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Vanillic acid attenuates cerebral hyperemia, blood-brain barrier disruption and anxiety-like behaviors in rats following transient bilateral common carotid occlusion and reperfusion

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Abstract

Transient bilateral common carotid artery occlusion (tBCCAO), followed by reperfusion, is a model of transient global hypoperfusion. In the present study we aimed to investigate the probable effects of Vanillic acid (VA) on some physiological parameters including cerebral hyperemia, blood-brain barrier (BBB) disruption, anxiety behaviors and neurological deficits induced by bilateral occlusion of the common carotid arteries and reperfusion (BCCAO/R) in rats. Rats were randomly divided into four groups; Sham, BCCAO/R, VA and VA+ BCCAO/R. Chronic cerebral hypoperfusion was induced after 2 weeks of pretreatment by VA. Subsequently, sensorimotor scores, elevated plus maze tests, cerebral hyperemia, and BBB disruption were evaluated 72 h after 30 min of BCCAO. Pretreatment of rats by VA improved sensory motor signs, anxiolytic behavior in BCCAO/R rats compared with untreated rats (p < 0.05). Further, VA attenuated reactive hyperemia and BBB disruption in BCCAO/R rats compared with untreated rats (p < 0.01). To our knowledge, this study is the first to reveal VA could attenuate reactive hyperemia and improve BBB disruption following BCCAO/R, and could improve neurological scores and anxiety like behaviors in this model of cerebral hypoperfusion. These results suggest that VA could be a promising pretreatment agent in cerebral hypoperfusion.

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References

  • Aronsson ÅF, Spulber S, Popescu LM, Winblad B, Post C, Oprica M, Schultzberg M (2006) α-Melanocyte-stimulating hormone is neuroprotective in rat global cerebral ischemia. Neuropeptides 40:65–75

    Article  CAS  Google Scholar 

  • Badavi M, Khoshbaten A, Hajizadeh S (2000) Decreased response of rat knee joint blood vessels to phenylephrine in chronic inflammation: involvement of nitric oxide. Exp Physiol 85:49–55

    Article  PubMed  CAS  Google Scholar 

  • Belayev L, Busto R, Ikeda M, Rubin LL, Kajiwara A, Morgan L, Ginsberg MD (1998) Protection against blood–brain barrier disruption in focal cerebral ischemia by the type IV phosphodiesterase inhibitor BBB022: a quantitative study. Brain Res 787:277–285

    Article  PubMed  CAS  Google Scholar 

  • Calixto-Campos C s, Carvalho TT, Hohmann MS, Pinho-Ribeiro FA, Fattori V, Manchope MF, Zarpelon AC, Baracat MM, Georgetti SR, Casagrande R (2015) Vanillic acid inhibits inflammatory pain by inhibiting neutrophil recruitment, oxidative stress, cytokine production, and NFκB activation in mice. J Nat Prod 78:1799–1808

    Article  PubMed  CAS  Google Scholar 

  • Chandler MJ, DeLeo J, Carney JM (1985) An unanesthetized-gerbil model of cerebral ischemia-induced behavioral changes. J Pharmacol Methods 14:137–146

    Article  PubMed  CAS  Google Scholar 

  • Chen D, Tang J, Khatibi NH, Zhu M, Li Y, Wang C, Jiang R, Tu L, Wang S (2011) Treatment with Z-ligustilide, a component of Angelica sinensis, reduces brain injury after a subarachnoid hemorrhage in rats. J Pharmacol Exp Ther 337:663–672

    Article  PubMed  CAS  Google Scholar 

  • Cheng C-Y, Su S-Y, Tang N-Y, Ho T-Y, Chiang S-Y, Hsieh C-L (2008) Ferulic acid provides neuroprotection against oxidative stress-related apoptosis after cerebral ischemia/reperfusion injury by inhibiting ICAM-1 mRNA expression in rats. Brain Res 1209:136–150

    Article  PubMed  CAS  Google Scholar 

  • Cho J-Y, Kim I-S, Jang Y-H, Kim A-R, Lee S-R (2006) Protective effect of quercetin, a natural flavonoid against neuronal damage after transient global cerebral ischemia. Neurosci Lett 404:330–335

    Article  PubMed  CAS  Google Scholar 

  • Coyle P, Panzenbeck MJ (1990) Collateral development after carotid artery occlusion in Fischer 344 rats. Stroke 21:316–321

    Article  PubMed  CAS  Google Scholar 

  • Delaquis P, Stanich K, Toivonen P (2005) Effect of pH on the inhibition of Listeria spp. by vanillin and vanillic acid. J. Food Prot 68:1472–1476

