Abstract
Adult male C57BL/6J mice have previously been reported to have motor and memory deficits after experimental closed head traumatic brain injury (TBI), without associated gross pathologic damage or neuroimaging changes detectable by magnetic resonance imaging or diffusion tensor imaging protocols. The presence of neurologic deficits, however, suggests neural damage or dysfunction in these animals. Accordingly, we undertook a histologic analysis of mice after TBI. Gross pathology and histologic analysis using Nissl stain and NeuN immunohistochemistry demonstrated no obvious tissue damage or neuron loss. However, Luxol Fast Blue stain revealed myelin injury in the optic tract, while Fluoro Jade B and silver degeneration staining revealed evidence of axonal neurodegeneration in the optic tract as well as the lateral geniculate nucleus of the thalamus and superior colliculus (detectable at 7 days, but not 24 hours, after injury). Fluoro Jade B staining was not detectable in other white matter tracts, brain regions or in cell somata. In addition, there was increased GFAP staining in these optic tract, lateral geniculate, and superior colliculus 7 days post-injury, and morphologic changes in optic tract microglia that were detectable 24 hours after injury but were more prominent 7 days post-injury. Interestingly, there were no findings of degeneration or gliosis in the suprachiasmatic nucleus, which is also heavily innervated by the optic tract. Using micro-computed tomography imaging, we also found that the optic canal appears to decrease in diameter with a dorsal-ventral load on the skull, which suggests that the optic canal may be the site of injury. These results suggest that there is axonal degeneration in the optic tract and a subset of directly innervated areas, with associated neuroinflammation and astrocytosis, which develop within 7 days of injury, and also suggest that this weight drop injury may be a model for studying indirect traumatic optic neuropathy.
Highlights
Traumatic brain injury (TBI) is one of the leading causes of death and disability, and leads to annual costs of at least $60 billion in the United States alone [1]
We have demonstrated in a murine closed head TBI model that there is reproducible damage not readily detectable by standard histological approaches, specific to the optic tract and some, but not all, brain regions receiving input from axons traveling in the optic tract
Because we found evidence of degenerating axons and gliosis in lateral geniculate nucleus of the thalamus (LGN) and superior colliculus (SC) but not in suprachiasmatic nucleus (SCN), it is possible that the optic tract injury found in our model spares some types of retinal ganglion cells
Summary
Traumatic brain injury (TBI) is one of the leading causes of death and disability, and leads to annual costs of at least $60 billion in the United States alone [1]. It was noted that mice undergoing TBI in this modified weight drop model developed blood-brain barrier permeability in the acute phase after injury, and serum and cytokine profiles consistent with inflammation. In the novel object recognition test, post-TBI mice were less able to recognize the novel object, as shown by a significantly lower ratio of time with the novel object to time with the familiar object than was observed in sham animals [5]. These deficits appeared to be due to inflammation secondary to the injury [6]. Specific brain areas affected by the injury were not identifiable by our previously utilized methods [5]
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