title: Biphalin protects against cognitive deficits in a mouse model of mild traumatic brain injury (mTBI).
abstract: Traumatic brain injury (TBI) is often a result of traffic accidents, contact sports or battlefield explosions. A mild form of traumatic brain injury (mTBI) is frequently underestimated, as the immediate physical symptoms decrease rapidly and conventional neuroimaging studies often do not show visible evidence of brain lesions. However, cognitive impairments persist for weeks, months or even years after the incident. Endogenous opioids were documented to play a role in thmodulation of mTBI pathology, whereas exogenous opioids were shown to possess neuroprotective properties. In the present study, biphalin, a dimeric enkephalin analog, improved cognitive performance in the Morris Water Maze and Novel Object Recognition tests in a mouse weight-drop model of mTBI. The effect of a single systemic injection of 10 mg/kg biphalin immediately after trauma was reversed by naltrexone, suggesting an opioid receptor-mediated mechanism. Biphalin also reduced cortical and hippocampal neurodegeneration, as shown by silver staining. Our data indicates that opioid receptor activation by biphalin may provide neuroprotection of post-traumatic neurodegeneration processes and may protect against memory impairments.
authors.affiliation: Mossakowski Medical Research Centre, Dept. of Neuropeptides, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland; Uppsala University, Dept. of Pharmaceutical Biosciences, Husargatan 3, Se-751 24 Uppsala, Sweden. Electronic address: alesniak@imdik.pan.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Lesniak
authors.affiliation: Tel Aviv University, Dept. of Anatomy, Sackler School of Medicine, Ramat-Aviv 69978, Tel Aviv, Israel.
authors.forename: Chaim G
authors.initials: CG
authors.lastname: Pick
authors.affiliation: Mossakowski Medical Research Centre, Dept. of Neuropeptides, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland; University of Warsaw, Faculty of Chemistry, Pasteura 1, 02-093 Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Misicka
authors.affiliation: Mossakowski Medical Research Centre, Dept. of Neuropeptides, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland.
authors.forename: Andrzej W
authors.initials: AW
authors.lastname: Lipkowski
authors.affiliation: Institute of Genetics and Animal Breeding, Dept. of Cytogenetics, Polish Academy of Sciences, Jastrzebiec, Postepu 36A, 05-552 Magdalenka, Poland. Electronic address: m.sacharczuk@ighz.pl.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Sacharczuk
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000178:diet therapy / Q000188:drug therapy / Q000209:etiology; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D004195:Disease Models, Animal; D004745:Enkephalins / Q000494:pharmacology / Q000627:therapeutic use*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D021641:Recognition, Psychology / Q000187:drug effects; D016622:Silver Staining
chemical_list: D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D009271:Naltrexone; C053673:biphalin
keywords: Biphalin; Mouse model; Neuroprotection; Traumatic brain injury