The Effects of Glucagon and Insulin Combination toward on Neurodegeneration Following Traumatic Brain Injury in Rat Model
DOI:
https://doi.org/10.3889/oamjms.2021.7490Keywords:
Traumatic brain injury, Insulin, Glucagon, Glutamate, Glucose, NecrosisAbstract
BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability in the productive age. Glutamate excitotoxicity and hyperglycemia those occur following TBI are among the factors those influence secondary brain injury.
AIM: This study aimed to determine the effect of glucagon and insulin combination on neuronal necrosis following TBI.
METHODS: A total of 28 male wistar rats were randomized into four experimental groups: placebo, insulin, glucagon, and combination of glucagon and insulin. Each animal underwent controlled cortical impact model of TBI. The blood glucose and glutamate levels were measured before and 4 h following TBI. The brain tissues were collected to evaluate neuronal necrosis.
RESULTS: Glucagon or glucagon and insulin combination were able to prevent the increased of blood glutamate levels following TBI (p < 0.05). Glucagon administration was associated high blood glucose level (198.10 ± 32.58 mg/dL); a combination with insulin was able to minimize the increased of blood glucose level (166.53 ± 18.48 mg/dL). Combination of glucagon and insulin had a lower number of neuronal necrosis compare to the other groups (p < 0.005).
CONCLUSION: The combination of glucagon and insulin potentially exhibit neuroprotection effect on rats following TBI as being demonstrated by lower number of neuronal necrosis. This finding further indicates the role of glucose homeostasis in neuroprotection.Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Ghajar J. Traumatic brain injury. Lancet. 2000;356(9233):923-9. http://doi.org/10.1016/S0140-6736(00)02689-1 PMid:11036909 DOI: https://doi.org/10.1016/S0140-6736(00)02689-1
Langlois J, Rutland-Brown W, Wald M. The epidemiology and impact of traumatic brain injury. J Head Trauma Rehab. 2006;21(5):375-8. http://doi.org/10.1097/00001199-200609000-00001 PMid:16983222 DOI: https://doi.org/10.1097/00001199-200609000-00001
Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, et al. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2019;130(4):1304-14. DOI: https://doi.org/10.3171/2017.10.JNS17352
Ng SY, Lee AY. Traumatic brain injuries: Pathophysiology and potential therapeutic targets. Front Cell Neurosci. 2019;13:528. http://doi.org/10.3389/fncel.2019.00528 PMid:31827423 DOI: https://doi.org/10.3389/fncel.2019.00528
Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anesth 2007;99(1):4-9. http://doi.org/10.1093/bja/aem131 PMid:17573392 DOI: https://doi.org/10.1093/bja/aem131
Fanne RA, Nassar T, Mazuz A, Waked O, Heyman SN, Hijazi N, et al. Neuroprotection by glucagon: Role of gluconeogenesis. J Neurosurg. 2011;114(1):85-91. http://doi.org/10.3171/2010.4.JNS10263 PMid:20509730 DOI: https://doi.org/10.3171/2010.4.JNS10263
Fanne RA, Nassar T, Heyman SN, Hijazi N, Higazi AR. Insulin and glucagon share the same mechanism of neuroprotection in diabetic rats: Role of glutamate. Am J Physiol Regul Integr Comp Physiol. 2011;301(3):668-73. http://doi.org/10.1152/ ajpregu.00058.2011 PMid:21677268 DOI: https://doi.org/10.1152/ajpregu.00058.2011
Zlotnik A, Gruenbaum BF, Klin Y, Gruenbaum SE, Ohayon S, Sheiner E, et al. The effects of insulin, glucagon, glutamate, and glucose infusion on blood glutamate and plasma glucose levels in naïve rats. J Neurosurg Anesthesiol. 2011;23(4):323-8. http://doi.org/10.1097/ANA.0b013e3182299b15 PMid:21836527 DOI: https://doi.org/10.1097/ANA.0b013e3182299b15
Osier ND, Dixon CE. The controlled cortical impact model: Applications, considerations for researchers, and future directions. Front Neurol. 2016;7:134. http://doi.org/10.3389/fneur.2016.00134 PMid:27582726 DOI: https://doi.org/10.3389/fneur.2016.00134
