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Current Neuropharmacology


ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Transient Opening of the Blood-Brain Barrier by Vasoactive Peptides to Increase CNS Drug Delivery: Reality Versus Wishful Thinking?

Author(s): Matthew A. Smith-Cohn*, Nicholas B. Burley and Stuart A. Grossman*

Volume 20, Issue 7, 2022

Published on: 11 May, 2022

Page: [1383 - 1399] Pages: 17

DOI: 10.2174/1570159X20999220131163504

Price: $65


Background: The blood-brain barrier inhibits the central nervous system penetration of 98% of small molecule drugs and virtually all biologic agents, which has limited progress in treating neurologic disease. Vasoactive peptides have been shown in animal studies to transiently disrupt the blood-brain barrier and regadenoson is currently being studied in humans to determine if it can improve drug delivery to the brain. However, many other vasoactive peptides could potentially be used for this purpose.

Methods: We performed a review of the literature evaluating the physiologic effects of vasoactive peptides on the vasculature of the brain and systemic organs. To assess the likelihood that a vasoactive peptide might transiently disrupt the blood-brain barrier, we devised a four-tier classification system to organize the available evidence.

Results: We identified 32 vasoactive peptides with potential blood-brain barrier permeabilityaltering properties. To date, none of these are shown to open the blood-brain barrier in humans. Twelve vasoactive peptides increased blood-brain barrier permeability in rodents. The remaining 20 had favorable physiologic effects on blood vessels but lacked specific information on permeability changes to the blood-brain barrier.

Conclusion: Vasoactive peptides remain an understudied class of drugs with the potential to increase drug delivery and improve treatment in patients with brain tumors and other neurologic diseases. Dozens of vasoactive peptides have yet to be formally evaluated for this important clinical effect. This narrative review summarizes the available data on vasoactive peptides, highlighting agents that deserve further in vitro and in vivo investigations.

Keywords: Blood-brain barrier, vasoactive peptides, pharmacokinetics, neurology, neuro-oncology, drug delivery, oncology, metastasis.

Graphical Abstract
Pardridge WM. Treatment of Alzheimer’s disease and blood-brain barrier drug delivery. Pharmaceuticals (Basel) 2020; 13(11): 394.
[] [PMID: 33207605]
Smith-Cohn MA, Celiku O, Gilbert MR. Molecularly targeted clinical trials. Neurosurg Clin N Am 2021; 32(2): 191-210.
[] [PMID: 33781502]
O’Connell K, Romo CG, Grossman SA. Brain metastases as a first site of recurrence in patients receiving chemotherapy with con-trolled systemic cancer: A critical but under-recognized clinical scenario. Curr Treat Options Neurol 2019; 21(11): 55.
[] [PMID: 31707548]
Krueger M, Mages B, Hobusch C, Michalski D. Endothelial edema precedes blood-brain barrier breakdown in early time points after experimental focal cerebral ischemia. Acta Neuropathol Commun 2019; 7(1): 17.
[] [PMID: 30744693]
Abrahao A, Meng Y, Llinas M, et al. First-in-human trial of blood-brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound. Nat Commun 2019; 10(1): 4373.
[] [PMID: 31558719]
O’Brown NM, Pfau SJ, Gu C. Bridging barriers: A comparative look at the blood-brain barrier across organisms. Genes Dev 2018; 32(7-8): 466-78.
[] [PMID: 29692355]
Profaci CP, Munji RN, Pulido RS, Daneman R. The blood-brain barrier in health and disease: Important unanswered questions. J Exp Med 2020; 217(4): e20190062.
[] [PMID: 32211826]
Sanchez-Covarrubias L, Slosky LM, Thompson BJ, Davis TP, Ronaldson PT. Transporters at CNS barrier sites: Obstacles or opportunities for drug delivery? Curr Pharm Des 2014; 20(10): 1422-49.
[] [PMID: 23789948]
Karmur BS, Philteos J, Abbasian A, et al. Blood-brain barrier disrup-tion in neuro oncology: Strategies, failures, and challenges to overcome. Front Oncol 2020; 10: 563840.
[] [PMID: 33072591]
D’Amico RS, Khatri D, Reichman N, et al. Super selective intra-arterial cerebral infusion of modern chemotherapeutics after blood-brain barrier disruption: Where are we now, and where we are going. J Neurooncol 2020; 147(2): 261-78.
[] [PMID: 32076934]
Fischell JM, Fishman PS. A multifaceted approach to optimizing AAV delivery to the brain for the treatment of neurodegenerative dis-eases. Front Neurosci 2021; 15: 747726.
[] [PMID: 34630029]
Luo H, Shusta EV. Blood-brain barrier modulation to improve glioma drug delivery. Pharmaceutics 2020; 12(11): 1085.