    Article  CAS  Google Scholar 

  • Dianat, M., G. R. Hamzavi, M. Badavi and A. Samarbaf-zadeh (2015) Effect of vanillic acid on ischemia-reperfusion of isolated rat heart: Hemodynamic parameters and infarct size assays

  • Dianat M, Radmanesh E, Badavi M, Mard SA, Goudarzi G (2016) Disturbance effects of PM10 on iNOS and eNOS mRNA expression levels and antioxidant activity induced by ischemia–reperfusion injury in isolated rat heart: protective role of vanillic acid. Environ Sci Pollut Res 23:5154–5165

    Article  CAS  Google Scholar 

  • Farbood Y, Sarkaki A, Khalaj L, Khodagholi F, Badavi M, Ashabi G (2015) Targeting Adenosine Monophosphate-Activated Protein Kinase by Metformin Adjusts Post-Ischemic Hyperemia and Extracellular Neuronal Discharge in Transient Global Cerebral Ischemia. Microcirculation 22:534–541

    Article  PubMed  CAS  Google Scholar 

  • Farkas E, Luiten PG, Bari F (2007) Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev 54:162–180

    Article  PubMed  CAS  Google Scholar 

  • Garcia JH, Wagner S, Liu K-F, Hu X-j (1995) Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Stroke 26:627–635

    Article  PubMed  CAS  Google Scholar 

  • Hori E, Uwano T, Tamura R, Miyake N, Nishijo H, Ono T (2002) Effects of a novel arginine-vasopressin derivative, NC-1900, on the spatial memory impairment of rats with transient forebrain ischemia. Cogn Brain Res 13:1–15

    Article  CAS  Google Scholar 

  • Hori M, Kitakaze M (1991) Adenosine, the heart, and coronary circulation. Hypertension 18:565–574

    Article  PubMed  CAS  Google Scholar 

  • Iwasaki Y, Ito S, Suzuki M, Nagahori T, Yamamoto T, Konno H (1989) Forebrain ischemia induced by temporary bilateral common carotid occlusion in normotensive rats. J Neurol Sci 90:155–165

    Article  PubMed  CAS  Google Scholar 

  • Jian H, Yi-Fang W, Qi L, Xiao-Song H, Gui-Yun Z (2013) Cerebral blood flow and metabolic changes in hippocampal regions of a modified rat model with chronic cerebral hypoperfusion. Acta Neurol Belg 113:313–317

    Article  PubMed  Google Scholar 

  • Jiang J, Wang W, Sun YJ, Hu M, Li F, Zhu DY (2007) Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing blood–brain barrier damage. Eur J Pharmacol 561:54–62

    Article  PubMed  CAS  Google Scholar 

  • Kam A, Li KM, Razmovski-Naumovski V, Nammi S, Chan K, Li Y, Li GQ (2012) The protective effects of natural products on blood-brain barrier breakdown. Curr Med Chem 19:1830–1845

    Article  PubMed  CAS  Google Scholar 

  • Khaksari M, Mahmmodi R, Shahrokhi N, Shabani M, Joukar S, Aqapour M (2013) The effects of shilajit on brain edema, intracranial pressure and neurologic outcomes following the traumatic brain injury in rat. Iranian J Basic Med Scie 16:858–864

    Google Scholar 

  • Khoshnam S, Sarkaki A, Khorsandi L, Winlow W, Badavi M, Moghaddam H, Farbooda Y (2017a) Vanillic acid attenuates effects of transient bilateral common carotid occlusion and reperfusion in rats. Biomed Pharmacotherapy = Biomed Pharmacotherapie 96:667

    Article  CAS  Google Scholar 

  • Khoshnam SE, Winlow W, Farbood Y, Moghaddam HF, Farzaneh M (2017b) Emerging Roles of microRNAs in Ischemic Stroke: As Possible Therapeutic Agents. J Stroke 19:166

    Article  PubMed  PubMed Central  Google Scholar 

  • Khoshnam, S. E., W. Winlow and M. Farzaneh (2017c) The Interplay of MicroRNAs in the Inflammatory Mechanisms Following Ischemic Stroke. Journal of Neuropathology & Experimental Neurology:nlx036

  • Khoshnam, S. E., W. Winlow, M. Farzaneh, Y. Farbood and H. F. Moghaddam (2017d) Pathogenic mechanisms following ischemic stroke. Neurological Sciences:1–20

  • Kim M-C, Kim S-J, Kim D-S, Jeon Y-D, Park SJ, Lee HS, Um J-Y, Hong S-H (2011) Vanillic acid inhibits inflammatory mediators by suppressing NF-κB in lipopolysaccharide-stimulated mouse peritoneal macrophages. Immunopharmacol Immunotoxicol 33:525–532

