The Effect of Remifentanil, MgSO4, or Remifentanil-MgSO4 as Neuroprotectors on BDNF, MAC, and Caspase-3 Levels in Wistar Rats with Traumatic Brain Injury

Authors

  • Ardana Tri Arianto Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia https://orcid.org/0000-0002-2375-728X
  • Soetrisno Soetrisno Postgraduate Study Program, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia
  • Purwoko Purwoko Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia
  • Dono Indarto Postgraduate Study Program, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia https://orcid.org/0000-0001-7420-5816

DOI:

https://doi.org/10.3889/oamjms.2022.10893

Keywords:

BDNF, MAC, Caspase-3, Traumatic brain injury, Remifentanil, MgSO4

Abstract

BACKGROUND: Traumatic brain injury (TBI) can lead to cell death and neurologic dysfunction. Meanwhile, Remifentanyl is an opioid with potent analgesia, while magnesium sulfate (MgSO4) has antinociceptive properties that can prevent hemodynamic instability during laryngoscopy.

AIM: This study aims to examine the effect of remifentanil, MgSO4 and their combination on BDNF, MAC, and Caspase-3 levels in Wistar rat models with TBI.

METHODOLOGY: An experimental study was conducted on 30 male Wistar rats which were randomly divided into five groups. The control group (G1) received normal saline, the induced group (G2) received normal saline after TBI induction using the modified Feeney method, and the treated group (G3, G4, and G5) received remifentanil, MgSO4, and their combination after TBI induction. The rats’ brain tissues were analyzed for BDNF, MAC, and Caspase-3 levels using ELISA. The data were analyzed statistically with ANOVA followed by post hoc Multiple Comparison Test (p < 0.05).

RESULTS: Treatment with remifentanil, MgSO4 or the combination of both in TBI subjects reduced MAC and Caspase-3 but increased the BDNF level. The post hoc multiple comparisons showed significant differences in all groups except groups 3 and 5 in terms of MAC (p = 0.190) and Caspase-3 (p = 0.999). The combination of remifentanil-MgSO4 increased BDNF levels significantly.

CONCLUSION: The administration of remifentanil, MgSO, or their combination can serve as a neuroprotector in Wistar rat models with TBI by lowering MAC and Caspase-3 as well as increasing BDNF levels.

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References

Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, et al. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2018;130:1-18. https://doi.org/10.3171/2017.10.JNS17352 PMid:29701556 DOI: https://doi.org/10.3171/2017.10.JNS17352

Gustafsson D, Klang A, Thams S, Rostami E. The role of BDNF in experimental and clinical traumatic brain injury. Int J Mol Sci. 2021;22(7):3582. https://doi.org/10.3390/ijms22073582 PMid:33808272 DOI: https://doi.org/10.3390/ijms22073582

Jarrahi A, Braun M, Ahluwalia M, Gupta RV, Wilson M, Munie S, et al. Revisiting traumatic brain injury: From molecular mechanisms to therapeutic interventions. Biomedicines. 2020;8(10):389. https://doi.org/10.3390/biomedicines8100389 PMid:33003373 DOI: https://doi.org/10.3390/biomedicines8100389

Tomita T. Apoptosis of pancreatic β-cells in Type 1 diabetes. Bosn J Basic Med Sci. 2017;17(3):183-93. https://doi.org/10.17305/bjbms.2017.1961 PMid:28368239 DOI: https://doi.org/10.17305/bjbms.2017.1961

Dalakas MC, Alexopoulos H, Spaeth PJ. Complement in neurological disorders and emerging complement-targeted therapeutics. Nat Rev Neurol. 2020;16(11):601-17. https://doi.org/10.1038/s41582-020-0400-0 PMid:33005040 DOI: https://doi.org/10.1038/s41582-020-0400-0

Bayly-Jones C, Bubeck D, Dunstone MA. The mystery behind membrane insertion: A review of the complement membrane attack complex. Philos Trans R Soc B Biol Sci. 2017;372(1726):20160221. https://doi.org/10.1098/rstb.2016.0221 PMid:28630159 DOI: https://doi.org/10.1098/rstb.2016.0221

Chen SD, Wu CL, Hwang WC, Yang DI. More insight into BDNF against neurodegeneration: Anti-apoptosis, anti-oxidation, and suppression of autophagy. Int J Mol Sci. 2017;18(3):1-12. https://doi.org/10.3390/ijms18030545 PMid:28273832 DOI: https://doi.org/10.3390/ijms18030545

Wiener J, McIntyre A, Janzen S, Mirkowski M, MacKenzie HM, Teasell R. Opioids and cerebral physiology in the acute management of traumatic brain injury: A systematic review. Brain Inj. 2019;33(5):559-66. https://doi.org/10.1080/02699052.2019.1574328 PMid:30696281 DOI: https://doi.org/10.1080/02699052.2019.1574328

