Inflammation following stroke

Perera, Marlon; Henry, Kate L.; Arakawa, Shuji; Howells, David W.; Markus, Romesh; Rowe, Christopher C.; Donnan, Geoffrey A.

doi:10.1016/j.jocn.2005.07.005

Cited by 172 publications

(103 citation statements)

References 102 publications

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“…During stroke, postischemic neuroinflammatory responses are characterized by microglial and astroglial activation and increased expression of inflammatory mediators [29,39,40,41] which cause the activation and translocation of the nuclear factor kappa light chain enhancer of activated B cells [42]. The knowledge about inflammasome activation during ischemic stroke is sketchy, and only in the past years were distinct inflammasome complexes discovered as mediators of inflammatory mechanism leading to cell death in ischemic stroke [10,43,44].…”

Section: Discussionmentioning

confidence: 99%

Poststroke Inflammasome Expression and Regulation in the Peri-Infarct Area by Gonadal Steroids after Transient Focal Ischemia in the Rat Brain

et al. 2015

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CNS ischemia results in locally confined and rapid tissue damage accompanied by a loss of neurons and their circuits. Early and time-delayed inflammatory responses are critical variables determining the extent of neural disintegration and regeneration. Inflammasomes are vital effectors in innate immunity. Their activation in brain-intrinsic immune cells contributes to ischemia-related brain damage. The steroids 17β-estradiol (E2) and progesterone (P) are neuroprotective and anti-inflammatory. Using a transient focal rat ischemic model, we evaluated the time response of different inflammasomes in the peri-infarct zone from the early to late phases after poststroke ischemia. We show that the different inflammasome complexes reveal a specific time-oriented sequential expression pattern with a maximum at approximately 24 h after the infarct. Within the limits of antibody availability, immunofluorescence labeling demonstrated that microglia and neurons are major sources of the locally activated inflammasomes NOD-like receptor protein-3 (NLRP3) and associated speck-like protein (ASC), respectively. E2 and P given for 24 h immediately after ischemia onset reduced hypoxia-induced mRNA expression of the inflammasomes NLRC4, AIM2 and ASC, and decreased the protein levels of ASC and NLRP3. In addition, mRNA protein levels of the cytokines interleukin-1β (IL1β), IL18 and TNFα were reduced by the steroids. The findings provide for the first time a detailed flow chart of hypoxia-driven inflammasome regulation in the peri-infarct cerebral cortex. Further, we demonstrate that E2 and P alleviate the expression of certain inflammasome components, sometimes in a hormone-specific way. Besides directly regulating other cellular neuroprotective pathways, the control of inflammasomes by these steroids might contribute to its neuroprotective potency.

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Section: Discussionmentioning

confidence: 99%

Poststroke Inflammasome Expression and Regulation in the Peri-Infarct Area by Gonadal Steroids after Transient Focal Ischemia in the Rat Brain

et al. 2015

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“…Some investigators have reported that IL-10 is the main down regulator of deleterious effects of proinflammatory cytokines. Clinical stroke studies have demonstrated that IL-10 decreases during ischemic events, and increases in IL-10 are associated with better patient outcomes [56,57]. Interestingly, the guanosine treatment after ischemia decreased the production of pro-inflammatory cytokines and restored IL-10 to sham levels.…”

Section: Discussionmentioning

confidence: 99%

Guanosine Protects Against Cortical Focal Ischemia. Involvement of Inflammatory Response

et al. 2014

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Stroke is the major cause of death and the most frequent cause of disability in the adult population worldwide. Guanosine plays an important neuroprotective role in several cerebral ischemic models and is involved in the modulation of oxidative responses and glutamatergic parameters. Because the excessive reactive oxygen species produced during an ischemic event can trigger an inflammatory response, the purpose of this study was to evaluate the hypothesis that guanosine is neuroprotective against focal cerebral ischemia, inhibits microglia/macrophages activation, and mediates an inflammatory response ameliorating the neural damage. Permanent focal cerebral ischemia was induced in adult rats, and guanosine was administered immediately, 1, 3, and 6 h after surgery. Twenty-four hours after ischemia, the asymmetry scores were evaluated by the cylinder test; neuronal damage was evaluated by Fluoro-Jade C (FJC) staining and propidium iodide (PI) incorporation; microglia and immune cells were evaluated by anti-Iba-1 antibody; and inflammatory parameters such as interleukins (IL): IL-1, IL-6, IL-10; tumor necrosis factors alpha (TNF-α); and interferon-gamma (INF-γ) were evaluated in the brain tissue and cerebrospinal fluid. The ischemic event increased the levels of Iba-1-positive cells and pro-inflammatory cytokines and decreased IL-10 levels (an anti-inflammatory cytokine) in the lesion periphery. The guanosine treatment attenuated the changes in these inflammatory parameters and also reduced the infarct volume, PI incorporation, and number of FJC-positive cells, improving the functional recovery. Thus, guanosine may have been a promising therapeutic agent for the treatment of ischemic brain injury by reduction of inflammatory process triggered in an ischemic event.

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“…Preclinical studies suggested that attenuation of inflammatory mediators reduce the progression of brain injury that occurs during the late stage of cerebral ischemia [31]. After transient MCAO (tMCAO) or pMCAO in rodents, the expression of iNOS and COX-2 are up-regulated and contribute to brain injury through their production such as NO and toxic prostanoids [6].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effect of Baicalin in a Rat Model of Permanent Focal Cerebral Ischemia

Yang

Shu

et al. 2009

Neurochem Res

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This investigation was performed to determine the neuroprotective effect of baicalin on permanent cerebral ischemia injury in rats and the potential mechanisms in this process. Adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO). The rats were then received intraperitoneal injection with baicalin (10, 30 and 100 mg/kg) or vehicle. Morphological characteristic, neurological deficit scores, cerebral infarct volume and the enzymatic activity of myeloperoxidase (MPO) were measured 24 h after pMCAO. The mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined by RT-PCR. Neuronal apoptosis was determined by TUNEL staining and Western blot. Baicalin (30 and 100 mg/kg) reduced neurological deficit scores and cerebral infarct volume 24 h after pMCAO. Baicalin significantly decreased the enzymatic activity of MPO and the expression of iNOS mRNA and COX-2 mRNA in rat brain, it also significantly inhibited neuronal apoptosis and the expression of cleaved caspase-3 protein after pMCAO. Our results suggested that baicalin possesses potent anti-inflammatory and anti-apoptotic properties and attenuates cerebral ischemia injury. This protection might be associated with the downregulated expression of iNOS mRNA, COX-2 mRNA, and cleaved caspase-3 protein.

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Inflammation following stroke

Cited by 172 publications

References 102 publications

Poststroke Inflammasome Expression and Regulation in the Peri-Infarct Area by Gonadal Steroids after Transient Focal Ischemia in the Rat Brain

Poststroke Inflammasome Expression and Regulation in the Peri-Infarct Area by Gonadal Steroids after Transient Focal Ischemia in the Rat Brain

Guanosine Protects Against Cortical Focal Ischemia. Involvement of Inflammatory Response

Neuroprotective Effect of Baicalin in a Rat Model of Permanent Focal Cerebral Ischemia

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