Ovoid Formation Research Articles

A CAUSE OF PAROXYSMAL HYPERTENSION NOT TO BE OVERLOODED: CHILDREN'S PHEOCHROMOCYTOMA

Objective: We aimed to assess the clinical presentation, natural history, and treatment response of hypertension in children with pheochromocytoma. Design and method: O. Mohamed, an 8-year-old boy, without past medical history, hospitalized for paroxysmal hypertension evolving for 6 months with severe headaches, generating insomnia. No similar episodes in the family. Clinical features: BMI of 15. 1 kg/m2 (height: 1.26 m, weight: 24 kg). heart rate of 128 bpm (tachycardia) and blood pressure of 175/84 mm Hg (stage 2 for systolic hypertension and stage 1 for diastolic hypertension, table 1). The physical examination was unremarkable except for tenderness in the right hypochondrium. Biological tests: serum creatinine and proteinuria testing was normal. Ophthalmic examination: stage I hypertensive retinopathy (Arterial narrowing). Abdominal ultrasound: right adrenal mass, measuring 65–57–61 mm in size, well-defined, heterogeneous echo structure, with multiple echogenic areas. No calcifications. Abdominal CT scan: Solid right adrenal mass (Figures 1 & 2) and no lymph node involvement. Urinary Vanyl Mandelic Acid: high level at 27.18 μmol/l (normal < 10 μmol/l). MIBG scintigraphy: intense pathological uptake, posterior, projecting over the right renal region, intensifying at 48 hours. No other sites of uptake. Results: In summary, right adrenal pheochromocytoma revealed by a severe paroxysmal hypertension. Preoperative management: Nicardipine IV. Alpha-blocker combined with a beta-blocker were not used. Evolution under medical treatment while waiting for excision of the tumor is favorable with a significant reduction in blood pressure. The child was operated with complete excision of the tumor. Pathological examination of the surgical specimen: ovoid formation made of epithelial cells with basophilic nuclei arranged in cords separated by thin vascular axes = aspect of pheochromocytoma Post-operative evolution was favorable with disappearance of symptoms and normalization of blood pressure after stopping antihypertensives. Actually, the patient is asymptomatic after 4-year follow-up with normal blood pressure and no relapse. The family investigation does not report any family cases. Conclusions: Pheochromocytoma is rare in children. It often presents with severe paroxysmal hypertension. Malignant forms are rare in children; however, rigorous surveillance is necessary for at least 5 years.

UMBILICAL ENDOMETRIOSIS: A CASE REPORT

Introduction: We report a recently observed case of secondary umbilical endometriosis (UE), with the main aim to discuss diagnosis and the management of this rare condition. Observation: A 41-year-old woman admitted to our facility with a nodular, bluish umbilical swelling, non- painful, gradually increasing in size, bleeding with her menstrual cycle. Ultrasonography did not reveal any images indicative of pelvic endometriotic lesions. A pelvic MRI was performed wich showed an ovoid formation at the umbilical level, suggestive of a UE implant. A biopsy of the lesion was also carried out, showing a morphological appearance compatible with parietal endometriosis. Histopathological analysis confirmed the diagnosis of UE. Neither symptoms or signs of local recurrence have been observed after 6 months. Discussion: Extra-pelvic endometriosis sites are not common, especially the umbilicus. It usually occurs secondary to surgical scars, specifically after laparoscopy or open abdominal surgery. UE should be taken into accounting differential diagnosis of umbilical disorders even in young nulliparous women with no typical symptoms of pelvic endometriosis. UE can be treated medically or surgically. Surgical treatment options are either local excision of the lesion or removal of the whole umbilicus with or without laparoscopic exploration of the peritoneal cavity. The decision should be tailored for the individual patient, taking into consideration the size of the lesion, the duration of symptoms and the presence of possible pelvic endometriosis. Conclusion: Local excision saving the umbilicus may be the treatment of choice in patients with small UE lesions.