Cappoli N, Aceto P, Tabolacci E, Mezzogori D, Sollazzi L, Navarra P, et al. Effects of remifentanil on human C20 microglial pro-inflammatory activation. Eur Rev Med Pharmacol Sci. 2021;25(16):5268-74. https://doi.org/10.26355/eurrev_202108_26547 PMid:34486703

Zhou Z, Ying M, Zhao R. Efficacy and safety of sevoflurane vs propofol in combination with remifentanil for anesthesia maintenance during craniotomy: A meta-analysis Medicine (Baltimore). 2021;100(51):e28400. https://doi.org/10.1097/MD.0000000000028400 PMid:34941178 DOI: https://doi.org/10.1097/MD.0000000000028400

Alnemari AM, Krafcik BM, Mansour TR, Gaudin D. A comparison of pharmacologic therapeutic agents used for the reduction of intracranial pressure after traumatic brain injury. World Neurosurg. 2017;106:509-28. https://doi.org/10.1016/j.wneu.2017.07.009 PMid:28712906 DOI: https://doi.org/10.1016/j.wneu.2017.07.009

Nooraei N, Dehkordi ME, Radpay B, Teimoorian H, Mohajerani SA. Effects of intravenous magnesium sulfate and lidocaine on hemodynamic variables following direct laryngoscopy and intubation in elective surgery patients. Tanaffos. 2013;12(1):57-63. PMid:25191450

Abdoli A, Rahimi-Bashar F, Torabian S, Sohrabi S, Makarchian HR. Efficacy of simultaneous administration of nimodipine, progesterone, and magnesium sulfate in patients with severe traumatic brain injury: A randomized controlled trial. Bull Emerg Trauma. 2019;7(2):124-9. https://doi.org/10.29252/beat-070206 PMid:31198800 DOI: https://doi.org/10.29252/beat-070206

Mussrat R, Zahoor A, Khan MA, Ahmad S. Comparison of perioperative magnesium sulphate infusion with placebo for postoperative analgesia. Prof Med J. 2019;26(11):1937-41. https://doi.org/10.29309/TPMJ/2019.26.11.3381 DOI: https://doi.org/10.29309/TPMJ/2019.26.11.3381

Kutlesic MS, Kutlesic RM, Mostic-Ilic T. Magnesium in obstetric anesthesia and intensive care. J Anesth. 2017;31(1):127-39. https://doi.org/10.1007/s00540-016-2257-3 PMid:27803982 DOI: https://doi.org/10.1007/s00540-016-2257-3

Bujalska-Zadrożny M, Tatarkiewicz J, Kulik K, Filip M, Naruszewicz M. Magnesium enhances opioid-induced analgesia-what we have learnt in the past decades? Eur J Pharm Sci. 2017;99:113-27. https://doi.org/10.1016/j.ejps.2016.11.020 PMid:27884758 DOI: https://doi.org/10.1016/j.ejps.2016.11.020

Corkrum M, Rothwell PE, Thomas MJ, Kofuji P, Araque A. Opioid-mediated astrocyte-neuron signaling in the nucleus accumbens. Cells. 2019;8(6):586. https://doi.org/10.3390/cells8060586 PMid:31207909 DOI: https://doi.org/10.3390/cells8060586

Filho SE, Sandes CS, Vieira JE, Cavalcanti IL. Analgesic effect of magnesium sulfate during total intravenous anesthesia: Randomized clinical study. Braz J Anesthesiol. 2021;71(5):550-7. https://doi.org/10.1016/j.bjane.2021.02.008 PMid:34537125 DOI: https://doi.org/10.1016/j.bjane.2021.02.008

Zhou J, Yang Z, Shen R, Zhong W, Zheng H, Chen Z, et al. Resveratrol improves mitochondrial biogenesis function and activates PGC-1α pathway in a preclinical model of early brain injury following subarachnoid hemorrhage. Front Mol Biosci. 2021;8:620683. https://doi.org/10.3389/fmolb.2021.620683 PMid:33968980 DOI: https://doi.org/10.3389/fmolb.2021.620683

Lorente L. Biomarkers associated with the outcome of traumatic brain injury patients. Brain Sci. 2017;7(11):142. https://doi.org/10.3390/brainsci7110142 PMid:29076989 DOI: https://doi.org/10.3390/brainsci7110142

Al-Kuraishy HM, Al-Hussaniy HA, Al-Gareeb AI, Negm WA, El-Kadem AH, Batiha GE, et al. Combination of Panax ginseng C. A. Mey and febuxostat boasted cardioprotective effects against doxorubicin-induced acute cardiotoxicity in rats. Front Pharmacol. 2022;13:905828. https://doi.org/10.3389/fphar.2022.905828 PMid:35814241 DOI: https://doi.org/10.3389/fphar.2022.905828

