Neuroprotective Effect of Atorvastatin Involves Suppression of TNF-α and Upregulation of IL-10 in a Rat Model of Intracerebral Hemorrhage

Tu, E-wen; Liu, Qiuting; Tang, Chaogang; Tang, Tao; Wu, Jun; Tan, Liming; Guang-hong, Xiang

doi:10.1007/s12013-012-9453-z

Cited by 38 publications

(25 citation statements)

References 15 publications

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“…Cerebral hemorrhage and edema are attenuated by anti-TNFα therapy (128), indicating that the main protective effect of IL-10 is derived from its inhibition on the production of proinflammatory cytokines, namely, TNFα (129–131). This same effect is found in adult male Sprague-Dawley rats, where statins (2, 5, 10 mg/kg) produce dose-dependent increases in IL-10 levels and are associated with dose-dependent decreases in TNFα, as well as fewer activated microglia, sensorimotor deficits, and inflammation and less edema 3 days after ICH (122). …”

Section: Intracerebral Hemorrhagesupporting

confidence: 52%

Role of Interleukin-10 in Acute Brain Injuries

et al. 2017

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Interleukin-10 (IL-10) is an important anti-inflammatory cytokine expressed in response to brain injury, where it facilitates the resolution of inflammatory cascades, which if prolonged causes secondary brain damage. Here, we comprehensively review the current knowledge regarding the role of IL-10 in modulating outcomes following acute brain injury, including traumatic brain injury (TBI) and the various stroke subtypes. The vascular endothelium is closely tied to the pathophysiology of these neurological disorders and research has demonstrated clear vascular endothelial protective properties for IL-10. In vitro and in vivo models of ischemic stroke have convincingly directly and indirectly shown IL-10-mediated neuroprotection; although clinically, the role of IL-10 in predicting risk and outcomes is less clear. Comparatively, conclusive studies investigating the contribution of IL-10 in subarachnoid hemorrhage are lacking. Weak indirect evidence supporting the protective role of IL-10 in preclinical models of intracerebral hemorrhage exists; however, in the limited number of clinical studies, higher IL-10 levels seen post-ictus have been associated with worse outcomes. Similarly, preclinical TBI models have suggested a neuroprotective role for IL-10; although, controversy exists among the several clinical studies. In summary, while IL-10 is consistently elevated following acute brain injury, the effect of IL-10 appears to be pathology dependent, and preclinical and clinical studies often paradoxically yield opposite results. The pronounced and potent effects of IL-10 in the resolution of inflammation and inconsistency in the literature regarding the contribution of IL-10 in the setting of acute brain injury warrant further rigorously controlled and targeted investigation.

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Section: Intracerebral Hemorrhagesupporting

confidence: 52%

Role of Interleukin-10 in Acute Brain Injuries

et al. 2017

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“…In line with in vitro studies, anti-inflammatory drugs induce IL-10 production in vivo. In an experimental model of intracerebral haemorrhage, atorvastatin, a 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor with known anti-inflammatory properties, upregulated IL-10 in vivo, which is accompanied by a reduction in the number of activated microglial cells, and consequently to downregulate that of TNF [115]. …”

Section: Cellular Sources Of Il-10 In the Cnsmentioning

confidence: 99%

Balancing the immune response in the brain: IL-10 and its regulation

Lobo-Silva

Carriche

Castro

et al. 2016

J Neuroinflammation

297

199

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BackgroundThe inflammatory response is critical to fight insults, such as pathogen invasion or tissue damage, but if not resolved often becomes detrimental to the host. A growing body of evidence places non-resolved inflammation at the core of various pathologies, from cancer to neurodegenerative diseases. It is therefore not surprising that the immune system has evolved several regulatory mechanisms to achieve maximum protection in the absence of pathology.Main bodyThe production of the anti-inflammatory cytokine interleukin (IL)-10 is one of the most important mechanisms evolved by many immune cells to counteract damage driven by excessive inflammation. Innate immune cells of the central nervous system, notably microglia, are no exception and produce IL-10 downstream of pattern recognition receptors activation. However, whereas the molecular mechanisms regulating IL-10 expression by innate and acquired immune cells of the periphery have been extensively addressed, our knowledge on the modulation of IL-10 expression by central nervous cells is much scattered. This review addresses the current understanding on the molecular mechanisms regulating IL-10 expression by innate immune cells of the brain and the implications of IL-10 modulation in neurodegenerative disorders.ConclusionThe regulation of IL-10 production by central nervous cells remains a challenging field. Answering the many remaining outstanding questions will contribute to the design of targeted approaches aiming at controlling deleterious inflammation in the brain.

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“…In animal studies, statins showed less neuronal tissue loss and inflammation; increased cell proliferation, angiogenesis, and synaptogenesis in the perihemorrhagic zone with better functional outcomes (85–87). Statins’ neuroprotective actions may be explained by their ability to induce expression of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) (88) to reduce activated microglia, MMP-9 (89), and cytokine-mediated inflammation (less TNF-α and higher interleukin-10 levels) (90, 91). Statins also reduce BBB dysfunction, edema, tissue loss, and improve CBF in the perihemorrhagic zone (92, 93).…”

Section: Perihemorrhagic Edemamentioning

confidence: 99%

Intracerebral Hemorrhage: Perihemorrhagic Edema and Secondary Hematoma Expansion: From Bench Work to Ongoing Controversies

Mittal

LacKamp

2016

Front. Neurol.

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Intracerebral hemorrhage (ICH) is a medical emergency, which often leads to severe disability and death. ICH-related poor outcomes are due to primary injury causing structural damage and mass effect and secondary injury in the perihemorrhagic region over several days to weeks. Secondary injury after ICH can be due to hematoma expansion (HE) or a consequence of repair pathway along the continuum of neuroinflammation, neuronal death, and perihemorrhagic edema (PHE). This review article is focused on PHE and HE and will cover the animal studies, related human studies, and clinical trials relating to these mechanisms of secondary brain injury in ICH patients.

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Neuroprotective Effect of Atorvastatin Involves Suppression of TNF-α and Upregulation of IL-10 in a Rat Model of Intracerebral Hemorrhage

Cited by 38 publications

References 15 publications

Role of Interleukin-10 in Acute Brain Injuries

Role of Interleukin-10 in Acute Brain Injuries

Balancing the immune response in the brain: IL-10 and its regulation

Intracerebral Hemorrhage: Perihemorrhagic Edema and Secondary Hematoma Expansion: From Bench Work to Ongoing Controversies

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