Moderate traumatic brain injury increases the vulnerability to neurotoxicity induced by systemic administration of 6-hydroxydopamine in mice

Autor: Marcelo Liborio Schwarzbold, Daniel Rial, Juliana Ben, Paulo Alexandre de Oliveira, Rui Daniel Prediger, Eduardo Luiz Gasnhar Moreira, Roger Walz, Filipe C. Matheus
Rok vydání: 2016
Předmět:
0301 basic medicine
medicine.medical_specialty
Tyrosine 3-Monooxygenase
Traumatic brain injury
Dopamine
Levodopa
03 medical and health sciences
Mice
0302 clinical medicine
Neurochemical
Internal medicine
Brain Injuries
Traumatic
Glial Fibrillary Acidic Protein
medicine
Neurotoxin
Animals
Oxidopamine
Molecular Biology
Hydroxydopamine
Glial fibrillary acidic protein
biology
Behavior
Animal
General Neuroscience
Dopaminergic Neurons
Dopaminergic
Neurotoxicity
Brain
Neurodegenerative Diseases
medicine.disease
Corpus Striatum
Disease Models
Animal
030104 developmental biology
Endocrinology
nervous system
Blood-Brain Barrier
Anesthesia
Brain Injuries
Systemic administration
biology.protein
Neurotoxicity Syndromes
Neurology (clinical)
Psychology
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Brain research. 1663
ISSN: 1872-6240
Popis: 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.
Databáze: OpenAIRE
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