spinal cord injury azithromycin treatment. Scientific reports 2017; 7: 40144.
2. Furlan JC, Sakakibara BM, Miller WC, Krassioukov AV. Global incidence and prevalence of traumatic spinal cord injury. The Canadian journal of neurological sciences Le journal canadien des sciences neurologiques 2013; 40(4): 456-64.
3. Badhiwala JH, Wilson JR, Fehlings MG. Global burden of traumatic brain and spinal cord injury. The Lancet Neurology 2019; 18(1): 24-25.
4. Eckert MJ, Martin MJ. Trauma: Spinal Cord Injury. The Surgical clinics of North America 2017; 97(5): 1031-45.
5. Witiw CD, Fehlings MG. Acute Spinal Cord Injury. Journal of spinal disorders & techniques 2015; 28(6): 202-10.
6. David G, Mohammadi S, Martin AR, Cohen-Adad J, Weiskopf N, Thompson A, Freund P. Traumatic and nontraumatic spinal cord injury: pathological insights from neuroimaging. Nature reviews Neurology 2019.
7. Fan B, Wei Z, Yao X, Shi G, Cheng X, Zhou X, Zhou H, Ning G, Kong X, Feng S. Microenvironment Imbalance of Spinal Cord Injury. Cell transplantation 2018; 27(6): 853-66.
8. Inoue K. A state-of-the-art perspective on microgliopathic pain. Open biology 2018; 8(11).
9. Milich LM, Ryan CB, Lee JK. The origin, fate, and contribution of macrophages to spinal cord injury pathology. Acta neuropathologica 2019; 137(5): 785-97.
10. Akhmetzyanova E, Kletenkov K, Mukhamedshina Y, Rizvanov A. Different Approaches to Modulation of Microglia Phenotypes After Spinal Cord Injury. Frontiers in systems neuroscience 2019; 13: 37.
11. Kopper TJ, Gensel JC. Myelin as an inflammatory mediator: Myelin interactions with complement, macrophages, and microglia in spinal cord injury. Journal of neuroscience research 2018; 96(6): 969-77.
12. Kroner A, Rosas Almanza J. Role of microglia in spinal cord injury. Neuroscience letters 2019; 709: 134370.
13. Orr MB, Gensel JC. Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 2018; 15(3): 541-53.
14. Tsuda M. Microglia in the CNS and Neuropathic Pain. Advances in experimental medicine and biology 2018; 1099: 77-91.
15. Anwar MA, Al Shehabi TS, Eid AH. Inflammogenesis of Secondary Spinal Cord Injury. Frontiers in cellular neuroscience 2016; 10: 98.
16. Di Sciascio G, Riva MA. Aripiprazole: from pharmacological profile to clinical use. Neuropsychiatr Dis Treat 2015; 11: 2635-47.
17. Muneer A. The Treatment of Adult Bipolar Disorder with Aripiprazole: A Systematic Review. Cureus 2016; 8(4): e562-e62.
18. Shapiro DA, Renock S, Arrington E, Chiodo LA, Liu L-X, Sibley DR, Roth BL, Mailman R. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology 2003; 28(8): 1400-11.
19. Yoo S, Kim M-Y, Cho JY. Syk and Src-targeted anti-inflammatory activity of aripiprazole, an atypical antipsychotic. Biochem Pharmacol 2018; 148: 1-12.
20. Stapel B, Sieve I, Falk CS, Bleich S, Hilfiker-Kleiner D, Kahl KG. Second generation atypical antipsychotics olanzapine and aripiprazole reduce expression and secretion of inflammatory cytokines in human immune cells. J Psychiatr Res 2018; 105: 95-102.
21. Juncal-Ruiz M, Riesco-Dávila L, Ortiz-García de la Foz V, Martínez-Garcia O, Ramírez-Bonilla M, Ocejo-Viñals JG, Leza JC, López-Hoyos M, Crespo-Facorro B. Comparison of the anti-inflammatory effect of aripiprazole and risperidone in 75 drug-naïve first episode psychosis individuals: A 3 months randomized study. Schizophr Res 2018; 202: 226-33.
22. Zargar S, Al-Majed A-RA, Wani TA. Potentiating and synergistic effect of grapefruit juice on the antioxidant and anti-inflammatory activity of aripiprazole against hydrogen peroxide induced oxidative stress in mice. BMC Complement Altern Med 2018; 18(1): 106-06.
23. Sato-Kasai M, Kato TA, Ohgidani M, Mizoguchi Y, Sagata N, Inamine S, Horikawa H, Hayakawa K, Shimokawa N, Kyuragi S, Seki Y, Monji A, Kanba S. Aripiprazole inhibits polyI:C-induced microglial activation possibly via TRPM7. Schizophr Res 2016; 178(1-3): 35-43.
