Stress-induced blood brain barrier disruption: Molecular mechanisms and signaling pathways

Welcome, M. Osain; Mastorakis, Nikos E.

doi:10.1016/j.phrs.2020.104769

Cited by 73 publications

(57 citation statements)

References 248 publications

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“…Indeed, activation of nerve fibers, enteric neurons or glia can stimulate or inhibit the activities of their control centers (enteric ganglia, brainstem nuclei or olfactory nuclei) (Fig. 1) (Mengeling et al 1972;Andries and Pensaert 1980;Butowt and Bilinska 2020).…”

Section: Neural Pathwaymentioning

confidence: 99%

Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection

Welcome

Mastorakis

2021

Inflammopharmacol

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Coronavirus disease 2019 (COVID-19) is caused by the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) first discovered in Wuhan, Hubei province, China in December 2019. SARS-CoV-2 has infected several millions of people, resulting in a huge socioeconomic cost and over 2.5 million deaths worldwide. Though the pathogenesis of COVID-19 is not fully understood, data have consistently shown that SARS-CoV-2 mainly affects the respiratory and gastrointestinal tracts. Nevertheless, accumulating evidence has implicated the central nervous system in the pathogenesis of SARS-CoV-2 infection. Unfortunately, however, the mechanisms of SARS-CoV-2 induced impairment of the central nervous system are not completely known. Here, we review the literature on possible neuropathogenic mechanisms of SARS-CoV-2 induced cerebral damage. The results suggest that downregulation of angiotensin converting enzyme 2 (ACE2) with increased activity of the transmembrane protease serine 2 (TMPRSS2) and cathepsin L in SARS-CoV-2 neuroinvasion may result in upregulation of proinflammatory mediators and reactive species that trigger neuroinflammatory response and blood brain barrier disruption. Furthermore, dysregulation of hormone and neurotransmitter signalling may constitute a fundamental mechanism involved in the neuropathogenic sequelae of SARS-CoV-2 infection. The viral RNA or antigenic peptides also activate or interact with molecular signalling pathways mediated by pattern recognition receptors (e.g., toll-like receptors), nuclear factor kappa B, Janus kinase/signal transducer and activator of transcription, complement cascades, and cell suicide molecules. Potential molecular targets and therapeutics of SARS-CoV-2 induced neurologic damage are also discussed.

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Section: Neural Pathwaymentioning

confidence: 99%

Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection

Welcome

Mastorakis

2021

Inflammopharmacol

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“…It has been demonstrated that the MAPK pathway is involved in the differentiation of astrocytes and other neuronal cells, synaptic plasticity, and neuron survival, as evidenced by the robust changes of MAPK signaling in the hippocampus in depressive animal models [6,[57][58][59]. These kinase subfamilies play central roles in the release of proinflammatory cytokines or the activation of NF-κB, a proinflammatory transcription factor, in response to various stimuli, such as psycho-emotional stressors, acute alcohol exposure, pathogenic products, or proinflammatory cytokines [60][61][62]. NF-κB is abundantly distributed in the brain, microglia, BBB, and peripheral immune responsive cells [60,61,63], and it is an essential mediator in several important physiological processes, including synaptogenesis, neurotransmission, neuroprotection, and neuroinflammation [64][65][66].…”

Section: Proinflammatory Signaling Pathwaymentioning

confidence: 99%

“…These kinase subfamilies play central roles in the release of proinflammatory cytokines or the activation of NF-κB, a proinflammatory transcription factor, in response to various stimuli, such as psycho-emotional stressors, acute alcohol exposure, pathogenic products, or proinflammatory cytokines [60][61][62]. NF-κB is abundantly distributed in the brain, microglia, BBB, and peripheral immune responsive cells [60,61,63], and it is an essential mediator in several important physiological processes, including synaptogenesis, neurotransmission, neuroprotection, and neuroinflammation [64][65][66]. In animal models, NF-κB activity can be elevated by the degradation of NF-κB kinase inhibitors [67], and it can also be activated by IL-1β signaling and proinflammatory cytokines released from both the peripheral immune cells and the brain [68,69].…”

