Stimulation or lesion of the medial vestibular nucleus increases the number of choline acetyltransferase-positive efferent vestibular neurons in the brainstem.

The vestibular center of the brainstem contains afferent and efferent vestibular neurons, which play an important role in information perception, processing, and sensory integration. Vestibular efferent neurons (VENs) can receive changes in vestibular afferent information and regulate peripheral vestibular function; however, it remains unclear how VENs change after vestibular afferent information increases or weakens. In this study, we used animal models with altered vestibular afferent information by electrically stimulating or destroying the vestibular medial nucleus (MVe). We confirmed the location of VENs in the brainstem by injecting five adult male Wistar rats in the vestibular region with a retrograde tracer. Following this, the MVe was stimulated electrically for 30 min in 20 naive rats. Rats were anesthetized and euthanized 1, 3, 6, and 12 h after stimulation. The MVe was electrolytically lesioned in another group (n=20); then, the rats were anesthetized and euthanized 1, 3, 5, and 7 days after lesioning. VENs were clearly identified dorsolateral to the genu of the facial nerve (g7) in coronal brainstem sections using choline acetyltransferase (ChAT) staining. The number of ChAT-positive VENs dorsolateral to g7 increased significantly on both sides compared with the control group 3 and 6 h after electrical stimulation. The number of ChAT-positive VENs dorsolateral to g7 was significantly greater on both sides compared with controls 3 and 5 days after electrolytic lesion. In summary, we found that the number of ChAT-positive VENs was significantly increased following a change in the excitability of MVe neurons. This suggests that VENs can respond to changes in afferent vestibular information and feedback, and regulate the peripheral vestibule. In addition, this shows that acetylcholine is an important neurotransmitter that plays an important role in the perception and fine regulation of the vestibular system.

The Degeneration of the Vestibular Efferent Neurons After Intratympanic Gentamicin Administration.

Intratympanic gentamicin (ITG) has been used to treat refractory Ménière's disease. Disequilibrium after ITG was still a challenge for some patients, and the underlying mechanism is poorly understood. Our previous study demonstrated that gentamicin distributed in the bilateral vestibular efferent neurons (VEN) after ITG; however, does it lead to VEN damage and cause further disequilibrium in patients following ITG? In this study, we observed severe damaged gentamicin-positive neurons of VEN and severe fractured myelin layer plates around neural fibers when viewed under transmission electron microscopy at day 3 after ITG. At day 30, neurons of VEN presented with relatively normal structures. Compared with the control group, the total number of choline acetyltransferase (CHAT) immunolabeling neurons in bilateral VEN showed a significant decrease both at day 3 and day 30. However, there was no significant difference in the total number of CHAT immunolabeling neurons between day 3 and day 30. It indicates that gentamicin is not only retrogradely transported into bilateral VEN, but also results in the degeneration of VEN after ITG. These findings may be related to patients' disequilibrium symptom after ITG. Furthermore, we speculate that VEN may play a role in vestibular compensation.

Modified Origins of Cortical Projections to the Superior Colliculus in the Deaf: Dispersion of Auditory Efferents.

Following the loss of a sensory modality, such as deafness or blindness, crossmodal plasticity is commonly identified in regions of the cerebrum that normally process the deprived modality. It has been hypothesized that significant changes in the patterns of cortical afferent and efferent projections may underlie these functional crossmodal changes. However, studies of thalamocortical and corticocortical connections have refuted this hypothesis, instead revealing a profound resilience of cortical afferent projections following deafness and blindness. This report is the first study of cortical outputs following sensory deprivation, characterizing cortical projections to the superior colliculus in mature cats (N = 5, 3 female) with perinatal-onset deafness. The superior colliculus was exposed to a retrograde pathway tracer, and subsequently labeled cells throughout the cerebrum were identified and quantified. Overall, the percentage of cortical projections arising from auditory cortex was substantially increased, not decreased, in early-deaf cats compared with intact animals. Furthermore, the distribution of labeled cortical neurons was no longer localized to a particular cortical subregion of auditory cortex but dispersed across auditory cortical regions. Collectively, these results demonstrate that, although patterns of cortical afferents are stable following perinatal deafness, the patterns of cortical efferents to the superior colliculus are highly mutable.SIGNIFICANCE STATEMENT When a sense is lost, the remaining senses are functionally enhanced through compensatory crossmodal plasticity. In deafness, brain regions that normally process sound contribute to enhanced visual and somatosensory perception. We demonstrate that hearing loss alters connectivity between sensory cortex and the superior colliculus, a midbrain region that integrates sensory representations to guide orientation behavior. Contrasting expectation, the proportion of projections from auditory cortex increased in deaf animals compared with normal hearing, with a broad distribution across auditory fields. This is the first description of changes in cortical efferents following sensory loss and provides support for models predicting an inability to form a coherent, multisensory percept of the environment following periods of abnormal development.

