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Axonal injury is the major correlate of permanent disability in neurodegenerative diseases such as multiple sclerosis (MS), especially in secondary-progressive MS following relapsing-remitting disease course. Proteolytic enzyme, calpain, is a potential candidate for causing axonal injury. Most current treatment options only target the inflammatory component of MS. Previous work using calpain inhibitor CYLA in our laboratory showed significant reduction in clinical sign, demyelination and tissue calpain content in acute experimental autoimmune encephalomyelitis (EAE). Here we evaluated markers of axonal injury (amyloid precursor protein, Nav1.6 channels), neuronal calpain content and the effect of CYLA on axonal protection using histological methods in chronic EAE [myelin oligodendrocyte glycoprotein (MOG) – induced disease model of MS]. Intraperitoneal application of CYLA (2mg/mouse/day) significantly reduced the clinical signs, tissue calpain content, demyelination and inflammatory infiltration of EAE. Similarly, markers for axonal injury were barely detectable in the treated mice. Thus, this novel drug, which markedly suppresses the disease course, axonal injury and its progression, is a candidate for the treatment of a neurodegenerative disease such as multiple sclerosis.

Semliki Forest Virus (SFV) encephalomyelitis has been used to study the pathogenesis of virus-induced demyelination and serves as a model for multiple sclerosis. SFV-infection of mice invariably leads to clinical weakness accompanied by CNS inflammation, viral clearance and primary demyelination by day 21 postinfection (pi), followed by recovery and remyelination by day 35 pi. We have applied this model to examination the effects of γδ T cells in antibody production and the pathogenesis of demyelinating lesions. SFV-infection of γδ T cell KO mice resulted in more severe clinical signs than in wild type (WT) B6 mice. SFV-infected WT and γδ KO mice both cleared virus by day 10 pi and inflammation was comparable. Demyelination also appeared to be similar in both groups except that KO mice did not exhibit extensive remyelination which was seen in WT mice by day 21. SFV-infected WT mice showed widespread remyelination by day 35 pi, whereas KO mice still displayed some demyelination through day 42 pi. Both WT and KO mice developed serum antibodies to SFV. However, the reactivity of WT sera with the SFV epitope, E2 Th peptide2, was significantly higher than in KO sera. Immunization with E2 Th peptide2 resulted in elevated antibody production to this peptide (p<0.05) and earlier remyelination (day 28 pi) in KO mice. Thus, our study has shown for the first time that immunization of SFV-infected γδ T cell KO mice with a viral peptide, E2 Th peptide2, led to enhanced recovery and repair of the CNS.

Background. Computerized electrocardiogram (ECG) analysis has been of tremendous help for noncardiologists, but can we rely on it? The importance of ST depression and T wave inversions in lead aVL has not been emphasized and not well recognized across all specialties. Objective. This study's goal was to analyze if there is a discrepancy of interpretation by physicians from different specialties and a computer-generated ECG reading in regard to a TWI in lead aVL. Methods. In this multidisciplinary prospective study, a single ECG with isolated TWI in lead aVL that was interpreted by the computer as normal was given to all participants to interpret in writing. The readings by all physicians were compared by level of education and by specialty to one another and to the computer interpretation. Results. A total of 191 physicians participated in the study. Of the 191 physicians 48 (25.1%) identified and 143 (74.9%) did not identify the isolated TWI in lead aVL. Conclusion. Our study demonstrated that 74.9% did not recognize the abnormality. New and subtle ECG findings should be emphasized in their training so as not to miss significant findings that could cause morbidity and mortality.

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