Abstract
Subarachnoid hemorrhage is an acute life-threatening cerebrovascular disease with high socio-economic impact. The most frequent cause, the rupture of an intracerebral aneurysm, is accompanied by abrupt changes in intracerebral pressure, cerebral perfusion pressure and, consequently, cerebral blood flow. As aneurysms rupture spontaneously, monitoring of these parameters in patients is only possible with a time delay, upon hospitalization. To study alterations in cerebral perfusion immediately upon ictus, animal models are mandatory. This article addresses the points necessarily to be included in an animal project proposal according to EU directive 2010/63/EU for the protection of animals used for scientific purposes and herewith offers an insight into animal welfare aspects of using rodent models for the investigation of cerebral perfusion after subarachnoid hemorrhage. It compares surgeries, model characteristics, advantages, and drawbacks of the most-frequently used rodent models—the endovascular perforation model and the prechiasmatic and single or double cisterna magna injection model. The topics of discussing anesthesia, advice on peri- and postanesthetic handling of animals, assessing the severity of suffering the animals undergo during the procedure according to EU directive 2010/63/EU and weighing the use of these in vivo models for experimental research ethically are also presented. In conclusion, rodent models of subarachnoid hemorrhage display pathophysiological characteristics, including changes of cerebral perfusion similar to the clinical situation, rendering the models suited to study the sequelae of the bleeding. A current problem is low standardization of the models, wherefore reporting according to the ARRIVE guidelines is highly recommended.
Graphical Abstract
Animal welfare aspects of rodent models of subarachnoid hemorrhage. Rodent models for investigation of cerebral perfusion after subarachnoid hemorrhage are compared regarding surgeries and model characteristics, and 3R measures are suggested. Anesthesia is discussed, and advice given on peri- and postanesthetic handling. Severity of suffering according to 2010/63/EU is assessed and use of these in vivo models weighed ethically.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
Enquiries about data availability should be directed to the author.
References
Allen GS, Ahn HS, Preziosi TJ, Battye R, Boone SC, Chou SN, Kelly DL, Weir BK, Crabbe RA, Lavik PJ, Rosenbloom SB, Dorsey FC, Ingram CR, Mellits DE, Bertsch LA, Boisvert DPJ, Hundley MB, Johnson RK, Strom JA, Transou CR (1983) Cerebral arterial spasm—a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med 308:619–624. https://doi.org/10.1056/NEJM198303173081103
Alpdogan S, Sander T, Zhang R, Khan D, Li X, Zhou H, Li K, Nickel AC, Zheng B, Skryabin A, Schieferdecker S, Hofmann BB, Donaldson DM, Cornelius JF, Hänggi D, Muhammad S (2022) Meta-review on perforation model of subarachnoid hemorrhage in mice: filament material as a possible moderator of mortality. Transl Stroke Res C. https://doi.org/10.1007/s12975-022-01106-4
Alpdogan S, Li K, Sander T, Cornelius JF, Muhammad S (2023) Cisterna magna injection mouse model of subarachnoid hemorrhage (SAH): a systematic literature review of preclinical SAH research. J Exp Neurol 4:11–20. https://doi.org/10.33696/Neurol.4.069
Altay O, Hasegawa Y, Sherchan P, Suzuki H, Khatibi NH, Tang J, Zhang JH (2012) Isoflurane delays the development of early brain injury after subarachnoid hemorrhage through sphingosine-related pathway activation in mice. Crit Care Med 40:1908–1913. https://doi.org/10.1016/CCM.0b013e3182474bc1
Altay O, Suzuki H, Hasegawa Y, Ostrowski RP, Tang J, Zhang JH (2014) Effects of isoflurane on brain inflammation after subarachnoid hemorrhage in mice. Neurobiol Dis 62:365–371. https://doi.org/10.1016/j.nbd.2013.09.016
Ansar S, Edvinsson L (2008) Subtype activation and interaction of protein kinase C and mitogen-activated protein kinase controlling receptor expression in cerebral arteries and microvessels after subarachnoid hemorrhage. Stroke 39:185–190. https://doi.org/10.1161/STROKEAHA.107.487827