Vagal cardiac efferent innervation in F344 rats: Effects of chronic intermittent hypoxia.

Chronic intermittent hypoxia (CIH), which is a physiological consequence of obstructive sleep apnea, reduces baroreflex control of heart rate (HR). Previously, we showed that the heart rate (HR) response to electrical stimulation of the vagal efferent nerve was significantly increased following CIH in F344 rats. Since vagal cardiac efferent from the nucleus ambiguus (NA) project to cardiac ganglia and regulate HR, we hypothesized that vagal cardiac efferent innervation of cardiac ganglia is reorganized. Young adult F344 rats were exposed either to room air (RA) or to intermittent hypoxia for 35-50days. Fluorescent tracer DiI was injected into the NA to label vagal efferent innervation of cardiac ganglia which had been counterstained by Fluoro-Gold (FG) injections (i.p). Confocal microscopy was used to examine vagal cardiac efferent axons and terminals in cardiac ganglia. NA axons entered cardiac ganglia and innervated principal neurons (PNs) with robust basket endings in both RA control and CIH animals. In addition, the percentage of PNs which were innervated by DiI-labeled fibers in ganglia was similar. In CIH rats, abnormally large swollen cardiac axon segments and disorganized terminals as well as leaky endings were observed. In general, vagal efferent terminal varicosities around PNs appeared larger and the number of varicosities was significantly increased. Interestingly, some cardiac axons had sprouting-like terminal structures in the cardiac ganglia as well as in cardiac muscle, which had not been found in RA control. Finally, CIH increased the size of PNs and reduced the ratio of nucleus to PN somata. Thus, CIH significantly remodeled the structure of vagal cardiac axons and terminals in cardiac ganglia as well as cardiac PNs.

Structural remodeling of vagal afferent innervation of aortic arch and nucleus ambiguus (NA) projections to cardiac ganglia in a transgenic mouse model of type 1 diabetes (OVE26).

Diabetes-induced structural changes of vagal aortic afferent and cardiac efferent axons are not well understood. FVB control and OVE26 diabetic mice at different ages received injections of the tracer tetramethylrhodamine dextran (TMR-D) into the nodose ganglion to label vagal aortic afferents (at 3 and 6 months), or DiI injections into the nucleus ambiguus to label vagal cardiac efferents (at 3, 6, and 9 months). The aortic arch and atria were examined by using confocal microscopy. In the aortic arch, TMR-D labeled large and small vagal afferent axons (axons(L) and axons(S)) that formed different types of terminals: axons(L) produced large flower-sprays (flower-sprays(L)) and end-nets (end-nets(L)), whereas axons(S) produced small flower-sprays (flower-sprays(S)) and end-nets (end-nets(S)). In the atria, DiI-labeled vagal efferent axons formed basket endings around ganglion principle neurons (PNs). The vagal afferents, PNs and vagal cardiac efferents in diabetic mice were compared with age-matched control mice. We found (P < 0.05) that: 1) the size of axons(L), flower-sprays(L), flower-sprays(S) and end-nets(S) were reduced at 6 and 9 months; 2) the size of cardiac ganglia and the somatic area of the PNs were decreased, and the PN density in cardiac ganglia was increased at all ages and the PN nuclei/soma area ratio was increased at 9 months; and 3) the percentage of DiI-labeled axons-innervated PNs was decreased at all ages. Furthermore, the number of synaptic-like terminal varicosities around PNs was decreased. Compared with 3 months, more advanced diabetes at 9 months further reduced the number of varicosities/PN. In addition to these changes, swollen axons and terminals, as well as leaky-like DiI-labeled terminals, were observed in long-term diabetic mice (6 and 9 months of age). Taken together, our data show that chronic diabetes induces a significant structural atrophy of vagal aortic afferent and cardiac efferent axons and terminals. Although different morphologies of vagal afferent terminals in the aortic arch may serve as substrates for the future investigation of aortic depressor afferent physiology, structural remodeling of vagal afferents and efferents provides a foundation for further analysis of diabetes-induced impairment of cardiac autonomic regulation.