[] [PMID: 33198244]
Regoli D, Cadieux A, D’Orléans-Juste P. Vasoactive Peptides and Their Receptors. In: Methods in Neurosciences. Blood Vessels 1990; 27(2-5): 137-45.
Chernukh AM, Gomazkov OA. Vasoactive Peptides and Regulation of Hemodynamics in Different Functional States of the Organism. Advances in Myocardiology 1983; 4: 201-14.
Jackson S, Anders NM, Mangraviti A, et al. The effect of regadenoson-induced transient disruption of the blood-brain barrier on temozolomide delivery to normal rat brain. J Neurooncol 2016; 126(3): 433-9.
[] [PMID: 26626489]
Chappa AK, Desino KE, Lunte SM. Functional Aspects of Vasoactive Peptides at the Blood–Brain Barrier. In: Handbook of Biologically Active Peptides 1461-1468.
Arvanitis CD, Ferraro GB, Jain RK. The blood-brain barrier and blood-tumour barrier in brain tumours and metastases. Nat Rev Cancer 2020; 20(1): 26-41.
[] [PMID: 31601988]
Sweeney MD, Ayyadurai S, Zlokovic BV. Pericytes of the neurovascular unit: key functions and signaling pathways. Nat Neurosci 2016; 19(6): 771-83.
[] [PMID: 27227366]
Wong AD, Ye M, Levy AF, Rothstein JD, Bergles DE, Searson PC. The blood-brain barrier: an engineering perspective. Front Neuroeng 2013; 6: 7. Epub ahead of print
[] [PMID: 24009582]
Andreone BJ, Lacoste B, Gu C. Neuronal and vascular interactions. Annu Rev Neurosci 2015; 38: 25-46.
[] [PMID: 25782970]
Blanchette M, Daneman R. Formation and maintenance of the BBB. Mech Dev 2015; 138(Pt 1): 8-16.
[] [PMID: 26215350]
Marchetti L, Engelhardt B. Immune cell trafficking across the blood-brain barrier in the absence and presence of neuroinflammation. Vasc Biol 2020; 2(1): H1-H18.
[] [PMID: 32923970]
Ratnam NM, Gilbert MR, Giles AJ. Immunotherapy in CNS cancers: the role of immune cell trafficking. Neuro-oncol 2019; 21(1): 37-46.
[] [PMID: 29771386]
Armulik A, Genové G, Mäe M, et al. Pericytes regulate the blood-brain barrier. Nature 2010; 468(7323): 557-61.
[] [PMID: 20944627]
Dalkara T, Gursoy-Ozdemir Y, Yemisci M. Brain microvascular pericytes in health and disease. Acta Neuropathol 2011; 122(1): 1-9.
[] [PMID: 21656168]
Janzer RC, Raff MC. Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 1987; 325(6101): 253-7.
[] [PMID: 3543687]
Abbott NJ, Rönnbäck L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 2006; 7(1): 41-53.
[] [PMID: 16371949]
Alvarez JI, Katayama T, Prat A. Glial influence on the blood brain barrier. Glia 2013; 61(12): 1939-58.
[] [PMID: 24123158]
Daneman R, Prat A. The blood-brain barrier. Cold Spring Harb Perspect Biol 2015; 7(1): a020412.
[] [PMID: 25561720]
Saili KS, Zurlinden TJ, Schwab AJ, et al. Blood-brain barrier devel-opment: Systems modeling and predictive toxicology. Birth Defects Res 2017; 109(20): 1680-710.
[] [PMID: 29251840]
Omidi Y, Barar J. Impacts of blood-brain barrier in drug delivery and targeting of brain tumors. Bioimpacts 2012; 2(1): 5-22.
Sabbagh MF, Heng JS, Luo C, et al. Transcriptional and epige-nomic landscapes of CNS and non-CNS vascular endothelial cells. eLife 2018; 7: e36187.
[] [PMID: 30188322]
Grossman SA, Romo CG, Rudek MA. Baseline requirements for novel agents being considered for phase II/III brain cancer efficacy trials:conclusions from the adult brain tumor consortium’s first workshop on CNS drug delivery. Neuro Oncol 2020; p. noaa142.
Ghose AK, Viswanadhan VN, Wendoloski JJ. A knowledge-based approach in designing combinatorial or medicinal chemistry librar-ies for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J Comb Chem 1999; 1(1): 55-68.
[] [PMID: 10746014]
Nau R, Sörgel F, Eiffert H. Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nerv-ous system infections. Clin Microbiol Rev 2010; 23(4): 858-83.
[] [PMID: 20930076]
Beccaria K, Canney M, Bouchoux G, Puget S, Grill J, Carpentier A. Blood-brain barrier disruption with low-intensity pulsed ultra-sound for the treatment of pediatric brain tumors: a review and perspectives. Neurosurg Focus 2020; 48(1): E10.