Arras M, Becker ZK, Ch H, Grosse-Siestrup BW, Küpper A, Kuhnt B (2001) Operative Eingriffe bei Versuchstieren
Arras M, Becker K, Bergadano A, Durst M, Eberspächer-Schweda E, Fleischmann T, Haberstroh J, Jirkof P, Sager M, Spadaveccia C, Zahner D (2020) Fachinformation Schmerztherapie bei Versuchstieren. pp. 1–70
Backer-Grøndahl A, Lindal S, Lorentzen MA, Eldevik P, Vorren T, Kristiansen B, Vangberg T, Ytrebø LM (2016) A new non-craniotomy model of subarachnoid hemorrhage in the pig: a pilot study. Lab Anim 50:379–389. https://doi.org/10.1177/0023677215619806
Barry CM, Helps SC, van den Heuvel C, Vink R (2011) Characterizing the role of the neuropeptide substance P in experimental subarachnoid hemorrhage. Brain Res 1389:143–151. https://doi.org/10.1016/j.brainres.2011.02.082
Becker K, Bergadano A, Eberspächer E, Haberstroh J, Henke J, Sager M, Zahner D, Arras M (2016a) Fachinformation zum Einsatz von Urethan bei Versuchen mit Nagetieren und Kaninchen. pp. 1–5
Becker K, Bergadano A, Eberspächer E, Haberstroh J, Henke J, Sager M, Zahner D, Arras M (2016b) Fachinformation zum Einsatz von α-Chloralose bei Versuchen mit Nagetieren und Kaninchen. pp. 1–7
Bederson JB, Germano IM, Guarino L (1995) Cortical blood flow and cerebral perfusion pressure in a new noncraniotomy model of subarachnoid hemorrhage in the rat. Stroke 26:1086–1092. https://doi.org/10.1161/01.STR.26.6.1086
Beg SS, Hansen-Schwartz JA, Vikman PJ, Xu C-B, Edvinsson LI (2007) Protein kinase C inhibition prevents upregulation of vascular ET(B) and 5-HT(1B) receptors and reverses cerebral blood flow reduction after subarachnoid haemorrhage in rats. J Cereb Blood Flow Metab 27:21–32. https://doi.org/10.1038/sj.jcbfm.9600313
Bendel O, Prunell G, Stenqvist A, Mathiesen T, Holmin S, Svendgaard N-A, von Euler G (2005) Experimental subarachnoid hemorrhage induces changes in the levels of hippocampal NMDA receptor subunit mRNA. Brain Res Mol Brain Res 137:119–125. https://doi.org/10.1016/j.molbrainres.2005.02.023
Brawley BW, Strandness DE, Kelly WA (1968) The biphasic response of cerebral vasospasm in experimental subarachnoid hemorrhage. J Neurosurg 28:1–8. https://doi.org/10.3171/jns.1968.28.1.0001
Busch M, Chourbaji S, Dammann P, Gerold S, Haemisch A, Jirkof P, Oehlert P, Osterkamp A, Ott S (2021) Statement of the committee for humane laboratory animal housing on single housing of mice for scientific purposes. pp. 1–11
Cai J, Sun Y, Yuan F, Chen L, He C, Bao Y, Chen Z, Lou M, Xia W, Yang GY, Ling F (2012) A novel intravital method to evaluate cerebral vasospasm in rat models of subarachnoid hemorrhage: a study with synchrotron radiation angiography. PLoS ONE 7:1–9. https://doi.org/10.1371/journal.pone.0033366
Cetas JS, Lee DR, Alkayed NJ, Wang R, Iliff JJ, Heinricher MM (2009) Brainstem control of cerebral blood flow and application to acute vasospasm following experimental subarachnoid hemorrhage. Neuroscience 163:719–779. https://doi.org/10.1016/j.neuroscience.2009.06.031
Cetas JS, McFarlane R, Kronfeld K, Smitasin P, Liu JJ, Raskin JS (2015) Brainstem opioidergic system is involved in early response to experimental SAH. Transl Stroke Res 6:140–147. https://doi.org/10.1007/s12975-014-0378-2
Chan V, Lindsay P, McQuiggan J, Zagorski B, Hill MD, O’Kelly C (2019) Declining admission and mortality rates for subarachnoid hemorrhage in Canada between 2004 and 2015. Stroke 50:181–184. https://doi.org/10.1161/STROKEAHA.118.022332
Chen S, Li Q, Wu H, Krafft PR, Wang Z, Zhang JH (2014) The harmful effects of subarachnoid hemorrhage on extracerebral organs. Biomed Res Int. https://doi.org/10.1155/2014/858496
Coelho LGBSA, Costa JMD, Silva EIPA (2016) Non-aneurysmal spontaneous subarachnoid hemorrhage: perimesencephalic versus non-perimesencephalic. Rev Bras Ter Intensiva 28:141–146. https://doi.org/10.5935/0103-507X.20160028
Conzen C, Becker K, Weiss M, Bach A, Lushina N, Steimers A (2018) The acute phase of experimental subarachnoid hemorrhage: intracranial pressure dynamics and their effect on cerebral blood flow and autoregulation. Transl Stroke Res. https://doi.org/10.1007/s12975-018-0674-3