    Article  PubMed  CAS  Google Scholar 

  • Kim S-J, Kim M-C, Um J-Y, Hong S-H (2010) The beneficial effect of vanillic acid on ulcerative colitis. Molecules 15:7208–7217

    Article  PubMed  CAS  Google Scholar 

  • Koh P-O (2012) Ferulic acid modulates nitric oxide synthase expression in focal cerebral ischemia. Lab Animal Res 28:273–278

    Article  Google Scholar 

  • Lapi D, Marchiafava P, Colantuoni A (2008) Pial microvascular responses to transient bilateral common carotid artery occlusion: effects of hypertonic glycerol. J Vasc Res 45:89–102

    Article  PubMed  CAS  Google Scholar 

  • Lapi, D., S. Vagnani, G. Pignataro, E. Esposito, M. Paterni and A. Colantuoni (2012a) Protective effects of quercetin on rat pial microvascular changes during transient bilateral common carotid artery occlusion and reperfusion. Front. Physiol 3

  • Lapi, D., S. Vagnani, G. Pignataro, E. Esposito, M. Paterni and A. Colantuoni (2012b) Rat pial microvascular responses to transient bilateral common carotid artery occlusion and reperfusion: quercetin’s mechanism of action. Front. Physiol 3

  • Latour LL, Kang DW, Ezzeddine MA, Chalela JA, Warach S (2004) Early blood–brain barrier disruption in human focal brain ischemia. Ann Neurol 56:468–477

    Article  PubMed  Google Scholar 

  • Leal L, Pierdoná T, Góes J, Fonsêca K, Canuto K, Silveira E, Bezerra A, Viana G (2011) A comparative chemical and pharmacological study of standardized extracts and vanillic acid from wild and cultivated Amburana cearensis AC Smith. Phytomedicine 18:230–233

    Article  PubMed  CAS  Google Scholar 

  • Li H, Wang J, Wang P, Rao Y, Chen L (2016) Resveratrol reverses the synaptic plasticity deficits in a chronic cerebral hypoperfusion rat model. J Stroke Cerebrovasc Dis 25:122–128

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Tang G, Li Y, Wang Y, Chen X, Gu X, Zhang Z, Wang Y, Yang G-Y (2014) Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion. J Neuroinflammation 11:177

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Menard J, Treit D (1998) The septum and the hippocampus differentially mediate anxiolytic effects of R (+)-8-OH-DPAT. Behav Pharmacol 9:93–101

    PubMed  CAS  Google Scholar 

  • Milot MR, Plamondon H (2009) Time-dependent effects of global cerebral ischemia on anxiety, locomotion, and habituation in rats. Behav Brain Res 200:173–180

    Article  PubMed  Google Scholar 

  • O'Connor CA, Cernak I, Vink R (2005) Both estrogen and progesterone attenuate edema formation following diffuse traumatic brain injury in rats. Brain Res 1062:171–174

    Article  PubMed  CAS  Google Scholar 

  • Onetti Y, Dantas AP, Pérez B, Cugota R, Chamorro A, Planas AM, Vila E, Jiménez-Altayó F (2015) Middle cerebral artery remodeling following transient brain ischemia is linked to early postischemic hyperemia: a target of uric acid treatment. Am J Phys Heart Circ Phys 308:H862–H874

    CAS  Google Scholar 

  • Pérez-Asensio FJ, De la Rosa X, Jiménez-Altayó F, Gorina R, Martínez E, Messeguer À, Vila E, Chamorro À, Planas AM (2010) Antioxidant CR-6 protects against reperfusion injury after a transient episode of focal brain ischemia in rats. J Cereb Blood Flow Metab 30:638–652

    Article  PubMed  CAS  Google Scholar 

  • Pietrelli A, Lopez-Costa J, Goni R, Brusco A, Basso N (2012) Aerobic exercise prevents age-dependent cognitive decline and reduces anxiety-related behaviors in middle-aged and old rats. Neuroscience 202:252–266

    Article  PubMed  CAS  Google Scholar 

  • Pillow, B. H. and J. H. Flavell (1985) Intellectual realism: The role of children's interpretations of pictures and perceptual verbs. Child Dev :664–670

  • Preitner F, Muzzin P, Revelli JP, Seydoux J, Galitzky J, Berlan M, Lafontan M, Giacobino JP (1998) Metabolic response to various β-adrenoceptor agonists in β3-adrenoceptor knockout mice: Evidence for a new β-adrenergic receptor in brown adipose tissue. Br J Pharmacol 124:1684–1688

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Prince PSM, Rajakumar S, Dhanasekar K (2011) Protective effects of vanillic acid on electrocardiogram, lipid peroxidation, antioxidants, proinflammatory markers and histopathology in isoproterenol induced cardiotoxic rats. Eur J Pharmacol 668:233–240

