Ghrelin ameliorates neuronal damage, oxidative stress, inflammatory parameters, and GFAP expression in traumatic brain injury

References

• Menon DK, Schwab K, Wright DW, Maas AI. Position statement: definition of traumatic brain injury. Arch Phys Med Rehab. 2010;91(11):1637–1640. doi:10.1016/j.apmr.2010.05.017.
   PubMed Web of Science ®Google Scholar
• WHO. Neurological disorders: public health challenges. Geneva: World Health Organization; 2006.
   Google Scholar
• Maas AI, Stocchetti N, Bullock R. Moderate and severe traumatic brain injury in adults. Lancet Neurol. 2008;7(8):728–741. doi:10.1016/S1474-4422(08)70164-9.
   PubMed Web of Science ®Google Scholar
• Rincon S, Gupta R, Ptak T. Imaging of head trauma. Handb Clin Neurol. 2016;135:447–77.
   PubMedGoogle Scholar
• Lamade AM, Anthonymuthu TS, Hier ZE, Gao Y, Kagan VE, Bayır H. Mitochondrial damage & lipid signaling in traumatic brain injury. Exp Neurol. 2020;329:113307. doi:10.1016/j.expneurol.2020.113307.
   PubMed Web of Science ®Google Scholar
• Kaur P, Sharma S. Recent advances in pathophysiology of traumatic brain injury. Curr Neuropharmacol. 2018;16(8):1224–1238. doi:10.2174/1570159X15666170613083606.
   PubMed Web of Science ®Google Scholar
• Osier ND, Carlson SW, DeSana A, Dixon CE. Chronic histopathological and behavioral outcomes of experimental traumatic brain injury in adult male animals. J Neurotrauma. 2015;32(23):1861–1882. doi:10.1089/neu.2014.3680.
   PubMed Web of Science ®Google Scholar
• Kabadi SV, Faden AI. Neuroprotective strategies for traumatic brain injury: improving clinical translation. Int J Mol Sci. 2014;15(1):1216–1236. doi:10.3390/ijms15011216.
   PubMed Web of Science ®Google Scholar
• Salehi A, Zhang JH, Obenaus A. Response of the cerebral vasculature following traumatic brain injury. J Cereb Blood Flow Metab. 2017;37(7):2320–2339. doi:10.1177/0271678X17701460.
   PubMed Web of Science ®Google Scholar
• Kojima M, Hosoda H, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–60. doi:10.1038/45230.
   PubMed Web of Science ®Google Scholar
• Ergul Erkec O, Yunusoglu O, Huyut Z. Evaluation of repeated ghrelin administration on seizures, oxidative stress and neurochemical parameters in pentyleneterazole induced kindling in rats. Int J Neurosci. 2022;1–9. doi:10.1080/00207454.2022.2107516.
   PubMed Web of Science ®Google Scholar
• Erşahin M, Toklu HZ, Erzik C, Çetinel Ş, Akakin D, Velioğlu-Öğünç A, Yeğen BÇ, Özdemir ZN, Şener G, Yeğen BÇ. The anti-inflammatory and neuroprotective effects of ghrelin in subarachnoid hemorrhage-induced oxidative brain damage in rats. J Neurotrauma. 2010;27(6):1143–55. doi:10.1089/neu.2009.1210.
   PubMed Web of Science ®Google Scholar
• Oztas B, Sahin D, Kir H, Eraldemir FC, Musul M, Kuskay S, Ates N. The effect of leptin, ghrelin, and neuropeptide-Y on serum Tnf-Alpha, Il-1beta, Il-6, Fgf-2, galanin levels and oxidative stress in an experimental generalized convulsive seizure model. Neuropeptides. 2017;61:31–37. doi:10.1016/j.npep.2016.08.002.
   PubMed Web of Science ®Google Scholar
• Lopez NE, Gaston L, Lopez K, Coimbra R, Hageny A, Putnam J, Eliceiri B, Coimbra R, Bansal V. Early ghrelin treatment attenuates disruption of the blood brain barrier and apoptosis after traumatic brain injury through a UCP-2 mechanism. Brain Res. 2012;1489:140–148. doi:10.1016/j.brainres.2012.10.031.
   PubMed Web of Science ®Google Scholar
• Lopez NE, Krzyzaniak MJ, Blow C, Putnam J, Ortiz-Pomales Y, Hageny A-M, Eliceiri B, Coimbra R, Bansal V. Ghrelin prevents disruption of the blood–brain barrier after traumatic brain injury. J Neurotrauma. 2012;29(2):385–393. doi:10.1089/neu.2011.2053.
