Nerve Fiber Bundles Research Articles

Pointwise linear progression criteria and the detection of visual field change in a glaucoma trial

Current pointwise linear regression (PLR) change criteria for visual field analysis are largely empirical. Two independent sets of Humphrey Field Analyzer fields were analysed using PLR. Set i, 56 patients, and set ii, 97 patients, were followed over 16 months. Criteria were tested against set i, and then validated using set ii. Each criterion specified a fixed critical slope of 1 dB/year and with a range of significance from P<0.001 to 0.05. The criteria were varied by altering location number, cluster arrangement, and by requiring points to show change over both 12 and 16 months. True glaucomatous change was differentiated from noise by looking for exclusive progression (EP), the detection of progression without detection of improvement. Set i required 1 point to have a slope of 1 dB/year and P<0.05 labelled 64% progressing and 58% improving, whereas several stricter criteria were capable of detecting EP. Two points in a perimetric nerve fibre bundle (PNFB) cluster gave optimal EP detection, labelling 8.9% progressing in set i and 7.2% progressing in set ii with a cutoff P-value of 0.026 inset i and 0.013 inset ii. Lax PLR criteria detect large amounts of change. Validating criteria using two data sets allow selection of better criteria, capable of detecting EP. The criterion involving 2 points changing in a PNFB cluster offers the best option for exclusively detecting progression.

Water Channel Aquaporin 1 (AQP1) Is Present in the Perineurium and Perichondrium

Aquaporin 1 (AQP1) is an isoform of membrane water channels. We examined the distribution of AQP1 in peripheral nerves. Immunofluorescence microscopy with specific antibodies to AQP1 was performed in the tissue sections of the rat tongue, esophagus, trachea, and sciatic nerve. AQP1 was present in the perineurium of nerve fiber bundles in the sciatic nerve and nerve fiber bundles in the tongue, esophagus, and trachea. Laser confocal microscopy of the double-labeled specimens for AQP1 and sugar transporter GLUT1 revealed that AQP1 was localized in the outer layer(s) of the perineurial cell layers, whereas GLUT1 was present throughout the entire perineurial cell layers. AQP1 and GLUT1 were also present in blood vessels inside the nerve fiber bundle. They were rarely found in the same blood vessels, namely, AQP1 was hardly detectable in GLUT1-positive blood vessels and GLUT1 was hardly detectable in AQP1-positive vessels. AQP1 in these sites of the blood-nerve barrier may participate in the water transfer across the barrier and contribute to the maintenance of the milieu of the nerve. In addition, we showed the presence of AQP1 in the perichondrium of the tracheal cartilage suggesting a possible role in water transfer between the cartilage and surrounding connective tissues.

Cellular Localization of Voltage-Gated Calcium Channels and Synaptic Vesicle-Associated Proteins in the Guinea Pig Cochlea

The cellular localization of voltage-gated calcium channels (VGCCs) and synaptic vesicle-associated proteins, SV2, synapsin I, and vesicle-associated membrane protein (VAMP) (synaptobrevin), was investigated in the guinea pig cochlea using immunocytochemistry and confocal laser scanning microscopy. Reactivity, in guinea pig, of antibodies to the alpha1 subunits of L-type, alpha1C [Cav1.2] and alpha 1D [Cav1.3]; P/Q-type, alpha1A [Cav2.1]; and R-type, a1E [Cav2.3] high voltage-activated calcium channels, was determined by Western blotting and immunolabeling of cerebellum. In the cochlea the sensory inner hair cells of the organ of Corti displayed strong intracellular staining, predominantly localized to their basolateral poles, with an antibody directed against the alpha1C subunit. Some alpha1C labeling was also observed in the inner pillar cells, in cell bodies of afferent neurons in the spiral ganglion, and in the inferior region of the spiral ligament. The supporting pillar cells were strongly immunoreactive throughout for alpha1D, but no alpha1D labeling of the inner hair cells was seen. The alpha1A subunit showed a cytoplasmic distribution in all three rows of outer hair cells. alpha1E labeling localized to the outer hair cells, predominantly in the subcuticular plate region, and also to nerve fiber bundles beneath these hair cells. Strong immunoreactivity was consistently seen with antibodies directed against SV2 and synapsin I in neuronal structures surrounding the basolateral surfaces of both the inner and outer hair cells but was absent from the sensory cells themselves. VAMP labeling was found throughout the cytoplasm of the inner hair cells and in neuronal structures beneath the hair cells. These results reveal a differential distribution of VGCC-types in the sensory and nonsensory elements of the guinea pig cochlea, with the inner hair cells expressing alpha1C L-type channels and VAMP but not synapsin I or SV2.