24. Sobiś J, Rykaczewska-Czerwińska M, Świętochowska E, Gorczyca P. Therapeutic effect of aripiprazole in chronic schizophrenia is accompanied by anti-inflammatory activity. Pharmacol Rep 2015; 67(2): 353-59.
25. Kato T, Mizoguchi Y, Monji A, Horikawa H, Suzuki SO, Seki Y, Iwaki T, Hashioka S, Kanba S. Inhibitory effects of aripiprazole on interferon-gamma-induced microglial activation via intracellular Ca2+ regulation in vitro. J Neurochem 2008; 106(2): 815-25.
26. Wang J-S, Zhu H-J, Donovan JL, Yuan H-J, Markowitz JS, Geesey ME, Devane CL. Aripiprazole brain concentration is altered in P-glycoprotein deficient mice. Schizophr Res 2009; 110(1-3): 90-94.
27. Baek K-S, Ahn S, Lee J, Kim JH, Kim HG, Kim E, Kim JH, Sung NY, Yang S, Kim MS, Hong S, Kim J-H, Cho JY. Immunotoxicological Effects of Aripiprazole: In vivo and In vitro Studies. Korean J Physiol Pharmacol 2015; 19(4): 365-72.
28. Kowalchuk C, Kanagasundaram P, Belsham DD, Hahn MK. Antipsychotics differentially regulate insulin, energy sensing, and inflammation pathways in hypothalamic rat neurons. Psychoneuroendocrinology 2019; 104: 42-48.
29. Arias-Salgado EG, Lizano S, Sarkar S, Brugge JS, Ginsberg MH, Shattil SJ. Src kinase activation by direct interaction with the integrin beta cytoplasmic domain. Proc Natl Acad Sci U S A 2003; 100(23): 13298-302.
30. Rowley RB, Burkhardt AL, Chao HG, Matsueda GR, Bolen JB. Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation motif binding and autophosphorylation. J Biol Chem 1995; 270(19): 11590-94.
31. Gil CH, Kim YR, Lee HJ, Jung DH, Shin HK, Choi BT. Aripiprazole exerts a neuroprotective effect in mouse focal cerebral ischemia. Exp Ther Med 2018; 15(1): 745-50.
32. Gholampour H, Moezi L, Shafaroodi H. Aripiprazole prevents renal ischemia/reperfusion injury in rats, probably through nitric oxide involvement. Eur J Pharmacol 2017; 813: 17-23.
33. Afshari K, Dehdashtian A, Haddadi NS, Haj-Mirzaian A, Iranmehr A, Ebrahimi MA, Tavangar SM, Faghir-Ghanesefat H, Mohammadi F, Rahimi N, Javidan AN, Dehpour AR. Anti-inflammatory effects of Metformin improve the neuropathic pain and locomotor activity in spinal cord injured rats: introduction of an alternative therapy. Spinal cord 2018; 56(11): 1032-41.
34. Zakeri M, Afshari K, Gharedaghi MH, Shahsiah R, Rahimian R, Maleki F, Dehpour AR, Javidan AN. Lithium protects against spinal cord injury in rats: role of nitric oxide. Journal of neurological surgery Part A, Central European neurosurgery 2014; 75(6): 427-33.
35. Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. Journal of neurotrauma 1995; 12(1): 1-21.
36. Singh P, Kongara K, Harding D, Ward N, Dukkipati VSR, Johnson C, Chambers P. Comparison of electroencephalographic changes in response to acute electrical and thermal stimuli with the tail flick and hot plate test in rats administered with opiorphin. BMC neurology 2018; 18(1): 43.
37. Arroz M, Came N, Lin P, Chen W, Yuan C, Lagoo A, Monreal M, de Tute R, Vergilio JA, Rawstron AC, Paiva B. Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting. Cytometry Part B, Clinical cytometry 2016; 90(1): 31-9.
38. Zhang HW, Ding JD, Zhang ZS, Zhao SS, Duan KY, Zhu BQ, Zhao WF, Chai ZT, Liu XW. Critical Role of p38 in Spinal Cord Injury by Regulating Inflammation and Apoptosis in a Rat Model. Spine 2019.
39. Fei L, Abrardi L, Mediati RD. Unexpected effect of aripiprazole on nociceptive pain. Ther Adv Psychopharmacol 2012; 2(5): 211-12.