De Rooij NK, Linn FHH, Van Der Plas JA, Algra A, Rinkel GJE (2007) Incidence of subarachnoid haemorrhage: a systematic review with emphasis on region, age, gender and time trends. J Neurol Neurosurg Psychiatry 78:1365–1372. https://doi.org/10.1136/jnnp.2007.117655
Directive 2010/63/EU (2010) of the European parliament and of the council of 22 September 2010 on the protection of animals used for scientific purposes
Donnelly J, Budohoski KP, Smielewski P, Czosnyka M (2016) Regulation of the cerebral circulation: bedside assessment and clinical implications. Crit Care 20:1–17. https://doi.org/10.1186/s13054-016-1293-6
du Sert NP, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, Emerson M, Garner P, Holgate ST, Howells DW, Karp NA, Lazic SE, Lidster K, MacCallum CJ, Macleod M, Pearl EJ, Petersen OH, Rawle F, Reynolds P, Rooney K, Sena ES, Silberberg SD, Steckler T, Würbel H (2020) The arrive guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol 18:1–12. https://doi.org/10.1371/journal.pbio.3000410
Eberspächer-Schweda E (2020) AnästhesieSkills—Perioperatives Management bei Klein-, Heim- und Großtieren, 2nd edn. Georg Thieme Verlag KG, Stuttgart
Etminan N, Chang HS, Hackenberg K, De Rooij NK, Vergouwen MDI, Rinkel GJE, Algra A (2019) Worldwide incidence of aneurysmal subarachnoid hemorrhage according to region, time period, blood pressure, and smoking prevalence in the population: a systematic review and meta-analysis. JAMA Neurol 76:588–597. https://doi.org/10.1001/jamaneurol.2019.0006
Feiler S, Friedrich B, Schöller K, Thal SC, Plesnila N (2010) Standardized induction of subarachnoid hemorrhage in mice by intracranial pressure monitoring. J Neurosci Methods 190:164–170. https://doi.org/10.1016/j.jneumeth.2010.05.005
Fisher CM, Kistler JP, Davis JM (1980) Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 6:1–9. https://doi.org/10.1097/00006123-198001000-00001
Francoeur CL, Mayer SA (2016) Management of delayed cerebral ischemia after subarachnoid hemorrhage. Crit Care 20:1–12. https://doi.org/10.1186/s13054-016-1447-6
Friedrich B, Müller F, Feiler S, Schöller K, Plesnila N (2012) Experimental subarachnoid hemorrhage causes early and long-lasting microarterial constriction and microthrombosis: an in-vivo microscopy study. J Cereb Blood Flow Metab 32:447–455. https://doi.org/10.1038/jcbfm.2011.154
Friedrich V, Bederson JB, Sehba FA (2013) Gender influences the initial impact of subarachnoid hemorrhage: an experimental investigation. PLoS ONE 8:1–11. https://doi.org/10.1371/journal.pone.0080101
Friedrich B, Michalik R, Oniszczuk A, Abubaker K, Kozniewska E, Plesnila N (2014) CO2 has no therapeutic effect on early microvasospasm after experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab. https://doi.org/10.1038/jcbfm.2014.96
Fujii M, Yan J, Rolland WB, Soejima Y, Caner B, Zhang JH (2013) Early brain injury, an evolving frontier in subarachnoid hemorrhage research. Transl Stroke Res 18:1199–1216. https://doi.org/10.1016/j.micinf.2011.07.011.Innate
Greenhalgh A, Brough D, Robinson EM, Girard S, Rothwell NJ, Allan SM (2012a) Interleukin-1 receptor antagonist is beneficial after subarachnoid haemorrhage in rat by blocking haem-driven inflammatory pathology. Dis Model Mech 5:823–833. https://doi.org/10.1242/dmm.008557
Greenhalgh AD, Rothwell NJ, Allan SM (2012b) An endovascular perforation model of subarachnoid haemorrhage in rat produces heterogeneous infarcts that increase with blood load. Transl Stroke Res 3:164–172. https://doi.org/10.1007/s12975-011-0124-y
Grüter BE, Croci D, Schöpf S, Nevzati E, D’Allonzo D, Lattmann J, Roth T, Bircher B, Muroi C, Dutilh G, Widmer HR, Plesnila N, Fandino J, Marbacher S (2020) Systematic review and meta-analysis of methodological quality in in vivo animal studies of subarachnoid hemorrhage. Transl Stroke Res 11:1175–1184. https://doi.org/10.1007/s12975-020-00801-4
Güresir E, Schuss P, Borger V, Vatter H (2015) Experimental subarachnoid hemorrhage: double cisterna magna injection rat model—assessment of delayed pathological effects of cerebral vasospasm. Transl Stroke Res 6:242–251. https://doi.org/10.1007/s12975-015-0392-z
Hansen-Schwartz J, Hoel NL, Zhou M, Xu C-B, Svendgaard NA, Edvinsson L (2003) Subarachnoid hemorrhage enhances endothelin receptor expression and function in rat cerebral arteries. Neurosurgery 52:1188–1194
