The impact of microglial activation on blood-brain barrier in brain diseases

Fonseca, Anna Carolina Carvalho da; Matias, Diana; García, Celina; Amaral, Rackele Ferreira do; Geraldo, Luiz Henrique Medeiros; Freitas, Catarina; Lima, Flávia Regina Souza

doi:10.3389/fncel.2014.00362

Cited by 426 publications

(301 citation statements)

References 188 publications

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“…These mediators bind to pattern recognition receptors on various cells, including microglia and endothelial cells, and lead to their activation [14]. Microglia sense changes in the ischemic brain [15]. They upregulate major histocompatibility complex class II molecules, and express and secrete cytokines, including tumour necrosis factor-α and interleukin (IL)-1 [16].…”

Section: Immune Mechanismsmentioning

confidence: 99%

Clinical Trials of Immunomodulation in Ischemic Stroke

Veltkamp

Gill

2016

Neurotherapeutics

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Inflammatory mechanisms are currently considered as a prime target for stroke therapy. There is evidence from animal studies that immune signals and mediators can have both detrimental and beneficial effects in particular stages of the disease process. Moreover, several of these mechanisms are turned on with sufficient delay after ischemia onset to make them amenable to therapeutic intervention. Several clinical proof-of concept trials have investigated the efficacy of different immunomodulatory approaches in patients with stroke. Trials targeting the innate immune system have focused on reduction of microglial activation, inhibition of neutrophil migration, and interleukin-1 receptor blockade, suggesting that interleukin-1 receptor blockade may be a promising strategy. Studies aiming at halting T-cell migration have also been undertaken with controversial findings regarding prevention of infarct growth in neuroimaging studies. Consistently, recent proof-of-concept trials targeting lymphocytes with drugs such as natalizumab and fingolimod have yielded some promising results on clinical endpoints, but confirmation in larger trials is needed. At present, the understanding of the role of immune mechanisms in neurorepair and neurodegeneration is limited. Improving long-term brain function by mitigating prolonged neuroinflammation that was triggered by acute brain injury could be a strategy in addition to neuroprotection.

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Section: Immune Mechanismsmentioning

confidence: 99%

Clinical Trials of Immunomodulation in Ischemic Stroke

Veltkamp

Gill

2016

Neurotherapeutics

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“…Microglial activation and released cytokines such as TNF-a have also been shown to disrupt the tight junctions of the BBB. 58 Yeast cells may also infect the mucosa and paranasal sinuses, but they do not usually spread intracranially. In contrast, hyphae are capable of contiguous spread through nearby sources such as the cribriform plate or periorbital and paranasal sinuses.…”

Section: Fungal Interaction With the Bbb And Cns Invasionmentioning

confidence: 99%

Role of microglia in fungal infections of the central nervous system

2016

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Most fungi are capable of disseminating into the central nervous system (CNS) commonly being observed in immunocompromised hosts. Microglia play a critical role in responding to these infections regulating inflammatory processes proficient at controlling CNS colonization by these eukaryotic microorganisms. Nonetheless, it is this inflammatory state that paradoxically yields cerebral mycotic meningoencephalitis and abscess formation. As peripheral macrophages and fungi have been investigated aiding our understanding of peripheral disease, ascertaining the key interactions between fungi and microglia may uncover greater abilities to treat invasive fungal infections of the brain. Here, we present the current knowledge of microglial physiology. Due to the existing literature, we have described to greater extent the opportunistic mycotic interactions with these surveillance cells of the CNS, highlighting the need for greater efforts to study other cerebral fungal infections such as those caused by geographically restricted dimorphic and rare fungi.

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“…TBI may cause mechanical deformation and damage to the entire NVU [20,35,36], compromising barrier integrity and leading to dysautoregulation of brain vessels and BBB disruption. In this context, brain edema may occur and result in increased ICP and decreased cerebral perfusion [37]. In fact, compensatory mechanisms are exceeded as brain volume increases due to edema, and ICP rises exponentially and correlates with increased mortality and poor functional outcomes [20,[38][39][40].…”

Section: Mechanisms Of Neural Injury In the Traumatic Penumbramentioning

confidence: 99%

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

Regner¹,

Meirelles²,

Simon³

2018

Traumatic Brain Injury - Pathobiology, Advanced Diagnostics and Acute Management

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Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Understanding the pathophysiology of TBI is crucial for the development of more effective therapeutic strategies. At the moment of the traumatic impact, transfer of kinetic forces causes neurologic damage; this primary injury triggers a secondary wave of biochemical cascades, together with metabolic and cellular changes, called secondary neural injury. These areas of ongoing secondary injury, or areas of "traumatic penumbra," represent crucial targets for therapeutic interventions. This chapter is focused on the interplay between progression of parenchymal injury and the neuroprotective and neurorestorative processes that are emerging and developing subsequently to traumatic impact. Thus, we emphasized the role of traumatic penumbra in TBI pathogenesis and suggested a crucial contribution of the neurovascular units (NVUs) and paracrine effects of exosomes and miRNAs in promoting neurological recovery.

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The impact of microglial activation on blood-brain barrier in brain diseases

Cited by 426 publications

References 188 publications

Clinical Trials of Immunomodulation in Ischemic Stroke

Clinical Trials of Immunomodulation in Ischemic Stroke

Role of microglia in fungal infections of the central nervous system

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

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