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Sci Transl Med. 2017 Aug 23;9(404). pii: eaan0972. doi: 10.1126/scitranslmed.aan0972.

A glucagon-like peptide-1 receptor agonist reduces intracranial pressure in a rat model of hydrocephalus.

Author information

1
Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston B15 2TT, UK.
2
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham B15 2TH, UK.
3
Danish Headache Center, Clinic of Neurology, Rigshospitalet-Glostrup, University of Copenhagen, Nordre Ringvej 69, 2600 Glostrup, Denmark.
4
Department of Neurology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, UK.
5
Institute of Inflammation and Ageing, University of Birmingham, Edgbaston B15 2TT, UK.
6
Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham and University of Nottingham, Midlands, UK.
7
Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston B15 2TT, UK. a.b.sinclair@bham.ac.uk.

Abstract

Current therapies for reducing raised intracranial pressure (ICP) under conditions such as idiopathic intracranial hypertension or hydrocephalus have limited efficacy and tolerability. Thus, there is a pressing need to identify alternative drugs. Glucagon-like peptide-1 receptor (GLP-1R) agonists are used to treat diabetes and promote weight loss but have also been shown to affect fluid homeostasis in the kidney. We investigated whether exendin-4, a GLP-1R agonist, is able to modulate cerebrospinal fluid (CSF) secretion at the choroid plexus and subsequently reduce ICP in rats. We used tissue sections and cell cultures to demonstrate expression of GLP-1R in the choroid plexus and its activation by exendin-4, an effect blocked by the GLP-1R antagonist exendin 9-39. Acute treatment with exendin-4 reduced Na+- and K+-dependent adenosine triphosphatase activity, a key regulator of CSF secretion, in cell cultures. Finally, we demonstrated that administration of exendin-4 to female rats with raised ICP (hydrocephalic) resulted in a GLP-1R-mediated reduction in ICP. These findings suggest that GLP-1R agonists can reduce ICP in rodents. Repurposing existing GLP-1R agonist drugs may be a useful therapeutic strategy for treating raised ICP.

PMID:
28835515
DOI:
10.1126/scitranslmed.aan0972
[Indexed for MEDLINE]

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