Volumetric histological characterization of optic nerve degeneration using tissue clearing: literature review and practical study.

Tissue clearing technologies can greatly improve the depth and accuracy with which the three-dimensional structure of tissues, especially those of th*-e nervous system, can be visualized. A review of the present literature suggests that the growing diversity and sophistication of various approaches have contributed to the expansion of this method to a greater variety of tissue types, experimental conditions, and imaging modalities. In the proof-of-concept study presented in this paper, a simplified and modified version of the tissue clearing method CUBIC (clear, unobstructed brain imaging cocktails and computational analysis) was used in conjunction with fluorescent staining and immunohistochemistry to illustrate the three-dimensional structure and molecular characteristics of inflammatory and degenerative activity in the mouse optic nerve. Based on the studies summarized in this mini-review, and our impression from using the mCUBIC method, it appears that tissue clearing could be a viable approach revealing three-dimensional histological features of myelin-rich tissues under normal conditions and after injury.

Inflammatory changes in optic nerve after closed-head repeated traumatic brain injury: Preliminary study.

BACKGROUND: Closed-head, repeated, mild traumatic brain injury (r-mTBI) leads to inflammatory and degenerative changes in the optic nerve of young wild type mice. This work has investigated whether similar changes may be present when the same model is applied to htau mice, a transgenic mouse in which the non-mutated human tau gene is expressed on a null murine tau background. METHODS: This study investigated neuropathological changes in the optic nerve in both young (15 weeks) and old (65-70 weeks) htau mice at 24 hours after r-mTBI or anaesthesia only (r-sham). Change in the level of cellularity, myelin content and astroglial reactivity were evaluated in optic nerve samples. RESULTS: Increased cellularity and areas of demyelination were clearly detectable in the intracranial portion of the optic nerve in both young (10-15 weeks) and old (65-75) htau r-mTBI mice at 24 hours post-injury, in contrast to r-sham. Increased astroglial reactivity was also observed, together with increased tau phosphorylation. CONCLUSIONS: Localized inflammatory and degenerative response of the intracranial part of the optic nerve was detected in htau mice after r-mTBI. Further studies to clarify the cause and consequences of this phenomenon are warranted.