[] [PMID: 31896084]
Linville RM, DeStefano JG, Sklar MB, Chu C, Walczak P, Searson PC. Modeling hyperosmotic blood-brain barrier opening with-in human tissue-engineered in vitro brain microvessels. J Cereb Blood Flow Metab 2020; 40(7): 1517-32.
[] [PMID: 31394959]
Bellavance M-A, Blanchette M, Fortin D. Recent advances in blood-brain barrier disruption as a CNS delivery strategy. AAPS J 2008; 10(1): 166-77.
[] [PMID: 18446517]
Matsukado K, Inamura T, Nakano S, Fukui M, Bartus RT, Black KL. Enhanced tumor uptake of carboplatin and survival in glio-ma-bearing rats by intracarotid infusion of bradykinin analog, RMP-7. Neurosurgery 1996; 39(1): 125-33.
[] [PMID: 8805148]
Dean RL, Emerich DF, Hasler BP, Bartus RT. Cereport (RMP-7) increases carboplatin levels in brain tumors after pretreatment with dexamethasone. Neuro-oncol 1999; 1(4): 268-74.
[PMID: 11550318]
Burks SR, Kersch CN, Witko JA, et al. Blood-brain barrier opening by intracarotid artery hyperosmolar mannitol induces sterile inflammatory and innate immune responses. Proc Natl Acad Sci USA 2021; 118(18): e2021915118.
[] [PMID: 33906946]
Borlongan CV, Emerich DF. Facilitation of drug entry into the CNS via transient permeation of blood brain barrier: laboratory and pre-liminary clinical evidence from bradykinin receptor agonist. Cereport Brain Res Bull 2003; 60(3): 297-306.
[] [PMID: 12754091]
Mackic JB, Stins M, Jovanovic S, Kim KS, Bartus RT, Zlokovic BV. Cereport (RMP-7) increases the permeability of human brain microvascular endothelial cell monolayers. Pharm Res 1999; 16(9): 1360-5.
[] [PMID: 10496650]
Prados MD, Schold SC Jr, Fine HA, et al. A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma. Neuro-oncol 2003; 5(2): 96-103.
[] [PMID: 12672281]
Carman AJ, Mills JH, Krenz A, Kim DG, Bynoe MS. Adenosine receptor signaling modulates permeability of the blood-brain barrier. J Neurosci 2011; 31(37): 13272-80.
[] [PMID: 21917810]
Kim D-G, Bynoe MS. A2A adenosine receptor regulates the human blood-brain barrier permeability. Mol Neurobiol 2015; 52(1): 664-78.
[] [PMID: 25262373]
Bynoe MS, Viret C, Yan A, Kim DG. Adenosine receptor signaling: a key to opening the blood-brain door. Fluids Barriers CNS 2015; 12: 20.
[] [PMID: 26330053]
Smith-Cohn M, Chen Z, Peereboom D. Maximizing function and quality of life of patients with glioblastoma after surgical resection: A review of current literature. J Cancer Ther 2016; 07: 857-88.
Kaya M, Ahishali B. Assessment of Permeability in Barrier Type of Endothelium in Brain Using Tracers: Evans Blue, Sodium Fluores-cein, and Horseradish Peroxidase. In: Permeability Barrier. 369-82.
Saunders NR, Dziegielewska KM, Møllgård K, Habgood MD. Markers for blood-brain barrier integrity: how appropriate is Evans blue in the twenty-first century and what are the alternatives? Front Neurosci 2015; 9: 385.
[] [PMID: 26578854]
Gurnik S, Devraj K, Macas J, et al. Angiopoietin-2-induced blood-brain barrier compromise and increased stroke size are rescued by VE-PTP-dependent restoration of Tie2 signaling. Acta Neuropathol 2016; 131(5): 753-73.
[] [PMID: 26932603]
Deli MA, Descamps L, Dehouck M-P, et al. Exposure of tumor necrosis factor-α to lu-minal membrane of bovine brain capillary endothelial cells cocultured with astrocytes induces a delayed increase of permeability and cy-toplasmic stress fiber formation of actin. J Neurosci Res 1995; 41(6): 717-26.
[] [PMID: 7500373]
Nollevaux G, Devillé C, El Moualij B, et al. Development of a serum-free co-culture of human intestinal epithelium cell-lines (Caco-2/HT29-5M21). BMC Cell Biol 2006; 7: 20.
[] [PMID: 16670004]
Yen LF, Wei VC, Kuo EY, Lai TW. Distinct patterns of cerebral extravasation by Evans blue and sodium fluorescein in rats. PLoS One 2013; 8(7): e68595.
[] [PMID: 23861924]
Eide PK, Ringstad G. MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain. Acta Radiol Open 2015; 4(11): 2058460115609635.
