title: Moderate traumatic brain injury increases the vulnerability to neurotoxicity induced by systemic administration of 6-hydroxydopamine in mice.
abstract: Moderate traumatic brain injury (TBI) might increase the vulnerability to neuronal neurodegeneration, but the basis of such selective neuronal susceptibility has remained elusive. In keeping with the disruption of the blood-brain barrier (BBB) caused by TBI, changes in BBB permeability following brain injury could facilitate the access of xenobiotics into the brain. To test this hypothesis, here we evaluated whether TBI would increase the susceptibility of nigrostriatal dopaminergic fibers to the systemic administration of 6-hydroxydopamine (6-OHDA), a classic neurotoxin used to trigger a PD-like phenotype in mice, but that in normal conditions is unable to cross the BBB. Adult Swiss mice were submitted to a moderate TBI using a free weight-drop device and, 5h later, they were injected intraperitoneally with a single dose of 6-OHDA (100mg/kg). Afterwards, during a period of 4weeks, the mice were submitted to a battery of behavioral tests, including the neurological severity score (NSS), the open field and the rotarod. Animals from the TBI plus 6-OHDA group displayed significant motor and neurological impairments that were improved by acute l-DOPA administration (25mg/kg, i.p.). Moreover, the observation of the motor deficits correlates with (i) a significant decrease in the tyrosine hydroxylase levels mainly in the rostral striatum and (ii) a significant increase in the levels of striatal glial fibrillary acidic protein (GFAP) levels. On the whole, the present findings demonstrate that a previous moderate TBI event increases the susceptibility to motor, neurological and neurochemical alterations induced by systemic administration of the dopaminergic neurotoxin 6-OHDA in mice.
authors.affiliation: Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Brazil.
authors.forename: Paulo Alexandre
authors.initials: PA
authors.lastname: de Oliveira
authors.affiliation: Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Brazil; Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Ben
authors.affiliation: Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Brazil.
authors.forename: Filipe Carvalho
authors.initials: FC
authors.lastname: Matheus
authors.affiliation: Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Brazil; Centro de Neurociências Aplicadas (CeNAp), Departamento de Clínica Médica, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Brazil.
authors.forename: Marcelo Liborio
authors.initials: ML
authors.lastname: Schwarzbold
authors.affiliation: Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Brazil; Departamento de Ciências Fisiológicas, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Brazil.
authors.forename: Eduardo Luiz Gasnhar
authors.initials: ELG
authors.lastname: Moreira
authors.affiliation: Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rial
authors.affiliation: Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Brazil; Centro de Neurociências Aplicadas (CeNAp), Departamento de Clínica Médica, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Brazil.
authors.forename: Roger
authors.initials: R
authors.lastname: Walz
authors.affiliation: Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Brazil; Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina, Florianópolis 88049-900, Brazil. Electronic address: ruidsp@hotmail.com.
authors.forename: Rui Daniel
authors.initials: RD
authors.lastname: Prediger
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D051379:Mice; D019636:Neurodegenerative Diseases; D020258:Neurotoxicity Syndromes / Q000378:metabolism; D016627:Oxidopamine / Q000378:metabolism / Q000633:toxicity*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D007980:Levodopa; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: 6-Hydroxydopamine (6-OHDA); Blood-brain barrier (BBB); Parkinson’s disease (PD); Traumatic brain injury (TBI)