Catherine M. Gliddon

Activation of the hypothalamic-pituitary-adrenal axis following vestibular deafferentation in pigmented guinea pig.

Twelve male pigmented guinea pigs underwent either a unilateral vestibular deafferentation (UVD) (n=6) or sham operation (n=6). Compared to the pre-operated salivary cortisol concentrations, the UVD operation resulted in a significant increase in night cortisol concentrations (P<0.05) and a significant interaction between the night cortisol concentration and time (P<0.05). There was no significant difference between the pre- and post-UVD morning salivary cortisol concentrations; nor between the pre- and post-sham morning or night salivary cortisol concentrations. This study suggests that the ocular-motor and postural syndrome is causing the activation of the hypothalamic-pituitary-adrenal (HPA) axis.

The Effects of Bilateral Vestibular Loss on Hippocampal Volume, Neuronal Number, and Cell Proliferation in Rats

Previous studies in humans have shown that bilateral loss of vestibular function is associated with a significant bilateral atrophy of the hippocampus, which correlated with the patients’ spatial memory deficits. More recently, patients who had recovered from unilateral vestibular neuritis have been reported to exhibit a significant atrophy of the left posterior hippocampus. Therefore, we investigated whether bilateral vestibular deafferentation (BVD) would result in a decrease in neuronal number or volume in the rat hippocampus, using stereological methods. At 16 months post-BVD, we found no significant differences in hippocampal neuronal number or volume compared to sham controls, despite the fact that these animals exhibited severe spatial memory deficits. By contrast, using bromodeoxyuridine (BrdU) as a marker of cell proliferation, we found that the number of BrdU-labeled cells significantly increased in the dentate gyrus of the hippocampus between 48 h and 1 week following BVD. Although a substantial proportion of these cells survived for up to 1 month, the survival rate was significantly lower in BVD animals when compared with that in sham animals. These results suggest a dissociation between the effects of BVD on spatial memory and hippocampal structure in rats and humans, which cannot be explained by an injury-induced increase in cell proliferation.

Interaction between the hypothalamic-pituitary-adrenal axis and behavioural compensation following unilateral vestibular deafferentation.

Vestibular compensation is defined as the process of behavioural recovery that occurs following the loss of sensory input from one or both vestibular labyrinths. The visual and postural instability resulting from the vestibular damage must alter the homeostasis of the subject; however, very little research has been conducted that investigates the interaction between vestibular compensation and the adaptive stress response of the body, i.e. the hypothalamic—pituitary—adrenal (HPA) axis. The aim of this review is to describe and evaluate the experimental evidence indicating a link between vestibular compensation and the bodys response to stress, via the HPA axis.

Rapid vestibular compensation in guinea pig even with prolonged anesthesia.

The results of previous studies have suggested that prolonged anesthesia following unilateral labyrinthectomy (UL) results in a retardation of vestibular compensation, the process of behavioral recovery that occurs following the lesion. In this study we investigated the effects of short-term (25 min) and long-term (4 h) anesthesia with isoflurane on the time course of vestibular compensation following UL in guinea pig. Although there were significant differences in the frequency of spontaneous nystagmus (SN) (p < 0.05) and its rate of compensation (p < 0.05) between the 25 min and 4h isoflurane groups, these differences appeared to be due largely to the 5, 9 and 13 h time points. There was also a significant difference in the rate of yaw head tilt (YHT) compensation, largely due to the 5 h time point. When exponential regression analysis was performed to evaluate the overall pattern of compensation, there was no significant difference in the time required to reach 100% SN or YHT compensation between the 25 min and 4 h isoflurane groups. Furthermore, there were no significant differences in roll head tilt (RHT) compensation between the two groups. These results suggest that the time course of vestibular compensation is largely independent of the duration of the anesthesia used for UL surgery.