   PubMed Web of Science ®Google Scholar
• Qi L, Cui X, Dong W, Barrera R, Coppa GF, Wang P, Wu R. Ghrelin protects rats against traumatic brain injury and hemorrhagic shock through upregulation of UCP2. Ann Surg. 2014;260(1):169–178. doi:10.1097/SLA.0000000000000328.
   PubMed Web of Science ®Google Scholar
• Cornelius C, Crupi R, Calabrese V, Graziano A, Milone P, Pennisi G, Radak Z, Calabrese EJ, Cuzzocrea S. Traumatic brain injury: oxidative stress and neuroprotection. Antioxid Redox Signal. 2013;19(8):836–853. doi:10.1089/ars.2012.4981.
   PubMed Web of Science ®Google Scholar
• Nita M, Grzybowski A. The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxid Med Cell Longev. 2016;2016:1–23. doi:10.1155/2016/3164734.
   Web of Science ®Google Scholar
• Monaghan P, Metcalfe NB, Torres R. Oxidative stress as a mediator of life history trade‐offs: mechanisms, measurements and interpretation. Ecol Lett. 2009;12(1):75–92. doi:10.1111/j.1461-0248.2008.01258.x.
   PubMed Web of Science ®Google Scholar
• Lee KH, Cha M, Lee BH. Neuroprotective effect of antioxidants in the brain. Int J Mol Sci. 2020;21(19):7152. doi:10.3390/ijms21197152.
   PubMed Web of Science ®Google Scholar
• Rustenhoven J, Aalderink M, Scotter EL, Oldfield RL, Bergin PS, Mee EW, Park TI, Faull RLM, Curtis MA, Park TI-H. TGF-beta1 regulates human brain pericyte inflammatory processes involved in neurovasculature function. J Neuroinflammation. 2016;13(1):1–15. doi:10.1186/s12974-016-0503-0.
   PubMedGoogle Scholar
• Ozen I, Ruscher K, Nilsson R, Flygt J, Clausen F, Marklund N. Interleukin-1 Beta Neutralization Attenuates Traumatic Brain Injury-Induced Microglia Activation and Neuronal Changes in the Globus Pallidus. Int J Mol Sci. 2020;21(2):387. doi:10.3390/ijms21020387.
   PubMed Web of Science ®Google Scholar
• Kushi H, Saito T, Makino K, Hayashi N (2003). L-8 is a key mediator of neuroinflammation in severe traumatic brain injuries. Paper presented at the Brain Edema XII: Proceedings of the 12 th International Symposium, Hakone, Japan, November 10–13, 2002.
   Google Scholar
• Feeney DM, Boyeson MG, Linn RT, Murray HM, Dail WG. Responses to cortical injury: I. Methodology and local effects of contusions in the rat. Brain Res. 1981;211(1):67–77. doi:10.1016/0006-8993(81)90067-6.
   PubMed Web of Science ®Google Scholar
• Gülşen İ, Ak H, Çölçimen N, Alp HH, Akyol ME, Demir I, Rağbetli MÇ, Balahroğlu R, Rağbetli MÇ. Neuroprotective effects of thymoquinone on the hippocampus in a rat model of traumatic brain injury. World Neurosurg. 2016;86:243–49. doi:10.1016/j.wneu.2015.09.052.
   PubMed Web of Science ®Google Scholar
• Kola PK, Akula A, NissankaraRao LS, Danduga R. Protective effect of naringin on pentylenetetrazole (PTZ)-induced kindling; possible mechanisms of antikindling, memory improvement, and neuroprotection. Epilepsy Behav. 2017;75:114–126. doi:10.1016/j.yebeh.2017.07.011.
   PubMed Web of Science ®Google Scholar
• Ceylani T, Teker H Taner, Keskin S, Samgane G, Acikgoz E and Gurbanov R. The rejuvenating influence of young plasma on aged intestine. J Cellular Molecular Medi. 2023;27(18), 2804–2816. doi: 10.1111/jcmm.17926.
   PubMed Web of Science ®Google Scholar
• Atkins CM. Decoding hippocampal signaling deficits after traumatic brain injury. Transl Stroke Res. 2011;2(4):546–555. doi:10.1007/s12975-011-0123-z.