[] [PMID: 26634147]
Emerich DF, Dean RL, Marsh J, et al. Intravenous cereport (RMP-7) enhances deliv-ery of hydrophilic chemotherapeutics and increases survival in rats with metastatic tumors in the brain. Pharm Res 2000; 17(10): 1212-9.
[] [PMID: 11145226]
Cloughesy TF, Black KL, Gobin YP, et al. Intra-arterial Cereport (RMP-7) and carboplatin: a dose escalation study for recurrent malignant gliomas. Neurosurgery 1999; 44(2): 270-8.
[] [PMID: 9932880]
Kim D-G, Bynoe MS. A2A adenosine receptor modulates drug efflux transporter P-glycoprotein at the blood-brain barrier. J Clin Invest 2016; 126(5): 1717-33.
[] [PMID: 27043281]
Sharedalal P, Gerard P, Jain D. Pharmacological stress myocardial perfusion imaging after an inadequate exercise stress test. J Nucl Cardiol 2021. Online ahead of print
[] [PMID: 34036527]
Jackson S, George RT, Lodge MA, et al. The effect of regadenoson on the integri-ty of the human blood-brain barrier, a pilot study. J Neurooncol 2017; 132(3): 513-9.
[] [PMID: 28315063]
Jackson S, Weingart J, Nduom EK, et al. The effect of an adenosine A2A agonist on intra-tumoral concentrations of temozolomide in patients with re-current glioblastoma. Fluids Barriers CNS 2018; 15(1): 2.
[] [PMID: 29332604]
Inamura T, Black KL. Bradykinin selectively opens blood-tumor barrier in experimental brain tumors. J Cereb Blood Flow Metab 1994; 14(5): 862-70.
[] [PMID: 8063881]
Su B, Wang R, Xie Z, et al. Effect of retro-inverso isomer of bradykinin on size-dependent penetration of blood-brain tumor barrier. Small 2018; 14(7): 1702331.
[] [PMID: 29292579]
Narushima I, Kita T, Kubo K, et al. Contribution of endothelin-1 to disruption of blood-brain barrier permeability in dogs. Naunyn Schmiedebergs Arch Pharmacol 1999; 360(6): 639-45.
[] [PMID: 10619180]
Bohara M, Kambe Y, Nagayama T, Tokimura H, Arita K, Miyata A. C-type natriuretic peptide modulates permeability of the blood-brain barrier. J Cereb Blood Flow Metab 2014; 34(4): 589-96.
[] [PMID: 24398935]
Stumm R, Culmsee C, Schäfer MK-H, Krieglstein J, Weihe E. Adaptive plasticity in tachykinin and tachykinin receptor expression after focal cerebral ischemia is differentially linked to gabaergic and glutamatergic cerebrocortical circuits and cerebrovenular endothelium. J Neurosci 2001; 21(3): 798-811.
[] [PMID: 11157066]
Wang Y, Jin S, Sonobe Y, et al. Interleukin-1β induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes. PLoS One 2014; 9(10): e110024.
[] [PMID: 25313834]
Sharma HS. Effect of captopril (a converting enzyme inhibitor) on blood-brain barrier permeability and cerebral blood flow in normoten-sive rats. Neuropharmacology 1987; 26(1): 85-92.
[] [PMID: 2436083]
Cerqueira MD, Verani MS, Schwaiger M, Heo J, Iskandrian AS. Safety profile of adenosine stress perfusion imaging: results from the Adenoscan Multicenter Trial Registry. J Am Coll Cardiol 1994; 23(2): 384-9.
[] [PMID: 8294691]
Blood AB, Hunter CJ, Power GG. The role of adenosine in regulation of cerebral blood flow during hypoxia in the near-term fetal sheep. J Physiol 2002; 543(Pt 3): 1015-23.
[] [PMID: 12231655]
Brink HL, Dickerson JA, Stephens JA, Pickworth KK. Comparison of the safety of adenosine and regadenoson in patients undergo-ing outpatient cardiac stress testing. Pharmacotherapy 2015; 35(12): 1117-23.
[] [PMID: 26684552]
Li JM, Fenton RA, Cutler BS, Dobson JG Jr. Adenosine enhances nitric oxide production by vascular endothelial cells. Am J Physiol 1995; 269(2 Pt 1): C519-23.
[] [PMID: 7653535]
Ikeda U, Kurosaki K, Ohya K, Shimada K. Adenosine stimulates nitric oxide synthesis in vascular smooth muscle cells. Cardiovasc Res 1997; 35(1): 168-74.
[] [PMID: 9302361]
Gao X, Yue Q, Liu Y, et al. Image-guided chemotherapy with specifically tuned blood brain barrier permeability in glioma margins. Theranostics 2018; 8(11): 3126-37.