Corneal Reinnervation after LASIK: Prospective 3-Year Longitudinal Study

To measure the return of innervation to the cornea during 3 years after LASIK. Seventeen corneas of 11 patients who had undergone LASIK to correct myopia from -2.0 D to -11.0 D were examined by confocal microscopy before surgery, and at 1, 3, 6, 12, 24, and 36 months after surgery. In all available scans, the number of nerve fiber bundles and their density (visible length of nerve per frame area), orientation (mean angle), and depth in the cornea were measured. The number and density of subbasal nerves decreased >90% in the first month after LASIK. By 6 months these nerves began to recover, and by 2 years they reached densities not significantly different from those before LASIK. Between 2 and 3 years they decreased again, so that at 3 years the numbers remained <60% of the pre-LASIK numbers (P <0.001). In the stromal flap most nerve fiber bundles were also lost after LASIK, and these began recovering by the third month, but by the third year they did not reach their original numbers (P <0.001). In the stromal bed (posterior to the LASIK flap interface), there were no significant changes in nerve number or density. As the subbasal nerves returned, their mean orientation did not change from the predominantly vertical orientation before LASIK. Nerve orientation in the stromal flap and the stromal bed also did not change. Both subbasal and stromal corneal nerves in LASIK flaps recover slowly and do not return to preoperative densities by 3 years after LASIK. The numbers of subbasal nerves appear to decrease between 2 and 3 years after LASIK. The orientation of the regenerated subbasal nerves remains predominantly vertical.

Regulation of galanin gene expression in human keratinocytes

Recently, we have detected abundant expression of specific immunoreactivity for galanin (GAL), a 29–30 amino acid neuropeptide, in the epidermis and in sweat glands in a non‐neuronal distribution and to a lesser extent in nerve fibre bundles and smooth muscle of blood vessels. In order to uncover a possible function of GAL in human epidermis, we investigated the regulation of GAL mRNA expression in cultured primary human keratinocytes (KCs). First, we determined whether PMA, a protein kinase C activator which is known to be a potent upregulator of GAL gene expression in chromaffin cells, has similar effects in KCs. Stimulation of human cultured primary KC with PMA resulted in a sixfold increase of GAL mRNA. Furthermore, we exposed KCs to a combination of the proinflammatory cytokines IL‐1β and TNF‐α which resulted in a twofold induction of GAL mRNA in comparison with a sixfold induction of ICAM‐1. Most interestingly, capsaicine, which usually leads to a secretion of neuropeptides from nerves endings, did not induce the secretion of GAL of KCs. In contrast, constitutive GAL mRNA expression and peptide secretion were reduced twofold upon treatment of KC with 10 µm capsaicine for 20 min and 24 h, respectively. To our knowledge, this is the first report on a direct regulatory effect by capsaicine on neuropeptide mRNA expression in non‐neuronal cells.

Variation of peripapillary retinal nerve fiber layer birefringence in normal human subjects.