Höllig A, Weinandy A, Nolte K, Clusmann H, Rossaint R, Coburn M (2015) Experimental subarachnoid hemorrhage in rats: comparison of two endovascular perforation techniques with respect to success rate, confounding pathologies and early hippocampal tissue lesion pattern. PLoS ONE 10:e0123398. https://doi.org/10.1371/journal.pone.0123398
Höllig A, Weinandy A, Liu J, Clusmann H, Rossaint R, Coburn M (2016) Beneficial properties of argon after experimental subarachnoid hemorrhage. Crit Care Med. https://doi.org/10.1097/CCM.0000000000001561
Hop JW, Rinkel GJE, Algra A, Van Gijn J (1997) Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review. Stroke 28:660–664. https://doi.org/10.1161/01.STR.28.3.660
Hop JW, Rinkel GJE, Algra A, Van Gijn J, Hemorrhage S (1999) Initial loss of consciousness and risk of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Stroke 30:2268–2271. https://doi.org/10.1161/01.STR.30.11.2268
Hubschmann OR, Kornhauser D (1980) Cortical cellular response in acute subarachnoid hemorrhage. J Neurosurg 52:456–462. https://doi.org/10.3171/jns.1980.52.4.0456
Ishikawa M, Kusaka G, Yamaguchi N, Sekizuka E, Nakadate H, Minamitani H, Shinoda S, Watanabe E (2009) Platelet and leukocyte adhesion in the microvasculature at the cerebral surface immediately after subarachnoid hemorrhage. Neurosurgery 64:546–553. https://doi.org/10.1227/01.NEU.0000337579.05110.F4
Johnston SC, Selvin S, Gress DR (1998) The burden, trends, and demographics of mortality from subarachnoid hemorrhage. Neurology 50:1413–1418. https://doi.org/10.1212/WNL.50.5.1413
Kader A (1989) Hemorrhage in Rats. Stroke 21:577–581. https://doi.org/10.1161/01.STR.21.4.577
Kiwak KJ, Moskowitz MA, Levine L (1985) Leukotriene production in gerbil brain after ischemic insult, subarachnoid hemorrhage, and concussive injury. J Neurosurg 62:865–869. https://doi.org/10.3171/jns.1985.62.6.0865
Koide M, Bonev AD, Nelson MT, Wellman GC (2012) Inversion of neurovascular coupling by subarachnoid blood depends on large-conductance Ca2+-activated K+ (BK) channels. Proc Natl Acad Sci USA 109:E1387–E1395. https://doi.org/10.1073/pnas.1121359109
Konczalla J, Vatter H, Weidauer S, Raabe A, Seifert V (2006) Alteration of the cerebrovascular function of endothelin B receptor after subarachnoidal hemorrhage in the rat. Exp Biol Med 231:1064–1068
Kooijman E, Nijboer CH, van Velthoven CTJ, Kavelaars A, Kesecioglu J, Heijnen CJ (2014) The rodent endovascular puncture model of subarachnoid hemorrhage: mechanisms of brain damage and therapeutic strategies. J Neuroinflammation 11:1–12. https://doi.org/10.1186/1742-2094-11-2
Kramer AH (2021) Critical ICP in subarachnoid hemorrhage: how high and how long? Neurocrit Care 34:714–716. https://doi.org/10.1007/s12028-021-01205-4
Kurki MI, Häkkinen SK, Frösen J, Tulamo R, Von Und Zu, Fraunberg M, Wong G, Tromp G, Niemelä M, Hernesniemi J, Jääskeläinen JE, Ylä-Herttuala S (2011) Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: an emerging regulative role of toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factors. Neurosurgery 68:1667–1675. https://doi.org/10.1227/NEU.0b013e318210f001
Kusaka G, Ishikawa M, Nanda A, Granger DN, Zhang JH (2004) Signaling pathways for early brain injury after subarachnoid hemorrhage. J Cereb Blood Flow Metab 24:916–925. https://doi.org/10.1097/01.WCB.0000125886.48838.7E
Kuwayama A, Zervas NT, Belson R, Shintani A, Pickren K (1972) A model for experimental cerebral arterial spasm. Stroke 3:49–56. https://doi.org/10.1161/01.STR.3.1.49
Kwon MS, Woo SK, Kurland DB, Yoon SH, Palmer AF, Banerjee U, Iqbal S, Ivanova S, Gerzanich V, Simard JM (2015) Methemoglobin is an endogenous Toll-like receptor 4 ligand—relevance to subarachnoid hemorrhage. Int J Mol Sci 16:5028–5046. https://doi.org/10.3390/ijms16035028
Lackner P, Vahmjanin A, Hu Q, Krafft PR, Rolland W, Zhang JH (2013) Chronic hydrocephalus after experimental subarachnoid hemorrhage. PLoS ONE 8:1–7. https://doi.org/10.1371/journal.pone.0069571
Lacy PS, Earle AM (1983) A small animal model for electrocardiographic abnormalities observed after an experimental subarachnoid hemorrhage. Stroke 14:371–377. https://doi.org/10.1161/01.STR.14.3.371