[] [PMID: 29896307]
Murrant CL, Dodd JD, Foster AJ, et al. Prostaglandins induce vasodilata-tion of the microvasculature during muscle contraction and induce vasodilatation independent of adenosine. J Physiol 2014; 592(6): 1267-81.
[] [PMID: 24469074]
Zhang H, Gu YT, Xue YX. Bradykinin-induced blood-brain tumor barrier permeability increase is mediated by adenosine 5′-triphosphate-sensitive potassium channel. Brain Res 2007; 1144: 33-41.
[] [PMID: 17331483]
Raymond JJ, Robertson DM, Dinsdale HB. Pharmacological modification of bradykinin induced breakdown of the blood-brain barri-er. Can J Neurol Sci 1986; 13(3): 214-20.
[] [PMID: 3742336]
Ningaraj NS, Rao M, Hashizume K, Asotra K, Black KL. Regulation of blood-brain tumor barrier permeability by calcium-activated potassium channels. J Pharmacol Exp Ther 2002; 301(3): 838-51.
[] [PMID: 12023511]
Liu LB, Xue YX, Liu YH, Wang YB. Bradykinin increases blood-tumor barrier permeability by down-regulating the expression levels of ZO-1, occludin, and claudin-5 and rearranging actin cytoskeleton. J Neurosci Res 2008; 86(5): 1153-68.
[] [PMID: 18183615]
Emerich DF, Dean RL, Osborn C, Bartus RT. The development of the bradykinin agonist labradimil as a means to increase the per-meability of the blood-brain barrier: from concept to clinical evaluation. Clin Pharmacokinet 2001; 40(2): 105-23.
[] [PMID: 11286321]
Gulati A. Endothelin Receptors, Mitochondria and Neurogenesis in Cerebral Ischemia. Curr Neuropharmacol 2016; 14(6): 619-26.
[] [PMID: 26786146]
MacCumber MW, Ross CA, Snyder SH. Endothelin in brain: receptors, mitogenesis, and biosynthesis in glial cells. Proc Natl Acad Sci USA 1990; 87(6): 2359-63.
[] [PMID: 2156267]
Lee ME, de la Monte SM, Ng SC, Bloch KD, Quertermous T. Expression of the potent vasoconstrictor endothelin in the human central nervous system. J Clin Invest 1990; 86(1): 141-7.
[] [PMID: 2195059]
Stanimirovic DB, McCarron R, Bertrand N, Spatz M. Endothelins release 51Cr from cultured human cerebromicrovascular endotheli-um. Biochem Biophys Res Commun 1993; 191(1): 1-8.
[] [PMID: 8447814]
Hartz AMS, Bauer B, Fricker G, Miller DS. Rapid regulation of P-glycoprotein at the blood-brain barrier by endothelin-1. Mol Pharmacol 2004; 66(3): 387-94.
[] [PMID: 15322229]
Suzuki Y, Satoh S, Kimura M, et al. Effects of vasopressin and oxytocin on canine cerebral circulation in vivo. J Neurosurg 1992; 77(3): 424-31.
[] [PMID: 1506890]
Lumsden NG, Khambata RS, Hobbs AJ. C-type natriuretic peptide (CNP): cardiovascular roles and potential as a therapeutic target. Curr Pharm Des 2010; 16(37): 4080-8.
[] [PMID: 21247399]
Nag S, Pang SC. Effect of atrial natriuretic factor on blood-brain barrier permeability. Can J Physiol Pharmacol 1989; 67(6): 637-40.
[] [PMID: 2528401]
Whitson PA, Huls MH, Sams CF. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells. J Cell Physiol 1991; 146(1): 43-51.
[] [PMID: 1846636]
Ermisch A, Rühle H-J, Kretzschmar R, Baethmann A. On the blood-brain barrier to peptides: specific binding of atrial natriuretic pep-tide in vivo and in vitro. Brain Res 1991; 554(1-2): 209-16.
[] [PMID: 1657288]
Kuhn M. Endothelial actions of atrial and B-type natriuretic peptides. Br J Pharmacol 2012; 166(2): 522-31.
[] [PMID: 22220582]
Umeda K, Ikenouchi J, Katahira-Tayama S, et al. ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell 2006; 126(4): 741-54.
[] [PMID: 16923393]
Mori Y, Takayasu M, Suzuki Y, Shibuya M, Yoshida J, Hidaka H. Vasodilator effects of C-type natriuretic peptide on cerebral arterioles in rats. Eur J Pharmacol 1997; 320(2-3): 183-6.
[] [PMID: 9059852]
Rodriguez PL, Jiang S, Fu Y, Avraham S, Avraham HK. The proinflammatory peptide substance P promotes blood-brain barrier breaching by breast cancer cells through changes in microvascular endothelial cell tight junctions. Int J Cancer 2014; 134(5): 1034-44.
