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

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

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.

Figures

Fig. 1
Fig. 1
The various parts of the device for ICP recording: pressure transducer (1), transducer catheter (2), plastic cannula (3) and tip of the sensor probe (4)
Fig. 2
Fig. 2
Freely moving rat with the measuring device on the skull
Fig. 3
Fig. 3
a AF-16 was deposited intranasally (0.3 μmol/kg in 25 μl) under Isoflurane anaesthesia, after which the concentration (ng/ml) of the peptide was determined in plasma (filled bars) and in CSF (unfilled bars) after a 15-min- or a 30-min-long period. Higher levels of AF-16 are found in plasma than in CSF at both times. Mean ± SEM. b Autoradiography showing distribution of 14C-AF-16 in the rat brain 30 min after intranasal administration of the peptide. X-ray film showing signal in the lateral (LV) and third ventricles (3V); hc hippocampus
Fig. 4
Fig. 4
ICP recording from a control rat showing pulsations due to the heart beats
Fig. 5
Fig. 5
Recordings of ICP 24 h after a cryogenic injury. a Before anaesthesia. b Transient increase in ICP during induction of anaesthesia. c Return to the pre-anaesthetic level after a couple of minutes. d Reduced ICP 30 min after AF-16 administration
Fig. 6
Fig. 6
Paraffin section from the brain of an injured rat showing a typical superficial, rounded lesion. Cresyl violet. Scale bar 500 μm

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Source: PubMed

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