    Article  CAS  Google Scholar 

  • Pun PB, Lu J, Moochhala S (2009) Involvement of ROS in BBB dysfunction. Free Radic Res 43:348–364

    Article  PubMed  CAS  Google Scholar 

  • Quartu M, Serra MP, Boi M, Pillolla G, Melis T, Poddighe L, Del Fiacco M, Falconieri D, Carta G, Murru E (2012) Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion. Lipids Health Dis 11:8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rosenberg GA (2012) Neurological diseases in relation to the blood–brain barrier. J Cereb Blood Flow Metab 32:1139–1151

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sarti C, Pantoni L, Bartolini L, Inzitari D (2002a) Cognitive impairment and chronic cerebral hypoperfusion: what can be learned from experimental models. J Neurol Sci 203:263–266

    Article  PubMed  Google Scholar 

  • Sarti C, Pantoni L, Bartolini L, Inzitari D (2002b) Persistent impairment of gait performances and working memory after bilateral common carotid artery occlusion in the adult Wistar rat. Behav Brain Res 136:13–20

    Article  PubMed  Google Scholar 

  • Shlosberg D, Benifla M, Kaufer D, Friedman A (2010) Blood–brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat Rev Neurol 6:393–403

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Singh JCH, Kakalij RM, Kshirsagar RP, Kumar BH, Komakula SSB, Diwan PV (2015) Cognitive effects of vanillic acid against streptozotocin-induced neurodegeneration in mice. Pharm Biol 53:630–636

    Article  PubMed  CAS  Google Scholar 

  • Takata F, Dohgu S, Matsumoto J, Machida T, Kaneshima S, Matsuo M, Sakaguchi S, Takeshige Y, Yamauchi A, Kataoka Y (2013) Metformin induces up-regulation of blood–brain barrier functions by activating AMP-activated protein kinase in rat brain microvascular endothelial cells. Biochem Biophys Res Commun 433:586–590

    Article  PubMed  CAS  Google Scholar 

  • Tsapenko, M., M. Weber, A. Moser, M. Keupp, W. Timmermann, S. Debus, A. Thiede and H. Henrich (2001) Restoration of blood circulation in reperfusion of ischemic tissues. Klin Khir :45–47

  • Ulrich PT, Kroppenstedt S, Heimann A, Kempski O (1998) Laser-Doppler scanning of local cerebral blood flow and reserve capacity and testing of motor and memory functions in a chronic 2-vessel occlusion model in rats. Stroke 29:2412–2420

    Article  PubMed  CAS  Google Scholar 

  • Urquiaga I, Leighton F (2000) Plant polyphenol antioxidants and oxidative stress. Biol Res 33:55–64

    Article  PubMed  CAS  Google Scholar 

  • Winter B, Juckel G, Viktorov I, Katchanov J, Gietz A, Sohr R, Balkaya M, Hörtnagl H, Endres M (2005) Anxious and hyperactive phenotype following brief ischemic episodes in mice. Biol Psychiatry 57:1166–1175

    Article  PubMed  Google Scholar 

  • Xu X, Li Z, Yang Z, Zhang T (2012) Decrease of synaptic plasticity associated with alteration of information flow in a rat model of vascular dementia. Neuroscience 206:136–143

    Article  PubMed  CAS  Google Scholar 

  • Yanpallewar S, Hota D, Rai S, Kumar M, Acharya S (2004) Nimodipine attenuates biochemical, behavioral and histopathological alterations induced by acute transient and long-term bilateral common carotid occlusion in rats. Pharmacol Res 49:143–150

    Article  PubMed  CAS  Google Scholar 

  • Zhao H, Steinberg GK, Sapolsky RM (2007) General versus specific actions of mild-moderate hypothermia in attenuating cerebral ischemic damage. J Cereb Blood Flow Metab 27:1879–1894

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This paper was extracted as a part of Seyed Esmaeil Khoshnam’s Ph.D. thesis. The study was financially supported by research affairs of Ahvaz Jundishapur University of Medical Sciences (Grant No. APRC-95-17). Furthermore, the authors would especially like to thank Professor William Winlow for outstanding editing and proof reading.

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Correspondence to Seyed Esmaeil Khoshnam or Yaghoob Farbood.

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Khoshnam, S.E., Farbood, Y., Fathi Moghaddam, H. et al. Vanillic acid attenuates cerebral hyperemia, blood-brain barrier disruption and anxiety-like behaviors in rats following transient bilateral common carotid occlusion and reperfusion. Metab Brain Dis 33, 785–793 (2018). https://doi.org/10.1007/s11011-018-0187-5

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