Renal nerves in the maintenance of hypertension: a potential therapeutic target.

Renal sympathetic efferent and afferent nerves, which lie within and immediately adjacent to the wall of the renal arteries, contribute to the maintenance of hypertension. Because the causative factors of hypertension change over time, denervation of both efferent and afferent renal nerves should result in long-term attenuation of hypertension. The importance of the renal nerves in hypertensive patients can now be defined with the novel development of percutaneous, minimally invasive renal denervation from within the renal artery using radiofrequency energy as a therapeutic strategy. Studies thus far show that catheter-based renal denervation in patients with resistant essential hypertension lowers systolic blood pressure 27 mm Hg by 12 months, with the estimated glomerular filtration rate remaining stable. The decrease in arterial pressure after renal denervation is associated with decreased peripheral sympathetic nervous system activity, suggesting that the kidney is a source of significant central sympathetic outflow via afferent renal nerve activity.

Impairment of baroreflex control of heart rate and structural changes of cardiac ganglia in conscious streptozotocin (STZ)-induced diabetic mice.

Baroreflex control of heart rate (HR) is impaired in human diabetes mellitus and in large experimental models. However, baroreflex impairment in diabetic mouse models and diabetes-induced remodeling of baroreflex circuitry are not well studied. We examined the impairment of baroreflex control of heart rate (HR) and assessed structural remodeling of cardiac ganglia in the streptozotocin (STZ)-induced diabetic mouse model. FVB mice were either injected with vehicle or STZ. Group 1: mice were anesthetized and the femoral artery and vein were catheterized at the 30th day after vehicle or STZ injection. On the second day after surgery, baroreflex-mediated HR responses to sodium nitroprusside (SNP) and phenylephrine (PE)-induced mean arterial blood pressure (MABP) changes were measured in conscious mice. Group 2: Fluoro-Gold was administered (i.p.) to label cardiac ganglia in each mouse at the 25th day after vehicle or STZ injection. After another five days, animals were perfused and cardiac ganglia were examined using confocal microscopy. Compared with control, we found in STZ mice: 1) the HR decreased, but MABP did not. 2) The PE-induced increases of MABP were decreased. 3) Baroreflex bradycardia was attenuated in the rapid MABP ascending phase but the steady-state DeltaHR/DeltaMABP was not different at all PE doses. 4) SNP-induced MABP decreases were not different. 5) Baroreflex tachycardia was attenuated. 6) The sizes of cardiac ganglia and ganglionic principal neurons were decreased. 7) The ratio of nucleus/cell body of cardiac ganglionic neurons was increased. We conclude that baroreflex control of HR is impaired in conscious STZ mice. In addition, diabetes may induce a significant structural remodeling of cardiac ganglia. Such an anatomical change of cardiac ganglia may provide new information for the understanding of diabetes-induced remodeling of the multiple components within the baroreflex circuitry.

[Efferent innervation of the arteries of human leptomeninx in arterial hypertension].

Structure of the efferent nerve plexuses (adrenergic, acetylcholinestherase- and cholinacetyltranspherase-positive, NO-dependent), was studied in the arteries of human leptomeninx with different diameters. Material was obtained from the corpses of the healthy people and of the patients with initial stages of arterial hypertension (AH). It was shown that the concentrations of cholinergic and adrenergic nerve fibers and varicosities in axon terminal part, innervating the arteries with the diameters ranging from 450 till 100 microm, were not significantly different. In these arteries, NO-ergic plexuses were also detected. In patients with AH, regardless the arterial diameters, the significant increase (up to 15-20%) of adrenergic nerve fiber and varicosity concentrations was found. The changes in cholinergic nerve fiber concentration were found to depend on the vessel diameter: the significant decrease of these parameter was observed only in arteries with the diameter of 100-200 microm. No significant changes in nerve plexus concentration was noticed in the arteries with greater or smaller diameter. In NO-ergic neural conductors, the enzyme activity decreased only in the large arteries, and remained almost unchanged in the small vascular branches. The changes in the vasomotor innervation described in AH, are interpreted as a vasomotor innervation dysfunction of the leptomeninx arteries that may result in the hemodynamic disturbances.