Traumatic axonopathy in spinal tracts after impact acceleration head injury: Ultrastructural observations and evidence of SARM1-dependent axonal degeneration

Traumatic axonal injury (TAI) and the associated axonopathy are common consequences of traumatic brain injury (TBI) and contribute to significant neurological morbidity. It has been previously suggested that TAI activates a highly conserved program of axonal self-destruction known as Wallerian degeneration (WD). In the present study, we utilize our well-established impact acceleration model of TBI (IA-TBI) to characterize the pathology of injured myelinated axons in the white matter tracks traversing the ventral, lateral, and dorsal spinal columns in the mouse and assess the effect of Sterile Alpha and TIR Motif Containing 1 (Sarm1) gene knockout on acute and subacute axonal degeneration and myelin pathology. In silver-stained preparations, we found that IA-TBI results in white matter pathology as well as terminal field degeneration across the rostrocaudal axis of the spinal cord. At the ultrastructural level, we found that traumatic axonopathy is associated with diverse types of axonal and myelin pathology, ranging from focal axoskeletal perturbations and focal disruption of the myelin sheath to axonal fragmentation. Several morphological features such as neurofilament compaction, accumulation of organelles and inclusions, axoskeletal flocculation, myelin degeneration and formation of ovoids are similar to profiles encountered in classical examples of WD. Other profiles such as excess myelin figures and inner tongue evaginations are more typical of chronic neuropathies. Stereological analysis of pathological axonal and myelin profiles in the ventral, lateral, and dorsal columns of the lower cervical cord (C6) segments from wild type and Sarm1 KO mice at 3 and 7 days post IA-TBI (n = 32) revealed an up to 90% reduction in the density of pathological profiles in Sarm1 KO mice after IA-TBI. Protection was evident across all white matter tracts assessed, but showed some variability. Finally, Sarm1 deletion ameliorated the activation of microglia associated with TAI. Our findings demonstrate the presence of severe traumatic axonopathy in multiple ascending and descending long tracts after IA-TBI with features consistent with some chronic axonopathies and models of WD and the across-tract protective effect of Sarm1 deletion.

Prenatal diagnosis of congenital soft tissue hemangioma of the fetal back

Congenital hemangiomas are benign vascular lesions found in fetuses. Congenital hemangiomas develop in utero, have a maximum size at birth (in the absence of subsequent bleeding). Such hemangiomas occur in 1–2% of newborns. Prenatal ultrasound diagnostics and magnetic resonance imaging occupy an important place in the diagnosis, which determines the tactics of management and treatment of the patient. To present a clinical case of prenatal diagnosis of congenital soft tissue hemangioma of the fetal back. A pregnant woman A., 34, was sent to St. Petersburg State Public Health Institution «Diagnostic Center» (medical and genetic) with suspected spina bifida of the fetus after screening in late pregnancy period in one of the Birth Centres. Performed prenatal ultrasound (US) pregnant A. for a period of 34 weeks. According to ultrasound data in the region of the spine at the level of XI–XII thoracic vertebrae, an ovoid formation with clear even contours, a fairly homogeneous solid structure, with a clear capsule, 33×24×30 mm in size (volume 12.4 cm3) is determined subcutaneously. The diagnosis made: hemangioma of the soft tissues of the fetal back. Prenatal screening plays a key role in the diagnosis of congenital hemangiomas. Timely detection of this benign formation affects the tactics of management and delivery.

