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Acta Neurochirurgica

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Open Access 01-01-2015 | Experimental Research - Brain Injury

Uptake of the antisecretory factor peptide AF-16 in rat blood and cerebrospinal fluid and effects on elevated intracranial pressure

Authors: Mohamed Al-Olama, Stefan Lange, Ivar Lönnroth, Kliment Gatzinsky, Eva Jennische

Published in: Acta Neurochirurgica | Issue 1/2015

Abstract

Background

AF-16 is a 16-amino-acid-long peptide derived from the amino-terminal part of the endogenous protein, antisecretory factor (AF). AF-16 in vivo has been shown to regulate dysfunctions in the water and ion transport system under various pathological conditions and also to counteract experimentally increased tissue pressure.

Methods

Rats were subjected to a cryogenic brain injury in order to increase the intracranial pressure (ICP). The distribution of AF-16 in blood and CSF after intravenous or intranasal administration was determined in injured and control rats. ICP was monitored in freely moving, awake rats, by means of an epidural pressure transducer catheter connected to a wireless device placed subcutaneously on the skull. The continuous ICP registrations were achieved by means of telemetry.

Results

Intranasal administration of AF-16 resulted in a significantly higher CSF concentrations of AF-16 in injured than in control rats, 1.3 versus 0.6 ng/ml, whereas no difference between injured and control rats was seen when AF-16 was given intravenously. Rats subjected to cryogenic brain injury developed gradually increasing ICP levels. Intranasal administration of AF-16 suppressed the increased ICP to normal values within 30 min.

Conclusion

Optimal AF-16 concentrations in CSF are achieved after intranasal administration in rats subjected to a cryogenic brain injury. The ability of AF-16 to suppress an increased ICP was manifested.

Balestreri M, Czosnyka M, Hutchinson P, Steiner LA, Hiler M, Smielewski P, Pickard JD (2006) Impact of intracranial pressure and cerebral perfusion pressure on severe disability and mortality after head injury. Neurocrit Care 4:8–13PubMedCrossRef

Nilsson OG, Lindgren A, Brandt L, Saveland H (2002) Prediction of death in patients with primary intracerebral hemorrhage: a prospective study of a defined population. J Neurosurg 97:531–536PubMedCrossRef

Rincon F, Mayer SA (2008) Clinical review: critical care management of spontaneous intracerebral hemorrhage. Crit Care 12:237PubMedCentralPubMedCrossRef

Johansson E, Lange S, Lonnroth I (1997) Identification of an active site in the antisecretory factor protein. Biochim Biophys Acta 1362:177–182PubMedCrossRef

Johansson E, Lonnroth I, Lange S, Jonson I, Jennische E, Lonnroth C (1995) Molecular cloning and expression of a pituitary gland protein modulating intestinal fluid secretion. J Biol Chem 270:20615–20620PubMedCrossRef

Jennische E, Bergstrom T, Johansson M, Nystrom K, Tarkowski A, Hansson HA, Lange S (2008) The peptide AF-16 abolishes sickness and death at experimental encephalitis by reducing increase of intracranial pressure. Brain Res 1227:189–197PubMedCrossRef

Hansson HA, Al-Olama M, Jennische E, Gatzinsky K, Lange S (2012) The peptide AF-16 and the AF protein counteract intracranial hypertension. Acta Neurochir Suppl 114:377–382PubMedCrossRef

Al-Olama M, Wallgren A, Andersson B, Gatzinsky K, Hultborn R, Karlsson-Parra A, Lange S, Hansson HA, Jennische E (2011) The peptide AF-16 decreases high interstitial fluid pressure in solid tumors. Acta Oncol 50:1098–1104PubMedCrossRef

Uldall M, Juhler M, Skjolding AD, Kruuse C, Jansen-Olesen I, Jensen R (2014) A novel method for long-term monitoring of intracranial pressure in rats. J Neurosci Methods 227:1–9PubMedCrossRef

10.

Silasi G, MacLellan CL, Colbourne F (2009) Use of telemetry blood pressure transmitters to measure intracranial pressure (ICP) in freely moving rats. Curr Neurovasc Res 6:62–69PubMedCrossRef

11.

Johansson E, Al-Olama M, Hansson HA, Lange S, Jennische E (2013) Diet-induced antisecretory factor prevents intracranial hypertension in a dosage-dependent manner. Br J Nutr 109:2247–2252PubMedCrossRef

12.

Saljo A, Bolouri H, Mayorga M, Svensson B, Hamberger A (2010) Low-level blast raises intracranial pressure and impairs cognitive function in rats: prophylaxis with processed cereal feed. J Neurotrauma 27:383–389PubMedCrossRef

13.

