Sarm1-mediated neurodegeneration within the enteric nervous system protects against local inflammation of the colon

Axonal degeneration is one of the key features of neurodegenerative disorders. In the canonical view, axonal degeneration destructs neural connections and promotes detrimental disease defects. Here, we assessed the enteric nervous system (ENS) of the mouse, non-human primate, and human by advanced 3D imaging. We observed the profound neurodegeneration of catecholaminergic axons in human colons with ulcerative colitis, and similarly, in mouse colons during acute dextran sulfate sodium-induced colitis. However, we unexpectedly revealed that blockage of such axonal degeneration by the Sarm1 deletion in mice exacerbated the colitis condition. In contrast, pharmacologic ablation or chemogenetic inhibition of catecholaminergic axons suppressed the colon inflammation. We further showed that the catecholaminergic neurotransmitter norepinephrine exerted a pro-inflammatory function by enhancing the expression of IL-17 cytokines. Together, this study demonstrated that Sarm1-mediated neurodegeneration within the ENS mitigated local inflammation of the colon, uncovering a previously-unrecognized beneficial role of axonal degeneration in this disease context.

Different pathological processes for acute white matter lesions in multiple sclerosis

@#Introduction: Multiple sclerosis (MS) has variable clinical presentations, prognoses, pathogeneses, and pathological patterns. We conducted a pathological review of acute MS-associated lesions that focused on the degree of axonal injury, myelin loss, and glial reaction to determine whether the observed demyelination was of the primary or secondary type. Materials and Methods: After searching the records for a 15-year period at the London Health Sciences Centre Pathology Department, we identified 8 cases of surgical acute lesion biopsies in which clinical MS diagnoses were made before or after the biopsy. Results: The white matter pathologies in these cases could be sorted into 3 morphological patterns. The first pattern, which represents typical demyelinated plaques, was observed in 4 cases and was characterised by nearly complete demyelination accompanied by variable degrees of axon preservation and axonal swelling. The second pattern was observed in 3 cases and was characterised by demyelinating lesions containing variable numbers of myelinated axons mixed with a few demyelinated axons and variable numbers of axonal swellings. The myelinated axons ranged from scattered fibres to bands of variable thickness, and the demyelination was a mixture of primary and secondary demyelination. The third pattern was observed in 1 case and was characterised by well-demarcated areas of reduced myelin staining and numerous apoptotic nuclei. Axonal staining revealed many fragmented axons with reduced myelin staining but no definitely demyelinated axons. Conclusion: This report shows that the predominant pathology underlying acute MS-related lesions is not limited to demyelination but can include axonal degeneration alone or in combination with primary demyelination which reflect different pathogenesis for these acute lesions.

Glial response following diffuse axonal injury / 解剖学报

Objective To explore the glial response and the relationship with secondary axonal degeneration in rats after diffuse axonal injury (DAI). Methods Adult male Sprague-Dawley rats were randomly assigned to control or DAI groups sacrificed at 1, 2, 3, 5 and 7 days with 10 rats in each group. DAI model was made referring to modified Marmarou method and glial fibrillary acidic protein (G F A P), ionized calcium binding adaptor molecule-1 (Ibal), recombinant oligodendrocyte lineage transcription factor 2 (Olig2), CC-1, NG2 immunohistochemistry, TUNEL staining and transmission electron microscopy were performed in brain stem. Results The number of Ibal labeled positive cells was significantly increased at day 3 and day 7 after injury. Moreover, different hypertrophic morphology was identified after injury. There was no effect of DAI on GFAP expression in brain stem. Numbers of mature oligodendrocyte marker CC-1 immunoreactivity cells within brain stem were significantly decreased at each of the time points after injury. The number of TUNEL positive cells in brain stem was significantly increased with injured time. Olig2 expression was significantly increased throughout the first week and reached peak at day 3 after injury in brain stem. The number of NG2 labeled positive cells was significantly increased at day 3 and day 7 after DAI. Ultrastructural evidence showed myelin release then further developed as widespread delamination and collapse, and leading to degeneration of axonal partner. Conclusion Mature oligodendrocytes are vulnerable in DAI and myelin loss may contribute to axonal degeneration. OPCs proliferate with activation of microglia. This insight of glial response will further explain the pathophysiological mechanism of secondary axonal damage in DAI.