Segmental formation of the main nerves of the sacral plexus

The study of segmental innervation may be of practical interest, as pathological processes involving organs and tissues can be caused by damage to both peripheral and individual segmental nerves. Also, the occurrence of a pathological condition of the pelvic limb structures can be associated with various injuries, damage to the spinal cord, roots and segmental nerves of the sacral spine. The aim of the experimental research was to study the segmental formation of the main nerves of the sacral plexus – n. ischiadicus, n. tibialis, n. peroneus communis in cats. Unilateral extravertebral ganglioectomy of the lumbosacral segments – L 4, L5, L6, L7, S1, S2 was performed for the study. Samples of the main nerves were examined in polarized light to detect signs of Wallerian's degeneration at x400 magnification. This method allows you to easily distinguish degenerated nerve fibers at different stages of degeneration from normal. The micromorphology of the initial stages of degeneration is characterized by uneven thickening of the fibers, smoothing of the Ranvier nodes, dilated Schmidt-Lanterman notches, an increasein the number of myelin segments. At later stages of Wallerian's degeneration, the following are observed: edema and significant thickening of the myelin sheath, smoothing of fiber contours, formation of ovoids and fragmentary glow of myelin. Statistical analysis of the results was performed using Student's t-test. In the course of research, it was found that in the formation of the main nerves of the sacral plexus: n. ischiadicus, n. tibialis, n. peroneus communis involves 6 segments of the lumbosacral spine - from L4 to S2. These nerves of the sacral plexus are polysegmental, which indicates their compensatory properties. The highest percentage of degenerated nerve fibers for the main nerves of the sacral plexus gives the 6th lumbar segment L6, which is the axial nerve. The obtained results can expand the knowledge of principles of segmentation in anatomy, to become a reference point for sacral regional epidural anesthesia for orthopedic operations on the pelvic limbs, nerve blockade to increase patient comfort in the postoperative period, lumbar puncture, neurotherapy. The method of polarization microscopy can be used as a clinically useful test for peripheral nerve biopsy to assess the state of neurodegenerative changes, monitoring regenerative and neuroprotective effects. Key words: Wallerian degeneration, segmental innervation, sacral plexus, polarization microscopy, cats.

A 13th-century cystic echinococcosis from the cemetery of the monastery of Badia Pozzeveri (Lucca, Italy)

ObjectiveTo differentially diagnose a calcified formation recovered from a 13th century AD grave from the Tuscan monastery of Badia Pozzeveri, Lucca, Italy. MaterialsA calcified formation from the thoraco-abdominal region of a skeleton buried in the monastery cemetery. MethodsCone Beam Computed Tomography, Scanning Electron Microscope and Energy Dispersive X-Ray Spectroscopy. ResultsA hollow, calcified ovoid formation was identified as typical of a hydatid cyst, permitting the diagnosis of cystic echinococcosis in a 35-45year-old female. ConclusionsThe study reveals the circulation of the parasite Echinococcus granulosus in the region of Lucca in late medieval Tuscany. SignificanceThis finding is the fourth case of cystic echinococcosis from an archaeological context in Italy and provides insight into environmental conditions that appear to have affected members of a community, irrespective of social status. LimitationsCaution and the application of multiple analyses must be exercised in the differential diagnosis to discriminate among calcified formations. Suggestions for further researchAnalysis of stable isotopes of the calcified formation, such as 15N and 13C, in order to compare them with isotopic values of the host individual and to further confirm the parasitic origin of the find.

Toxic effect of acetamiprid on Rana ridibunda sciatic nerve (electrophysiological and histopathological potential)

In this study, the effects of a neonicotinoid insecticide acetamiprid on the sciatic nerve of Rana ridibunda were investigated by using electrophysiological and histological methods. A total of 35 preparations of sciatic nerve isolated from 35 frogs (Nervus ischiadicus) were used in the experiments. Experiments were designed as four different dose groups (n = 8 per group). Acetamiprid solutions of 1 (group 1), 10 (group 2), 100 (group 3), and 1000 µM (group 4) were applied to the nerves in dose groups. In each group, action potentials were recorded before application of acetamiprid which served as control data. The extracellular action potentials were recorded for each group of 30th, 60th, 90th and 120th min of application time. Action potential amplitude and area were measured from recordings. Histological evaluation was performed by transmission electron microscopy.In electrophysiological examination, all doses in which acetamiprid applied have shown the effect from the 30th min and suppressed the sciatic nerve action potential. Acetamiprid significantly reduced the amplitude at the rate of 78–96% and the area at the rate of 79–98% (p < 0.05). In electron microscopic examination, the control nerves were in normal appearance. Disorganization, irregularity, dense ovoid body formation, fragmentation of the myelin sheath, and loss on some axoplasm of the nerves in the dose group have been observed. Our findings showed that acetamiprid can cause neuropathic changes in sciatic nerve at all applied doses. These results indicate that acetamiprid as other insecticides can have harmful effects on non-target organisms.

Proteolipid protein-deficient myelin promotes axonal mitochondrial dysfunction via altered metabolic coupling.

