1. Repeated Closed Head Injury in Mice Results in Sustained Motor and Memory Deficits and Chronic Cellular Changes.
- Author
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Bolton Hall AN, Joseph B, Brelsfoard JM, and Saatman KE
- Subjects
- Animals, Brain Concussion metabolism, Brain Concussion pathology, Cerebral Cortex metabolism, Cerebral Cortex pathology, Corpus Callosum metabolism, Corpus Callosum pathology, Disease Models, Animal, Gene Expression, Gliosis metabolism, Gliosis pathology, Gliosis physiopathology, Head Injuries, Closed metabolism, Head Injuries, Closed pathology, Hippocampus metabolism, Hippocampus pathology, Male, Memory Disorders metabolism, Memory Disorders pathology, Mice, Mice, Inbred C57BL, Neurofilament Proteins genetics, Neurofilament Proteins metabolism, Neuroglia metabolism, Neuroglia pathology, Neurons metabolism, Neurons pathology, Optic Nerve metabolism, Optic Nerve pathology, Optic Nerve physiopathology, Optic Tract metabolism, Optic Tract pathology, Optic Tract physiopathology, Psychomotor Performance, Pyramidal Tracts metabolism, Pyramidal Tracts pathology, Pyramidal Tracts physiopathology, Brain Concussion physiopathology, Cerebral Cortex physiopathology, Corpus Callosum physiopathology, Head Injuries, Closed physiopathology, Hippocampus physiopathology, Memory Disorders physiopathology
- Abstract
Millions of mild traumatic brain injuries (TBIs) occur every year in the United States, with many people subject to multiple head injuries that can lead to chronic behavioral dysfunction. We previously reported that mild TBI induced using closed head injuries (CHI) repeated at 24h intervals produced more acute neuron death and glial reactivity than a single CHI, and increasing the length of time between injuries to 48h reduced the cumulative acute effects of repeated CHI. To determine whether repeated CHI is associated with behavioral dysfunction or persistent cellular damage, mice receiving either five CHI at 24h intervals, five CHI at 48h intervals, or five sham injuries at 24h intervals were evaluated across a 10 week period after injury. Animals with repeated CHI exhibited motor coordination and memory deficits, but not gait abnormalities when compared to sham animals. At 10wks post-injury, no notable neuron loss or glial reactivity was observed in the cortex, hippocampus, or corpus callosum. Argyrophilic axons were found in the pyramidal tract of some injured animals, but neither silver stain accumulation nor inflammatory responses in the injury groups were statistically different from the sham group in this region. However, argyrophilic axons, microgliosis and astrogliosis were significantly increased within the optic tract of injured animals. Repeated mild CHI also resulted in microgliosis and a loss of neurofilament protein 200 in the optic nerve. Lengthening the inter-injury interval from 24h to 48h did not effectively reduce these behavioral or cellular responses. These results suggest that repeated mild CHI results in persistent behavioral dysfunction and chronic pathological changes within the visual system, neither of which was significantly attenuated by lengthening the inter-injury interval from 24h to 48h.
- Published
- 2016
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