The retinal nerve fiber layer (RNFL) exhibits linear birefringence due to the oriented cylindrical structure of ganglion cell axons. The birefringence (Deltan) depends on the density and composition of axonal organelles. The purpose of this study was to evaluate the distribution of birefringence around the optic nerve head (ONH) in normal subjects. Birefringence was calculated along circular scan paths around the ONH as Deltan = R/T, where R is RNFL retardance measured by scanning laser polarimetry (SLP) and T is RNFL thickness measured by optical coherence tomography (OCT). OCT scans on a 3.4 mm diameter circle were obtained from 26 normal subjects aged 18 to 53 years. Scans on circles with various diameters were obtained from 17 of these subjects. The average reproducibility of Deltan measured on three separate days in four subjects was +/- 0.05 nm/microm. In most subjects Deltan varied significantly along a circular path around the ONH, with maxima in superior and inferior bundles, minima temporally and nasally, and a mean of 0.32 +/- 0.03 nm/microm. Deltan profiles on circles of different diameter were similar, suggesting that Deltan did not vary along nerve fiber bundles. RNFL birefringence varies with position around the ONH. This variation may result from known structural differences among nerve fiber bundles that serve different retinal regions. Constant Deltan along bundles is consistent with this hypothesis. Measurements of RNFL birefringence may provide a means to detect early subcellular changes in glaucoma.

Microglial responses in the avascular quail retina following transection of the optic nerve

This study was undertaken to investigate microglial responses in the avascular central nervous system using the quail retina that is known to be devoid of blood vessels. Following intraorbital optic nerve transection (ONT), the quail retina was examined immunohistochemically at various times up to 6 months. A few days after transection, microglia in the inner retinal layers revealed features of activation. Activated cells displayed an amoeboid shape and enhanced QH1-immunoreactivity. The numbers of these amoeboid cells were rapidly increased, first in the inner plexiform layer (IPL), and then in the ganglion cell/nerve fiber layer (GCL/NFL) of the retina where retrograde degenerating ganglion cell processes and perikarya were located. By 6 months after transection, microglia regained their resting morphology, and their cell counts returned to control levels. At early time points of microglial activation, numerous QH1+ amoeboid cells were observed along the vitreal surface of the pecten and retinal region adjacent to the insertion of the pecten, where some amoeboid cells were attached underneath the internal limiting membrane, and appeared to squeeze through the optic nerve fiber bundles. A considerable number of these amoeboid cells in the GCL/NFL and the IPL were labeled with PCNA, suggesting that active exogenous migration (from the pecten) and in situ proliferation of precursor cells contribute to the increase in microglial population of the degenerating retina. On the other hand, TUNEL-positive microglia appeared in the GCL/NFL at later time points indicate that the decrease of microglial numbers is in part due to apoptosis in these layers. Although some aspects of microglial activation in the avascular retina appear unique, their consequences were similar to those described in vascular retinae of mammals, a finding indicates that blood vessels are not a prerequisite for microglial activation, and microglial precursors could migrate long distance to reach the lesioned site, which is not accessible via blood vessels. Our data provide the first analysis of microglial activation in the avascular central nervous system (CNS), and suggest that the quail retina is a useful model for studies of microglial behavior in CNS.

Corneal sensation after laser epithelial keratomileusis for the correction of myopia

Subepithelial nerve fibre bundles and stromal nerves are damaged during laser epithelial keratomileusis (LASEK). The aim of this study was to investigate the recovery of corneal sensation after LASEK for the correction of myopia. Corneal sensation was evaluated in 40 eyes of 20 patients using a Cochet-Bonnet aesthesiometer before surgery and 3 days, 14 days, 1, 3 and 6 months after LASEK for the correction of mild to moderate myopia (range -2.5 D to -8.0 D). At every examination corneal sensation was tested in the apex of the cornea and in one point each at the 12, 3, 6 and 9 o' clock positions 2 mm from the centre of the cornea. Corneal sensation was significantly reduced at 3 days and 14 days after surgery (P<0.01). The loss of corneal sensation was greatest 3 days after surgery and corneal sensation increased during the first month after LASEK. After 1 month, 3 months and 6 months no significant difference was found between preoperative and postoperative sensation. There was no significant difference in sensation between different areas of the cornea after LASEK. Corneal nerves are disrupted during LASEK surgery and the procedure results in a significant reduction in corneal sensation. During the first month after surgery the depressed corneal sensation improved and subsequently went back to preoperative values, staying stable 3 months and 6 months after surgery.

Morphology of the long and short uveal nerves in the human eye.