[] [PMID: 23934616]
Newby DE, Sciberras DG, Ferro CJ, et al. Substance P-induced vas-odilatation is mediated by the neurokinin type 1 receptor but does not contribute to basal vascular tone in man. Br J Clin Pharmacol 1999; 48(3): 336-44.
[] [PMID: 10510144]
Ghabriel MN, Lu MX, Leigh C, Cheung WC, Allt G. Substance P-induced enhanced permeability of dura mater microvessels is accompanied by pronounced ultrastructural changes, but is not dependent on the density of endothelial cell anionic sites. Acta Neuropathol 1999; 97(3): 297-305.
[] [PMID: 10090678]
Zhu J, Li X, Yin J, Hu Y, Gu Y, Pan S. Glycocalyx degradation leads to blood-brain barrier dysfunction and brain edema after asphyxia cardiac arrest in rats. J Cereb Blood Flow Metab 2018; 38(11): 1979-92.
[] [PMID: 28825336]
Blamire AM, Anthony DC, Rajagopalan B, Sibson NR, Perry VH, Styles P. Interleukin-1β -induced changes in blood-brain barri-er permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: a magnetic resonance study. J Neurosci 2000; 20(21): 8153-9.
[] [PMID: 11050138]
Bolton SJ, Anthony DC, Perry VH. Loss of the tight junction proteins occludin and zonula occludens-1 from cerebral vascular endo-thelium during neutrophil-induced blood-brain barrier breakdown in vivo. Neuroscience 1998; 86(4): 1245-57.
[] [PMID: 9697130]
Förster C, Burek M, Romero IA. Differential effects of hydrocortisone and TNFα on tight junction proteins in an in vitro model of the human blood-brain barrier: Hydrocortisone and BBB properties in brain endothelial cell line. J Physiol 2008; 586: 1937-49.
[] [PMID: 18258663]
Shukla A, Dikshit M, Srimal RC. Nitric oxide-dependent blood-brain barrier permeability alteration in the rat brain. Experientia 1996; 52(2): 136-40.
[] [PMID: 8608814]
Claesson-Welsh L. Vascular permeability--the essentials. Ups J Med Sci 2015; 120(3): 135-43.
[] [PMID: 26220421]
Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 1990; 28(2): 183-7.
[] [PMID: 1699472]
Juul R, Aakhus S, Björnstad K, Gisvold SE, Brubakk AO, Edvinsson L. Calcitonin gene-related peptide (human α-CGRP) coun-teracts vasoconstriction in human subarachnoid haemorrhage. Neurosci Lett 1994; 170(1): 67-70.
[] [PMID: 8041516]
Russell FA, King R, Smillie S-J, Kodji X, Brain SD. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev 2014; 94(4): 1099-142.
[] [PMID: 25287861]
Kee Z, Kodji X, Brain SD. The role of calcitonin gene related peptide (CGRP) in neurogenic vasodilation and its cardioprotective ef-fects. Front Physiol 2018; 9: 1249.
[] [PMID: 30283343]
Lassen LH, Jacobsen VB, Haderslev PA, et al. Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients. J Headache Pain 2008; 9(3): 151-7.
[] [PMID: 18437288]
Borkum JM. CGRP and Brain Functioning: Cautions for Migraine Treatment. Headache 2019; 59(8): 1339-57.
[] [PMID: 31328279]
Dogan A, Suzuki Y, Koketsu N, et al. Intravenous infusion of adrenomedullin and increase in regional cerebral blood flow and prevention of ischemic brain injury after middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab 1997; 17(1): 19-25.
[] [PMID: 8978383]
Lang MG, Paternò R, Faraci FM, Heistad DD. Mechanisms of adrenomedullin-induced dilatation of cerebral arterioles. Stroke 1997; 28(1): 181-5.
[] [PMID: 8996509]
Baskaya MK, Suzuki Y, Anzai M, et al. Effects of adrenomedullin, calcitonin gene-related peptide, and amylin on cerebral circulation in dogs. J Cereb Blood Flow Metab 1995; 15(5): 827-34.
[] [PMID: 7673375]
Chuquet J, Lecrux C, Chatenet D, et al. Effects of uro-tensin-II on cerebral blood flow and ischemia in anesthetized rats. Exp Neurol 2008; 210(2): 577-84.
[] [PMID: 18191840]
Heistad DD, Marcus ML, Said SI, Gross PM. Effect of acetylcholine and vasoactive intestinal peptide on cerebral blood flow. Am J Physiol 1980; 239(1): H73-80.
[PMID: 7396021]
Russell FD. Emerging roles of urotensin-II in cardiovascular disease. Pharmacol Ther 2004; 103(3): 223-43.
