title: Effects of beta-hydroxybutyrate on brain vascular permeability in rats with traumatic brain injury.
abstract: This study investigates the effect of beta-hydroxybutyrate (BHB) on blood-brain barrier (BBB) integrity during traumatic brain injury (TBI) in rats. Evans blue (EB) and horseradish peroxidase (HRP) were used as determinants of BBB permeability. Glutathione (GSH) and malondialdehyde (MDA) levels were estimated in the right (injury side) cerebral cortex of animals. The gene expression levels for occludin, glucose transporter (Glut)-1, aquaporin4 (AQP4) and nuclear factor-kappaB (NF-κB) were performed, and Glut-1 and NF-κB activities were analyzed. BHB treatment decreased GSH and MDA levels in intact animals and in those exposed to TBI (P<0.05). Glut-1 protein levels decreased in sham, BHB and TBI plus BHB groups (P<0.05). NF-κB protein levels increased in animals treated with BHB and/or exposed to TBI (P<0.05). The expression levels of occludin and AQP4 did not significantly change among experimental groups. Glut-1 expression levels increased in BHB treated and untreated animals exposed to TBI (P<0.05). While NF-κB expression levels increased in animals in TBI (P<0.01), a decrease was noticed in these animals upon BHB treatment (P<0.01). In animals exposed to TBI, EB extravasation was observed in the ipsilateral cortex regardless of BHB treatment. Ultrastructurally, BHB attenuated but did not prevent the presence of HRP in brain capillary endothelial cells of animals with TBI; moreover, the drug also led to the observation of the tracer when used in intact rats (P<0.01). Altogether, these results showed that BHB not only failed to provide overall protective effects on BBB in TBI but also led to BBB disruption in healthy animals.
authors.affiliation: Department of Neuroscience, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Nurcan
authors.initials: N
authors.lastname: Orhan
authors.affiliation: Department of Laboratory Animals Science, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey; Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Canan
authors.initials: C
authors.lastname: Ugur Yilmaz
authors.affiliation: Department of Forensic Medicine, Tepecik Training and Research Hospital, Izmir, Turkey.
authors.forename: Oguzhan
authors.initials: O
authors.lastname: Ekizoglu
authors.affiliation: Department of Histology and Embryology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Ahishali
authors.affiliation: Department of Laboratory Animals Science, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Mutlu
authors.initials: M
authors.lastname: Kucuk
authors.affiliation: Department of Forensic Medicine, Tepecik Training and Research Hospital, Izmir, Turkey.
authors.forename: Nadir
authors.initials: N
authors.lastname: Arican
authors.affiliation: Department of Forensic Medicine, Tepecik Training and Research Hospital, Izmir, Turkey.
authors.forename: Imdat
authors.initials: I
authors.lastname: Elmas
authors.affiliation: Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Candan
authors.initials: C
authors.lastname: Gürses
authors.affiliation: Department of Physiology, Koç University School of Medicine, Istanbul, Turkey. Electronic address: mehmetkaya@ku.edu.tr.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kaya
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D062793:Occludin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D051272:Glucose Transporter Type 1; D016328:NF-kappa B; D018696:Neuroprotective Agents; D062793:Occludin; D008315:Malondialdehyde; D005978:Glutathione; D020155:3-Hydroxybutyric Acid
keywords: Beta-hydroxybutyrate; Blood–brain barrier; Glucose transporter-1; Horseradish peroxidase; Occludin; Traumatic brain injury