Effects of ghrelin on neuronal survival in cells derived from dorsal motor nucleus of the vagus.

BACKGROUND: The effects of intestinal inflammation on the central neurons projecting to the enteric nervous system are unknown. The dorsal motor nucleus of the vagus signals to the gastrointestinal system. Ghrelin is elevated in patients with inflammatory bowel disease and has been implicated as an inflammatory mediator. The purpose of this study was to investigate the effects of gastrointestinal inflammation on the dorsal motor nucleus of the vagus in rats, as well as the effects of proinflammatory cytokines and ghrelin on neurons from the dorsal motor nucleus of the vagus in vitro. METHODS: DiI was injected into the stomach wall of rats to retrogradely label neurons of the dorsal motor nucleus of the vagus. Intestinal inflammation was induced with indomethacin injection. Serial serum ghrelin measurements were performed. Tissue was examined under fluorescent microscopy. In vitro studies using primary culture of neurons from the dorsal motor nucleus of the vagus were performed. Reverse transcriptase-polymerase chain reaction for cytokine transcripts and immunohistochemistry for cytokine receptors were performed. Cell proliferation and apoptosis were measured by enzyme-linked immunosorbent assay. RESULTS: A significant decrease of DiI labeling was demonstrated in the dorsal motor nucleus of the vagus of animals injected with indomethacin. Serum levels of ghrelin were significantly elevated 2 days after induction of inflammation. In vitro, apoptosis and cell proliferation were measured after 24-hour exposure to experimental conditions. Ghrelin alone had no effect on apoptosis. Exposure to interleukin (IL)-1 beta or tumor necrosis factor (TNF)-alpha increased apoptosis. The addition of ghrelin to cytokine resulted in significant decreases in apoptosis compared to cytokine alone. Ghrelin significantly increased neuronal proliferation. Exposure to IL-1 beta, IL-6, or TNF-alpha significantly decreased proliferation. The addition of ghrelin to TNF-alpha or IL-6 significantly increased cellular proliferation compared to cytokine alone. CONCLUSIONS: Neurons from the dorsal motor nucleus of the vagus that project to the stomach are reduced in number after induction of colitis in rats. In vitro, proinflammatory cytokines increase apoptosis and decrease cell proliferation of neurons from the dorsal motor nucleus of the vagus. These effects are attenuated by ghrelin.

Angiotensin II type 1 receptors may not influence response of spinal autonomic neurons to axonal damage.

OBJECTIVES: Angiotensin II can promote cell stress, and the expression of its AT1 receptor is characteristic of neuronal populations that die off in multiple systems atrophy and Parkinson's disease. To explore the possible significance of these facts, we undertook to: (1) clarify the distribution of AT(1) in rat neurons; (2) use selective antagonists as a means of determining whether AT1 activation predisposes stressed neurons to die. METHODS: AT1-expression was examined by immunohistochemistry and by autoradiography for [125I]-sarcosine1-angiotensin II binding in sensory, motor and autonomic neurons. To induce cell loss in a specific neuronal population, rats were given systemic i.v. injection of anti-acetylcholinesterase antibodies, which cause a delayed death of pre-ganglionic sympathetic neurons in the intermediolateral nucleus (IML). As pharmacologic intervention, some immunolesioned rats were treated with the selective AT1 antagonist, Candesartan. RESULTS: Immunohistochemistry and autoradiography revealed AT1 expression in dorsal root ganglia, superior cervical ganglion. In the dorsal horn of the spinal cord, AT1 immunostainining and angiotensin binding were both prominent. In ventral horn and IML, immunoreactivity for AT1 and choline acetyltransferase co-localized in pre-ganglionic sympathetic and somatic motor neurons. Immunolesion caused over 50% loss of IML perikarya within 3 months. Concurrent treatment with the AT1 antagonist, Candesartan, did not affect the outcome. DISCUSSION: AT1 expression is surprisingly widespread in sensory, autonomic and somatic motor neurons of the rat. This expression may be important to the normal physiology of these systems. Present data, however, do not support the concept that AT1 activation contributes to the loss of autonomic neurons after axonal damage.

