Dataset Information

Short and Long Term Behavioral and Pathological Changes in a Novel Rodent Model of Repetitive Mild Traumatic Brain Injury.

ABSTRACT: A history of concussion, particularly repeated injury, has been linked to an increased risk for the development of neurodegenerative diseases, particularly chronic traumatic encephalopathy (CTE). CTE is characterized by abnormal accumulation of hyperphosphorylated tau and deficits in learning and memory. As yet the mechanisms associated with the development of CTE are unknown. Accordingly, the aim of the current study was to develop and characterize a novel model of repetitive mTBI that accurately reproduces the key short and long-term functional and histopathological features seen clinically. Forty male Sprague-Dawley rats were randomly assigned to receive 0, 1 or 3x mTBI spaced five days apart using a modified version of the Marmarou impact-acceleration diffuse-TBI model to deliver 110G of linear force. Functional outcomes were assessed six and twelve weeks post-injury, with histopathology assessed twenty-four hours and twelve weeks post-injury. Repetitive mTBI resulted in mild spatial and recognition memory deficits as reflected by increased escape latency on the Barnes maze and decreased time spent in the novel arm of the Y maze. There was a trend towards increased anxiety-like behavior, with decreased time spent in the inner portion of the open field. At 24 hours and 12 weeks post injury, repetitive mTBI animals showed increased tau phosphorylation and microglial activation within the cortex. Increases in APP immunoreactivity were observed in repetitive mTBI animals at 12 weeks indicating long-term changes in axonal integrity. This novel model of repetitive mTBI with its persistent cognitive deficits, neuroinflammation, axonal injury and tau hyperphosphorylation, thus represents a clinically relevant experimental approach to further explore the underlying pathogenesis of CTE.

SUBMITTER: McAteer KM

PROVIDER: S-EPMC4978416 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Short and Long Term Behavioral and Pathological Changes in a Novel Rodent Model of Repetitive Mild Traumatic Brain Injury.

McAteer Kelly M KM Corrigan Frances F Thornton Emma E Turner Renee Jade RJ Vink Robert R

PloS one 20160809 8

A history of concussion, particularly repeated injury, has been linked to an increased risk for the development of neurodegenerative diseases, particularly chronic traumatic encephalopathy (CTE). CTE is characterized by abnormal accumulation of hyperphosphorylated tau and deficits in learning and memory. As yet the mechanisms associated with the development of CTE are unknown. Accordingly, the aim of the current study was to develop and characterize a novel model of repetitive mTBI that accurate ...[more]

PMID: 27505027

Similar Datasets

Project description:Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue was examined for cellularity, myelin content, protein and lipid changes. Increased cellularity and areas of demyelination were clearly detectable in optic nerves in r-mTBI, but not in r-sham. These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs. Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL), tubulin (TUBB2A, TUBA4A), microtubule-associated proteins (MAP1A, MAP1B), collagen (COL6A1, COL6A3) and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1), APOE and cathepsin D. Lipidomic analysis showed quantitative changes in a number of phospholipid species, including a significant increase in the total amount of lysophosphatidylcholine (LPC), including the molecular species 16:0, a known demyelinating agent. The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased. Results from the biochemical analysis correlate well with changes detected by histological and immunohistochemical methods and indicate the involvement of several important molecular pathways. This will allow future identification of therapeutic targets for improving the visual consequences of r-mTBI.

Dataset Information

Short and Long Term Behavioral and Pathological Changes in a Novel Rodent Model of Repetitive Mild Traumatic Brain Injury.

Publications

Short and Long Term Behavioral and Pathological Changes in a Novel Rodent Model of Repetitive Mild Traumatic Brain Injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets