The pro-inflammatory cytokine interferon-gamma is an important driver of neuropathology and behavioural sequelae in experimental pneumococcal meningitis

Too, Lay Khoon; Ball, Helen J.; McGregor, Iain S.; Hunt, Nicholas H.

doi:10.1016/j.bbi.2014.02.020

Cited by 46 publications

(38 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The production of IFN-γ was shown to be triggered by activation of the inflammasome complex, which contributed to the pathogenesis during experimental pneumococcal meningitis in mice [66]. Furthermore, knock-out of IFN-γ in the same experimental model resulted in a less severe course of the disease, evidenced by increased survival, decreased CSF concentrations of pro-inflammatory cytokines, attenuated brain injury and improved neurofunctional outcomes [67].…”

Section: Pathophysiological Aspects Of Bacterial Meningitismentioning

confidence: 97%

Bacterial Meningitis: Insights Into Pathogenesis and Evaluation of New Treatment Options: A Perspective from Experimental Studies

2015

View full text Add to dashboard Cite

Bacterial meningitis is associated with high mortality and morbidity rates. Bacterial components induce an overshooting inflammatory reaction, eventually leading to brain damage. Pathological correlates of neurofunctional deficits include cortical necrosis, damage of the inner ear and hippocampal apoptosis. The hippocampal dentate gyrus is important for memory acquisition and harbors a neuronal stem cell niche, thus being potentially well equipped for regeneration. Adjuvant therapies aimed at decreasing the inflammatory reaction, for example, dexamethasone, and those protecting the brain from injury have been evaluated in animal models of the disease. They include nonbacteriolytic antibiotics (e.g., daptomycin), metalloproteinase inhibitors and modulators of the immunological response, for example, granulocyte colony-stimulating factor. Increasing research interest has recently been focused on interventions aimed at supporting regenerative processes.

show abstract

Section: Pathophysiological Aspects Of Bacterial Meningitismentioning

confidence: 97%

Bacterial Meningitis: Insights Into Pathogenesis and Evaluation of New Treatment Options: A Perspective from Experimental Studies

2015

View full text Add to dashboard Cite

show abstract

“…3). PMNs (e.g., neutrophils) and monocytes dominate bacterial meningitis, whereas lymphocytes (especially T lymphocytes) are increased in viral CNS infections [18,[60][61][62][63][64]. Enterovirus (EV) is the most common pathogen causing viral meningitis, which is less fatal than septic meningitis and is associated with T cell migration at the BBB and BCSFB [44,65].…”

Section: Meningitismentioning

confidence: 99%

Clinical implications of leukocyte infiltration at the choroid plexus in (neuro)inflammatory disorders

Demeestere

Libert

Vandenbroucke

2015

Drug Discovery Today

View full text Add to dashboard Cite

“…There is also evidence in mice that aspects of the meningeal response to S. pneumoniae cause more harm than benefit. When infected with S. pneumoniae, interferon-γ (IFNγ) knockout (KO) mice exhibit prolonged survival compared to their wildtype (WT) counterparts [54]. Furthermore, with antibiotic treatment the IFNγ KO mice not only survive long term, but also have no neurological sequelae.…”

Section: The Double-edged Sword Of Neuro-meningeal Inflammationmentioning

confidence: 99%

“…Furthermore, with antibiotic treatment the IFNγ KO mice not only survive long term, but also have no neurological sequelae. Classic pro-inflammatory mediators, most predominately TNF, IL-1β, and reactive oxygen species (ROS), are also implicated in microbial-induced meningeal inflammation [54–56]. ROS are particularly damaging to the CNS given the high oxygen consumption relative to other organs.…”

Section: The Double-edged Sword Of Neuro-meningeal Inflammationmentioning

confidence: 99%

The meninges: new therapeutic targets for multiple sclerosis

Russi

Brown

2015

Translational Research

View full text Add to dashboard Cite

The CNS is largely comprised of non-regenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an “immune specialized” status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data has established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood barrier integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting of the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the blood brain barrier. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments.

show abstract

The pro-inflammatory cytokine interferon-gamma is an important driver of neuropathology and behavioural sequelae in experimental pneumococcal meningitis

Cited by 46 publications

References 67 publications

Bacterial Meningitis: Insights Into Pathogenesis and Evaluation of New Treatment Options: A Perspective from Experimental Studies

Bacterial Meningitis: Insights Into Pathogenesis and Evaluation of New Treatment Options: A Perspective from Experimental Studies

Clinical implications of leukocyte infiltration at the choroid plexus in (neuro)inflammatory disorders

The meninges: new therapeutic targets for multiple sclerosis

Contact Info

Product

Resources

About