Projections from the vestibular nuclei to the hypothalamic paraventricular nucleus: morphological evidence for the existence of a vestibular stress pathway in the rat brain.

Although it has been reported by several laboratories that vestibular stress activates the hypothalamo-pituitary-adrenocortical axis (HPA), the existence of neuronal connections between vestibular and hypothalamic paraventricular neurons has not yet been demonstrated. By the use of a virus-based retrograde trans-synaptic tracing technique in the rat, here we demonstrate vestibular projections to the paraventricular nucleus (PVN). Pseudorabies virus (Bartha strain, type BDR62) was injected into the PVN, and the progression of the infection along synaptically connected neurons was followed in the pons and the medulla, 3 and 4 days post-inoculation. Virus-infected neurons were revealed mainly in the medial vestibular nucleus. Labeled cells were scattered in the spinal, and very rarely in the superior nuclei, but none of them in the lateral vestibular nucleus. Injections of cholera toxin B subunit, a monosynaptic retrograde tracer into the PVN failed to label any cells in the vestibular nuclei. These results provide anatomical evidence for the existence of a vestibulo-paraventricular polysynaptic pathway and support the view that the HPA axis is modulated by vestibular stress.

Deafferentation-associated changes in afferent and efferent processes in the guinea pig cochlea and afferent regeneration with chronic intrascalar brain-derived neurotrophic factor and acidic fibroblast growth factor.

Deafferentation of the auditory nerve from loss of sensory cells is associated with degeneration of nerve fibers and spiral ganglion neurons (SGN). SGN survival following deafferentation can be enhanced by application of neurotrophic factors (NTF), and NTF can induce the regrowth of SGN peripheral processes. Cochlear prostheses could provide targets for regrowth of afferent peripheral processes, enhancing neural integration of the implant, decreasing stimulation thresholds, and increasing specificity of stimulation. The present study analyzed distribution of afferent and efferent nerve fibers following deafness in guinea pigs using specific markers (parvalbumin for afferents, synaptophysin for efferent fibers) and the effect of brain derived neurotrophic factor (BDNF) in combination with acidic fibroblast growth factor (aFGF). Immediate treatment following deafness was compared with 3-week-delayed NTF treatment. Histology of the cochlea with immunohistochemical techniques allowed quantitative analysis of neuron and axonal changes. Effects of NTF were assessed at the light and electron microscopic levels. Chronic BDNF/aFGF resulted in a significantly increased number of afferent peripheral processes in both immediate- and delayed-treatment groups. Outgrowth of afferent nerve fibers into the scala tympani were observed, and SGN densities were found to be higher than in normal hearing animals. These new SGN might have developed from endogenous progenitor/stem cells, recently reported in human and mouse cochlea, under these experimental conditions of deafferentation-induced stress and NTF treatment. NTF treatment provided no enhanced maintenance of efferent fibers, although some synaptophysin-positive fibers were detected at atypical sites, suggesting some sprouting of efferent fibers.

Degeneration of vagal efferent axons and terminals in cardiac ganglia of aged rats.

Baroreflex control of the heart rate is significantly reduced during aging. However, neural mechanisms that underlie such a functional reduction are not fully understood. We injected the tracer DiI into the left nucleus ambiguus (NA), then used confocal microscopy and a Neurolucida Digitization System to examine qualitatively and quantitatively vagal efferent projections to cardiac ganglia of young adult (5-6 months) and aged (24-25 months) rats (Sprague Dawley). Fluoro-Gold was injected intraperitoneally to counterstain cardiac ganglionic principal neurons (PNs). In aged, as in young rats, NA axons projected to all cardiac ganglia and formed numerous basket endings around PNs in the hearts. However, significant structural changes were found in aged rats compared with young rats. Vagal efferent axons contained abnormally swollen axonal segments and exhibited reduced or even absent synaptic-like terminals around PNs, such that the numbers of vagal fibers and basket endings around PNs were substantially reduced (P < 0.01). Furthermore, synaptic-like varicose contacts of vagal cardiac axons with PNs were significantly reduced by approximately 50% (P < 0.01). These findings suggest that vagal efferents continue to maintain homeostatic control over the heart during aging. However, the marked morphological reorganization of vagal efferent axons and terminals in cardiac ganglia may represent the structural substrate for reduced vagal control of the heart rate and attenuated baroreflex function during aging.

