The Inflammatory Response After Ischemic Stroke: Targeting β2 and β1 Integrins

Edwards, Danielle; Bix, Gregory

doi:10.3389/fnins.2019.00540

Cited by 31 publications

(29 citation statements)

References 126 publications

(140 reference statements)

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“…Moreover, it has been shown that HBO treatment inhibits ischemia reperfusion-induced neutrophil adhesion to endothelium by blocking β 2 integrin polarization [23,24] and may also reduce leukocytes recruitment as it impaired adhesion molecule function by S-nitrosation [25]. Conversely, the role played by α 4 β 1 integrin in neutrophil-mediated adhesion to endothelium has been poorly investigated but an important role of α 4 β 1 in β 2 integrin-independent migration of neutrophils across heart endothelium has been demonstrated in vitro, suggesting a similar in vivo situation in neutrophil trafficking in reperfused myocardium [26].…”

Section: Introductionmentioning

confidence: 99%

Integrin-mediated adhesive properties of neutrophils are reduced by hyperbaric oxygen therapy in patients with chronic non-healing wound

et al. 2020

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In recent years, several studies suggested that the ability of hyperbaric oxygen therapy (HBOT) to promote healing in patients with diabetic ulcers and chronic wounds is due to the reduction of inflammatory cytokines and to a significant decrease in neutrophils recruitment to the damaged area. α 4 and β 2 integrins are receptors mediating the neutrophil adhesion to the endothelium and the comprehension of the effects of hyperbaric oxygenation on their expression and functions in neutrophils could be of great importance for the design of novel therapeutic protocols focused on anti-inflammatory agents. In this study, the α 4 and β 2 integrins' expression and functions have been evaluated in human primary neutrophils obtained from patients with chronic non-healing wounds and undergoing a prolonged HBOT (150 kPa per 90 minutes). The effect of a peptidomimetic α 4 β 1 integrin antagonist has been also analyzed under these conditions. A statistically significant decrease (68%) in β 2 integrin expression on neutrophils was observed during the treatment with HBO and maintained one month after the last treatment, while α 4 integrin levels remained unchanged. However, cell adhesion function of both neutrophilic integrins α 4 β 1 and β 2 was significantly reduced 70 and 67%, respectively), but α 4 β 1 integrin was still sensitive to antagonist inhibition in the presence of fibronectin, suggesting that a combined therapy between HBOT and integrin antagonists could have greater antinflammatory efficacy.

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Section: Introductionmentioning

confidence: 99%

Integrin-mediated adhesive properties of neutrophils are reduced by hyperbaric oxygen therapy in patients with chronic non-healing wound

et al. 2020

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“…[26]. The leukocytes were attracted to vascular endothelium and aggregated in ischemic area, thus activating the secondary in ammatory reaction downstream and forming a vicious circle [27,28]. At the same time, 2-4 hours after the early stage of cerebral ischemia, microglia were activated by in ammatory cytokines, which further aggravated brain injury [29].…”

Section: Discussionmentioning

confidence: 99%

JAK2/STAT3 Signaling Pathway Plays a Key Role in Nicotine Mediated Neuroinflammation Suppression in an Ischemic Rat Model

