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 |
Externí odkaz: |