Cell proliferation in the cochlear nucleus following acoustic trauma in rat

Our previous studies have suggested that surgical lesions of the rat cochlea induce cell proliferation in the cochlear nucleus (CN) that may be related to neurogenesis. The aim of the present study was to further investigate the nature of cell proliferation in the CN, following acoustic trauma that has previously been shown to induce tinnitus in rats. Rats were subjected either to a unilateral acoustic trauma (16-kHz pure tone, 115dB for 1h under anesthesia) or a sham procedure. Bromodeoxyuridine (BrdU) immunohistochemistry was used to measure cell proliferation and newborn cell survival; an antibody to interleukin-6 was used to investigate inflammatory responses; and double immunolabeling for BrdU and Ki-67, BrdU and CD-11b, and BrdU and doublecortin (DCX), was used to investigate the origin of the proliferating cells. There was a time-dependent increase in the number of BrdU(+ve) cells in the CN following acoustic trauma; however, the number of BrdU(+ve) cells that survived was comparable to that of control animals at 4 weeks post-trauma. Cell proliferation was unlikely to be due to proliferating inflammatory cells as a result of a trauma-induced inflammatory response as the IL-6 expression level was comparable between sham and exposed groups. Immunolabeling revealed the BrdU(+ve) cells to co-express Ki-67 and DCX, but not CD-11b. However, there was no difference in DCX expression between sham and exposed animals. The results suggest that DCX-expressing cells in the CN may proliferate in response to acoustic trauma; however, the proportion of cells proliferating and the survival rate of the newborn cells may not support functional neurogenesis in the CN.

Effects of acute altered gravity during parabolic flight and/or vestibular loss on cell proliferation in the rat dentate gyrus

Both parabolic flight, i.e. a condition of altered gravity, and loss of vestibular function, have been suggested to affect spatial learning and memory, which is known to be influenced by neurogenesis in the hippocampus. In this study we investigated whether short alternated micro- and hyper-gravity stimulations during parabolic flight and/or loss of vestibular function, would alter cell proliferation in the hippocampal dentate gyrus of rats, by measuring the number of bromodeoxyuridine (BrdU)-incorporated cells. Rats were randomly allocated to the following experimental groups: (1) sham transtympanic saline injection only (n=5); (2) bilateral vestibular deafferentation (BVD) by sodium arsanilate transtympanic injection only (n=5); (3) sham treatment and parabolic flight (n=5); (4) BVD and parabolic flight (n=6). Forty-two days following transtympanic injection, the animals were subjected to parabolic flight in an awake restrained condition after habituation. A modified Airbus A300 aircraft was flown on a parabolic path, creating 20s of 1.8G during both climbing and descending and 22s of 0G at the apex of each parabola. The no flight animals were subjected to the same housing for the same duration. Immediately after the parabolic flight or control ground condition, animals were injected with BrdU (300mg/kg, i.p). Twenty-four hs after BrdU injection, rats were sacrificed. BrdU immunolabelling was performed and the number of BrdU+ve cells in the dentate gyrus of the hippocampus was quantified using a modified fractionator method. BVD caused a large and significant reduction in the number of BrdU-positive cells compared to sham animals (P≤0.0001); however, flight and all interactions were non-significant. These results indicate that BVD significantly decreased cell proliferation irrespective of the short exposure to altered/modified gravity.

Effect of Low Body Temperature During Unilateral Labyrinthectomy on Vestibular Compensation in the Guinea Pig

Objectives - Vestibular compensation, the recovery that follows unilateral vestibular deafferentation (UVD), is a model for central nervous system plasticity. Recovery from the static symptoms of UVD may involve temperature-dependent processes that modulate the immediate effects of UVD and/or the capability of the central nervous system to undergo adaptive plasticity. In this study we investigated changes in oculomotor and postural vestibular symptoms resulting from low body temperature during UVD. Material and methods - To study the effect of low temperatures at the time of UVD on vestibular compensation, we compared the rate of compensation and peak values for postural [roll head tilt (RHT) and yaw head tilt (YHT)] and oculomotor [spontaneous nystagmus (SN)] symptoms in three groups of guinea pigs. Animals in Group 1 (n=6) were maintained at 38°C throughout unilateral labyrinthectomy (UL). Animals in Group 2 (n=6) were not temperature-controlled and animals in Group 3 (n=4) were cooled with ice to 25°C throughout UL. Results - Cooled animals showed significantly higher rates of SN upon recovery from anaesthesia and took a significantly longer time to compensate. Cooled animals were also slower to compensate for postural symptoms (RHT and YHT), with 2 animals showing no compensation for RHT 52 h after UL. Conclusion - Hypothermia (25°C) during UVD surgery exacerbates postural and oculomotor symptoms following UL and significantly slows recovery.