Compartmentalization of inflammation in the CNS: A major mechanism driving progressive multiple sclerosis

Meinl, Edgar; Krumbholz, Markus; Derfuss, Tobias; Junker, Andreas; Hohlfeld, Reinhard

doi:10.1016/j.jns.2008.06.032

Cited by 78 publications

(48 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The perivascular region of CNS is prone to movement by antibodies and lymphocytes. These are also observed in demyelinated lesions suggesting inflammatory response [14,90]. In relapsing-remitting MS, despite remyelination take place during remission; the process remains compromised and causing severe neurodegeneration [91,92].…”

Section: Ms Is An Autoimmune Disorder Characterizedmentioning

confidence: 99%

“…Reports in this regard, consider elevated IL-6 and IL-8 levels, endothelial nitric oxide synthase uncoupling, hyperglutamatergia, and oxidative stress as the primary mechanism behind inflammation. Major depressive disorders (MDD), is a severe neurological disorder associated with elevated levels of inflammatory markers like chemokines, cytokines and acute phase proteins alongside neurovascular dysfunction [14,34,36].…”

Section: Depressionmentioning

confidence: 99%

“…The basic function of inflammatory cells like microglia is to supervise the ambient microenvironment containing glia and neurons [13]. Whenever there is any questionable particle or damage in CNS, inflammatory responses starts to communicate the supporting system to control the damage and initiate the tissue repair mechanisms [14,15]. Unfortunately, inflammatory mechanisms also promote the production of toxic entities, which not only amplify the disease tenure but also drag the fate of life support system into grave danger [16,17].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Effect and Disease Indicative Role of Inflammation in Neurodegenerative Pathology: A Mechanistic Crosstalk of Promise and Dilemma

Choudhury¹,

Chakraborty²,

Banerjee³

et al. 2018

Neuropsychiatry

View full text Add to dashboard Cite

The pathobiology of neuronal cell loss due to various endogenous or exogenous influences is clinically termed as neurodegeneration. Neurodegeneration has been reported to be the major contributor to aging and central nervous system diseases. Apart from aging and endogenous involvement, neurodegeneration also has been reported from viral infection and prion diseases. Studies have shown that, chronic degeneration of neuronal cells initiate the pathology of Alzheimer's disease-the most prevalent neurodegenerative disorder in the world. Similar neurodegenerative pathology is also evident in Parkinson's disease, multiple sclerosis, and Amyotrophic Lateral Sclerosis. Neurodegeneration negatively affects the mental and physical functioning of the patient. Intriguingly, the involvement of inflammation has been linked as the most crucial entity in the mechanistic progress of neurodegeneration. Moreover, recent data also have shown that inflammatory biomarkers can prognosticate the silent progress of neurodegeneration through low-cost diagnostic approach. Mainly, Th17 and MDSCs are the particular immune cells, which have been reported to assist adequately to get a detailed insight into the underlying pathological process in neurodegeneration. Similarly, depression and dementia are also having a crucial association with pro-inflammatory cytokines, which in chronic spectrum indicates the degenerative pathology. Together, available literatures are depicting a direct association between neuroinflammation and neurodegeneration. In the present review, we have summed up all the neuropathologies in light of inflammation and emphasized the possible diagnostic measures by using inflammatory cells and mediators as biomarkers for neurodegenerative diseases.

show abstract

Section: Ms Is An Autoimmune Disorder Characterizedmentioning

confidence: 99%

Section: Depressionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Effect and Disease Indicative Role of Inflammation in Neurodegenerative Pathology: A Mechanistic Crosstalk of Promise and Dilemma

Choudhury¹,

Chakraborty²,

Banerjee³

et al. 2018

Neuropsychiatry

View full text Add to dashboard Cite

show abstract

“…Effects on T cells would include altered polarization towards a Th2 phenotype, an issue to be considered in more detail in the following section discussing GA. Krumbholz et al demonstrated that IFNβ can promote production of B cell activating factor (BAFF); persistent B cells in the CNS are a hallmark of MS throughout the disease course [19,20]. Such B cells could interact with astrocytes and microglia [21].…”