Jimenez-Gonzalez A, García-Concejo A, López-Benito S, Gonzalez-Nunez V, Arévalo JC, Rodriguez RE. Role of morphine, miR-212/132 and mu opioid receptor in the regulation of Bdnf in zebrafish embryos. Biochim Biophys Acta. 2016;1860(6):1308-16. https://doi.org/10.1016/j.bbagen.2016.03.001 PMid:26947007 DOI: https://doi.org/10.1016/j.bbagen.2016.03.001

Qiu LL, Pan W, Luo D, Zhang GF, Zhou ZQ, Sun XY, et al. Dysregulation of BDNF/TrkB signaling mediated by NMDAR/ Ca2+/calpain might contribute to postoperative cognitive dysfunction in aging mice. J Neuroinflammation. 2020;17(1):23. https://doi.org/10.1186/s12974-019-1695-x PMid:31948437 DOI: https://doi.org/10.1186/s12974-019-1695-x

Turchan A, Fahmi A, Kurniawan A, Bajamal AH, Fauzi A, Apriawan T. The change of serum and CSF BDNF level as a prognosis predictor in traumatic brain injury cases: A systematic review. Surg Neurol Int. 2022;13:250. https://doi.org/10.25259/SNI_1245_2021 PMid:35855138 DOI: https://doi.org/10.25259/SNI_1245_2021

Tourrel F, De Lendeu PK, Abily-Donval L, Chollat C, Marret S, Dufrasne F, et al. The antiapoptotic effect of remifentanil on the immature mouse brain: An ex vivo study. Anesth Analg. 2014;118(5):1041-51. https://doi.org/10.1213/ANE.0000000000000159 PMid:24781573 DOI: https://doi.org/10.1213/ANE.0000000000000159

Fluiter K, Opperhuizen AL, Morgan BP, Baas F, Ramaglia V. Inhibition of the membrane attack complex of the complement system reduces secondary neuroaxonal loss and promotes neurologic recovery after traumatic brain injury in mice. J Immunol. 2014;192(5):2339-48. https://doi.org/10.4049/jimmunol.1302793 PMid:24489093 DOI: https://doi.org/10.4049/jimmunol.1302793

Sulistyowati S, Bachnas MA, Ekasari S, Wijayanti AS. Correlation of the magnesium serum levels in maternal and fetal over the fetal brain-derived neurotrophic factor (BDNF) after antenatal magnesium sulphate (MgSO4) provision in the preterm birth neuroprotection strategy. Syst Rev Pharm. 2021;12(1):1624-9. https://doi.org/10.31838/srp.2021.1.231

İmamoğlu S, İmamoğlu EY, Erdenöz S, Cumbul A, Uslu Ü, Aktaş Ş, et al. Possible antiapoptotic and neuroprotective effects of magnesium sulphate on retina in a preterm hypoxic-ischemic rat model. Turk J Med Sci. 2021;51(4):2198-205. https://doi.org/10.3906/sag-2012-119 PMid:33932970 DOI: https://doi.org/10.3906/sag-2012-119

Shi CX, Qi QH, Xu J, Zhao WW. Protective effect of magnesium sulfate on cranial nervesin preeclampsia rats through NF-κB/ICAM-1 pathway. Eur Rev Med Pharmacol Sci. 2020;24(6):2785-94. https://doi.org/10.26355/eurrev_202003_20639 PMid:32271395

Hosseini-Sharifabad A, Rabbani M, Seyed-Yousefi Y, Safavi M. Magnesium increases the protective effect of citicoline on aluminum chloride-induced cognitive impairment. Clin Psychopharmacol Neurosci. 2020;18(2):241-8. https://doi.org/10.9758/cpn.2020.18.2.241 PMid:32329305 DOI: https://doi.org/10.9758/cpn.2020.18.2.241

Ryu JH, Sohn IS, Do SH. Controlled hypotension for middle ear surgery: A comparison between remifentanil and magnesium sulphate. Br J Anaesth. 2009;103(4):490-5. https://doi.org/10.1093/bja/aep229 PMid:19687032 DOI: https://doi.org/10.1093/bja/aep229

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Published

2022-11-12

How to Cite

1.
Arianto AT, Soetrisno S, Purwoko P, Indarto D. The Effect of Remifentanil, MgSO4, or Remifentanil-MgSO4 as Neuroprotectors on BDNF, MAC, and Caspase-3 Levels in Wistar Rats with Traumatic Brain Injury. Open Access Maced J Med Sci [Internet]. 2022 Nov. 12 [cited 2024 Nov. 27];10(B):2399-404. Available from: https://oamjms.eu/index.php/mjms/article/view/10893