Degenerative axonopathy associated with copper deficiency in pigs / Axonopatia degenerativa associada com deficiência de cobre em suínos

The epidemiological, clinic and morphological (pathological and ultrastructural) aspects of four outbreaks of copper deficiency affecting 21- to 90-day-old pigs in the Northeast region of Brazil are reported. Clinical signs began with paraparesis and ataxia and progressed to flaccid or spastic paralysis of the pelvic and thoracic limbs, followed by sternal and/or lateral recumbence. In addition, some animals showed dog-sitting position and intention tremors. The clinical manifestation period was 5-20 days. Significant gross lesions were not observed; however, microscopically, symmetrical degeneration of the white matter with ballooned myelin sheaths containing occasional macrophages was observed, mainly in the spinal cord. Two pigs presented with necrosis ad loss of Purkinje cells and ectopic Purkinje cells in the granular layer and cerebellar white matter. A ultrastructural analysis showed different degrees of damage of myelinated axons in the spinal segments, including an absence of the axoplasm structures with only axonal residues remaining. The myelin sheaths were degenerated and often collapsed into the space previously occupied by the axon. These results suggest that myelin degeneration is secondary to the axonal lesion. Finally, the concentration of copper in the liver was determined using atomic absorption spectrophotometry and was found to be low (ranging from 2.2 to 10.8 ppm). In conclusion, in the Brazilian semiarid region, Cu deficiency occurs in 21 to 90-day-old pigs that ingested different types of waste in their food.(AU)

São relatados os achados epidemiológicos, clínicos e morfológicos (patológicos e ultraestruturais) de quatro surtos de deficiência de cobre em suínos afetados entre 21 e 90 dias de idade na região Nordeste do Brasil. Os sinais clínicos iniciaram com paraparesia e ataxia, que progrediu a paralisia flácida ou espástica dos membros pélvicos e torácicos, seguido de decúbito esternal e/ou lateral. Além disso, alguns animais apresentaram posição de cão sentado e tremores de intenção. O período de manifestação clínica variou de 5-20 dias. Não foram observadas lesões macroscópicas significativas; no entanto, microscopicamente, foi observada degeneração simétrica da substância branca com fragmentação das bainhas de mielina, contendo ocasionais macrófagos, principalmente na medula espinal. Dois suínos apresentaram necrose e perda de células de Purkinje e células de Purkinje ectópicos na camada granular da substância branca cerebelar. A análise ultraestrutural mostrou diferentes graus de lesões em axônios mielinizados em segmentos da medula espinhal, incluindo o desaparecimento de estruturas do axoplasma, restando apenas restos axonais. A bainha de mielina encontrava-se degenerada e muitas vezes, colapsada dentro do espaço previamente ocupado pelo axônio. Esses resultados sugerem que a degeneração da mielina é secundária à lesão axonal. Finalmente, a concentração do cobre no fígado foi determinada usando espectrometria de absorção atômica e revelou baixos valores (variando de 2,2-10,8ppm). Conclui-se que na região semiárida do Brasil ocorre deficiência de cobre em suínos de 21 a 90 dias de idade alimentados com diferentes tipos de resíduos.(AU)

Guillain-Barré syndrome in northwestern China / 中国组织工程研究

We reviewed 100 cases with Guillain-Barré syndrome (GBS) from 1980 to 1999, and found that the features of GBS in electrophysiological classification, age, area, seasonal distributions, and in preceding illness in northwestern China are different in some aspects from those in Europe and North America or in northern China. The demyelinating pattern appeares as a major subtype not only in different age groups, but also in different test times after symptom onset.

Clinical Review of Organophosphate Poisoning & Sequelae ; Organophosphate Induced Delayed Polyneuropathy

BACKGROUND: Organophosphate induced delayed polyneuropathy(OIDP) by ingestion is not common, and the mechanism is not well known. In this study, we present clinical characteristics, electrophysiological findings and pathology of sural nerve in our four cases with OIDP. METHODS: Retrospectively, we reviewed 38 patients diagnosed as organophosphate intoxication at Asan Medical Center from January, 1990 to July, 1998. Among these patients we present four patients with OIDP, who received electrophysiological and pathological studies and discuss similar cases from the literature. RESULTS: OIDP occurred usually 2-4 weeks after exposure. They complained quadriplegia, paresthesia and pain mainly in distal extremities. Two patients had facial diplegia. No definite pyramidal sign was found in all patients. Elelctrophysiological study showed sensorimotor(predominantly motor) axonal polyneuropathy with marked denervation potentials in all tested muscles. Follow-up electrophysiological study after two years showed slightly increased amplitude of sensory nerve or compound motor action potentials with persistent denervation potentials in the distal muscles. Sural nerve biopsy confirmed severe axonal neuropathy with marked decrease of large and small myelinated fibers with myelin ovoids. CONCLUSIONS: OIDP was a cause of severe generalized weakness and paresthesia, decreased sensation in distal extremities after high dose organophosphate ingestion and usually occurred two to four weeks later. The prognosis was poor in patients who had severe weakness of four extremities with facial diplegia at the initial examination.