Lantigua H, Ortega-Gutierrez S, Schmidt JM, Lee K, Badjatia N, Agarwal S, Claassen J, Connolly ES, Mayer SA (2015) Subarachnoid hemorrhage: who dies, and why? Crit Care. https://doi.org/10.1186/s13054-015-1036-0
LeBlanc RH, Chen R, Selim MH, Hanafy KA (2016) Heme oxygenase-1-mediated neuroprotection in subarachnoid hemorrhage via intracerebroventricular deferoxamine. J Neuroinflammation 13:1–15. https://doi.org/10.1186/s12974-016-0709-1
Leclerc JL, Garcia JM, Diller MA, Carpenter AM, Kamat PK, Hoh BL, Doré S (2018) A comparison of pathophysiology in humans and rodent models of subarachnoid hemorrhage. Front Mol Neurosci. https://doi.org/10.3389/fnmol.2018.00071
Lee S, Stier G, Marcantonio S, Lekic T, Allard M, Martin R, Zhang J (2008) 3% hypertonic saline following subarachnoid hemorrhage in rats. Acta Neurochir Suppl 102:405–408
Lee J-Y, Sagher O, Keep R, Hua Y, Xi G (2009) Comparison of experimental rat models of early brain injury after subarachnoid hemorrhage. Neurosurgery 65:331–43. https://doi.org/10.1227/01.NEU.0000345649.78556.26
Li P, Chaudhary N, Gemmete JJ, Thompson BG, Hua Y, Xi G, Pandey AS (2016) Intraventricular injection of noncellular cerebrospinal fluid from subarachnoid hemorrhage patient into rat ventricles leads to ventricular enlargement and periventricular injury. In: Acta neurochirurgica, Supplement, pp. 331–334
Liao F, Li G, Yuan W, Chen Y, Zuo Y, Rashid K, Zhang JH, Feng H, Liu F (2016) LSKL peptide alleviates subarachnoid fibrosis and hydrocephalus by inhibiting TSP1-mediated TGF-β1 signaling activity following subarachnoid hemorrhage in rats. Exp Ther Med 12:2537–2543. https://doi.org/10.3892/etm.2016.3640
Lin N-N, Cheng C-C, Lee Y-F, Fu Y-C, Chen J-S, Ho S-P, Chiu Y-T (2013) Early activation of myocardial matrix metalloproteinases and degradation of cardiac troponin I after experimental subarachnoid hemorrhage. J Surg Res 179:e41–e48. https://doi.org/10.1016/j.jss.2012.02.008
Lindauer U, Villringer A, Dirnagl U (1993) Characterization of CBF response to somatosensory stimulation: model and influence of anesthetics. Am J Physiol 264:H1223–H1228. https://doi.org/10.1152/ajpheart.1993.264.4.H1223
Löhr M, Tzouras G, Molcanyi M, Ernestus RI, Hampl JA, Fischer JH, Sahin K, Arendt T, Härtig W (2008) Degeneration of cholinergic rat basal forebrain neurons after experimental subarachnoid hemorrhage. Neurosurgery 63:336–344. https://doi.org/10.1227/01.NEU.0000320422.54985.6D
Luo C, Yao X, Li J, He B, Liu Q, Ren H, Liang F, Li M, Lin H, Peng J, Yuan TF, Pei Z, Su H (2016) Paravascular pathways contribute to vasculitis and neuroinflammation after subarachnoid hemorrhage independently of glymphatic control. Cell Death Dis 7:1–12. https://doi.org/10.1038/cddis.2016.63
Marbacher S, Grüter B, Schöpf S, Croci D, Nevzati E, D’Alonzo D, Lattmann J, Roth T, Bircher B, Wolfert C, Muroi C, Dutilh G, Widmer HR, Fandino J (2019) Systematic review of in vivo animal models of subarachnoid hemorrhage: species, standard parameters, and outcomes. Transl Stroke Res 10:250–258. https://doi.org/10.1007/s12975-018-0657-4
Matsumura K, Kumar TP, Guddanti T, Yan Y, Blackburn SL, McBride DW (2019) Neurobehavioral deficits after subarachnoid hemorrhage in mice: sensitivity analysis and development of a new composite score. J Am Heart Assoc. https://doi.org/10.1161/JAHA.118.011699
Mees SMD, Rinkel GJE, Feigin VL, Algra A, Van Den Bergh WM, Vermeulen M, Van Gijn J (2008) Calcium antagonists for aneurysmal subarachnoid hemorrhage. Stroke 39:514–515. https://doi.org/10.1161/STROKEAHA.107.496802
Megyesi JF, Vollrath B, Cook DA, Findlay JM (2000) In vivo animal models of cerebral vasospasm: a review. Neurosurgery 46:448–460. https://doi.org/10.1097/00006123-200009000-00065
Migliorino E, Nonino F, Amici R, Tupone D, Aspide R (2023) Neurogenic fever after subarachnoid hemorrhage in animal models: a systematic review. Int J Mol Sci 24:1–14. https://doi.org/10.3390/ijms241411514
Milner E, Johnson AW, Nelson JW, Harries MD, Gidday JM, Han BH, Zipfel GJ (2015) HIF-1α mediates isoflurane-induced vascular protection in subarachnoid hemorrhage. Ann Clin Transl Neurol 2:325–337. https://doi.org/10.1002/acn3.170
