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Bone marrow is a highly cellular connective tissue, containing both fixed elements (blood vessels, adipocytes, stromal and staminal cells) and mobile cells (blood cellular elements and their precursors). Since mature immune cells are also found in other connective tissues, especially during inflammation, the only way to identify bone marrow with certainty is by labelling its unique components, i.e. blood cell precursors and stromal components. This however creates two problems: 1-mobile cells are lost, in variable measure, during tissue sectioning, and 2-most bone marrow cells do not display unique epitopes, just unique combinations of them. Within most bones, these problems do not significantly affect marrow identification, since the latter is contained in large, well-defined bone cavities, and even after some cell loss, most of its elements are still present in sufficient quantity to be visualized by immunofluorescence. The temporal bone, however, displays unique structural complexity, and in particular the petrosal bone surrounding the inner ear is made of extremely dense bone formed by endochondral ossification (different from calvaria, which are formed by membranous ossification) and even displays cartilage remnants in the adult. Although immune cells have been observed throughout the petrosal bone, only at the petrosal apex bone marrow has been identified as such. Recently, however, in the human temporal bone, cavities compatible with bone marrow were found by synchrotron imaging to be located between the cochlear base and endolymphatic sac and connected with the latter through bone channels (Liu et al., 2024, doi: 10.3389/fneur.2024.1355785). In a similar position, by using tissue clearing, we observed in the rat temporal bone highly cellular cavities with a similar connection pattern (Perin et al., 2024, doi: 10.3389/fneur.2024.1386654). These cavities could be as small as only containing a few hundred cells only, and in previous work they had been addressed as perivascular connective. However, even the smallest cavities contained megakaryocytes, which are platelet precursor and are confined to marrow in other bones. Therefore, the small cavities within the petrosal bone can be identified as bone marrow, and may be involved in local inner ear immune responses. [ABSTRACT FROM AUTHOR]

Using tissue clearing and immunofluorescence, we have recently characterized the adult rat temporal bone marrow distribution, and in particular the distribution and connections to the inner ear of petrosal bone marrow (doi: 10.3389/ fneur.2024.1386654). Bone marrow was identified by its high cellular content and by the presence of cell populations belonging to the hemopoietic niche (e.g. megakaryocytes, see companion abstract from our group). In the cleared rat pet-rosal bone, autofluorescence allowed delineation of the otic capsule. The largest marrow island was found outside of the otic capsule, surrounding semicircular canal arms, and connecting to the dura through bone channels similar to those of calvarial bone, with only a few channels directed towards the bony labyrinth. Unexpectedly, bone marrow was also observed within the otic capsule endochondral layer, forming small clusters associated to the vestibule (VEM) and cochlear apex (CAEM). Endochondral bone marrow was connected through vascular loops to the labyrinth, and through straight channels to dural sinuses. The latter also received vascular connection from marrow located in surrounding bones, suggesting a role as immune barrier restricting pathogen spread from ear to brain. In mouse, petrosal bone marrow distribution was overall similar to the rat but displayed a few differences. The most evident difference was the volume ratio of CAEM over total petrosal bone marrow (23 ± 1% in mouse, n = 2; 2 ± 1% in rat, n = 8; p < 10E-8). Moreover, CAEM and VEM were connected by vascular bridges in mouse but not in rat. Given the importance of local bone marrow in the immune reactions of brain (doi: 10.1111/imr.13120) and middle ear (doi: 10.3389/fgene.2022.985214), this difference in CAEM volume and connectivity calls for attention in choosing a model for human inner ear immune reactions. [ABSTRACT FROM AUTHOR]