Hereditary spastic paraplegia (HSP) is a neurological syndrome characterized by degeneration of central nervous system (CNS) axons. Mutated HSP proteins include myelin proteolipid protein (PLP) and axon-enriched proteins involved in mitochondrial function, smooth endoplasmic reticulum (SER) structure, and microtubule (MT) stability/function. We characterized axonal mitochondria, SER, and MTs in rodent optic nerves where PLP is replaced by the peripheral nerve myelin protein, P0 (P0-CNS mice). Mitochondrial pathology and degeneration were prominent in juxtaparanodal axoplasm at 1 mo of age. In wild-type (WT) optic nerve axons, 25% of mitochondria-SER associations occurred on extensions of the mitochondrial outer membrane. Mitochondria-SER associations were reduced by 86% in 1-mo-old P0-CNS juxtaparanodal axoplasm. 1-mo-old P0-CNS optic nerves were more sensitive to oxygen-glucose deprivation and contained less adenosine triphosphate (ATP) than WT nerves. MT pathology and paranodal axonal ovoids were prominent at 6 mo. These data support juxtaparanodal mitochondrial degeneration, reduced mitochondria-SER associations, and reduced ATP production as causes of axonal ovoid formation and axonal degeneration.

Reciprocal relationship between membrane type 1 matrix metalloproteinase and the algesic peptides of myelin basic protein contributes to chronic neuropathic pain

Myelin basic protein (MBP) is an auto-antigen able to induce intractable pain from innocuous mechanical stimulation (mechanical allodynia). The mechanisms provoking this algesic MBP activity remain obscure. Our present study demonstrates that membrane type 1 matrix metalloproteinase (MT1-MMP/MMP-14) releases the algesic MBP peptides from the damaged myelin, which then reciprocally enhance the expression of MT1-MMP in nerve to sustain a state of allodynia. Specifically, MT1-MMP expression and activity in rat sciatic nerve gradually increased starting at day 3 after chronic constriction injury (CCI). Inhibition of the MT1-MMP activity by intraneural injection of the function-blocking human DX2400 monoclonal antibody at day 3 post-CCI reduced mechanical allodynia and neuropathological signs of Wallerian degeneration, including axon demyelination, degeneration, edema and formation of myelin ovoids. Consistent with its role in allodynia, the MT1-MMP proteolysis of MBP generated the MBP69-86-containing epitope sequences in vitro. In agreement, the DX2400 therapy reduced the release of the MBP69-86 epitope in CCI nerve. Finally, intraneural injection of the algesic MBP69-86 and control MBP2-18 peptides differentially induced MT1-MMP and MMP-2 expression in the nerve. With these data we offer a novel, self-sustaining mechanism of persistent allodynia via the positive feedback loop between MT1-MMP and the algesic MBP peptides. Accordingly, short-term inhibition of MT1-MMP activity presents a feasible pharmacological approach to intervene in this molecular circuit and the development of neuropathic pain.

Actin Polymerization Is Essential for Myelin Sheath Fragmentation during Wallerian Degeneration

The mechanisms that trigger Wallerian degeneration (WD) of peripheral nerves after injury are not well understood. During the early period of WD, fragmentation of myelin into ovoid structures occurs near the Schmidt-Lantermann incisures (SLI), a noncompact region of the myelin sheath containing autotypical adherens junction. In this study, we found that new filamentous actin polymerization occurs in the SLI of mouse sciatic nerves after injury and that its inhibition prevented not only the degradation of E-cadherin in the SLI but also myelin ovoid formation. However, the inhibition of actin polymerization could not block Schwann cell dedifferentiation. The activation of Rac GTPase was observed in the distal stump of the injured nerves, and a specific Rac inhibitor, a dominant-negative Rac, and Rac1-RNA interference blocked myelin ovoid formation. Together, these findings suggest that dynamic changes in actin in the SLI are essential for initiation of demyelination after peripheral nerve injury.