Mori K, Miyazaki M, Iwata J, Yamamoto T, Nakao Y (2008) Intracisternal infusion of magnesium sulfate solution improved reduced cerebral blood flow induced by experimental subarachnoid hemorrhage in the rat. Neurosurg Rev 31:197–203. https://doi.org/10.1007/s10143-008-0122-z
Neulen A, Pantel T, Kosterhon M, Kramer A, Kunath S, Petermeyer M, Moosmann B, Lotz J, Kantelhardt SR, Ringel F, Thal SC (2019) Neutrophils mediate early cerebral cortical hypoperfusion in a murine model of subarachnoid haemorrhage. Sci Rep 9:1–10. https://doi.org/10.1038/s41598-019-44906-9
Nieuwkamp DJ, Setz LE, Algra A, Linn FH, de Rooij NK, Rinkel GJ (2009) Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis. Lancet Neurol 8:635–642. https://doi.org/10.1016/S1474-4422(09)70126-7
Nilsson OG, Lindgren A, Ståhl N, Brandt L, Säveland H (2000) Incidence of intracerebral and subarachnoid haemorrhage in southern Sweden. J Neurol Neurosurg Psychiatry 69:601–607. https://doi.org/10.1136/jnnp.69.5.601
Østergaard L, Aamand R, Karabegovic S, Tietze A, Blicher JU, Mikkelsen IK, Iversen NK, Secher N, Engedal TS, Anzabi M, Jimenez EG, Cai C, Koch KU, Naess-Schmidt ET, Obel A, Juul N, Rasmussen M, Sørensen JCH (2013) The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage. J Cereb Blood Flow Metab 33:1825–1837. https://doi.org/10.1038/jcbfm.2013.173
Ostrowski RP, Colohan ART, Zhang JH (2005) Mechanisms of hyperbaric oxygen-induced neuroprotection in a rat model of subarachnoid hemorrhage. J Cereb Blood Flow Metab 25:554–571. https://doi.org/10.1038/sj.jcbfm.9600048
Pappas AC, Koide M, Wellman GC (2015) Astrocyte Ca2+ signaling drives inversion of neurovascular coupling after subarachnoid hemorrhage. J Neurosci. https://doi.org/10.1523/JNEUROSCI.1551-15.2015
Park S, Yamaguchi M, Zhou C, Calvert JW, Tang J, Zhang JH (2004) Neurovascular protection reduces early brain injury after subarachnoid hemorrhage. Stroke 35:2412–2417. https://doi.org/10.1161/01.STR.0000141162.29864.e9
Park IS, Meno JR, Witt CE, Suttle TK, Chowdhary A, Nguyen TS, Ngai AC, Britz GW (2008) Subarachnoid hemorrhage model in the rat: modification of the endovascular filament model. J Neurosci Methods 172:195–200. https://doi.org/10.1016/j.jneumeth.2008.04.027
Petruk KC, West GR, Marriott MR, McIntyre JW, Overton TR, Weib BK (1972) Cerebral blood flow following induced subarachnoid hemorrhage in the monkey. J Neurosurg 37:316–324. https://doi.org/10.3171/jns.1972.37.3.0316
Pinkernell S, Becker K, Lindauer U (2016) Severity assessment and scoring for neurosurgical models in rodents. Lab Anim 50:442–452. https://doi.org/10.1177/0023677216675010
Prunell GF, Mathiesen T, Svendgaard N-A (2002) A new experimental model in rats for study of the pathophysiology of subarachnoid hemorrhage. NeuroReport 13:2553–2556. https://doi.org/10.1097/01.wnr.0000052320.62862.37
Prunell GF, Mathiesen T, Diemer NH, Svendgaard N-A (2003) Experimental subarachnoid hemorrhage: subarachnoid blood volume, mortality rate, neuronal death, cerebral blood flow, and perfusion pressure in three different rat models. Neurosurgery 52:165–176. https://doi.org/10.1097/00006123-200301000-00022
Prunell GF, Svendgaard N-A, Alkass K, Mathiesen T (2005) Delayed cell death related to acute cerebral blood flow changes following subarachnoid hemorrhage in the rat brain. J Neurosurg 102:1046–1054. https://doi.org/10.3171/jns.2005.102.6.1046
Rinkel GJE, van Gijn J, Wijdicks EF (1993) Subarachnoid hemorrhage without detectable aneurysm. Stroke 24:1403–1409. https://doi.org/10.1161/01.str.24.9.1403
Rohrer B (2008) Untersuchung von Hämoglobin-Deoxygenierungs-abhängigen Mechanismen der neurovaskulären Kopplung im cerebralen Kortex der Ratte. Dissertation, Freie Universität Berlin
Rowe RK, Harrison JL, Thomas TC, Pauly JR, Adelson PD, Lifshitz J (2013) Using anesthetics and analgesics in experimental traumatic brain injury. Lab Anim (NY) 42:286–291. https://doi.org/10.1038/laban.257
Sabri M, Lass E, MacDonald RL (2013) Early brain injury: a common mechanism in subarachnoid hemorrhage and global cerebral ischemia. Stroke Res Treat. https://doi.org/10.1155/2013/394036