Constantin von Economo's contribution to the understanding of movement disorders.

Constantin von Economo's (CvE) main scientific achievements were his studies on the cytoarchitectonics of the cerebral cortex, sleep, and encephalitis lethargica (EL). He found a close relationship between motor symptoms and psychiatric and behavioral disorders in EL and postencephalitic Parkinsonism and identified the underlying neuropathology in the diencephalon and the brainstem. In agreement with Tretiakoff's findings in Parkinson's disease, CvE related postencephalitic Parkinsonism to neuronal loss in the substantia nigra. Several of CvE's early, less well-known publications also deal with the basal ganglia and movement disorders. He demonstrated in rabbits that the substantia nigra modulates automatization, coordination, and succession of masticatory movements and swallowing. In a study on the effects of experimental lesions of the cerebral peduncle in cats and monkeys, CvE hypothesized a corticotegmental pathway that maintains motor functions after pyramidal tract lesions. Recent studies have identified this pathway, which ends in the pedunculopontine nucleus. In a study on posthemiplegic chorea, CvE discussed various pathophysiological hypotheses that partly resemble modern concepts of chorea. In a clinicopathological study on Wilson's disease, CvE traced the striofugal fibers and visualized the basal ganglia outflow pathways. CvE was an outstanding multidisciplinary movement disorder specialist who contributed substantially to modern basal ganglia research.

Thoracic vagal efferent nerve stimulation evokes substance P-induced early airway bronchonstriction and late proinflammatory and oxidative injury in the rat respiratory tract.

Electrical stimulation of efferent thoracic vagus nerve (TVN) evoked neurogenic inflammation in respiratory tract of atropine-treated rats by an undefined mechanism. We explored whether efferent TVN stimulation via substance P facilitates neurogenic inflammation via action of nuclear factor-kappaB (NF-kappaB) activation and reactive oxygen species (ROS) production. Our results showed that increased frequency of TVN stimulation concomitantly increased substance P-enhanced hypotension, and bronchoconstriction (increases in smooth muscle electromyographic activity and total pulmonary resistance). The enhanced SP release evoked the appearance of endothelial gap in silver-stained leaky venules, India-ink labeled extravasation, and accumulations of inflammatory cells in the respiratory tract, contributing to trachea plasma extravasation as well as increases in blood O (2)(-) and H(2)O(2) ROS amount. L-732138 (NK(1) receptor antagonist), SR-48968 (NK(2) receptor antagonist), dimethylthiourea (H(2)O(2) scavenger) or catechins (O (2)(-) and H(2)O(2) scavenger) pretreatment reduced efferent TVN stimulation-enhanced hypotension, bronchoconstriction, and plasma extravasation. Increased frequency of TVN stimulation significantly upregulated the expression of nuclear factor-kappaB (NF-kappaB) in nuclear protein and intercellular adhesion molecule-1 (ICAM-1) in total protein of the lower respiratory tract tissue. The upregulation of NF-kappaB and ICAM-1 was attenuated by NK receptor antagonist and antioxidants. In conclusion, TVN efferent stimulation increases substance P release to trigger NF-kappaB mediated ICAM-1 expression and O (2)(-) and H(2)O(2) ROS production in the respiratory tract.

Degeneration of myelinated efferent fibers prompts mitosis in Remak Schwann cells of uninjured C-fiber afferents.

