Effect of intranasal administration of concentrated growth factors on regeneration of the olfactory epithelium in an olfactory dysfunction-induced rat model.

OBJECTIVE: The development of treatments that promote the regenerative capacity of the olfactory epithelium (OE) is desirable. This study aimed to evaluate the effects of intranasal administration of concentrated growth factors (CGFs) in a rat model of olfactory dysfunction. STUDY DESIGN: Animal study. METHODS: Nineteen male rats were used. Fourteen olfactory dysfunction models were created by intraperitoneal administration of 3-methylindole. We randomly divided the rats from the olfactory dysfunction model after 1 week into the CGF or saline group; CGFs were administered to seven animals and saline to seven animals. Behavioral assessments using the avoidance test were conducted until day 28 after CGF/saline administration. On day 28, histological evaluation was conducted to determine olfactory epithelial thickness and the olfactory marker protein (OMP)-positive cell count. Five animals were intraperitoneally injected with saline as the control group. RESULTS: The avoidance rate remained decreased until 28 days after CGF/saline administration, and there was no significant difference between the two groups. Olfactory epithelial thicknesses on day 28 were 38.64 ± 3.17 µm and 32.84 ± 4.50 µm in the CGF and saline groups, respectively. OE thickness was significantly thicker in the CGF group than in the saline group (P = 0.013). The numbers of OMP-positive cells were 40.29 ± 9.77/1.0 × 104 µm2 and 31.00 ± 3.69/1.0 × 104 µm2 in the CGF and saline groups, respectively. The number of OMP+ cells in the CGF group was significantly increased compared with that in the saline group (P = 0.009). Both groups showed no improvement compared with the control group (OE thickness: 54.08 ± 3.36 µm; OMP+ cell count: 56.90 ± 9.91/1.0 × 104 µm2). CONCLUSIONS: The CGF group showed improved olfactory epithelial thickness and OMP-positive cell numbers compared with that in the saline group.

Histological changes in the olfactory bulb and rostral migratory stream due to interruption of olfactory input.

OBJECTIVE: Periglomerular and granule cells in the adult mammalian olfactory bulb modulate olfactory signal transmission. These cells originate from the subventricular zone, migrate to the olfactory bulb via the Rostral Migratory Stream (RMS), and differentiate into mature cells within the olfactory bulb throughout postnatal life. While the regulation of neuroblast development is known to be affected by external stimuli, there is a lack of information concerning changes that occur during the recovery process after injury caused by external stimuli. To address this gap in research, the present study conducted histological observations to investigate changes in the olfactory bulb and RMS occurring after the degeneration and regeneration of olfactory neurons. METHODS: To create a model of olfactory neurodegeneration, adult mice were administered methimazole intraperitoneally. Nasal tissue and whole brains were removed 3, 7, 14 and 28 days after methimazole administration, and EdU was administered 2 and 4 h before removal of these tissues to monitor dividing cells in the RMS. Methimazole-untreated mice were used as controls. Olfactory nerve fibers entering the olfactory glomerulus were observed immunohistochemically using anti-olfactory marker protein. In the brain tissue, the entire RMS was observed and the volume and total number of cells in the RMS were measured. In addition, the number of neuroblasts and dividing neuroblasts passing through the RMS were measured using anti-doublecortin and anti-EdU antibodies, respectively. Statistical analysis was performed using the Tukey test. RESULTS: Olfactory epithelium degenerated was observed after methimazole administration, and recovered after 28 days. In the olfactory glomeruli, degeneration of OMP fibers began after methimazole administration, and after day 14, OMP fibers were reduced or absent by day 28, and overall OMP positive fibers were less than 20%. Glomerular volume tended to decrease after methimazole administration and did not appear to recover, even 28 days after recovery of the olfactory epithelium. In the RMS, EdU-positive cells decreased on day 3 and began to increase on day 7. However, they did not recover to the same levels as the control methimazole-untreated mice even after 28 days. CONCLUSION: These results suggest that the division and maturation of neuroblasts migrating from the RMS was suppressed by olfactory nerve degeneration or the disruption of olfactory input.

Histological evaluation of the alpaca (Vicugna pacos) vomeronasal organ.

Little is known about the neuronal structure of the vomeronasal organ (VNO), a receptor organ responsible for pheromone perception, in the alpaca (Vicugna pacos). This study was performed to determine the localization of neuronal elements, including protein gene product 9.5 (PGP 9.5), a pan-neuronal marker, olfactory marker protein (OMP), a marker of mature olfactory receptor cells, and phospholipase C beta 2 (PLC-ß2), a marker of solitary chemoreceptor cells (SCCs), in the VNO. OMP was identified in receptor cells of the vomeronasal sensory epithelium (VSE), while PGP 9.5 and PLC-ß2 were localized in both the VSE and vomeronasal non-sensory epithelium. Collectively, these results suggested that the alpaca VNO possesses SCCs and olfactory receptor cells, which recognize both harmful substances and pheromones.