Objective: Hyperglycemia is one of the main risk factors for early brain injury and an outcome in patients with subarachnoid hemorrhage (SAH). Agents that regulate blood glucose levels can prevent the development of early brain injury. The present experimental study aimed to investigate the histological and anti-apoptotic effects of metformin on SAH in a rat model. Material and Methods: An SAH model was applied in 28 male Wistar rats who were randomly grouped as follows: control (Group 1), SAH alone (Group 2), SAH with hyperglycemia (Group 3), and metformin-treated SAH with hyperglycemia (Group 4). Intraperitoneal streptozotocin (50 mg/kg) was administered for 7 d to induce hyperglycemia before conducting the experiment. All rats were sacrified 72 hours after SAH. Histopathological and immunohistochemical evaluations were also conducted. Results: The thickness of the basilar artery wall was significantly different among the four groups (p=0.003). The thickness of the basilar artery wall was higher in Group 3 than in Groups 1 and 2. Blood glucose values were significantly different among the four groups (p
Keywords: Early brain injury; hyperglycemia; metformin; subarachnoid hemorrhage
Amaç: Subaraknoid kanama (SAK) sonrası gelişen hiperglisemi, erken beyin hasarı ve sağkalım için ana risk faktörlerinden biridir. Kan glukoz seviyesini düzenleyen ajanlar erken beyin hasarını önleyebilirler. Bu deneysel çalışma ratlarda SAK modelinde metforminin histolojik ve anti-apoptotik etkilerini etkilerini ortaya koymayı amaçlamıştır. Gereç ve Yöntemler: Toplam 28 adet Wistar albino cinsi rata deneysel SAK modeli uygulanarak rastgele 4 gruba ayrıldı: kontrol (Grup1), sadece SAK uygulananlar (Grup 2), SAK ve hiperglisemi geliştirilenler (Grup 3), SAK ve hiperglisemi uygulanıp metformin verilenler (Grup 4). Deney öncesi ratlarda hiperglisemi intraperitoneal streptozosin (50 mg/kg) ile sağlandı. SAK sonrası 72. saatte ratlar sakrifiye edildi. Histopatolojik ve immünohistokimyasal incelemeler yapıldı. Bulgular: Dört grupta baziller arter kalınlıklarının anlamlı farklı olarak saptandı (p=0,003). Grup 3'te baziller arter duvar kalınlıkları grup 1 ve 2'den daha fazla bulundu. Kan glukoz seviye değerleri dört grup arasında farklı olarak saptandı (p
Anahtar Kelimeler: Erken beyin hasarı; hiperglisemi; metformin; subaraknoid kanama
- Brisman JL, Song JK, Newell DW.Cerebral aneurysms. N Engl J Med. 2006;31;355(9):928-39.[Crossref] [PubMed]
- Dority JS, Oldham JS. SubarachnoidHemorrhage: an update. Anesthesiol Clin. 2016;34(3):577-600.[Crossref] [PubMed]
- Linn FH, Rinkel GJ, Algra A, vanGijn J. Incidence of subarachnoid hemorrhage: role of region, year, and rate of computedtomography: a meta-analysis. Stroke. 1996;27(4):625-9.[Crossref] [PubMed]
- Sarrafzadeh A, Haux D, Sakowitz O,Benndorf G, Herzog H, Kuechler I, et al. Acute focal neurological deficits in aneurysmalsubarachnoid hemorrhage: relation of clinical course, CT findings, and metaboliteabnormalities monitored with bedside microdialysis. Stroke. 2003;34(6):1382-8.[Crossref] [PubMed]
- Burns SK, Brewer KJ, Jenkins C,Miller S. Aneurysmal subarachnoid hemorrhage and vasospasm. AACN Adv Crit Care.2018;29(2):163-74.[Crossref] [PubMed]
- Chang CM, Su YF, Chang CZ, ChungCL, Tsai YJ, Loh JK, et al. Progesterone attenuates experimental subarachnoidhemorrhage-induced vasospasm by upregulation of endothelial nitric oxide synthase via Aktsignaling pathway. Biomed Res Int. 2014;2014:207616.[Crossref] [PubMed] [PMC]
- Frontera JA, Fernandez A, SchmidtJM, Claassen J, Wartenberg KE, Badjatia N, et al. Defining vasospasm after subarachnoidhemorrhage: what is the most clinically relevant definition? Stroke. 2009;40(6):1963-8.[Crossref] [PubMed]
- Vergouwen MD, Ilodigwe D,Macdonald RL. Cerebral infarction after subarachnoid hemorrhage contributes to poor outcomeby vasospasm-dependent and -independent effects. Stroke. 2011;42(4):924-9.[Crossref] [PubMed]
- Yuksel S, Tosun YB, Cahill J,Solaroglu I. Early brain injury following aneurysmal subarachnoid hemorrhage: emphasis oncellular apoptosis. Turk Neurosurg. 2012;22(5):529-33.[Crossref] [PubMed]