The aim of this study was to examine the architecture of the uveal nerves in the sclera and suprachoroid of human eyes. Eyes from 17 adult human donors were investigated. The uveal nerves in different regions (retrobulbar, intrascleral, suprachoroidal, pars plana) were prepared and studied by light and electron microscopy. In addition, immunohistochemistry was performed for various neuronal markers. The long uveal nerves showed a characteristic suprachoroidal location with no branches supplying the choroid. It was found that typically they are composed of myelinated (75%) and non-myelinated (25%) nerve fibres. They mainly contain aminergic and sensory nerve fibres. A separate set of cholinergic non-myelinated nerve fibre bundles runs parallel with these long uveal nerves. The short uveal nerves supply the suprachoroidal nerve plexus with approximately 13% of their nerve fibres. The nerves and the branches supplying the choroid appear as mixed nerves containing sympathetic, parasympathetic and sensory axons. This study therefore provides new information about the quantity, type and distribution of myelinated and non-myelinated nerve fibres in the posterior uvea of the human eye.

The value of autopsy in determining the cause of failure to respond to resuscitation at birth

Autopsy is invaluable in identifying the causes of severe depression and very low Apgar score after birth and in assessing contributory conditions. Brain scans are increasingly used in the care of neonates who fail to respond to resuscitation at birth but their interpretation depends on the information gained from sound neuropathological studies. Asphyxia, both acute intrapartum asphyxia and chronic asphyxia, is an important cause of low Apgar scores. The gestational age and the nature of the asphyxial insult both have a profound influence on the ultimate pattern of injury. Asphyxia in the preterm brain tends to damage preferentially the white matter but some white matter damage is also seen in many infants who have an hypoxia-ischaemic insult at term though the predominant site of injury is to the central grey matter. The nature of the cellular damage and reactive change seen at autopsy is described. There is an association between low Apgar scores and intrauterine exposure to infection and maternal pyrexia. Detailed autopsy examination should include the search for infection. The placenta, cord and membranes should be examined in view of the mounting evidence of the association between intrauterine infection of the placenta and fetal membranes and prenatal brain damage. Additionally, the presence of placental thrombosis and infarction should be sought in relation to focal and global injury in the full term infant. Acquired prepartum lesions rarely cause the infant to present with a low Apgar score. The exception to this is severe damage to the brainstem and basal ganglia. Traumatic injury to the brain is now much less common than in previous decades. Subdural haemorrhage occurs more frequently than intraventricular or subarachnoid haemorrhage. Instrumental and assisted deliveries are associated with an increased incidence of subdural haemorrhage though these rarely cause significant long term damage. Careful autopsy, particularly of the neck and paravertebral tissues, spinal cord, brainstem and nerve roots is important where trauma is suspected. Tearing of nerve roots or fibre bundles in the spinal cord is readily demonstrated under the microscope using immunocytochemistry to β-amyloid precursor protein. Disorders of the spinal cord, peripheral nerve and muscle as well as some metabolic diseases may cause a baby to be both floppy and weak. Metabolic disease, including peroxisomal disorders, non-ketotic hyperglycinaemia, lipid and glycogen storage disorders and mitochondrial diseases may cause profound hypotonia and respiratory failure at birth or shortly afterwards.

Astrocyte-endothelial cell relationships during human retinal vascular development.

To evaluate evidence for the presence of vascular precursor cells (angioblasts) and astrocyte precursor cells (APCs) in the developing human retina and determine their relationship. Pax-2/GFAP/CD-34 triple-label immunohistochemistry was applied to four retinas aged 12, 14, 16, and 20 weeks of gestation (WG) to label APCs, astrocytes, and patent blood vessels. APCs are Pax-2(+)/GFAP(-), whereas astrocytes are Pax-2(+)/GFAP(+). Adenosine diphosphatase (ADPase) enzyme histochemistry, which identifies endothelial cells and vascular precursors, was applied to human retinas aged 12, 16, 17, and 19 WG. Nissl stain, a nonspecific cell soma marker, was applied to 14.5-, 18-, and 21-WG retinas. Established blood vessels were visualized with CD34 and ADPase. Topographical analysis of the distribution of Nissl-stained spindle cells and ADPase(+) vascular cells showed that these two populations have similar distributions at corresponding ages. ADPase(+) vascular precursor cells preceded the leading edge of patent vessels by more than 1 millimeter. In contrast, Pax-2(+)/GFAP(-) APCs preceded the leading edge of CD34(+) blood vessels by a very small margin, and committed astrocytes (Pax-2(+)/GFAP(+)) were associated with formed vessels and nerve fiber bundles. Two populations of ADPase(+) cells were evident, a spindle-shaped population located superficially and a deeper spherical population. The outer limits of these populations remain static with maturation. A combination of Pax-2/GFAP/CD34 immunohistochemistry, Nissl staining, and ADPase histochemistry showed that the vascular precursor cells (angioblasts), identified using ADPase and Nissl, represent a population distinct from Pax-2(+)/GFAP(-) APCs in the human retina. These results lead to the conclusion that formation of the initial human retinal vasculature takes place through vasculogenesis from the prior invasion of vascular precursor cells.