Saito A, Kamii H, Kato I, Takasawa S, Kondo T, Chan PH, Okamoto H, Yoshimoto T (2001) Transgenic CuZn-superoxide dismutase inhibits NO synthase induction in experimental subarachnoid hemorrhage. Stroke 32:1652–1657. https://doi.org/10.1161/01.str.32.7.1652
Satoh M, Date I, Nakajima M, Takahashi K (2001) Inhibition of poly(ADP-Ribose) polymerase attenuates cerebral vasospasm after subarachnoid hemorrhage in rabbits. Stroke 32:225–231. https://doi.org/10.1161/01.STR.32.1.225
Schubert GA, Poli S, Mendelowitsch A, Schilling L, Thomé C (2008a) Hypothermia reduces early hypoperfusion and metabolic alterations during the acute phase of massive subarachnoid hemorrhage: a laser-Doppler-flowmetry and microdialysis study in rats. J Neurotrauma 25:539–548. https://doi.org/10.1089/neu.2007.0500
Schubert GA, Poli S, Schilling L, Heiland S, Thomé C (2008b) Hypothermia reduces cytotoxic edema and metabolic alterations during the acute phase of massive SAH: a diffusion-weighted imaging and spectroscopy study in rats. J Neurotrauma 25:841–852. https://doi.org/10.1089/neu.2007.0443
Schubert GA, Seiz M, Hegewald AA, Manville J, Thomé C (2009) Acute hypoperfusion immediately after subarachnoid hemorrhage: a xenon contrast-enhanced CT study. J Neurotrauma 26:2225–2231. https://doi.org/10.1089/neu.2009.0924
Schubert GA, Seiz M, Hegewald AA, Manville J, Thomé C (2011) Hypoperfusion in the acute phase of subarachnoid hemorrhage. Acta Neurochir Suppl 110:35–38. https://doi.org/10.1007/978-3-7091-0353-1_6
Schwartz AY, Masago A, Sehba FA, Bederson JB (2000) Experimental models of subarachnoid hemorrhage in the rat: a refinement of the endovascular filament model. J Neurosci Methods 96:161–167. https://doi.org/10.1016/S0165-0270(00)00156-4
Sehba FA, Mostafa G, Knopman J, Friedrich V, Bederson JB (2004) Acute alterations in microvascular basal lamina after subarachnoid hemorrhage. J Neurosurg 101:633–640. https://doi.org/10.3171/jns.2004.101.4.0633
Sehba FA, Hou J, Pluta RM, Zhang JH (2012) The importance of early brain injury after subarachnoid hemorrhage. Prog Neurobiol 97:14–37. https://doi.org/10.1016/j.pneurobio.2012.02.003
Sheng H, Spasojevic I, Tse HM, Jung JY, Hong J, Zhang Z, Piganelli JD, Batinic-Haberle I, Warner DS (2011) Neuroprotective efficacy from a lipophilic redox-modulating Mn(III) N-hexylpyridylporphyrin, MnTnHex-2-PyP: rodent models of ischemic stroke and subarachnoid hemorrhage. J Pharmacol Exp Ther 338:906–916. https://doi.org/10.1124/jpet.110.176701
Springborg JB, Ma X, Rochat P, Knudsen GM, Amtorp O, Paulson OB, Juhler M, Olsen NV (2002) A single subcutaneous bolus of erythropoietin normalizes cerebral blood flow autoregulation after subarachnoid haemorrhage in rats. Br J Pharmacol 135:823–829. https://doi.org/10.1038/sj.bjp.0704521
Steinmann J, Hartung B, Bostelmann R, Kaschner M, Karadag C, Muhammad S, Li L, Büttner A, Petridis AK (2020) Rupture of intracranial aneurysms in patients with blunt head trauma: review of the literature. Clin Neurol Neurosurg. https://doi.org/10.1016/j.clineuro.2020.106208
Sun Y, Shen Q, Watts LT, Muir ER, Huang S, Yang G-Y, Suarez JI, Duong TQ (2016) Multimodal MRI characterisation of experimental subarachnoid hemorrhage. Neuroscience 316:53–62. https://doi.org/10.1016/j.neuroscience.2015.12.027
Suwatcharangkoon S, Meyers E, Falo C, Schmidt JM, Agarwal S, Claassen J, Mayer SA (2016) Loss of consciousness at onset of subarachnoid hemorrhage as an important marker of early brain injury. JAMA Neurol 73:28–35. https://doi.org/10.1001/jamaneurol.2015.3188
Takeuchi K, Renic M, Bohman QC, Harder DR, Miyata N, Roman RJ (2005) Reversal of delayed vasospasm by an inhibitor of the synthesis of 20-HETE. Am J Physiol Hear Circ Physiol 289:2203–2211. https://doi.org/10.1152/ajpheart.00556
Takeuchi K, Miyata N, Renic M, Harder DR, Roman RJ (2006) Hemoglobin, NO, and 20-HETE interactions in mediating cerebral vasoconstriction following SAH. Am J Physiol Regul Integr Comp Physiol 290:R84–R89. https://doi.org/10.1152/ajpregu.00445.2005
Titova E, Ostrowski RP, Zhang JH, Tang J (2009) Experimental models of subarachnoid hemorrhage for studies of cerebral vasospasm. Neurol Res 31:568–581. https://doi.org/10.1179/174313209X382412