The factors inducing normally innervated Schwann cells in peripheral nerve to divide are poorly understood. Transection of the fourth and fifth lumbar ventral roots (L4/5 ventral rhizotomy) of the rat is highly selective, sparing unmyelinated axons and myelinated sensory axons; Wallerian degeneration is restricted to myelinated efferent fibers. We found that L4/5 ventral rhizotomy prompted many normally innervated nonmyelinating (Remak) Schwann cells to enter cell cycle; myelinating Schwann cells of intact (sensory) axons did not. Three days after L4/5 ventral rhizotomy, [3H]thymidine incorporation into Remak Schwann cells increased 30-fold. Schwann cells of degenerating efferents and endoneurial cells also incorporated label. Increased [3H]thymidine incorporation persisted at least 10 d after ventral rhizotomy. Despite Remak Schwann cell proliferation, the morphology of unmyelinated nerve (Remak) bundles was static. Seven days after L5 ventral rhizotomy, Remak Schwann cells in the L5-predominant lateral plantar nerve increased slightly; endoneurial cells doubled. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive nuclei increased dramatically in peripheral nerve after L5 ventral rhizotomy; many of these were macrophage nuclei. In summary, we find that the degeneration of myelinated motor axons produced signals that were mitogenic for nonmyelinating Schwann cells with intact axons but not for myelinating Schwann cells with intact axons.

Efferent system degeneration in the human temporal bone.

Sense organ deposits have been described in temporal bones from patients with vestibular neuronitis, Meniere's disease, and benign paroxysmal positional vertigo that are not found in a comparable series of temporal bones without vestibulopathy. Because the recurrent vestibulopathies are caused by vestibular ganglionitis and the vestibulocochlear anastomosis was degenerated in these temporal bones, the deposits may represent the end buds of regenerating efferent axons injured in passage through the vestibular ganglion. Such neural buds have been described with transmission electron microscopy in animals after vestibular nerve transection and in a human temporal bone with endolymphatic hydrops. The buds may be visible by light microscopy, because their size is comparable to that of hair cell nuclei and they stain blue with hematoxylin because of their nucleic acid content. The variable location and size of these deposits (buds) in the labyrinthine sense organs is described to aid in the recognition of efferent system injury in human temporal bones.

Long-term regeneration of abdominal vagus: efferents fail while afferents succeed.

Vagal afferents regenerate, by 18 weeks after subdiaphragmatic transection, to reinnervate the gut and to differentiate into the two types of terminals normally found in the smooth muscle wall of the gastrointestinal (GI) tract (Phillips et al. [2000] J Comp Neurol. 421:325-346). Regeneration, however, is neither complete nor entirely accurate by 18 weeks. Moreover, the capacity of the vagal efferents to reinnervate the GI tract under comparable conditions has not been evaluated. Therefore, to determine whether a more extended postaxotomy survival interval would (1). result in more extensive reinnervation of smooth muscle, (2). facilitate correction of the inaccuracies of the regenerated axons and terminals, and (3). yield motor as well as sensory reinnervation of GI targets, Sprague-Dawley rats received either complete subdiaphragmatic vagotomies (n = 18) or sham surgeries (n = 12). Physiological endpoints that might normalize as vagal elements regenerated, including body weight, daily food intake, size of first daily meal, and metabolic efficiency, were monitored. At 45 weeks after the vagotomies, the animals were randomly assigned to afferent (wheat germ agglutinin-horseradish peroxidase) or efferent (cholera toxin subunit B-horseradish peroxidase) mapping conditions, and labeled axons and terminals in the stomach and first 8 cm of the small intestine were inventoried in whole-mounts. Afferent regeneration was more extensive at 45 weeks than previously observed at 18 weeks after surgery; however, the amount of GI innervation was still not comparable to the intact pattern of the sham rats. Furthermore, abnormal patterns of sensory organization occurred throughout the reinnervated field, with small bundles of axons forming complex tangles and some individual axons terminating in ectopic locations. The presence of growth cone profiles suggested that vagal reorganization was ongoing even 45 weeks after surgery. In contrast to this relatively extensive, albeit incomplete, sensory reinnervation of the gut, motor fibers had failed to reinnervate the GI tract. Thus, dramatic differences exist in the regenerative capacities of the sensory and motor arms of the vagus under the same surgical and maintenance conditions. Furthermore, the functional measures of disordered energy regulation did not normalize over the 45 weeks during which afferent but not efferent innervation was restored.