Wang

Han

Lai

et al. 2021

Preprint

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BackgroundTo explore the mechanism of nicotine mediated improvement of cognitive impairment in an established ischemic rat model. MethodsEndothelin-1 (ET-1) was injected into the left thalamic region in adult male Sprague-Dawley (SD) rats to establish ischemia model. 6 groups of rats (6 rats in each group) were then treated with nicotine, nicotine+DHβE, DHβE, AG490, nicotine +AG490 and saline respectively via intraperitoneal injection for 9 days. Another sham operation group was treated with saline as above. Morris Water Maze (MWM) test was performed for 6 consecutive days starting on the 4th day after operation to detect the cognitive function of rats in each group. 2-[18F]-A-85380 microPET imaging was performed on day 10 to evaluate the changes of α4β2 nAChRs in different brain regions of rats. Real-time PCR and Western blot were used to detect the amount of α4β2 nAChRs, JAK2, STAT3 and inflammatory factors in thalamus of rats in each group. ResultsThe results of MWM test showed the spatial learning and memory abilities of rats in the nicotine and sham operation groups were significantly better than the saline treating group in this ischemic rat model (p<0.05). There was no significant difference in other groups (p>0.05). MicroPET imaging showed more uptake of 2-[18F]-A-85380 in the nicotine, nicotine+AG490 and sham operation groups than in saline treating group, while there was no significant difference found in other groups (p>0.05). The expression of α4- and β2-nAChR in nicotine, nicotine+AG490 and sham operation groups was significantly higher than the saline treating group (p<0.05). In the nicotine group, the expression of p-JAK2 and p-STAT3 in left thalamus of rats was significantly higher than the saline treating group (p<0.05), and the expression of IL-1β and IL-6 protein was found to be lower than the saline treating group (p<0.05). While the expression of p-JAK2, p-STAT3 and inflammatory factors was not significantly different in all the other groups (p>0.05). ConclusionThe study suggests nicotine inhibits the expression of inflammatory factors by activating α4β2 nAChRs through the activation of JAK2-STAT3 signaling pathway to improve cognitive impairment in ischemic rats.

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“…Therefore, inhibition of integrin α2β1 may be a potential therapy for ischemic stroke. The expression and the role of integrins α8β1, α9β1, and αvβ6 have not yet been elucidated following stroke ( 147 ). At present, it is unknown if integrins influence TNC expression.…”

Section: Contribution Of Gfs and Integrins To Regulating Tnc Expressimentioning

confidence: 99%

“…In contrast, b1 integrins form laminin-binding, collagen-binding (a2b1), RGD-binding (a8b1), or ECMsbinding (a9b1) heterodimers (147)(148)(149)(150). The b1 integrins are increased in cerebral blood vessels in ischemic cortex, and induce angiogenesis as well as leukocyte adhesion and migration following ischemic stroke (147,151). In addition, increased b1 integrins in neuronal cells were associated with neuronal adhesion, and neurite outreach and regeneration (151).…”

Section: Integrinsmentioning

confidence: 99%

The Role of Tenascin-C in Tissue Injury and Repair After Stroke

Okada

Suzuki

2021

Front. Immunol.

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Stroke is still one of the most common causes for mortality and morbidity worldwide. Following acute stroke onset, biochemical and cellular changes induce further brain injury such as neuroinflammation, cell death, and blood-brain barrier disruption. Matricellular proteins are non-structural proteins induced by many stimuli and tissue damage including stroke induction, while its levels are generally low in a normal physiological condition in adult tissues. Currently, a matricellular protein tenascin-C (TNC) is considered to be an important inducer to promote neuroinflammatory cascades and the resultant pathology in stroke. TNC is upregulated in cerebral arteries and brain tissues including astrocytes, neurons, and brain capillary endothelial cells following subarachnoid hemorrhage (SAH). TNC may be involved in blood-brain barrier disruption, neuronal apoptosis, and cerebral vasospasm via the activation of mitogen-activated protein kinases and nuclear factor-kappa B following SAH. In addition, post-SAH TNC levels in cerebrospinal fluid predicted the development of delayed cerebral ischemia and angiographic vasospasm in clinical settings. On the other hand, TNC is reported to promote fibrosis and exert repair effects for an experimental aneurysm via macrophages-induced migration and proliferation of smooth muscle cells. The authors review TNC-induced inflammatory signal cascades and the relationships with other matricellular proteins in stroke-related pathology.

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The Inflammatory Response After Ischemic Stroke: Targeting β2 and β1 Integrins

Cited by 31 publications

References 126 publications

Integrin-mediated adhesive properties of neutrophils are reduced by hyperbaric oxygen therapy in patients with chronic non-healing wound

Integrin-mediated adhesive properties of neutrophils are reduced by hyperbaric oxygen therapy in patients with chronic non-healing wound

JAK2/STAT3 Signaling Pathway Plays a Key Role in Nicotine Mediated Neuroinflammation Suppression in an Ischemic Rat Model

The Role of Tenascin-C in Tissue Injury and Repair After Stroke

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