[] [PMID: 15464591]
Lacza ZW, Busija D. Urotensin-II is a nitric oxide-dependent vasodilator in the pial arteries of the newborn pig. Life Sci 2006; 78(23): 2763-6.
[] [PMID: 16337243]
Japundžić-Žigon, N. Vasopressin and oxytocin in control of the cardiovascular system. Curr Neuropharmacol 2013; 11(2): 218-30.
[] [PMID: 23997756]
Katusic ZS, Shepherd JT, Vanhoutte PM. Oxytocin causes endothelium-dependent relaxations of canine basilar arteries by activating V1-vasopressinergic receptors. J Pharmacol Exp Ther 1986; 236(1): 166-70.
[PMID: 3001282]
Viñuela-Berni V, Gómez-González B, Quintanar-Stephano A. Blockade of Arginine Vasopressin receptors prevents blood-brain barrier breakdown in Experimental Autoimmune Encephalomyelitis. Sci Rep 2020; 10(1): 467.
[] [PMID: 31949182]
Dogrukol-Ak D, Tore F, Tuncel N. Passage of VIP/PACAP/secretin family across the blood-brain barrier: therapeutic effects. Curr Pharm Des 2004; 10(12): 1325-40.
[] [PMID: 15134484]
Wilson DA, O’Neill JT, Said SI, Traystman RJ. Vasoactive intestinal polypeptide and the canine cerebral circulation. Circ Res 1981; 48(1): 138-48.
[] [PMID: 7438343]
Donelan J, Boucher W, Papadopoulou N, et al. Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process. Proc Natl Acad Sci USA 2006; 103(20): 7759-64.
[] [PMID: 16682628]
Chrobak I, Lenna S, Stawski L, Trojanowska M. Interferon-γ promotes vascular remodeling in human microvascular endothelial cells by upregulating endothelin (ET)-1 and transforming growth factor (TGF) β2. J Cell Physiol 2013; 228(8): 1774-83.
[] [PMID: 23359533]
Nan Y-S, Feng G-G, Hotta Y, et al. Neuropeptide Y en-hances permeability across a rat aortic endothelial cell monolayer. Am J Physiol Heart Circ Physiol 2004; 286(3): H1027-33.
[] [PMID: 14576078]
Wylezinski LS, Hawiger J. Interleukin 2 activates brain microvascular endothelial cells resulting in destabilization of adherens junctions. J Biol Chem 2016; 291(44): 22913-23.
[] [PMID: 27601468]
Berraondo P, Sanmamed MF, Ochoa MC, et al. Cytokines in clinical cancer immunotherapy. Br J Cancer 2019; 120(1): 6-15.
[] [PMID: 30413827]
Castro F, Cardoso AP, Gonçalves RM, Serre K, Oliveira MJ. Interferon-gamma at the crossroads of tumor immune surveillance or evasion. Front Immunol 2018; 9: 847.
[] [PMID: 29780381]
Yi M, Li H, Wu Z, et al. A Promising therapeutic target for metabolic diseases: neuropeptide y receptors in humans. Cell Physiol Biochem 2018; 45(1): 88-107.
[] [PMID: 29310113]
Jan M, Keppel H. Kambo and its multitude of biological effects: adverse events or pharmacological effects? Int Arch Clin Pharmacol 2018; 4: 31. Epub ahead of print
Maeda S, Sutliff RL, Qian J, et al. Targeted overexpression of parathyroid hormone-related protein (PTHrP) to vascular smooth muscle in transgenic mice lowers blood pressure and alters vascular contractility. Endocrinology 1999; 140(4): 1815-25.
[] [PMID: 10098520]
Benson T, Menezes T, Campbell J, Bice A, Hood B, Prisby R. Mechanisms of vasodilation to PTH 1-84, PTH 1-34, and PTHrP 1-34 in rat bone resistance arteries. Osteoporos Int 2016; 27(5): 1817-26.
[] [PMID: 26733378]
Moro O, Lerner EA. Maxadilan, the vasodilator from sand flies, is a specific pituitary adenylate cyclase activating peptide type I recep-tor agonist. J Biol Chem 1997; 272(2): 966-70.
[] [PMID: 8995389]
Barker DM, Corder R. Studies of the role of endothelium-dependent nitric oxide release in the sustained vasodilator effects of cortico-trophin releasing factor and sauvagine. Br J Pharmacol 1999; 126(1): 317-25.
[] [PMID: 10051151]
Itoh H, Lederis K. Relationship of urotensin I induced vasodilatory action in rat thoracic aorta to Ca2+ regulation. Can J Physiol Pharmacol 1987; 65(3): 298-302.
[] [PMID: 3034389]
Bhatt DK, Gupta S, Olesen J, Jansen-Olesen I. PACAP-38 infusion causes sustained vasodilation of the middle meningeal artery in the rat: possible involvement of mast cells. Cephalalgia 2014; 34(11): 877-86.
