Non-progressive cerebellar ataxia with previous acute cerebellar injury of undetermined origin: a puzzling neurological disorder

Teive, Hélio Afonso Ghizoni

doi:10.1590/0004-282x20150158

Cited by 2 publications

(3 citation statements)

References 7 publications

(17 reference statements)

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“…Cerebellar ataxias (CAs) are motor neuron diseases caused by pathological processes affecting the cerebellum or its associated pathways 1 , 2 . They are characterised by symptoms such as abnormal coordination of balance, movement and gait.…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide administration for a mouse model of cerebellar ataxia with neuroinflammation

Hong

Yoon

Nam

et al. 2020

Sci Rep

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Most cerebellar ataxias (cAs) are incurable neurological disorders, resulting in a lack of voluntary control by inflamed or damaged cerebellum. Although CA can be either directly or indirectly related to cerebellar inflammation, there is no suitable animal model of CA with neuroinflammation. In this study, we evaluated the utility of an intracerebellar injection of lipopolysaccharide (LpS) to generate an animal model of inflammatory CA. We observed that LPS administration induced the expression of pro-inflammatory molecules following activation of glial cells. In addition, the administration of LPS resulted in apoptotic purkinje cell death and induced abnormal locomotor activities, such as impaired motor coordination and abnormal hindlimb clasping posture. Our results suggest that intracerebellar LPS administration in experimental animals may be useful for studying the inflammatory component of CA. Cerebellar ataxias (CAs) are motor neuron diseases caused by pathological processes affecting the cerebellum or its associated pathways 1,2. They are characterised by symptoms such as abnormal coordination of balance, movement and gait. Currently, most CAs are incurable, with few exceptions, and only symptom alleviation is possible 3. CAs can be caused by genetic defects, sporadic neurodegenerative disorders, and acquired conditions (for example, infections, toxic reactions, alcohol, and vitamin deficiencies), but they can also arise for unknown reasons 1,3,4. In particular, many reports have shown a close relationship between cerebellar inflammation and CA 1,3,5. The activation of glial cells resulting in the production of pro-inflammatory molecules has been observed in many animal models of CA and is also evident in the cerebellums of patients with CA 6-9. Furthermore, cerebellar inflammation has been shown to induce the loss of Purkinje cells, which results in cerebellar dysfunction 1,7. Although the understanding of CA pathogenesis associated with genetic causes, cerebellar neurotoxicity, and physical damage has contributed to the development of some animal models of CA 1,3 , there is no suitable animal model to study CA following glial activation and neurotoxic cerebellar inflammation in vivo. Neuroinflammation plays a crucial role in the pathogenesis and progression of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease 10. As a potent stimulator of neuroinflammation, lipopolysaccharide (LPS) has been used to mediate neurodegenerative progression 11. An accumulation of evidence has shown that LPS-induced neuroinflammation causes neuronal damage through activation of microglia and astrocytes, M1 microglial polarization and the release of pro-inflammatory mediators. For example, LPS injected into the substantia nigra induces microglia activation, which causes the degeneration of dopamine neurons that constitutes the pathological basis of Parkinson's disease 12. In addition, LPS causes an increase in amyloid beta, which results in demyelination and oligodendrocyte injury in mice brains, w...

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Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide administration for a mouse model of cerebellar ataxia with neuroinflammation

Hong

Yoon

Nam

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Recently, accumulated evidence demonstrates that cerebellar inflammation contributes to the progression of CAs. For example, many types of acquired ataxia (e.g., toxin-induced cerebellar ataxia and immune or infection-mediated cerebellar ataxia) are known to be closely associated with cerebellar inflammation [2]. Moreover, the production of inflammatory mediators in over-activated glial cells as part of the neurotoxic inflammatory responses are observed in patients and in animal models of spinocerebellar ataxia [8][9][10].…”

Section: Discussionmentioning

confidence: 99%

“…Cerebellar ataxias (CAs) are heterogeneous neurological disorders caused by cerebellar damage that can affect balance and coordination of movement [1,2]. Some studies have reported that the application of targeted therapies to cerebellar ataxia with vitamin E deficiency (AVED) and gluten ataxia suppresses disease progression and improves neurological function.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Effects of Human Mesenchymal Stem Cells in a Mouse Model of Cerebellar Ataxia with Neuroinflammation

Nam

Yoon

Hong

et al. 2020

JCM

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Cerebellar ataxias (CAs) are neurological diseases characterized by loss of muscle coordination that is a result of damage and inflammation to the cerebellum. Despite considerable efforts in basic and clinical research, most CAs are currently incurable. In this study, we evaluated the therapeutic potential of human mesenchymal stem cells (hMSCs) against CAs associated with neuroinflammation. We observed that hMSC treatment significantly inhibited the symptoms of ataxia in lipopolysaccharide (LPS)-induced inflammatory CA (ICA) mice, which were recently reported as a potential animal model of ICA, through the anti-inflammatory effect of hMSC-derived TNFα-stimulated gene-6 (TSG-6), the protection of Purkinje cells by inhibition of apoptosis, and the modulatory effect for microglial M2 polarization. Thus, our results suggest that hMSC treatment may be an effective therapeutic approach for preventing or improving ataxia symptoms.

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Non-progressive cerebellar ataxia with previous acute cerebellar injury of undetermined origin: a puzzling neurological disorder

Cited by 2 publications

References 7 publications

Lipopolysaccharide administration for a mouse model of cerebellar ataxia with neuroinflammation

Lipopolysaccharide administration for a mouse model of cerebellar ataxia with neuroinflammation

Therapeutic Effects of Human Mesenchymal Stem Cells in a Mouse Model of Cerebellar Ataxia with Neuroinflammation

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