Jensen K, Krusenstjerna-Hafstrom R, Lohse J, Petersen KH, Derand H. A novel quantitative immunohistochemistry method for precise protein measurements directly in formalin-fixed, paraffin-embedded specimens: Analytical performance measuring HER2. Modern Pathol. 2017;30(2):180-93. http://doi.org/10.1038/modpathol.2016.176 PMid:27767098 DOI: https://doi.org/10.1038/modpathol.2016.176
Bang SA, Song YS, Moon BS, Lee BC, Lee H, Kim JM, et al. Neuropsychological, metabolic, and GABA a receptor studies in subjects with repetitive traumatic brain injury. J Neurotrauma. 2016;33(11):1005-14. http://doi.org/10.1089/neu.2015.4051 PMid:26414498 DOI: https://doi.org/10.1089/neu.2015.4051
Dorsett CR, McGuire JL, DePasquale EA, Gardner AE, Floyd CL, McCullumsmith RE. Glutamate neurotransmission in rodent models of traumatic brain injury. J Neurotrauma. 2017;34(2):263-72. http://doi.org/10.1089/neu.2015.4373 PMid:27256113 DOI: https://doi.org/10.1089/neu.2015.4373
Mancini A, Chielini A, Di Capua A, Castelli L, Brogi S, Paolino M, et al. Synthesis and biological evaluation of a new class of benzothiazines as neuroprotective agents. Eur J Med Chem. 2017;126:614-30. http://doi.org/10.1016/j.ejmech.2016.11.053 PMid:27923201 DOI: https://doi.org/10.1016/j.ejmech.2016.11.053
Ji SL, Cao KK, Zhao XX, Kang NX, Zhang Y, Xu QM, et al. Antioxidant activity of phenylethanoid glycosides on glutamate-induced neurotoxicity. Biosci Biotechnol Biochem. 2019;83(11):2016-26. http://doi.org/10.1080/09168451.2019.16 37243 Mid:31272310 DOI: https://doi.org/10.1080/09168451.2019.1637243
Rau CS, Wu SC, Chen YC, Chen PC, Hsieh HY, Kuo PJ, et al. Stress-induced hyperglycemia, but not diabetic hyperglycemia, is associated with higher mortality in patients with isolated moderate and severe traumatic brain injury: Analysis of a propensity score-matched population. Int J Environ Res Public Health. 2017;14(11):1340. http://doi.org/10.3390/ijerph14111340 PMid:29099813 DOI: https://doi.org/10.3390/ijerph14111340
Smith RL, Lin JC, Adelson PD, Kochanek PM, Fink EL, Wisniewski S, et al. Relationship between hyperglycemia and outcome in children with severe traumatic brain injury. Pediatr Crit Care Med. 2012;13(1):85-91. http://doi.org/10.1097/PCC.0b013e3182192c30 PMid:21499170 DOI: https://doi.org/10.1097/PCC.0b013e3182192c30
Kinoshita K, Kraydieh S, Alonso O, Hayashi N, Dietrich WD. Contusion volume and neutrophil accumulation after moderate fluid-percussion brain injury in rats. J Neurotrauma. 2002;19(6):681-92. http://doi.org/10.1089/neu.1994.11.499 PMid:7861443 DOI: https://doi.org/10.1089/08977150260139075
Stefani MA, Modkovski R, Hansel G, Zimmer ER, Kopczynski A, Muller AP, et al. Elevated glutamate and lactate predict brain death after severe head trauma. Ann Clin Transl Neurol. 2017;4(6):392-402. http://doi.org/10.1002/acn3.416 Mid:28589166 DOI: https://doi.org/10.1002/acn3.416
Ruppel RA, Kochanek PM, Adelson PD, Rose ME, Wisniewski SR, Bell MJ, et al. Excitatory amino acid concentrations in ventricular cerebrospinal fluid after severe traumatic brain injury in infants and children: The role of childe abuse. J Pediatr. 2001;138(1):18-25. http://doi.org/10.1067/mpd.2001.110979 PMid:11148507 DOI: https://doi.org/10.1067/mpd.2001.110979
Yang Li, Han B, Zhang Z, Wang S, Bai Y, Zhang Y, et al. Extracellular vesicle-mediated delivery of circular RNA SCMH1 promotes functional recovery in rodent and nonhuman primate ischemic stroke models. Circulation. 2020;142:556-74. http://doi.org/10.1161/CIRCULATIONAHA.120.045765 PMid:32441115 DOI: https://doi.org/10.1161/CIRCULATIONAHA.120.045765
Dadwal P, Mahmud N, Sinai L, Azimi A, Fatt M, Wondisford FE, et al. Activating endogenous neural precursor cells using metformin leads to neural repair and functional recovery in a model of childhood brain injury. Stem Cell Rep. 2015;5(2):166-73. http://doi.org/10.1016/j.stemcr.2015.06.011 PMid:26235894 DOI: https://doi.org/10.1016/j.stemcr.2015.06.011
Downloads
Published
How to Cite
License
Copyright (c) 2021 Akhmad Imron, Bethy Hernowo, Dany Hilmanto, Kahdar Wiriadisastra, Yulius Hermanto (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
http://creativecommons.org/licenses/by-nc/4.0