Proteasome inhibition suppresses injury‐induced myelin ovoid formation and Schwann cell dedifferentiation in the peripheral nerves

The ubiquitin‐proteasome system (UPS), lysosomes and autophagy are essential protein degradation systems for the regulation of a variety of cellular physiological events including the cellular response to injury. It was recently reported that axonal degeneration by traumatic insults or retrieval of nerve growth factors is mediated by the UPS and autophagy. In the peripheral nerves, axonal degeneration after injury is accompanied by myelin degradation which is tightly related to the reactive changes of Schwann cells called dedifferentiation. In this study, we examined the role of the UPS, lysosomal proteases and autophagy in the early phase of Wallerian degeneration of injured peripheral nerves. We found that nerve injury induced an increase in ubiquitin conjugation and lysosomal‐associated membrane protein‐1 expression within one day without any biochemical evidence for autophagy activation. Using an ex vivo explant culture of the sciatic nerve, we observed that inhibiting proteasomes or lysosomal serine proteases prevented myelin degradation, whereas this was not observed when inhibiting autophagy. Interestingly, proteasome inhibition, but not leupeptin, prevented Schwann cells from inducing dedifferentiation markers such as p75 nerve growth factor receptor and glial fibrillary acidic protein in vitro and in vivo. In addition, proteasome inhibitors induced cell cycle arrest and cellular process formation in cultured Schwann cells. Taken together, these findings indicate that the UPS plays a role in phenotype changes of Schwann cells in response to nerve injury.

Ultrasound aspects in the infiltrative neoplasia of the colon

In the tumor pathology of the colon, the ultrasound can guide the diagnostic, being completed by some other medical imagery tests (endoscope, radiographic, pathologic). The present study follows the ultrasound description on patients to whom the ultrasound was of primordial intent, appointed for acute abdominal pain, palpable abdominal mass, occlusive manifestations or a weight loss syndrome. The ultrasound examination has shown the presence of an ovoid formation situated with a colon's projection area with a regulated exterior line being composed from three concentric zones as such: in the central region an intense hyperechoic band of variable thickness given by the existing colon air, the echoic or hypoechoic middle layer of significant width proportional with the degree of tumor infiltration which has an irregular line of separation from the other layers, the exterior hypoechoic layer made by the rest of the colon (muscles, serous). In the extended infiltrative processes a kidney-like aspect can be described. There was a persisting image non influenced in repeated examinations.

Characterization of the nematocidal toxocyst in Pleurotus subgen. Coremiopleurotus

Toxocysts of the genus Pleurotus are blastoconidia-like ovoid structures surrounded by a liquid droplet containing a toxin that paralyzes nematodes. This study investigated toxocyst development using a strain S396 of Pleurotus cystidiosus subsp. abalonus (subgen. Coremiopleurotus). The surface of the liquid droplet was found to be an elastic envelope. When a nematode touches the toxocyst, the envelope adheres to the worm and bursts. Toxocysts are induced simultaneously with coremia formation in the absence of nematodes and developed only from aerial hyphae in which nuclear division had ceased. In the early stage of toxocyst development, liquid springs repeatedly from the tip of the sterigma-like stipe before ovoid (blastoconidium- like structure) formation. A certain substance in the liquid might polymerize to form the envelope while the ovoid simultaneously budded in the droplet. The nucleus tends to locate near the toxocyst, especially in early stage of toxocyst development. Each dikaryotic cell predominantly formed one or two toxocyst(s) while each monokaryotic cell predominantly formed one. In rare cases, a nucleus existed in the toxocyst, suggesting the possibility that the toxocyst is a vestigial blastoconidium.

Characterization of the nematocidal toxocyst in &lt;i&gt;Pleurotus&lt;/i&gt; subgen. &lt;i&gt;Coremiopleurotus&lt;/i&gt;

Toxocysts of the genus Pleurotus are blastoconidia-like ovoid structures surrounded by a liquid droplet containing a toxin that paralyzes nematodes. This study investigated toxocyst development using a strain S396 of Pleurotus cystidiosus subsp. abalonus (subgen. Coremiopleurotus). The surface of the liquid droplet was found to be an elastic envelope. When a nematode touches the toxocyst, the envelope adheres to the worm and bursts. Toxocysts are induced simultaneously with coremia formation in the absence of nematodes and developed only from aerial hyphae in which nuclear division had ceased. In the early stage of toxocyst development, liquid springs repeatedly from the tip of the sterigma-like stipe before ovoid (blastoconidium-like structure) formation. A certain substance in the liquid might polymerize to form the envelope while the ovoid simultaneously budded in the droplet. The nucleus tends to locate near the toxocyst, especially in early stage of toxocyst development. Each dikaryotic cell predominantly formed one or two toxocyst(s) while each monokaryotic cell predominantly formed one. In rare cases, a nucleus existed in the toxocyst, suggesting the possibility that the toxocyst is a vestigial blastoconidium.

