Disorders of the Cranial Nerves and Brainstem

This chapter briefly repeats key anatomic characteristics and then reviews clinical disorders affecting each cranial nerve in addition to the brainstem. More specifically, this chapter covers cranial nerves I, V, VII, and IX through XII plus the brainstem. The olfactory nerve is a special visceral afferent nerve that functions in the sense of smell. The axons of the olfactory receptor cells within the nasal cavity extend through the cribriform plate to the olfactory bulb. These olfactory receptor cell axons synapse with mitral cells in the olfactory bulb. Mitral cell axons project to the primary olfactory cortex and amygdala. The olfactory cortex interconnects with various autonomic and visceral centers.

Aging and Olfaction

Decreased ability to smell is common in older persons. Some demonstrable smell loss is present in more than 50% of those 65 to 80 years of age, with up to 10% having no smell at all (anosmia). Over the age of 80, 75% exhibit some loss with up to 20% being totally anosmic. The causes of these decrements appear multifactorial and likely include altered intranasal airflow patterns, cumulative damage to the olfactory receptor cells from viruses and other environmental insults, decrements in mucosal metabolizing enzymes, closure of the cribriform plate foramina through which olfactory receptor cells axons project to the brain, loss of selectivity of receptor cells to odorants, and altered neurotransmission, including that exacerbated in some age-related neurodegenerative diseases.

The Impact of Ovariectomy on Olfactory Neuron Regeneration in Mice

Estrogen has been shown to affect differentiation and proliferation as a mitogen in various neural systems. Olfactory receptor cells are unique within the nervous system, and have the ability to regenerate even after an individual has reached maturity. Olfactory receptor cells also regenerate after experimentally induced degeneration. The purpose of this study is to observe the influence of estrogen depletion induced by ovariectomy on olfactory nerve regeneration. Female mice underwent bilateral ovariectomy at 8 weeks of age and received intraperitoneal administration of methimazole 1 week later. At 2, 4, and 6 weeks after methimazole administration, the olfactory mucosa was analyzed histochemically to determine olfactory epithelium (OE) thickness, olfactory marker protein distribution, and Ki-67 immunoreactivity. Furthermore, 2 weeks after ovariectomy, trkA protein distribution in the OE and nerve growth factor (NGF) levels in the olfactory bulb were determined by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. Our results showed that in ovariectomized mice OMP, Ki-67, and trkA-immunopositive cells expression decreased at 2 weeks after methimazole injection, a time point at which regeneration is underway. At this same time point, although NGF production in the olfactory bulb had increased before methimazole administration, no differences were observed between the ovx and control groups. These results suggest that estrogen depletion induces a suppressive effect on regeneration of olfactory neurons, and that estrogen may have a potential use in the treatment of sensorineural olfactory dysfunction.

Enhancement of the Olfactory Response by Lipocalin Cp-Lip1 in Newt Olfactory Receptor Cells: An Electrophysiological Study

Previously, we have detected the expression of 2 lipocalin genes (lp1 and lp2) in the olfactory epithelium of the Japanese newt Cynops pyrrhogaster. Recombinant proteins of these genes (Cp-Lip1 and Cp-Lip2, respectively) exhibited high affinities to various odorants, suggesting that they work like the odorant-binding proteins (OBPs). However, the physiological functions of OBP generally remain inconclusive. Here, we examined the effect of Cp-Lip1 on the electrophysiological responses of newt olfactory receptor cells. We observed that the electro-olfactogram induced by the vapor of an odorant with high affinity to Cp-Lip1 appeared to increase in amplitude when a tiny drop of Cp-Lip1 solution was dispersed over the olfactory epithelium. However, the analysis was difficult because of possible interference by intrinsic components in the nasal mucus. We subsequently adopted a mucus-free condition by using suction electrode recordings from isolated olfactory cells, in which impulses were generated by puffs of odorant solution. When various concentration (0–5 µM) of Cp-Lip1 was mixed with the stimulus solution of odorants highly affinitive to Cp-Lip1, the impulse frequency increased in a concentration-dependent manner. The increase by Cp-Lip1 was seen more evidently at lower concentration ranges of stimulus odorants. These results strongly suggest that Cp-Lip1 broadens the sensitivity of the olfactory cells toward the lower concentration of odorants, by which animals can detect very low concentration of odorants.