Tromp G, Weinsheimer S, Ronkainen A, Kuivaniemi H (2014) Molecular basis and genetic predisposition to intracranial aneurysm. Ann Med 46:597–606. https://doi.org/10.3109/07853890.2014.949299
Tso MK, MacDonald RL (2013) Acute microvascular changes after subarachnoid hemorrhage and transient global cerebral ischemia. Stroke Res Treat. https://doi.org/10.1155/2013/425281
Umansky F, Kaspi T, Shalit MN (1983) Regional cerebral blood flow in the acute stage of experimentally induced subarachnoid hemorrhage. J Neurosurg 58:210–216. https://doi.org/10.3171/jns.1983.58.2.0210
van Gijn J, Kerr RS, Rinkel GJE (2007) Subarachnoid haemorrhage. Lancet (London, England) 369:306–318. https://doi.org/10.1016/S0140-6736(07)60153-6
Veelken JA, Laing RJC, Jakubowski J (1995) The sheffield model of subarachnoid hemorrhage in rats. Stroke 26:1279–1283. https://doi.org/10.1161/01.str.26.7.1279
Visser-Meily JMA, Rhebergen ML, Rinkel GJE, Van Zandvoort MJ, Post MWM (2009) Long-term health-related quality of life after aneurysmal subarachnoid hemorrhage relationship with psychological symptoms and personality characteristics. Stroke 40:1526–1529. https://doi.org/10.1161/STROKEAHA.108.531277
Wang Z, Wu L, You W, Ji C, Chen G (2013) Melatonin alleviates secondary brain damage and neurobehavioral dysfunction after experimental subarachnoid hemorrhage: possible involvement of TLR4-mediated inflammatory pathway. J Pineal Res 55:399–408. https://doi.org/10.1111/jpi.12087
Warner L, Bach-Hagemann A, Albanna W, Clusmann H, Schubert GA, Lindauer U, Conzen-Dilger C (2022) Vascular reactivity to hypercapnia is impaired in the cerebral and retinal vasculature in the acute phase after experimental subarachnoid hemorrhage. Front Neurol 12:1–12. https://doi.org/10.3389/fneur.2021.757050
Wartenberg KE, Mayer SA (2010) Medical complications after subarachnoid hemorrhage. Neurosurg Clin N Am 21:325–338. https://doi.org/10.1016/j.nec.2009.10.012
Wellman GC, Koide M (2013) Impact of subarachnoid hemorrhage on parenchymal arteriolar function. Acta Neurochir Suppl 115:1–5. https://doi.org/10.1007/978-3-7091-1192-5
Westermaier T, Jauss A, Eriskat J, Kunze E, Roosen K (2009a) Acute vasoconstriction: decrease and recovery of cerebral blood flow after various intensities of experimental subarachnoid hemorrhage in rats. J Neurosurg 110:996–1002. https://doi.org/10.3171/2008.8.JNS08591
Westermaier T, Jauss A, Eriskat J, Kunze E, Roosen K (2009b) Time-course of cerebral perfusion and tissue oxygenation in the first 6 h after experimental subarachnoid hemorrhage in rats. J Cereb Blood Flow Metab 29:771–779. https://doi.org/10.1038/jcbfm.2008.169
Xiong Y, Mahmood A, Chopp M (2013) Animal models of traumatic brain injury. Nat Rev Neurosci 14:128–142. https://doi.org/10.1038/nrn3407
Zhang D, Zhang H, Hao S, Yan H, Zhang Z, Hu Y, Zhuang Z, Li W, Zhou M, Li K, Hang C (2016) Akt specific activator SC79 protects against early brain injury following subarachnoid hemorrhage. ACS Chem Neurosci 7:710–718. https://doi.org/10.1021/acschemneuro.5b00306
Zhuang Z, Zhao X, Wu Y, Huang R, Zhu L, Zhang Y, Shi J (2011) The anti-apoptotic effect of PI3K-Akt signaling pathway after subarachnoid hemorrhage in rats. Ann Clin Lab Sci 41:364–372
Acknowledgements
Thanks to Inga Brüsch, PhD, Dipl. ECLAM, for valuable insights into handling of laboratory animal welfare legislation throughout the European union, and to Emily Fillion, BSc., for proofreading the manuscript.
Funding
No funds, grants, or other support was received.
Author information
Authors and Affiliations
Contributions
KB conducted conceptualization, literature search, analysis, prepared tables and drafted the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The author has no competing interests to declare that are relevant to the content of this article.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Becker, K. Animal Welfare Aspects in Planning and Conducting Experiments on Rodent Models of Subarachnoid Hemorrhage. Cell Mol Neurobiol 43, 3965–3981 (2023). https://doi.org/10.1007/s10571-023-01418-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-023-01418-5