Up-regulation of brain cytokines and metalloproteinases 1 and 2 contributes to neurological deficit and brain damage in transient ischemic stroke

Victoria, Edna Constanza Gómez; Toscano, Eliana Cristina de Brito; Oliveira, Fabrício Marcus Silva; Carvalho, Bárbara Andrade de; Caliari, Marcelo Vidigal; Teixeira, Antônio Lúcio; Miranda, Aline Silva de

doi:10.1016/j.mvr.2019.103973

Cited by 25 publications

(16 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Secondly, it stimulates the synthesis/secretion of chemotactic factors that stimulate peripheral blood leukocytes and activates other cytokines like IL-1, IL-6, and interferon-gamma (IFN-γ) 10 . TNF-α also enhances MMPs activity 84 , thereby increasing endothelial cell permeability and BBB dysfunction 85 . Our study is the first to demonstrate that salivary TNF-α can be a potential biomarker of stroke patient’s functioning.…”

Section: Discussionmentioning

confidence: 99%

Salivary cytokine profile in patients with ischemic stroke

Maciejczyk

Mil

Gerreth

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Inflammation plays a crucial role in stroke pathogenesis. Thus, it is not surprising that cytokines, chemokines, and growth factors have been advocated in stroke diagnostics. Our study is the first to evaluate the salivary cytokine profile in patients with ischemic stroke. Twenty-five patients with subacute ischemic stroke and an age-, sex-, and oral hygiene status-matched control group were enrolled in the study. The number of patients was set a priori based on our previous experiment (α = 0.05, test power = 0.9). Salivary concentrations of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 10 (IL-10) were assessed using an ELISA method. We showed that salivary TNF-α and IL-6 were significantly higher, whereas IL-10 content was statistically lower in both non-stimulated (NWS) and stimulated (SWS) whole saliva of ischemic stroke patients. However, evaluation of cytokines in NWS rather than in SWS may be of greater diagnostic value. Of particular note is salivary TNF-α, which may indicate cognitive/physical impairment in post-stroke individuals. This parameter distinguishes stroke patients from healthy controls and correlates with cognitive decline and severity of functional impairment. It also differentiates (with high sensitivity and specificity) stroke patients with normal cognition from mild to moderate cognitive impairment. Saliva may be an alternative to blood for assessing cytokines in stroke patients, although further studies on a larger patient population are needed.

show abstract

Section: Discussionmentioning

confidence: 99%

Salivary cytokine profile in patients with ischemic stroke

Maciejczyk

Mil

Gerreth

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Indeed, peripheral immune cells can have dual roles in BBB integrity depending on different microenvironment and their subtypes, but more evidence show that the infiltration of peripheral immune cells contributes to the disruption of BBB in several neurodegenerative disorders, and even that BBB damage may occur before effector immune cells infiltrate at local sites due to peripheral inflammation‐related or irrelated reasons 126‐129 . For example, the inflammatory factors secreted by immune cells, such ROS, and MMPs (MMP‐1 and MMP‐2), promote their own migration into the CNS and increase BBB permeability simultaneously, forming a vicious cycle 74,130,131 …”

Section: Mechanisms Of Peripheral Inflammation‐induced Bbb Disruptionmentioning

confidence: 99%

Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms

2020

View full text Add to dashboard Cite

The blood–brain barrier (BBB) is an important physiological barrier that separates the central nervous system (CNS) from the peripheral circulation, which contains inflammatory mediators and immune cells. The BBB regulates cellular and molecular exchange between the blood vessels and brain parenchyma. Normal functioning of the BBB is crucial for the homeostasis and proper function of the brain. It has been demonstrated that peripheral inflammation can disrupt the BBB by various pathways, resulting in different CNS diseases. Recently, clinical research also showed CNS complications following SARS‐CoV‐2 infection and chimeric antigen receptor (CAR)‐T cell therapy, which both lead to a cytokine storm in the circulation. Therefore, elucidation of the mechanisms underlying the BBB disruption induced by peripheral inflammation will provide an important basis for protecting the CNS in the context of exacerbated peripheral inflammatory diseases. In the present review, we first summarize the physiological properties of the BBB that makes the CNS an immune‐privileged organ. We then discuss the relevance of peripheral inflammation‐induced BBB disruption to various CNS diseases. Finally, we elaborate various factors and mechanisms of peripheral inflammation that disrupt the BBB.

