Abstract
We aimed to investigate the blood brain barrier (BBB) change caused by subarachnoid hemorrhage (SAH) and to explore the molecular mechanisms of acute brain injury after SAH. The SD rat model of SAH was firstly established by endovascular filament perforation technique. The changes of regional cerebral blood flow (rCBF), BBB permeability and ultrastructure of brain tissue at different time points after SAH were respectively observed by Doppler flowmetry, evans blue extravasation and transmission electron microscopy. Meanwhile, the expression changes of Claudin-5, Occludin, Zo-1 and Caveolin-1 were detected by immunohistochemistry and Western blot. Furthermore, the expressions of Akt, P-Akt and Foxo1A were also measured by Western blot. The change of BBB permeability showed two peaks at 3 and 72 h after SAH, corresponding to the change of rCBF. The BBB tight junction opening can be observed after SAH, and the largest opening was occurred at 3 h and 72 h. There was no significant change in Caveolin-1, Claudin-5 and Akt expressions after SAH (P > 0.05), while Zo-1 and Occludin were significantly down-regulated (P < 0.05). The expression of P-Akt was obviously reduced at 30 min and then increased at 1 and 24 h, while Foxo1A was up-regulated at 1 and 24 h after SAH (P < 0.05). Down-regulated Zo-1 and Occludin, as well as Akt/FOXO signaling pathway may be involved in the regulation of tight junction opening and the BBB permeability in the early stage after SAH.
References
Aijaz S, Balda MS, Matter K (2006) Tight junctions: molecular architecture and function. Int Rev Cytol 248:261–298. doi:10.1016/S0074-7696(06)48005-0
Assari S, Laksari K, Barbe M, Darvish K Cerebral blood pressure rise during blast exposure in a rat model of blast-induced traumatic brain injury. In: ASME 2013 International Mechanical Engineering Congress and Exposition, 2013. American Society of Mechanical Engineers, pp V03AT03A016-V003AT003A016
Ayer RE, Zhang JH (2008) Oxidative stress in subarachnoid haemorrhage: significance in acute brain injury and vasospasm. Acta Neurochir Suppl 104:33–41
Bederson JB et al (2009) Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council. Am Heart Assoc Stroke 40:994–1025. doi:10.1161/STROKEAHA.108.191395
Broderick JP, Brott TG, Duldner JE, Tomsick T, Leach A (1994) Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage. Stroke 25:1342–1347
Brunet A et al (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96:857–868
Deng J et al (2012) The role of caveolin-1 in blood-brain barrier disruption induced by focused ultrasound combined with microbubbles. J Mol Neurosci: MN 46:677–687
Doczi T (1985) The pathogenetic and prognostic significance of blood-brain barrier damage at the acute stage of aneurysmal subarachnoid haemorrhage. Clinical and experimental studies. Acta Neurochir 77:110–132
Dóczi T, Joó F, Ádám G, Bozóky B, Szerdahelyi P (1986) Blood-brain barrier damage during the acute stage of subarachnoid hemorrhage, as exemplified by a new animal model. Neurosurgery 18:733–739
Endo H, Nito C, Kamada H, Yu F, Chan PH (2006) Akt/GSK3beta survival signaling is involved in acute brain injury after subarachnoid hemorrhage in rats. Stroke 37:2140–2146
Feiler S, Plesnila N, Thal SC, Zausinger S, Schöller K (2011) Contribution of matrix metalloproteinase-9 to cerebral edema and functional outcome following experimental subarachnoid hemorrhage. Cerebrovasc Dis 32:289–295
Florczak-Rzepka M, Grond-Ginsbach C, Montaner J, Steiner T (2012) Matrix metalloproteinases in human spontaneous intracerebral hemorrhage: an update. Cerebrovasc Dis 34:249–262
Fujii M, Duris K, Altay O, Soejima Y, Sherchan P, Zhang JH (2012) Inhibition of Rho kinase by hydroxyfasudil attenuates brain edema after subarachnoid hemorrhage in rats. Neurochem Int 60:327–333. doi:10.1016/j.neuint.2011.12.014
Fujimura M, Inoue T, Shimizu H, Saito A, Mugikura S, Tominaga T (2012) Efficacy of prophylactic blood pressure lowering according to a standardized postoperative management protocol to prevent symptomatic cerebral hyperperfusion after direct revascularization surgery for moyamoya disease. Cerebrovasc Dis 33:436–445
Fukunaga K, Ishigami T, Kawano T (2005) Transcriptional regulation of neuronal genes and its effect on neural functions: expression and function of forkhead transcription factors in neurons. J Pharmacol Sci 98:205–211
Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S (1993) Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 123:1777–1788
Germano A, d’Avella D, Imperatore C, Caruso G, Tomasello F (2000) Time-course of blood-brain barrier permeability changes after experimental subarachnoid haemorrhage. Acta Neurochir (Wien) 142:575–580
Greer EL, Brunet A (2005) FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 24:7410–7425. doi:10.1038/sj.onc.1209086
