title: Alteration in BDNF and its receptors, full-length and truncated TrkB and p75(NTR) following penetrating traumatic brain injury.
abstract: The evidence that BDNF is involved in neuroprotection, neuronal repair and recovery after traumatic brain injury (TBI) is substantial. We have previously shown that the polymorphism of the human BDNF gene predicts cognitive recovery and outcome following penetrating TBI. The distribution of expression of BDNF and its receptors after penetrating TBI has not been investigated. In this study we examined the expression of these genes in a rat model of penetrating TBI. The injury is produced by a controlled penetration of a 2mm thick needle-shaped object, which is accelerated with a pellet from an air gun. We used in situ hybridization and investigated the mRNA expression of BDNF and its receptors: the full-length and the truncated TrkB and p75(NTR), from 1 day to 8 weeks following penetrating TBI. In addition, the protein level of BDNF in frontal cortex and hippocampus was measured by reverse phase protein microarray (RPPM). The mRNA expression of BDNF and its receptors decreased in the hippocampus in the border zone ipsilateral to the injury while there was an increase in mRNA expression at the contralateral side. The increase in BDNF mRNA expression in the hippocampus was sustained for 2 weeks following injury, with the highest expression noted in the CA3 cell layer. Furthermore, the protein analysis by RPPM showed increased levels of BDNF in the frontal cortex and the hippocampus up to 2 weeks after TBI. At 8 weeks following injury there was an intense labeling of the truncated TrkB receptor and the p75(NTR) in the area surrounding the cavity. Our study is the first report on the expression of BDNF and its receptors following penetrating TBI and suggests that their expression is altered long after the acute phase of injury. Further studies are needed to investigate if the late expressions of these receptors are beneficial or deleterious. In either case it indicates the possibility to influence the recovery after brain injury during the chronic phase and the development of treatments that may improve the outcome of TBI patients.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, S-171 77 Stockholm, Sweden(1); Department of Neuroscience and Neurosurgery, Uppsala University Hospital, Uppsala, Sweden. Electronic address: Elham.rostami@ki.se.
authors.forename: Elham
authors.initials: E
authors.lastname: Rostami
authors.affiliation: Department of Molecular Neuroscience, George Mason University, Fairfax, VA, USA; Department of Psychology, George Mason University, Fairfax, VA, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Krueger
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, S-171 77 Stockholm, Sweden(1).
authors.forename: Stefan
authors.initials: S
authors.lastname: Plantman
authors.affiliation: Division of Vehicle Safety, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Davidsson
authors.affiliation: Department of Anatomy, Physiology and Genetics, Uniformed Services University, Bethesda, MD, USA.
authors.forename: Denes
authors.initials: D
authors.lastname: Agoston
authors.affiliation: Brain Injury Research, Cognitive Neuroscience Laboratory, Rehabilitation Institute of Chicago, IL, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Grafman
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, S-171 77 Stockholm, Sweden(1).
authors.forename: Mårten
authors.initials: M
authors.lastname: Risling
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; C579455:BDNF protein, human; D020813:Receptor, trkB
keywords: BDNF; Neurotrophins; Traumatic brain injury; TrkB; p75(NTR)