Visual manifestations of visible and buried optic disc drusen.

It has been reported that visible optic disc drusen are associated with decreased visual acuity and loss of peripheral visual field. Patients with buried optic disc drusen have not been as well characterized. An observational, retrospective review was made of 92 eyes with funduscopic or ultrasonographic evidence of optic disc drusen. Demographics, presenting symptoms, visual acuity, refractive error, intraocular pressure, presence of an afferent pupillary defect, cup-to-disc ratio, appearance of the optic nerve, and visual field were recorded. Fifty-one (55%) of the eyes were symptomatic; among them, 63% had symptoms of visual acuity loss, and 49% had symptoms of visual field loss. Seventy-nine (86%) of the optic discs appeared abnormal on ophthalmoscopy, but only 42% of these had visible drusen. Forty-five (49%) of the eyes had a visual field defect, and 73% of these were nerve fiber bundle in type. Overall, 73% of optic discs with visible drusen had abnormal visual fields compared with only 36% of optic discs with buried drusen (P < 0.05). Among 92 eyes with optic disc drusen, only slightly more than 50% produced visual symptoms. Fewer than 50% of drusen were visible ophthalmoscopically. Buried optic disc drusen identified by ultrasound had a significantly lower frequency of associated visual field defects than did visible optic disc drusen.

Age-related changes in the morphology of the myenteric plexus of the human colon

Aging is believed to affect the structure and function of the enteric nervous system, but little specific information on this topic is available, particularly in humans. The aim of this study was to investigate the effect of age on the structure of myenteric ganglia in the human colon. We examined myenteric ganglia in colonic specimens obtained from 168 patients aged 10 days to 91 years. Nerves were stained in whole mount preparations using the vital fluorescent dye 4-(4-dimethylaminostyryl)-methylpyridinium iodide (4-Di-2-ASP) and other staining methods. Human myenteric ganglia were classified into three types: normal, those containing empty spaces (‘cavities’) and those containing large nerve fiber bundles. We found a statistically significant increase with age in the proportion of ganglia with cavities. Conversely, there was a decrease with age in the proportion of normal ganglia. The proportion of fiber-containing ganglia did not change with age. These findings indicate that there is an increase with age in the number of abnormally appearing myenteric ganglia in the human colon, which may contribute to the disturbed colonic motility in the aging population.

Corneal healing after uncomplicated LASIK and its relationship to refractive changes: a six-month prospective confocal study.

To investigate corneal healing and the factor(s) possibly responsible for refractive changes after laser in situ keratomileusis (LASIK). Twenty eyes of 10 patients who underwent LASIK for myopia were examined clinically and by real-time confocal microscopy for 6 months. Epithelial and posterior stromal thicknesses and the thickness of the keratocyte activation zone were measured, and refractive changes were compared with these values. Keratocyte morphology, flap thickness, and subbasal nerve fiber bundle morphology after LASIK were also investigated. No significant change was detected over time in epithelial thickness after LASIK treatment; however, the posterior stromal thickness was found to be significantly higher 1 month after surgery. A slight but statistically significant negative correlation was detected between the thickness of the keratocyte activation zone and the spheroequivalent refraction after LASIK. The subbasal nerve fiber bundle's morphology returned to its preoperative appearance 6 months after LASIK, but in the flap stroma the nerve fiber bundle morphology remained abnormal at 6 months after LASIK surgery. A weak but significant negative correlation between the thickness of the keratocyte activation zone and spheroequivalent refraction was found after LASIK. The different refractive properties of activated keratocytes may be responsible for the myopic shift after LASIK. Further studies are needed to clarify this hypothesis.

