Neuro-Immune Crosstalk in CNS Diseases

AbstractTo identify markers in the CSF of multiple sclerosis (MS) subtypes, we used a two-step proteomic approach: (i) Discovery proteomics compared 169 pooled CSF from MS subtypes and inflammatory/degenerative CNS diseases (NMO spectrum and Alzheimer disease) and healthy controls. (ii) Next, 299 proteins selected by comprehensive statistics were quantified in 170 individual CSF samples. (iii) Genes of the identified proteins were also screened among transcripts in 73 MS brain lesions compared to 25 control brains. F-test based feature selection resulted in 8 proteins differentiating the MS subtypes, and secondary progressive (SP)MS was the most different also from controls. Genes of 7 out these 8 proteins were present in MS brain lesions: GOLM was significantly differentially expressed in active, chronic active, inactive and remyelinating lesions, FRZB in active and chronic active lesions, and SELENBP1 in inactive lesions. Volcano maps of normalized proteins in the different disease groups also indicated the highest amount of altered proteins in SPMS. Apolipoprotein C-I, apolipoprotein A-II, augurin, receptor-type tyrosine-protein phosphatase gamma, and trypsin-1 were upregulated in the CSF of MS subtypes compared to controls. This CSF profile and associated brain lesion spectrum highlight non-inflammatory mechanisms in differentiating CNS diseases and MS subtypes and the uniqueness of SPMS.

Download Full-text

Potassium Channels and CNS Diseases

CNS & Neurological Disorders - Drug Targets ◽

10.2174/187152731704180706105155 ◽

2018 ◽

Vol 17 (4) ◽

pp. 245-247 ◽

Cited By ~ 1

Author(s):

Yian Huang ◽

Jie Tao ◽

Rong Zhao

Keyword(s):

Potassium Channels ◽

Cns Diseases

Download Full-text

GLYCINE RECEPTOR ANTIBODY—A MARKER FOR NMO/ NON-MS DEMYELINATION?

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2015-312379.130 ◽

2015 ◽

Vol 86 (11) ◽

pp. e4.36-e4

Author(s):

Shahd Hamid ◽

Liene Elsone ◽

Patrick Waters ◽

Mark Woodhall Woodhall ◽

Kerry Mutch ◽

...

Keyword(s):

Optic Neuritis ◽

Neurological Disorders ◽

Glycine Receptor ◽

Prognostic Significance ◽

Transverse Myelitis ◽

Functional Disorders ◽

Glycine Receptors ◽

Cns Diseases ◽

Receptor Antibody

BackgroundAntibodies against glycine receptors (GlyR Ab) have been strongly linked to progressive encephalomyelitis with rigidity and myoclonus (PERM). Their association with other neurological disorders is poorly understood.MethodsWe looked retrospectively at all patients who were tested for (GlyR Abs) in the Walton Centre between 2010–2014.Results138 patients were tested. The pre-test diagnoses (n) were transverse myelitis (34), NMO (22, (7 AQP4 IgG+ve and 15 AQP4 IgG-ve), optic neuritis (17), MS (22), ADEM (4), other atypical demyelination (4), encephalitis (11), epilepsy (4), dementia (4), parkinsonism (3), functional disorders (3) and others (10). 53.6% (74) had a relapsing course6/138 (4%) were positive for GlyR Ab. The diagnoses (n) were optic neuritis (2) one of which was AQP4 IgG+ve, NMO-AQP4-IgG negative (1), transverse myelitis (1), tumefactive demyelination (1) and undiagnosed spastic ataxic syndrome with normal imaging (1). 5/6 had a relapsing course and are on immunosuppressants.ConclusionAntibodies against GlyR are not common and seem to be associated with some non-PERM inflammatory CNS diseases, with a relapsing course. Larger studies are required to understand the clinical and prognostic significance of these early findings.

Download Full-text

Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases

Molecular Brain ◽

10.1186/s13041-016-0265-8 ◽

2016 ◽

Vol 9 (1) ◽

Cited By ~ 20

Author(s):

Keiko Sugai ◽

Ryuji Fukuzawa ◽

Tomoko Shofuda ◽

Hayato Fukusumi ◽

Soya Kawabata ◽

...

