A glucagon-like peptide-1 receptor agonist reduces intracranial pressure in a rat model of hydrocephalus
| العنوان: | A glucagon-like peptide-1 receptor agonist reduces intracranial pressure in a rat model of hydrocephalus |
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| المؤلفون: | James L Mitchell, Rigmor Jensen, Maria Uldall, Alexandra J Sinclair, Snorre Malm Hagen, David J. Hodson, Hannah Botfield, Ana Maria Gonzalez, Connar Westgate |
| المصدر: | Science Translational Medicine. 9 |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Agonist, endocrine system, medicine.medical_specialty, Consciousness, Intracranial Pressure, medicine.drug_class, Glucagon-Like Peptide-1 Receptor, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Internal medicine, Cyclic AMP, medicine, Animals, Humans, RNA, Messenger, Receptor, Glucagon-like peptide 1 receptor, Intracranial pressure, Kidney, Venoms, business.industry, digestive, oral, and skin physiology, Antagonist, General Medicine, 3. Good health, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Postmortem Changes, Choroid Plexus, Exenatide, Female, Choroid plexus, Sodium-Potassium-Exchanging ATPase, Peptides, business, hormones, hormone substitutes, and hormone antagonists, 030217 neurology & neurosurgery, Hydrocephalus |
| الوصف: | 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. |
| تدمد: | 1946-6242 1946-6234 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::87911b2ba2bdba79994b9b14a26bd5fbTest https://doi.org/10.1126/scitranslmed.aan0972Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....87911b2ba2bdba79994b9b14a26bd5fb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19466242 19466234 |
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