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Local drug delivery based on nanoparticles (NP) represents a novel strategy to improve inner ear treatments. The intratympanic delivery of NP may be suitable to treat or prevent hearing loss originating from damage to hair cells and spiral ganglion neurons in the cochlea. Numerous experimental studies support in vitroand in vivothe biocompatibility of NP, their physical stability, target specificity, cell/tissue uptake and ability to internalize therapeutic agents. The topical use of NP helps to reduce the amount of drug required and avoid systemic side effects. This review focuses on recent findings and applications of different NP systems locally delivered to the inner ear. The perspectives for clinical application of NP in inner ear drug delivery are also discussed.

We investigated the fate of human cord blood CD133+ hematopoietic stem cells (HSC) transplanted intravenously (IV) into irradiated nodscid mice previously made deaf by ototoxic treatment with kanamycin and/or intense noise, to verify whether HSC engraft the cochlea and contribute to inner ear restoration, in vivo. We tested the presence of HLA.DQα1 by PCR, used for traceability of engrafted cells, finding evidence that HSC migrated to various host tissues, including the organ of Corti (OC). By histology, antibody and lectin-staining analysis, we confirmed that HSC IV transplantation in mice previously damaged by ototoxic agents correlated with the repair process and stimulation ex novo of morphological recovery in the inner ear, while the cochlea of control oto-injured, nontransplanted mice remained seriously damaged. Dual color FISH analysis also provided evidence of positive engraftment in the inner ear and in various mouse tissues, also revealing small numbers of heterokaryons, probably derived from fusion of donor with endogenous cells, for up to 2 months following transplantation. These observations offer the first evidence that transplanted human HSC migrating to the inner ear of oto-injured mice may provide conditions for the resumption of deafened cochlea, emerging as a potential strategy for inner ear rehabilitation.

The present immunoperoxidase cytochemical study describes the distribution of glial intermediate filament molecular markers, glial fibrillary acidic protein (GFAP) and vimentin, in the brain and spinal cord of the adult lizard, Podarcis sicula. GFAP immunoreactivity is abundant and the positive structures are mainly represented by fibres of different lengths which are arranged in a rather regular radial pattern throughout the CNS. They emerge from generally immunopositive radial ependymoglia and are directed from the ventricular wall towards the meningeal surface. The glial fibres give origin to endfeet which are apposed to the blood vessel walls and subpial surface where they form the continous perivascular and subpial glia envelopes, respectively. In the optic tectum and spinal cord, star‐shaped astrocytes coexist with radial glia. In the spinal cord, cell bodies of immunopositive radial glia are displaced from the ependyma. While vimentin immunoreactive elements are almost completely absent in the brain except for a few diencephalic radial fibres, the spinal cord ependyma exhibits a clearly vimentin positivity and no GFAP staining. In the PodarcisCNS the immunocytochemical response of the astroglial intermediate filaments appears typical of mature astroglia cell lineage since it fundamentally expresses GFAP immunoreactivity. Moreover, this immunocytochemical study shows that the Podarcisfibre pattern with predominant radial glial cells is morphologically more immature than in avians and mammalians, a condition suggesting that reptiles represent a fundamental step in the phylogenetic evolution of vertebrate astroglial cells.

The structure and 3‐dimensional pattern of the intraparenchymal microvessels in the brain of the lizard, Podarcis sicula, were studied by a combination of light and transmission electron microscopy as well as scanning electron microscopy of vascular corrosion casts. The angioarchitecture pattern consists of narrow hairpin‐shaped microvascular loops of different length originating from the meningeal surface. In each loop, descending and ascending vessels are closely apposed to one another throughout their length and are connected by a narrow U‐shaped terminal loop at their tips. The 2 limbs of the vessel pairs show a slightly different diameter but lack other structural differences. While some paired vessels give rise to a secondary hairpin‐shaped loop with 2 possible branching patterns, there are no anastomotic intraparenchymal connections with analogous neighbouring structures. The cerebral vascular pattern of Podarcis sicularesembles that found in a few representatives of other vertebrate classes. All cerebral vessels structurally appear to be capillaries. Also the observations carried out on semithin and thin sections strongly support the capillary loop model in the Podarcisbrain vasculature and, in accordance with studies carried out on various vertebrates, the general submicroscopic features of the brain capillary wall suggest the presence of an endothelial type blood‐brain barrier.

Lectin binding was performed on the olfactory system of Polypterusand Erpetoichthys, the living genera of the subclass of Brachiopterygii. The lectin histochemicalpatterns and the Western-blot analysis indicate that the receptor cells of the olfactory mucosa arecharacterized by high density of specific glycoconjugate residues. The presence of glycoproteins,whose terminal sugars are detected by lectin binding, might be related to the reception of an odorstimulus and its transduction into a nervous signal or to the histogenesis of the olfactory system.© 1999 ISDN. Published by Elsevier Science Ltd. All rights reserved

Regenerative capacity of the optic tectum in reptiles was studied in adults of Lacerta viridis kept for 24 hours at 4°C before extraction of a dorsomedial portion of the right optic tectum. Five months after surgery brain sections were prepared with standard autoradiographic techniques.From this investigation it emerged that five months after surgery, cell divisions in the brain were still very numerous, while in the lesioned area continuity of the ependyma had been regained. Above the ependyma in some areas, a zone of reformed nervous tissue was present with clear signs of cell and fibre stratification.These observations strengthen the hypothesis of a connection between loss of regenerative capacity by the C.N.S. with installation of blood-brain barrier and, conversely, of the reinstating of such capacity after alteration of this barrier.

The appearance and distribution of acetylcholinesterase (AChE) activity in the nervous parenchyma and intracerebral capillaries in Rana esculenta tadpoles were studied. Histochemical data showed that at the onset of metamorphosis (stage 34), AChE activity was low and limited to a few scattered neurons. At the capillary level, AChE was found only in a few short tracts of the basal membrane. In the following stages AChE activity increased because neurons synthetized greater amounts of the enzyme and because the number of AChE-synthetizing neurons had increased. The amount of the enzyme in the intracerebral capillaries progressively increased up to stage 50, at which point the whole basal membrane was AChE-positive.Biochemical assays confirmed that the AChE level progressively increased from stage 34 to stage 50 to reach a level similar to that found in the adult animal.