show abstract

“…CHOONG HYUN LEE 1* , JI HYEON AHN 2,3* , BAI HUI CHEN 4 , DAE WON KIM 5 , HYEJIN SIM 3 , TAE-KYEONG LEE 6 , JOON HA PARK 7 , MOO-HO WON 3 and SOO YOUNG CHOI 6 most vulnerable to tFI (1). tFI-induced neuronal death in the pyramidal neurons of hippocampal CA1 region is called as the delayed neuronal death (DND), because it occurs a few days following tFI (1).…”

Section: Differences In Tnf-α and Tnf-r1 Expression In Damaged Neurons And Activated Astrocytes Of The Hippocampal Ca1 Region Between Youmentioning

confidence: 99%

“…To explain the tFI-induced DND, many underlying mechanisms has been suggested, including neuroinflammatory processes. Following cerebral ischemia, neuroinflammatory responses and upregulation of inflammatory cytokines occurs generally in the brain, and the imbalance between pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, and anti-inflammatory cytokines could lead to the neuronal damage after ischemic injury (2)(3)(4)(5). In addition, the cerebral ischemia-induced neuronal damage has been also known to be affected by various factors, including ischemic duration, the age and sex of experimental animals (6)(7)(8)(9).…”

Section: Differences In Tnf-α and Tnf-r1 Expression In Damaged Neurons And Activated Astrocytes Of The Hippocampal Ca1 Region Between Youmentioning

confidence: 99%

Differences in TNF‑α and TNF‑R1 expression in damaged neurons and activated astrocytes of the hippocampal CA1 region between young and adult gerbils following transient forebrain ischemia

et al. 2021

View full text Add to dashboard Cite

Tumor necrosis factor (TNF)-α and TNF receptor 1 (TNF-R1) play diverse roles in modulating the neuronal damage induced by cerebral ischemia. The present study compared the time-dependent changes of TNF-α and TNF-R1 protein expression levels in the hippocampal subfield cornu ammonis 1 (CA1) between adult and young gerbils following transient forebrain ischemia (tFI), via western blot and immunohistochemistry analyses. In adult gerbils, delayed neuronal death of pyramidal neurons, the principal neurons in CA1, was recorded 4 days after tFI; however, in young gerbils, delayed neuronal death was recorded 7 days after tFI. TNF-α protein expression levels gradually increased in both groups following tFI; however, TNF-α expression was higher in young gerbils compared with adult gerbils. TNF-R1 protein expression levels markedly increased in both groups 1 day after tFI. Subsequently, TNF-R1 expression gradually decreased in young gerbils, whereas TNF-R1 expression levels were irregularly altered in adult gerbils following tFI. Notably, TNF-α immunoreactivity significantly increased in pyramidal neurons in both groups 1 day after tFI; however, the patterns altered between both groups. In adult gerbils, TNF-α immunoreactivity was rarely exhibited in pyramidal neurons 4 days after tFI due to neuronal death, suggesting that TNF-α immunoreactivity was newly expressed in astrocytes. In young gerbils, TNF-α immunoreactivity increased in pyramidal neurons 4 days after tFI, and TNF-α immunoreactivity was newly expressed in astrocytes. In addition, TNF-R1 immunoreactivity was exhibited in pyramidal cells of both sham groups, and significantly increased 1 day after tFI; however, the patterns altered between both groups. In adult gerbils, TNF-R1 immunoreactivity was rarely exhibited 4 days after tFI, and astrocytes newly expressed TNF-R1 immunoreactivity. In young gerbils, TNF-R1 immunoreactivity increased in pyramidal neurons 4 days after tFI; however, TNF-R1 immunoreactivity was not reported in pyramidal neurons and astrocytes thereafter. Taken together, the results of the present study suggest that different expression levels of TNF-α and TNF-R1 in ischemic CA1 between adult and young gerbils may be due to age-dependent differences of tFI-induced neuronal death.

show abstract

Up-regulation of brain cytokines and metalloproteinases 1 and 2 contributes to neurological deficit and brain damage in transient ischemic stroke

Cited by 25 publications

References 26 publications

Salivary cytokine profile in patients with ischemic stroke

Salivary cytokine profile in patients with ischemic stroke

Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms

Differences in TNF‑α and TNF‑R1 expression in damaged neurons and activated astrocytes of the hippocampal CA1 region between young and adult gerbils following transient forebrain ischemia

Contact Info

Product

Resources

About