Section: Ifnβmentioning

confidence: 99%

Regulation of human glia by multiple sclerosis disease modifying therapies

2015

View full text Add to dashboard Cite

This review focuses on the effects of the agents currently approved (or in late clinical trials) as therapies for multiple sclerosis (MS) on the glial cell populations of the central nervous system (CNS). These are comprised of astrocytes, microglia, and oligodendrocytes (OLs), and their progenitors (OPCs). Although the efficacy of these agents is to date established only for the relapsing component of the disease and linked to effects on the systemic immune system, each has been examined with regard to effects on the CNS compartment. The impact of therapies on glia would include modulating these cells immune reactivity, which is considered to underlie the tissue injury process in MS and to any subsequent repair process. As reviewed, these agents can exert their effects either indirectly by modulating the constituents of the systemic immune system or directly depending on their capacity to traverse the blood brain barrier (BBB). Most available data has been derived from administration of these agents in animal models or application to glial cells in vitro. The challenge remains of translating these observations into effective means to impact on the progressive course of disease and reverse existent disabilities.

show abstract

“…It implies that CNS inflammation drives the disease process in both the chronic and acute stages [4]. While there is a close interaction between the peripheral immune system and the CNS during acute inflammation, with invasion of macrophages, B and T cells into the latter, in chronic processes the immune response is thought to be increasingly secluded from the peripheral immune system (‘compartmentalization' of the inflammatory process) [5,][6]. Chronic MS, for example, is primarily characterized by disseminated activation of microglial cells.…”

Section: Introductionmentioning

confidence: 99%

Immunology of Schizophrenia

Müller¹

2014

Neuroimmunomodulation

View full text Add to dashboard Cite

Increased proinflammatory markers like cytokines have been described in the blood and cerebrospinal fluid of patients suffering from schizophrenia. Animal models have shown that a hit in early life to the immune system might trigger a lifelong increased immune reactivity. Many epidemiological and clinical studies show the role of various infectious agents as risk factors for schizophrenia with overlap to other psychoses. The first large-scale epidemiological study in psychiatry from Denmark clearly demonstrates severe infections and autoimmune disorders during lifetime to be risk factors for schizophrenia. Genetic studies have shown the strongest signal for schizophrenia on chromosome 6p22.1, in a region related to the major histocompatibility complex and other immune functions. The vulnerability-stress-inflammation model is important as stress may increase proinflammatory cytokines and even contribute to a lasting proinflammatory state. The immune system itself is considered an important further piece in the puzzle, as in autoimmune disorders in general, which are always linked to three factors: genes, the environment and the immune system. Alterations of dopaminergic, serotonergic, noradrenergic and glutamatergic neurotransmission have been shown with low-level neuroinflammation and may directly be involved in the generation of schizophrenic symptoms. Loss of central nervous system volume and microglial activation has been demonstrated in schizophrenia in neuroimaging studies, which supports the assumption of a low-level neuroinflammatory process. Further support comes from the therapeutic benefit of anti-inflammatory medications in specific studies and the anti-inflammatory and immunomodulatory intrinsic effects of antipsychotics.

show abstract

Compartmentalization of inflammation in the CNS: A major mechanism driving progressive multiple sclerosis

Cited by 78 publications

References 34 publications

Effect and Disease Indicative Role of Inflammation in Neurodegenerative Pathology: A Mechanistic Crosstalk of Promise and Dilemma

Effect and Disease Indicative Role of Inflammation in Neurodegenerative Pathology: A Mechanistic Crosstalk of Promise and Dilemma

Regulation of human glia by multiple sclerosis disease modifying therapies

Immunology of Schizophrenia

Contact Info

Product

Resources

About