Akata T, Kanna T, Yoshino J, Takahashi S (2003) Mechanisms of direct inhibitory action of isoflurane on vascular smooth muscle of mesenteric resistance arteries. Anesthesiology 99:666–677PubMedCrossRef

14.

Greenblatt EP, Loeb AL, Longnecker DE (1992) Endothelium-dependent circulatory control—a mechanism for the differing peripheral vascular effects of isoflurane versus halothane. Anesthesiology 77:1178–1185PubMedCrossRef

15.

Li Y, Field PM, Raisman G (2005) Olfactory ensheathing cells and olfactory nerve fibroblasts maintain continuous open channels for regrowth of olfactory nerve fibres. Glia 52:245–251PubMedCrossRef

16.

Balin BJ, Broadwell RD, Salcman M, el-Kalliny M (1986) Avenues for entry of peripherally administered protein to the central nervous system in mouse, rat, and squirrel monkey. J Comp Neurol 251:260–280PubMedCrossRef

17.

Dhuria SV, Hanson LR, Frey WH 2nd (2010) Intranasal delivery to the central nervous system: mechanisms and experimental considerations. J Pharm Sci 99:1654–1673PubMed

18.

Baker H, Spencer RF (1986) Transneuronal transport of peroxidase-conjugated wheat germ agglutinin (WGA-HRP) from the olfactory epithelium to the brain of the adult rat. Exp Brain Res 63:461–473PubMedCrossRef

19.

Lochhead JJ, Thorne RG (2012) Intranasal delivery of biologics to the central nervous system. Adv Drug Deliv Rev 64:614–628PubMedCrossRef

20.

Lange S, Lonnroth I (2001) The antisecretory factor: synthesis, anatomical and cellular distribution, and biological action in experimental and clinical studies. Int Rev Cytol 210:39–75PubMedCrossRef

21.

Eriksson A, Shafazand M, Jennische E, Lange S (2003) Effect of antisecretory factor in ulcerative colitis on histological and laborative outcome: a short period clinical trial. Scand J Gastroenterol 38:1045–1049PubMedCrossRef

22.

Eriksson A, Shafazand M, Jennische E, Lonnroth I, Lange S (2003) Antisecretory factor-induced regression of Crohn’s disease in a weak responder to conventional pharmacological treatment. Inflamm Bowel Dis 9:398–400PubMedCrossRef

23.

Johansson E, Jennische E, Lange S, Lonnroth I (1997) Antisecretory factor suppresses intestinal inflammation and hypersecretion. Gut 41:642–645PubMedCentralPubMedCrossRef

24.

Davidson TS, Hickey WF (2004) Antisecretory factor expression is regulated by inflammatory mediators and influences the severity of experimental autoimmune encephalomyelitis. J Leukoc Biol 76:835–844PubMedCrossRef

25.

Davidson TS, Hickey WF (2004) Distribution and immunoregulatory properties of antisecretory factor. Lab Invest 84:307–319PubMedCrossRef

26.

Mane J, Loren V, Pedrosa E, Ojanguren I, Domenech E, Gassull MA, Cabre E (2011) Therapeutic effect of antisecretory factor-rich egg yolk on the late phases of 2,4,6-trinitrobenzenesulphonic acid colitis in mice. Br J Nutr 106:1522–1528PubMedCrossRef

27.

Rapallino MV, Cupello A, Lange S, Lonnroth I (2003) Antisecretory factor peptide derivatives specifically inhibit [3H]-gamma-amino-butyric acid/36Cl- out→in permeation across the isolated rabbit Deiters’ neuronal membrane. Acta Physiol Scand 179:367–371PubMedCrossRef

28.

Kim M, Wasling P, Xiao MY, Jennische E, Lange S, Hanse E (2005) Antisecretory factor modulates GABAergic transmission in the rat hippocampus. Regul Pept 129:109–118PubMedCrossRef

Title: Uptake of the antisecretory factor peptide AF-16 in rat blood and cerebrospinal fluid and effects on elevated intracranial pressure
Authors: Mohamed Al-Olama
Stefan Lange
Ivar Lönnroth
Kliment Gatzinsky
Eva Jennische
Publication date: 01-01-2015
Publisher: Springer Vienna
Published in: Acta Neurochirurgica / Issue 1/2015
Print ISSN: 0001-6268
Electronic ISSN: 0942-0940
DOI: https://doi.org/10.1007/s00701-014-2221-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Uptake of the antisecretory factor peptide AF-16 in rat blood and cerebrospinal fluid and effects on elevated intracranial pressure

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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