Haorah J, Ramirez SH, Schall K, Smith D, Pandya R, Persidsky Y (2007) Oxidative stress activates protein tyrosine kinase and matrix metalloproteinases leading to blood-brain barrier dysfunction. J Neurochem 101:566–576. doi:10.1111/j.1471-4159.2006.04393.x
Hop JW, Rinkel GJ, Algra A, van Gijn J (1997) Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review. Stroke 28:660–664
Kago T, Takagi N, Date I, Takenaga Y, Takagi K, Takeo S (2006) Cerebral ischemia enhances tyrosine phosphorylation of occludin in brain capillaries. Biochem Biophys Res Commun 339:1197–1203. doi:10.1016/j.bbrc.2005.11.133
Kahles T et al (2007) NADPH oxidase plays a central role in blood-brain barrier damage in experimental stroke. Stroke 38:3000–3006. doi:10.1161/STROKEAHA.107.489765
Kondo T, Hafezi-Moghadam A, Thomas K, Wagner DD, Kahn CR (2004) Mice lacking insulin or insulin-like growth factor 1 receptors in vascular endothelial cells maintain normal blood-brain barrier. Biochem Biophys Res Commun 317:315–320
Li D, Qu Y, Mao M, Zhang X, Li J, Ferriero D, Mu D (2009) Involvement of the PTEN-AKT-FOXO3a pathway in neuronal apoptosis in developing rat brain after hypoxia-ischemia. J Cereb Blood Flow Metab 29:1903–1913
Lohmann C, Krischke M, Wegener J, Galla HJ (2004) Tyrosine phosphatase inhibition induces loss of blood-brain barrier integrity by matrix metalloproteinase-dependent and -independent pathways. Brain Res 995:184–196
Mesiwala AH, Farrell L, Wenzel HJ, Silbergeld DL, Crum LA, Winn HR, Mourad PD (2002) High-intensity focused ultrasound selectively disrupts the blood-brain barrier in vivo. Ultrasound Med Biol 28:389–400
Schubert GA, Thome C (2008) Cerebral blood flow changes in acute subarachnoid hemorrhage. Front Biosci 13:1594–1603
Sehba FA, Bederson JB (2006) Mechanisms of acute brain injury after subarachnoid hemorrhage. Neurol Res 28:381–398
Sehba FA, Mostafa G, Friedrich V Jr, Bederson JB (2005) Acute microvascular platelet aggregation after subarachnoid hemorrhage. J Neurosurg 102:1094–1100. doi:10.3171/jns.2005.102.6.1094
Sehba FA, Friedrich V Jr, Makonnen G, Bederson JB (2007) Acute cerebral vascular injury after subarachnoid hemorrhage and its prevention by administration of a nitric oxide donor. J Neurosurg 106:321–329. doi:10.3171/jns.2007.106.2.321
Soma T, Chiba H, Kato-Mori Y, Wada T, Yamashita T, Kojima T, Sawada N (2004) Thr(207) of claudin-5 is involved in size-selective loosening of the endothelial barrier by cyclic AMP. Exp Cell Res 300:202–212
Stamatovic SM, Dimitrijevic OB, Keep RF, Andjelkovic AV (2006) Protein kinase Calpha-RhoA cross-talk in CCL2-induced alterations in brain endothelial permeability. J Biol Chem 281:8379–8388
Stamatovic SM, Keep RF, Andjelkovic AV (2008) Brain endothelial cell-cell junctions: how to “open” the blood brain barrier. Curr Neuropharmacol 6:179–192
Stevenson BR, Siliciano JD, Mooseker MS, Goodenough DA (1986) Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. J Cell Biol 103:755–766
Suarez JI, Tarr RW, Selman WR (2006) Aneurysmal subarachnoid hemorrhage. N Engl J Med 354:387–396. doi:10.1056/NEJMra052732
Tiebosch IA, van den Bergh WM, Bouts MJ, Zwartbol R, van der Toorn A, Dijkhuizen RM (2013) Progression of brain lesions in relation to hyperperfusion from subacute to chronic stages after experimental subarachnoid hemorrhage: a multiparametric MRI study. Cerebrovasc Dis 36:167–172
Ueno M (2007) Molecular anatomy of the brain endothelial barrier: an overview of the distributional features. Curr Med Chem 14:1199–1206
van Gijn J, Rinkel GJ (2001) Subarachnoid haemorrhage: diagnosis, causes and management. Brain J Neurol 124:249–278
van Gijn J, Kerr RS, Rinkel GJ (2007) Subarachnoid haemorrhage. Lancet 369:306–318. doi:10.1016/S0140-6736(07)60153-6
Voldby B, Enevoldsen EM (1982) Intracranial pressure changes following aneurysm rupture. Part 1: clinical and angiographic correlations. J Neurosurg 56:186–196
Zhan L, Wang T, Li W, Xu ZC, Sun W, Xu E (2010) Activation of Akt/FoxO signaling pathway contributes to induction of neuroprotection against transient global cerebral ischemia by hypoxic pre-conditioning in adult rats. J Neurochem 114:897–908. doi:10.1111/j.1471-4159.2010.06816.x
Zhao H, Sapolsky RM, Steinberg GK (2006) Phosphoinositide-3-kinase/akt survival signal pathways are implicated in neuronal survival after stroke. Mol Neurobiol 34:249–270
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Li, Z., Liang, G., Ma, T. et al. Blood–brain barrier permeability change and regulation mechanism after subarachnoid hemorrhage. Metab Brain Dis 30, 597–603 (2015). https://doi.org/10.1007/s11011-014-9609-1
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DOI: https://doi.org/10.1007/s11011-014-9609-1