[] [PMID: 24563332]
den Brave PS, Bruins E, Bronkhorst MWGA. Phyllomedusa bicolor skin secretion and the Kambô ritual. J Venom Anim Toxins Incl Trop Dis 2014; 20: 40.
[] [PMID: 26413084]
Joanna P. Łapiński, T.W. Toxic hepatitis caused by the excretions of the Phyllomedusa bicolor frog – a case reportby the excretions of the Phyllomedusa bicolor frog – a case report. Clin Exp Hepatol 2017; 1: 33-4.
Tella SH, Kommalapati A, Correa R. Profile of abaloparatide and its potential in the treatment of postmenopausal osteoporosis. Cureus 2017; 9(5): e1300. Epub ahead of print
[] [PMID: 28680788]
Grevelink SA, Osborne J, Loscalzo J, Lerner EA. Vasorelaxant and second messenger effects of maxadilan. J Pharmacol Exp Ther 1995; 272(1): 33-7.
[PMID: 7815348]
Vuppaladhadiam L, Ehsan C, Akkati M, Bhargava A. Corticotropin-releasing factor family: a stress hormone-receptor system’s emerging role in mediating sex-specific signaling. Cells 2020; 9(4): 839.
[] [PMID: 32244319]
Harmar AJ, Fahrenkrug J, Gozes I, et al. Pharma-cology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol 2012; 166(1): 4-17.
[] [PMID: 22289055]
Klinger JR, Kadowitz PJ. The Nitric Oxide Pathway in Pulmonary Vascular Disease. Am J Cardiol 2017; 120(8S): S71-9.
[] [PMID: 29025573]
Weyerbrock A, Walbridge S, Saavedra JE, Keefer LK, Oldfield EH. Differential effects of nitric oxide on blood-brain barrier integ-rity and cerebral blood flow in intracerebral C6 gliomas. Neuro-oncol 2011; 13(2): 203-11.
[] [PMID: 21041233]
Mughal A, Sun C. OʼRourke, S.T. Apelin reduces nitric oxide-induced relaxation of cerebral arteries by inhibiting activation of large-conductance, calcium-activated K channels. J Cardiovasc Pharmacol 2018; 71(4): 223-32.
[] [PMID: 29620606]
Belykh E, Shaffer KV, Lin C, Byvaltsev VA, Preul MC, Chen L. Blood-brain barrier, blood-brain tumor barrier, and fluores-cence-guided neurosurgical oncology: delivering optical labels to brain tumors. Front Oncol 2020; 10: 739.
[] [PMID: 32582530]
Brown V, Liu F. Intranasal delivery of a peptide with antidepressant-like effect. Neuropsychopharmacology 2014; 39(9): 2131-41.
[] [PMID: 24633557]
Iwasaki S, Yamamoto S, Sano N, et al. Direct drug delivery of low-permeable compounds to the central nervous system via intranasal administration in rats and monkeys. Pharm Res 2019; 36(5): 76.
[] [PMID: 30937626]
Fieger SM, Wong BJ. Adenosine receptor inhibition with theophylline attenuates the skin blood flow response to local heating in hu-mans. Exp Physiol 2010; 95(9): 946-54.
[] [PMID: 20562295]
Ribeiro JA, Sebastião AM. Caffeine and adenosine. J Alzheimers Dis 2010; 20(Suppl. 1): S3-S15.
[] [PMID: 20164566]
Neumar RW, Otto CW, Link MS, et al. Part 8: adult advanced cardiovascular life sup-port: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122(18)(Suppl. 3): S729-67.
[] [PMID: 20956224]
Baños G, Martínez F, Grimaldo JI, Franco M. Adenosine participates in regulation of smooth muscle relaxation in aortas from rats with experimental hypothyroidism. Can J Physiol Pharmacol 2002; 80(6): 507-14.
[] [PMID: 12117299]
Somasundaram V, Basudhar D, Bharadwaj G. et al. Molecular mechanisms of nitric oxide in cancer progression, signal transduction, and metabolism. Antioxid Redox Signal 2019; 30: 1124-43.
Girotti AW, Fahey JM. Upregulation of pro-tumor nitric oxide by anti-tumor photodynamic therapy. Biochem Pharmacol 2020; 176: 113750.
Soricelli A, Postiglione A, Cuocolo A, et al. Effect of adenosine on cerebral blood flow as evaluated by single-photon emission computed tomography in normal subjects and in patients with occlusive carotid dis-ease. A comparison with acetazolamide. Stroke 1995; 26(9): 1572-6.
[] [PMID: 7660400]
Vanlandewijck M, He L, Mäe MA, et al. A molecular atlas of cell types and zonation in the brain vasculature. Nature 2018; 554(7693): 475-480.
[] [PMID: 29443965]

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