Axon Reactive B Cells Clonally Expanded in the Cerebrospinal Fluid of Patients with Multiple Sclerosis

Demyelination and axonal loss have been described as the histological hallmarks of inflammatory lesions of multiple sclerosis (MS) and are the pathological correlates of persistent disability. However, the immune mechanisms underlying axonal damage in MS remain unknown. Here, we report the use of single chain-variable domain fragments (scFv) from clonally expanded cerebrospinal fluid (CSF) B cells to show the role of an anti-axon immune response in the central nervous system (CNS) in MS. The cellular and subcellular distribution of the antigen(s) recognized by these CSF-derived clonal scFv antibodies (CSFC-scFv Abs) was studied by immunochemical staining of brain tissues obtained at autopsy from patients with MS. Immunochemistry showed specific binding of CSFC-scFv Abs to axons in acute MS lesions. The stained axons showed three major types of axonal pathological changes: 1) linear axons, axonal ovoid formation, and axonal transection were seen in the myelinated white matter adjacent to the lesion; 2) accumulation of axonal ovoid formations and Wallerian degeneration were seen at the border between demyelinated lesions and the adjacent white matter; and 3) Wallerian degeneration occurred at the center and edge of acute demyelinated lesions. These findings suggest a B cell axonal specific immune response in the CNS in MS.

Wallerian Degeneration in the Optic Nerve of the Rabbit

Progressive anterograde axonal degeneration is known to follow after transection of the axon from the soma, which to some extent correlates with the passage of time after the lesion. However, the minimum time required for such changes to begin remains unresolved. In this study, 20 young adult rabbits of either sex underwent experimental monocular enucleation (left eye) under general anaesthesia. Left optic nerves from such animals were treated as experimental and those from either side of non-operated animals served as controls. Animals were sacrificed postoperatively at periods ranging from 12 h to 3 months. Brains were fixed with 10% formalin and Karnovsky fixatives by an intracardiac perfusion method. Light microscopy of 8-µm paraffin sections and 0.5-µm araldite sections from the optic nerves did not reveal any changes at 12 h. At 24 h, focal minute cavities appeared across the optic nerves. Those nerves from late postoperative stages revealed such cavities with increasing dimensions, disarray of fascicular organization, fragmentation, ovoid formation and finally dissolution of the myelin sheaths. There was an appreciable increase in the number, size and aggregation of glia cells. The debris of degeneration remained prominent even 3 months after enucleation. Electron microscopy revealed splitting of myelin, intramyelinic and periaxonal oedema and occurrence of amorphous and electron-dense materials in the degenerating nerve fibres. It was concluded that while the optic nerve showed degenerative changes as early as 24 h after enucleation, debris of degeneration was only partly removed even after 3 months.

Anti-neurofilament antibodies in neuropathy with monoclonal gammopathy of undetermined significance produce experimental motor nerve conduction block.