Keyword(s):

Progenitor Cells ◽

Safety Assessment ◽

Cns Diseases ◽

Pathological Classification ◽

Neural Stem Progenitor Cells ◽

Human Ipsc ◽

Transplantation Therapy

Download Full-text

MRI imaging features of HIV-related central nervous system diseases: diagnosis by pattern recognition in daily practice

Japanese Journal of Radiology ◽

10.1007/s11604-021-01150-4 ◽

2021 ◽

Author(s):

Mio Sakai ◽

Masahiro Higashi ◽

Takuya Fujiwara ◽

Tomoko Uehira ◽

Takuma Shirasaka ◽

...

Keyword(s):

Central Nervous System ◽

Pattern Recognition ◽

Nervous System ◽

Immune Reconstitution Inflammatory Syndrome ◽

Immune Reconstitution ◽

Opportunistic Infections ◽

Primary Cns Lymphoma ◽

Imaging Features ◽

Cns Diseases ◽

Inflammatory Syndrome

AbstractWith the advent of antiretroviral therapy (ART), the prognosis of people infected with human immunodeficiency virus (HIV) has improved, and the frequency of HIV-related central nervous system (CNS) diseases has decreased. Nevertheless, mortality from HIV-related CNS diseases, including those associated with ART (e.g., immune reconstitution inflammatory syndrome) remains significant. Magnetic resonance imaging (MRI) can improve the outlook for people with HIV through early diagnosis and prompt treatment. For example, HIV encephalopathy shows a diffuse bilateral pattern, whereas progressive multifocal leukoencephalopathy, HIV-related primary CNS lymphoma, and CNS toxoplasmosis show focal patterns on MRI. Among the other diseases caused by opportunistic infections, CNS cryptococcosis and CNS tuberculosis have extremely poor prognoses unless diagnosed early. Immune reconstitution inflammatory syndrome shows distinct MRI findings from the offending opportunistic infections. Although distinguishing between HIV-related CNS diseases based on imaging alone is difficult, in this review, we discuss how pattern recognition approaches can contribute to their early differentiation.

Download Full-text

AAV9 is considered the most efficient AAV serotype targeting blood-brain barriers. To enhance effective gene therapy for CNS illnesses, testing novel vectors with more efficient crossing capabilities is vital

10.31219/osf.io/7bf5s ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Gene Therapy ◽

Intravenous Injection ◽

Peripheral Circulation ◽

Full Potential ◽

Cns Diseases ◽

Aav Vector ◽

Early Clinical Trial ◽

Blood Brain ◽

Efficient Gene ◽

Trial Outcomes

Although gene therapy for CNS diseases shows promise in cell and animal investigations, most human trials have failed to satisfy the requisite requirements. Finding novel techniques to boost the efficacy of gene therapy in treating CNS diseases is still crucial. A growing number of clinical trials have proved the efficacy and safety of using AAV vectors, making AAV vector research a gene therapy hotspot. However, due to the presence of the BBB, many siRNA and DNA with potential therapeutic value are difficult to transport from peripheral circulation to the brain using AAV vectors, limiting the clinical impact of gene therapy drugs in the CNS and posing a major challenge to the field of CNS gene therapy. In early studies, AAV9 was considered the most effective AAV serotype for getting through the blood-brain barrier and transduction to central nervous system cells following intravenous injection. Aavrh10 isolated from rhesus monkeys was equal to, if not superior to, AAV9. AAV-PHP.B, a newly built capsid, exhibits 40-fold greater efficacy than AAV9 in astrocyte and neuron transduction. AAV-PHP.eB, a modified AAV-PHP.B variety, was identified to retain PHP.B's AAV-capacity to transduce astrocytes while enhancing neuronal transduction. While the four serotypes AAV9, AAVrh10, AAV-PHP.B, and AAV-PHP.eB have been validated to penetrate mice's BBB following intravenous injection, the number of AAV vectors that can do so is low. Moreover, the manner in which AAV vectors penetrate the BBB remains unclear. To promote efficient gene therapy for CNS diseases, it is still important to test new vectors with more efficient crossing abilities and understand their crossing processes. In addition to technical challenges, AAV vectors in treating CNS diseases may be limited by cautious attitudes to innovative treatments. Continued advances in AAV vector research, together with early clinical trial outcomes, might help researchers achieve the full potential of AAV-based CNS disease therapies.

Download Full-text