Visual field changes after laser in situ keratomileusis in myopic eyes

Purpose: To evaluate the effect of acute elevation of intraocular pressure (IOP) during laser in situ keratomileusis (LASIK) on the visual field in myopic eyes. Setting : Istanbul University, Cerrahpassa Medical Faculty, Istanbul, Turkey. Methods: Thirty-seven eyes of 37 patients were included in the study. The LASIK procedure was performed using the Hansatome® microkeratome (Bausch & Lomb) and the Summit SVS Apex Plus® 193 nm argon–fluoride excimer laser. Visual field testing was performed twice before LASIK and 1 day and 24 months after LASIK. Seventy-six points, 6 degrees apart, in the central visual field (Central 30-2) were tested for threshold sensitivity (Humphrey). The mean threshold sensitivity of baseline and post-LASIK visual field examinations was calculated in each patient. Seventy-six points of the Central 30-2 test were divided into 21 clusters corresponding to perimetric nerve-fiber bundles derived from Peridata software version 6.2a (Interzaag AG). The mean threshold sensitivity of each cluster and the visual field indices (mean deviation [MD] and corrected pattern standard deviation [CPSD]) in baseline and follow-up visual fields were compared using analysis of variance. Results: The mean age of the 23 men and 14 women was 31.04 years ± 6.55 (SD). The mean spherical equivalent refraction was −4.21 ± 1.66 diopters (D) (range −2.25 to −6.75 D). The mean duration of suction was 42.29 ± 29.06 seconds. The mean visual field sensitivity at baseline and the 2 follow-up examinations was 25.97 ± 2.04 dB, 25.70 ± 1.99 dB, and 27.17 ± 1.68 dB, respectively ( P = .181). There was no difference between preoperative and postoperative visual field clusters except in area 13. In area 13, threshold sensitivity was decreased at 1 day ( P = .039) and at the preoperative level at 24 months. The MD of the visual fields was −3.53 ± 1.67 dB, −3.61 ± 2.91 dB, and −2.61 ± 1.66 dB at the preoperative and 2 postoperative examinations, respectively ( P = .495). The mean CPSD of the visual fields was 1.76 ± 1.24 dB, 1.42 ± 0.85 dB, and 1.74 ± 0.86 dB, respectively ( P = .680). Conclusion: Laser in situ keratomileusis did not cause visual field defects in mild to moderate myopic patients who had no risk factors that might render the optic nerve more vulnerable to damage.

Peptidergic innervation in pars distalis of the human anterior pituitary

It has been previously shown that the peptidergic nerve fibers are present in the anterior pituitary of monkeys, dogs and rats. In our study, which is reported here, thick nerve fiber bundles, large numbers of peptidergic nerve fibers and their varicosities, which are substance P (SP)-, calcitonin gene-related peptide (CGRP)- and galanin (GAL)-immunoreactive (ir), are found in the human pituitary stalk. All these peptidergic nerve fibers run along the pituitary stalk and enter the pars distalis, and some GAL-ir nerve fibers even reach the center of the human anterior pituitary as well as in parenchyma of adenohypophysis. The number of SP-ir nerve fibers is much more than that of other kinds of peptidergic nerve fibers. All these peptidergic nerve fibers are mainly located in the medial part of the gland and distributed in its dorsal-posterior region. A substantial amount of these peptidergic nerve fibers with numerous varicosities are found to be close to the glandular tissue in the pars distalis of the human anterior pituitary. Furthermore, same SP-ir and CGRP-ir cells have been demonstrated in the pars distalis of the anterior pituitary. More or less, these peptidergic nerve fibers came also from the meningeal shell and enter the parenchyma of the anterior pituitary. Whatever the function of peptidergic nerve fibers in the human anterior pituitary might be, the concept that the adenohypophysis is regulated only hormonally by way of the portal system could be challenged.