   PubMed Web of Science ®Google Scholar
• Girgis F, Pace J, Sweet J, Miller JP. Hippocampal neurophysiologic changes after mild traumatic brain injury and potential neuromodulation treatment approaches. Front Syst Neurosci. 2016;10:8. doi:10.3389/fnsys.2016.00008.
   PubMed Web of Science ®Google Scholar
• Bennett MH, Trytko B, Jonker B. Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury. Cochrane Db Syst Rev. 2012. doi:10.1002/14651858.CD004609.pub3.
   Web of Science ®Google Scholar
• Yi J-H, Hazell AS. Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury. Neurochem Int. 2006;48(5):394–403. doi:10.1016/j.neuint.2005.12.001.
   PubMed Web of Science ®Google Scholar
• Baracaldo-Santamaría D, Ariza-Salamanca DF, Corrales-Hernández MG, Pachón-Londoño MJ, Hernandez-Duarte I, Calderon-Ospina C-A. Revisiting excitotoxicity in traumatic brain injury: from bench to bedside. Pharmaceutics. 2022;14(1):152. doi:10.3390/pharmaceutics14010152.
   PubMed Web of Science ®Google Scholar
• Wang J, Wang F, Mai D, Qu S. Molecular mechanisms of glutamate toxicity in Parkinson’s disease. Front Neurosci. 2020;14:585584. doi:10.3389/fnins.2020.585584.
   PubMed Web of Science ®Google Scholar
• Ng SY, Lee AYW. Traumatic brain injuries: pathophysiology and potential therapeutic targets. Front Cell Neurosci. 2019;13:528. doi:10.3389/fncel.2019.00528.
   PubMed Web of Science ®Google Scholar
• Khatri N, Thakur M, Pareek V, Kumar S, Sharma S, Datusalia AK. Oxidative stress: Major threat in traumatic brain injury. CNS Neurol Disord Drug Targets. 2018;17(9):689–695. doi:10.2174/1871527317666180627120501.
   PubMed Web of Science ®Google Scholar
• Lorente L. New prognostic biomarkers in patients with traumatic brain injury. Arch Trauma Res. 2015;4(4). doi:10.5812/atr.30165.
   PubMedGoogle Scholar
• Sun N, Wang H, Ma L, Lei P, Zhang Q. Ghrelin attenuates brain injury in septic mice via PI3K/Akt signaling activation. Brain Res Bull. 2016;124:278–285. doi:10.1016/j.brainresbull.2016.06.002.
   PubMed Web of Science ®Google Scholar
• Sun J, Li X, Gu X, Du H, Zhang G, Wu J, Wang F. Neuroprotective effect of hydrogen sulfide against glutamate-induced oxidative stress is mediated via the p53/glutaminase 2 pathway after traumatic brain injury. Aging (Albany NY). 2021;13(5):7180. doi:10.18632/aging.202575.
   PubMedGoogle Scholar
• Lee S, Kim Y, Li E, Park S. Ghrelin protects spinal cord motoneurons against chronic glutamate excitotoxicity by inhibiting microglial activation. The Korean Journal Of Physiology & Pharmacology. 2012;16(1):43–48. doi:10.4196/kjpp.2012.16.1.43.
   PubMed Web of Science ®Google Scholar
• Lim E, Lee S, Li E, Kim Y, Park S. Ghrelin protects spinal cord motoneurons against chronic glutamate-induced excitotoxicity via ERK1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-3β pathways. Exp Neurol. 2011;230(1):114–122. doi:10.1016/j.expneurol.2011.04.003.
   PubMed Web of Science ®Google Scholar
• García-Cáceres C, Argente-Arizón P, Díaz F, Freire-Regatillo M, Granado A, Castro-González D, Argente J, Ceballos ML, Frago LM, Dickson SL. Ghrelin regulates glucose and glutamate transporters in hypothalamic astrocytes. Sci Rep. 2016;6(1):1–15. doi:10.1038/srep23673.
   PubMedGoogle Scholar
• Zhang L, Wang H. Targeting the NF-E2-related factor 2 pathway: a novel strategy for traumatic brain injury. Mol Neurobiol. 2018;55(2):1773–1785. doi:10.1007/s12035-017-0456-z.