40. Almeida-Santos AF, Ferreira RC, Duarte ID, Aguiar DC, Romero TR, Moreira FA. The antipsychotic aripiprazole induces antinociceptive effects: Possible role of peripheral dopamine D2 and serotonin 5-HT1A receptors. Eur J Pharmacol 2015; 765: 300-6.
41. Ferreira RCM, Almeida-Santos AF, Duarte IDG, Aguiar DC, Moreira FA, Romero TRL. Peripheral Antinociception Induced by Aripiprazole Is Mediated by the Opioid System. BioMed research international 2017; 2017: 8109205.
42. Zhao Q-L, Ito H, Kondo T, Uehara T, Ikeda M, Abe H, Saitoh J-I, Noguchi K, Suzuki M, Kurachi M. Antipsychotic drugs scavenge radiation-induced hydroxyl radicals and intracellular ROS formation, and protect apoptosis in human lymphoma U937 cells. Free Radic Res 2019; 53(3): 304-12.
43. Liu J, Li K, Zhou J, Sun T, Yang C, Wei J, Xie K, Luo Q, Tang Y. Bisperoxovanadium induces M2-type macrophages and promotes functional recovery after spinal cord injury. Molecular immunology 2019; 116: 56-62.
44. Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. The Journal of neuroscience : the official journal of the Society for Neuroscience 2009; 29(43): 13435-44.
45. Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F, Seifi B, Mohammadi A, Afshari JT, Sahebkar A. Macrophage plasticity, polarization, and function in health and disease. Journal of cellular physiology 2018; 233(9): 6425-40.
46. Francos-Quijorna I, Amo-Aparicio J, Martinez-Muriana A, Lopez-Vales R. IL-4 drives microglia and macrophages toward a phenotype conducive for tissue repair and functional recovery after spinal cord injury. Glia 2016; 64(12): 2079-92.
47. Orecchioni M, Ghosheh Y, Pramod AB, Ley K. Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively Activated Macrophages. Frontiers in immunology 2019; 10: 1084.
48. Silveira LS, Antunes Bde M, Minari AL, Dos Santos RV, Neto JC, Lira FS. Macrophage Polarization: Implications on Metabolic Diseases and the Role of Exercise. Critical reviews in eukaryotic gene expression 2016; 26(2): 115-32.
49. Guo Y-F, Fu H-B, Liu Z-Y, Lu W, Luo K-Y, Zhu H-R, Ning W-D, Chen F, Yang L-Y, Zhou X-D. Effects of the modified electric convulsive treatment (MECT) on cell factors of schizophrenia. Exp Ther Med 2017; 13(3): 873-76.
50. Wang X, Cao K, Sun X, Chen Y, Duan Z, Sun L, Guo L, Bai P, Sun D, Fan J, He X, Young W, Ren Y. Macrophages in spinal cord injury: phenotypic and functional change from exposure to myelin debris. Glia 2015; 63(4): 635-51.
51. Xie C, Liu C, Wu B, Lin Y, Ma T, Xiong H, Wang Q, Li Z, Ma C, Tu Z. Effects of IRF1 and IFN-beta interaction on the M1 polarization of macrophages and its antitumor function. International journal of molecular medicine 2016; 38(1): 148-60.
52. Orihuela R, McPherson CA, Harry GJ. Microglial M1/M2 polarization and metabolic states. British journal of pharmacology 2016; 173(4): 649-65.
53. Yang HC, Park HC, Quan H, Kim Y. Immunomodulation of Biomaterials by Controlling Macrophage Polarization. Advances in experimental medicine and biology 2018; 1064: 197-206.
54. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, Gordon S, Hamilton JA, Ivashkiv LB, Lawrence T, Locati M, Mantovani A, Martinez FO, Mege JL, Mosser DM, Natoli G, Saeij JP, Schultze JL, Shirey KA, Sica A, Suttles J, Udalova I, van Ginderachter JA, Vogel SN, Wynn TA. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014; 41(1): 14-20.
55. Gensel JC, Kopper TJ, Zhang B, Orr MB, Bailey WM. Predictive screening of M1 and M2 macrophages reveals the immunomodulatory effectiveness of post spinal cord injury azithromycin treatment. Scientific reports 2017; 7: 40144.
| Files | ||
| Issue | Vol 60 No 9 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/acta.v60i9.11100 | |
| Keywords | ||
| Aripiprazole Spinal cord injury Neuropathy Neuroinflammation Microglia Macrophages | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Rismanbaf A, Afshari K, Haddadi N-S, Dehpour AR, Shafaroodi H. Aripiprazole Improves Spinal Cord Injury in Rats: Involvement of Inflammatory Pathways. Acta Med Iran. 2022;60(9):583-593.