Elevated levels of serum antibodies to neurofilament proteins have been associated with a variety of neurological diseases, including autoimmune disorders such as neuropathy with monoclonal gammopathy of undetermined significance (MGUS). The pathological significance of anti-neurofilament antibodies in sera of affected patients, however, remains unclear. In this study, we report our findings of polyclonal antibodies in sera from 4 of 16 IgG MGUS neuropathy patients that react strongly on immunoblot with a high molecular weight neurofilament protein (NFH). The effect of anti-NFH polyclonal antibody on peripheral nerve function was tested in vivo by intraneural injection. Sera containing anti-NFH antibody, but not sera from age-matched control subjects, injected into the endoneurium of rat sciatic nerve significantly attenuated proximal-evoked motor nerve compound muscle action potential (CMAP) amplitudes in a complement-dependent manner. In contrast, ankle-evoked CMAP amplitudes were unaffected by intraneural injection of sera containing anti-NFH antibody. Anti-NFH serum-injected nerves showed changes in both axon caliber (shrinkage) and myelin ultrastructure (vesiculation and ovoid formation), suggestive of intramyelinic edema. Preincubation of sera containing anti-NFH antibody with purified NFH protein abolished immunoreactivity to NFH protein and neutralized the serum-mediated toxicity. The data suggest that anti-NFH polyclonal antibodies occurring in sera of some patients with IgG MGUS neuropathy may elicit peripheral nerve conduction block independent of the patients' IgG paraprotein. Anti-neural polyclonal antibodies in sera of IgG MGUS neuropathy patients may have a greater pathological significance than previously anticipated.

Electrically active axons degenerate when exposed to nitric oxide

Axonal degeneration is a major cause of permanent deficit in inflammatory neurological diseases such as multiple sclerosis. Axons undergo degeneration specifically at the site of the inflammatory lesions, suggesting that locally produced inflammatory factors mediate the phenomenon. One such factor is nitric oxide (NO), which we have previously reported can cause reversible conduction block in axons. Here we confirm these observations and extend them to show that axons exhibit the early stages of wallerian degeneration if they are conducting impulses at physiological frequencies while they are exposed to the low micromolar concentrations of NO that are likely to occur at sites of inflammation. Rat dorsal roots were concurrently exposed in vivo to both NO and sustained impulse activity at 1, 50, or 100 Hz. Although our in vivo observations necessarily focused on the more acute responses, morphological examination of exposed roots at the end of the recording period revealed nodal and paranodal changes consistent with acute wallerian degeneration in roots stimulated at 50 or 100 Hz. This interpretation was confirmed in a few experiments that were prolonged to permit more obvious indicators of degeneration to develop. In these experiments the formation of myelin ovoids and frank axonolysis occurred in more than 95% of fibers. Roots stimulated at only 1 Hz appeared normal. We propose that the combination of normal impulse traffic and NO at sites of inflammation may cause axonal degeneration and that electrical activity may therefore be an important factor in causing permanent disability in patients with neuroinflammatory disorders.

Electrically active axons degenerate when exposed to nitric oxide

Axonal degeneration is a major cause of permanent deficit in inflammatory neurological diseases such as multiple sclerosis. Axons undergo degeneration specifically at the site of the inflammatory lesions, suggesting that locally produced inflammatory factors mediate the phenomenon. One such factor is nitric oxide (NO), which we have previously reported can cause reversible conduction block in axons. Here we confirm these observations and extend them to show that axons exhibit the early stages of wallerian degeneration if they are conducting impulses at physiological frequencies while they are exposed to the low micromolar concentrations of NO that are likely to occur at sites of inflammation. Rat dorsal roots were concurrently exposed in vivo to both NO and sustained impulse activity at 1, 50, or 100 Hz. Although our in vivo observations necessarily focused on the more acute responses, morphological examination of exposed roots at the end of the recording period revealed nodal and paranodal changes consistent with acute wallerian degeneration in roots stimulated at 50 or 100 Hz. This interpretation was confirmed in a few experiments that were prolonged to permit more obvious indicators of degeneration to develop. In these experiments the formation of myelin ovoids and frank axonolysis occurred in more than 95% of fibers. Roots stimulated at only 1 Hz appeared normal. We propose that the combination of normal impulse traffic and NO at sites of inflammation may cause axonal degeneration and that electrical activity may therefore be an important factor in causing permanent disability in patients with neuroinflammatory disorders. Ann Neurol 2001;49:470–476

Morphological analysis of protease treatment of damaged nerves

Intravitam phase-contrast microscopy of individual isolated myelin fibers of rabbit tibial nerves shows that 40-min treatment with 0.2% pronase solution is harmless to intact myelin fibers. In injured nerves such treatment causes sharply expressed proteolysis and a rapid process of wallerian degeneration with ruptures of the axial cylinders and the formation of degeneration ovoids. The findings prove the feasibility and desirability of early primary protease treatment of nerve wounds.