   PubMed Web of Science ®Google Scholar
• Kossmann T, Stahel PF, Lenzlinger PM, Redl H, Dubs RW, Trentz O, Morganti-Kossmann MC, Morganti-Kossmann MC. Interleukin-8 released into the cerebrospinal fluid after brain injury is associated with blood–brain barrier dysfunction and nerve growth factor production. J Cereb Blood Flow Metab. 1997;17(3):280–89. doi:10.1097/00004647-199703000-00005.
   PubMed Web of Science ®Google Scholar
• Wang Y, Jin S, Sonobe Y, Cheng Y, Horiuchi H, Parajuli B, Kawanokuchi J, Mizuno T, Takeuchi H, Suzumura A. Interleukin-1β induces blood–brain barrier disruption by downregulating sonic hedgehog in astrocytes. PloS One. 2014;9(10):e110024. doi:10.1371/journal.pone.0110024.
   PubMed Web of Science ®Google Scholar
• Hasturk AE, Yilmaz ER, Turkoglu E, Kertmen H, Horasanli B, Hayirli N, Erguder IB, Evirgen O. Therapeutic evaluation of interleukin 1-beta antagonist Anakinra against traumatic brain injury in rats. Ulus Travma Acil Cerrahi Derg. 2015;21(1):1–8. doi:10.5505/tjtes.2015.57894.
   PubMed Web of Science ®Google Scholar
• Tylicka M, Matuszczak E, Hermanowicz A, Dębek W, Karpińska M, Kamińska J, Koper-Lenkiewicz OM. BDNF and IL-8, but not UCHL-1 and IL-11, are markers of brain injury in children caused by mild head trauma. Brain Sci. 2020;10(10):665. doi:10.3390/brainsci10100665.
   PubMed Web of Science ®Google Scholar
• Mathur N, Mehdi SF, Anipindi M, Aziz M, Khan SA, Kondakindi H, Roth J, Wang P, Roth J. Ghrelin as an anti-sepsis peptide. Front Immunol. 2021;11:610363. doi:10.3389/fimmu.2020.610363.
   PubMed Web of Science ®Google Scholar
• Davis CK, Vemuganti R. Antioxidant therapies in traumatic brain injury. Neurochem Int. 2022;152:105255. doi:10.1016/j.neuint.2021.105255.
   PubMed Web of Science ®Google Scholar
• Yuan J, Wang D, Liu Y, Chen X, Zhang H, Shen F, Liu J, Fu J. Hydrogen-rich water attenuates oxidative stress in rats with traumatic brain injury via Nrf2 pathway. J Surg Res. 2018;228:238–246. doi:10.1016/j.jss.2018.03.024.
   PubMed Web of Science ®Google Scholar
• Lee J, Lim E, Kim Y, Li E, Park S. Ghrelin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus. J Endocrinol. 2010;205(3):263–270. doi:10.1677/JOE-10-0040.
   PubMed Web of Science ®Google Scholar
• Pekny M, Pekna M. Astrocyte intermediate filaments in CNS pathologies and regeneration. The Journal Of Pathology: A Journal Of The Pathological Society Of Great Britain And Ireland. 2004;204(4):428–437. doi:10.1002/path.1645.
   Google Scholar
• Zhang S, Wu M, Peng C, Zhao G, Gu R. GFAP expression in injured astrocytes in rats. Exp Ther Med. 2017;14(3):1905–1908. doi:10.3892/etm.2017.4760.
   PubMed Web of Science ®Google Scholar
• Loane DJ, Kumar A. Microglia in the TBI brain: the good, the bad, and the dysregulated. Exp Neurol. 2016;275:316–327. doi:10.1016/j.expneurol.2015.08.018.
   PubMed Web of Science ®Google Scholar
• Frago LM, Chowen JA. Involvement of astrocytes in mediating the central effects of ghrelin. Int J Mol Sci. 2017;18(3):536. doi:10.3390/ijms18030536.
   PubMed Web of Science ®Google Scholar
• Wang KK, Yang Z, Zhu T, Shi Y, Rubenstein R, Tyndall JA, Manley GT. An update on diagnostic and prognostic biomarkers for traumatic brain injury. Expert Rev Mol Diagn. 2018;18(2):165–180. doi:10.1080/14737159.2018.1428089.
   PubMed Web of Science ®Google Scholar
• Garin MC, Burns CM, Kaul S, Cappola AR. Clinical review: the human experience with ghrelin administration. J Clin Endocrinol Metab. 2013;98(5):1826–1837. doi:10.1210/jc.2012-4247.
   PubMed Web of Science ®Google Scholar