Schnabel cavernous degeneration. A vascular change of the aging eye

Schnabel cavernous degeneration of the optic nerve occurs is a histologic finding in eyes consisting of atrophy with pools of glycosaminoglycan deposited in the areas of nerve fiber bundles. This finding had been attributed to chronically increased intraocular pressure, although the precise nature of the finding is unknown. In order to determine the basic cause of the formation of cavernous spaces in the proximal optic nerve and its clinical significance, a retrospective analysis of 4500 autopsy eyes processed for histologic evaluation between 1967 and 1991 was undertaken. Ninety-three (2.1%) of the eyes exhibited Schnabel cavernous degeneration. The majority of the eyes were from women (81%). The mean age of the entire group was 88 years (range, 54 N103 years). Severe vascular anomalies were present in 75% of the individuals. Cavernous degeneration was unilateral in 82% of the cases. Loss of ganglion cells and the nerve fiber layer, consistent with glaucoma, was found in only 23.7% of the individuals. Clinical information was available for 15 individuals (16%). Half of them were thought to have some clinical optic nerve damage; in the remainder, no specific optic disk abnormalities were noted. Histologic findings or arteriosclerosis in the optic nerve circulation were common. Schnabel cavernous optic atrophy appears to be a unilateral condition of elderly women with systemic vascular disease and few clinically characteristic ocular features. This study indicates that a chronic vascular occlusive disease of the proximal optic nerve is more likely involved with the pathogenesis of Schnabel cavernous atrophy than is a sustained increase of intraocular pressure. Hans E. Grossniklaus

Simulation Study of Magnetic Fields Produced by an Active Bundle of Nerve Fibers to Estimate the Distribution of Fiber Diameter

Simulation Study of Magnetic Fields Produced by an Active Bundle of Nerve Fibers to Estimate the Distribution of Fiber Diameter

Segmental spinal nerve ligation model of neuropathic pain.

Since its introduction in 1992, the spinal nerve ligation (SNL) model of neuropathic pain has been widely used for various investigative works on neuropathic pain mechanisms as well as in screening tests for the development of new analgesic drugs. This model was developed by tightly ligating one (L5) or two (L5 and L6) segmental spinal nerves in the rat. The operation results in long-lasting behavioral signs of mechanical allodynia, heat hyperalgesia, cold allodynia, and ongoing pain. In the process of widespread usage, however, many different variations of the SNL model have been produced, either intentionally or unintentionally, by different investigators. Although the factors that cause these variations themselves are interesting and important topics to be studied, the pain mechanisms involved in these variations are likely different from the original model. Therefore, this chapter describes, in detail, the method for producing the spinal nerve ligation model that will minimally induce potential factors that may contribute to these variations. It is hoped that this description will help many investigators to produce a consistent animal model with uniform pathophysiological mechanisms.

Single-fiber recording: in vivo and in vitro preparations.

This chapter focuses on in vivo and in vitro recording setups of extracellular single-unit recordings of peripheral sensory nerve or dorsal root fibers in rodents. Extracellular single-unit recording methods have been used to obtain a wealth of data about the properties of peripheral nervous system (PNS) and central nervous system (CNS) structures. The rationale for studying the activity of single-unit primary afferent fibers is predicated on the significance of relatively fine variations of fiber responsiveness to mechanical, chemical, and/or thermal stimuli. It involves microdissection of nerve fiber bundles until the electrical activity of a single fiber is isolated. Electrophysiological changes in thresholds and discharge rates of peripheral nociceptors to polymodal stimuli can provide neurophysiological correlation to behavioral hyperalgesia and allodynia as well as to cellular differences observable with immunohistochemistry. This chapter gives an overview about the necessary general and special equipment, details about the different setups and tissue preparations. Additionally, the chapter informs about the procedure of recording from single units, data acquisition and analysis including unit isolation criteria and techniques for spike discrimination techniques and fiber classification. It describes criteria for the classification of nociceptors and identification of cutaneous afferent units.