- Broderick JP, Brott TG, DuldnerJE, Tomsick T, Leach A. Initial and recurrent bleeding are the major causes of deathfollowing subarachnoid hemorrhage. Stroke. 1994;25 (7):1342-7.[Crossref] [PubMed]
- Ciurea AV, Palade C, Voinescu D, Nica DA. Subarachnoid hemorrhage andcerebral vasospasm - literature review. J Med Life. 2013;15;6(2):120-5.[PubMed] [PMC]
- Hasegawa Y, Suzuki H, Sozen T,Altay O, Zhang JH. Apoptotic mechanisms for neuronal cells in early brain injury aftersubarachnoid hemorrhage. Acta Neurochir Suppl. 2011;110(Pt 1):43-8.[Crossref] [PubMed]
- Alberti O, Becker R, Benes L,Wallenfang T, Bertalanffy H. Initial hyperglycemia as an indicator of severity of the ictusin poor-grade patients with spontaneous subarachnoid hemorrhage. Clin Neurol Neurosurg.2000;102(2):78-83.[Crossref] [PubMed]
- Beseoglu K, Steiger HJ. Elevatedglycated hemoglobin level and hyperglycemia after aneurysmal subarachnoid hemorrhage. ClinNeurol Neurosurg. 2017;163:128-32.[Crossref] [PubMed]
- Frontera JA, Fernandez A,Claassen J, Schmidt M, Schumacher HC, Wartenberg K, et al. Hyperglycemia after SAH:predictors, associated complications, and impact on outcome. Stroke. 2006;37(1):199-203.[Crossref] [PubMed]
- Ray B, Ludwig A, Yearout LK,Thompson DM, Bohnstedt BN. Stress-induced hyperglycemia after spontaneous subarachnoidhemorrhage and its role in predicting cerebrospinal fluid diversion. World Neurosurg.2017;100:208-15.[Crossref] [PubMed]
- Badjatia N, Topcuoglu MA,Buonanno FS, Smith EE, Nogueira RG, Rordorf GA, et al. Relationship between hyperglycemiaand symptomatic vasospasm after subarachnoid hemorrhage. Crit Care Med. 2005;33(7):1603-9.[Crossref] [PubMed]
- Zhao LP, Sheng XY, Zhou S, YangT, Ma LY, Zhou Y, et al. Metformin versus insulin for gestational diabetes mellitus: ameta-analysis. Br J Clin Pharmacol. 2015;80(5):1224-34.[Crossref] [PubMed] [PMC]
- Huang YH, Chung CL, Tsai HP, WuSC, Chang CZ, Chai CY, et al. Hyperglycemia aggravates cerebral vasospasm after subarachnoidhemorrhage in a rat model. Neurosurgery. 2017;1;80(5):809-15.[Crossref] [PubMed]
- Chen Y, Imai H, Ito A, Saito N. Novel modified method for injection intothe cerebrospinal fluid via the cerebellomedullary cistern in mice. Acta Neurobiol Exp(Wars). 2013;73(2):304-11.[PubMed]
- Ashabi G, Khodagholi F, Khalaj L,Goudarzvand M, Nasiri M. Activation of AMP-activated protein kinase by metformin protectsagainst global cerebral ischemia in male rats: interference of AMPK/PGC-1α pathway. MetabBrain Dis. 2014;29(1):47-58.[Crossref] [PubMed]
- Ge XH, Zhu GJ, Geng DQ, Zhang HZ,He JM, Guo AZ, et al. Metformin protects the brain against ischemia/reperfusion injurythrough PI3K/Akt1/JNK3 signaling pathways in rats. Physiol Behav. 2017;1;170:115-23.[Crossref] [PubMed]
- Kruyt ND, Biessels GJ, DeVriesJH, Luitse MJ, Vermeulen M, Rinkel GJ, et al. Hyperglycemia in aneurysmal subarachnoidhemorrhage: a potentially modifiable risk factor for poor outcome. J Cereb Blood Flow Metab.2010;30(9):1577-87.[Crossref] [PubMed] [PMC]
- Latorre JG, Chou SH, Nogueira RG,Singhal AB, Carter BS, Ogilvy CS, et al. Effective glycemic control with aggressivehyperglycemia management is associated with improved outcome in aneurysmal subarachnoidhemorrhage. Stroke. 2009;40(5):1644-52.[Crossref] [PubMed] [PMC]
- Gui J, Liu Q, Feng L. Metforminvs insulin in the management of gestational diabetes: a meta-analysis. PLoS One.2013;278(5): e64585.[Crossref] [PubMed] [PMC]
- Kruyt ND, Musters A, Biessels GJ,Devries JH, Coert BA, Vergouwen MD, et al. Beta-cell dysfunction and insulin resistanceafter subarachnoid haemorrhage. Neuroendocrinology. 2011;93(2):126-32.[Crossref] [PubMed]
- Adeva-Andany MM, Ra-al-Muí-o E,Fernández-Fernández C, Pazos-García C, Vila-Altesor M. Metabolic effects of metformin inhumans. Curr Diabetes Rev. 2019;15(4):328-39.[Crossref] [PubMed]
- Chen D, Xia D, Pan Z, Xu D, ZhouY, Wu Y, et al. Metformin protects against apoptosis and senescence in nucleus pulposuscells and ameliorates disc degeneration in vivo. Cell Death Dis. 2016;27;7(10):e2441.[Crossref] [PubMed] [PMC]
- Elmadhun NY, Sabe AA, LassalettaAD, Chu LM, Sellke FW. Metformin mitigates apoptosis in ischemic myocardium. J Surg Res.2014;192(1):50-8.[Crossref] [PubMed] [PMC]
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