title: Preservation of the blood brain barrier and cortical neuronal tissue by liraglutide, a long acting glucagon-like-1 analogue, after experimental traumatic brain injury.
abstract: Cerebral edema is a common complication following moderate and severe traumatic brain injury (TBI), and a significant risk factor for development of neuronal death and deterioration of neurological outcome. To this date, medical approaches that effectively alleviate cerebral edema and neuronal death after TBI are not available. Glucagon-like peptide-1 (GLP-1) has anti-inflammatory properties on cerebral endothelium and exerts neuroprotective effects. Here, we investigated the effects of GLP-1 on secondary injury after moderate and severe TBI. Male Sprague Dawley rats were subjected either to TBI by Controlled Cortical Impact (CCI) or sham surgery. After surgery, vehicle or a GLP-1 analogue, Liraglutide, were administered subcutaneously twice daily for two days. Treatment with Liraglutide (200 μg/kg) significantly reduced cerebral edema in pericontusional regions and improved sensorimotor function 48 hours after CCI. The integrity of the blood-brain barrier was markedly preserved in Liraglutide treated animals, as determined by cerebral extravasation of Evans blue conjugated albumin. Furthermore, Liraglutide reduced cortical tissue loss, but did not affect tissue loss and delayed neuronal death in the thalamus on day 7 post injury. Together, our data suggest that the GLP-1 pathway might be a promising target in the therapy of cerebral edema and cortical neuronal injury after moderate and severe TBI.
authors.affiliation: Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, Lund University, BMC A13, Lund, Sweden; Department of Neurosurgery, Copenhagen University Hospital, Risgshospitalet, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Hakon
authors.affiliation: Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, Lund University, BMC A13, Lund, Sweden.
authors.forename: Karsten
authors.initials: K
authors.lastname: Ruscher
authors.affiliation: Department of Neurosurgery, Copenhagen University Hospital, Risgshospitalet, Denmark; Department of Neurosurgery, University Hospital of Lund, Lund, Sweden.
authors.forename: Bertil
authors.initials: B
authors.lastname: Romner
authors.affiliation: Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, Lund University, BMC A13, Lund, Sweden; Department of Neurosurgery, University Hospital of Lund, Lund, Sweden.
authors.forename: Gregor
authors.initials: G
authors.lastname: Tomasevic
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069450:Liraglutide / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D066191:Sensorimotor Cortex / Q000187:drug effects / Q000503:physiopathology
chemical_list: D001786:Blood Glucose; D018696:Neuroprotective Agents; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1
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