Section: Proinflammatory Signaling Pathwaymentioning

confidence: 99%

Chinese Herbal Medicine for the Treatment of Depression: Effects on the Neuroendocrine-Immune Network

Huang

Zhang

2021

Pharmaceuticals

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The neuroimmune and neuroendocrine systems are two critical biological systems in the pathogenesis of depression. Clinical and preclinical studies have demonstrated that the activation of the neuroinflammatory response of the immune system and hyperactivity of the hypothalamus–pituitary–adrenal (HPA) axis of the neuroendocrine system commonly coexist in patients with depression and that these two systems bidirectionally regulate one another through neural, immunological, and humoral intersystem interactions. The neuroendocrine-immune network poses difficulties associated with the development of antidepressant agents directed toward these biological systems for the effective treatment of depression. On the other hand, multidrug and multitarget Chinese Herbal Medicine (CHM) has great potential to assist in the development of novel medications for the systematic pharmacotherapy of depression. In this narrative essay, we conclusively analyze the mechanisms of action of CHM antidepressant constituents and formulas, specifically through the modulation of the neuroendocrine-immune network, by reviewing recent preclinical studies conducted using depressive animal models. Some CHM herbal constituents and formulas are highlighted as examples, and their mechanisms of action at both the molecular and systems levels are discussed. Furthermore, we discuss the crosstalk of these two biological systems and the systems pharmacology approach for understanding the system-wide mechanism of action of CHM on the neuroendocrine-immune network in depression treatment. The holistic, multidrug, and multitarget nature of CHM represents an excellent example of systems medicine in the effective treatment of depression.

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“…Repetitive acute stress exposure is a precipitant of microglial activation and peripheral monocyte recruitment to the CNS; however, fewer studies have explored the neuroinflammatory effects of a single, acute stressor [ 56 , 57 , 58 ]. HPA-axis activation, a rough biological correlate of the acute stress response, has been shown to disrupt the blood-brain barrier, thus further facilitating the migration of monocytes to the brain [ 59 ]. Recently, it was demonstrated that an increase in expression of pro-inflammatory mediators, including interleukin 16 (IL-16) and nuclear factor kappa light chain enhancer of activated B cells (NF-kB), is also observed in mice subjected to a single exposure of 12 h to cold stress, which is a relatively acute, non-repetitive stress paradigm [ 60 ].…”

Section: Acute Stress In Epilepsymentioning

confidence: 99%

Impact of Stress on Epilepsy: Focus on Neuroinflammation—A Mini Review

Espinosa‐García

Zeleke

Rojas

2021

IJMS

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Epilepsy, one of the most common neurological disorders worldwide, is characterized by recurrent seizures and subsequent brain damage. Despite strong evidence supporting a deleterious impact on seizure occurrence and outcome severity, stress is an overlooked component in people with epilepsy. With regard to stressor duration and timing, acute stress can be protective in epileptogenesis, while chronic stress often promotes seizure occurrence in epilepsy patients. Preclinical research suggests that chronic stress promotes neuroinflammation and leads to a depressive state. Depression is the most common psychiatric comorbidity in people with epilepsy, resulting in a poor quality of life. Here, we summarize studies investigating acute and chronic stress as a seizure trigger and an important factor that worsens epilepsy outcomes and psychiatric comorbidities. Mechanistic insight into the impact of stress on epilepsy may create a window of opportunity for future interventions targeting neuroinflammation-related disorders.

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Stress-induced blood brain barrier disruption: Molecular mechanisms and signaling pathways

Cited by 73 publications

References 248 publications

Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection

Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection

Chinese Herbal Medicine for the Treatment of Depression: Effects on the Neuroendocrine-Immune Network

Impact of Stress on Epilepsy: Focus on Neuroinflammation—A Mini Review

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