Anti-inflammatory strategies in stroke: a potential therapeutic target

Siniscalchi, Antonio; Iannacchero, Rosario; Anticoli, Sabrina; Pezzella, Francesca Romana; Sarro, Giovambattista De; Gallelli, Luca

doi:10.2174/1570161113666150923111329

Cited by 41 publications

(31 citation statements)

References 120 publications

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“…Glial cell size was increased in the multiparous brain after stroke, suggesting that parity can chronically alter cellular cytoarchitecture and prime microglia toward an M2-like activation state following injury. Whereas depressive behavior and deficits in hippocampal neurogenesis are often associated with systemic immunosuppression in the postpartum period (32), it is well established that antiinflammatory environments and M2-like polarization of activated microglia generally favor positive outcomes following ischemic stroke (33). Consistent with this understanding, others have found that peritoneal macrophages from primiparous females exhibited less of a PMA-induced oxidative burst than nulliparous macrophages (34).…”

Section: Discussionmentioning

confidence: 93%

Multiparity improves outcomes after cerebral ischemia in female mice despite features of increased metabovascular risk

Ritzel

Patel

Spychala

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Females show a varying degree of ischemic sensitivity throughout their lifespan, which is not fully explained by hormonal or genetic factors. Epidemiological data suggest that sex-specific life experiences such as pregnancy increase stroke risk. This work evaluated the role of parity on stroke outcome. Age-matched virgin (i.e., nulliparous) and multiparous mice were subjected to 60 min of reversible middle cerebral artery occlusion and evaluated for infarct volume, behavioral recovery, and inflammation. Using an established mating paradigm, fetal microchimeric cells present in maternal mice were also tracked after parturition and stroke. Parity was associated with sedentary behavior, weight gain, and higher triglyceride and cholesterol levels. The multiparous brain exhibited features of immune suppression, with dampened baseline microglial activity. After acute stroke, multiparous mice had smaller infarcts, less glial activation, and less behavioral impairment in the critical recovery window of 72 h. Behavioral recovery was significantly better in multiparous females compared with nulliparous mice 1 mo after stroke. This recovery was accompanied by an increase in poststroke angiogenesis that was correlated with improved performance on sensorimotor and cognitive tests. Multiparous mice had higher levels of VEGF, both at baseline and after stroke. GFP + fetal cells were detected in the blood and migrated to areas of tissue injury where they adopted endothelial morphology 30 d after injury. Reproductive experience has profound and complex effects on neurovascular health and disease. Inclusion of female mice with reproductive experience in preclinical studies may better reflect the life-long patterning of ischemic stroke risk in women.sex differences | multiparity | microglia | ischemic stroke | microchimerism N early 800,000 people in the United States experience a new or recurrent stroke each year, and 55,000 more women than men are affected by stroke (1). Stroke is a sexually dimorphic disease impacted by genetics, hormones, and the environment (2). According to CDC data, 85% of women in the United States have given birth by age 40, whereas the number of lifetime pregnancies per woman varies by race and socioeconomic status. Therefore, child-bearing women represent a significant proportion of the female population, including those at risk for stroke. Moreover, this suggests that a large proportion of the elderly female populationwho is at highest risk for stroke-may be differentially at risk. Epidemiological data suggest that increasing parity is associated with higher risk of cardiovascular disease (CVD) and stroke and late-life vascular comorbidities, including carotid atherosclerosis (3, 4). However, recent reports suggest that parity has a significant protective effect against CVD mortality (5). The effect of parity on outcome following ischemic stroke is yet unresolved.Pregnancy induces profound acute and long-term physiological changes in the body that influence future vascular health through hormonally med...

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Section: Discussionmentioning

confidence: 93%

Multiparity improves outcomes after cerebral ischemia in female mice despite features of increased metabovascular risk

Ritzel

Patel

Spychala

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…69 Hu et al 34 found that macrophage subtype shifted from early beneficial M2 microglia to M1 microglia and suggested that new therapies should focus on adjusting the balance between good and bad subtypes. Recently, this shift from the M1 to the M2 phenotype in stroke was found to be mTOR mediated.…”

Section: Inflammatory/stress Response and Immune Modulationmentioning

confidence: 99%

“…One explanation is that rodents' and humans' inflammatory responses post-stroke involve different integrins and signaling responses. 69 Remote ischemic preconditioning has been found to protect against focal ischemia and preserve neurological function via ameliorating postocclusion reduction in CD3+/CD8+ T cells and CD3+/ CD161a+ natural killer T cells. It induces interleukin-6 expression and tumor necrosis factor-α expression while increasing the number of noninflammatory monocytes (CD43+/CD172a+).…”

Section: Inflammatory/stress Response and Immune Modulationmentioning

confidence: 99%

Experimental neuroprotection in ischemic stroke: a concise review

Rajah

Ding

2017

FOC

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Acute ischemic stroke (AIS) is a leading cause of disability and death worldwide. To date, intravenous tissue plasminogen activator and mechanical thrombectomy have been standards of care for AIS. There have been many advances in diagnostic imaging and endovascular devices for AIS; however, most neuroprotective therapies seem to remain largely in the preclinical phase. While many neuroprotective therapies have been identified in experimental models, none are currently used routinely to treat stroke patients. This review seeks to summarize clinical studies pertaining to neuroprotection, as well as the different preclinical neuroprotective therapies, their presumed mechanisms of action, and their future applications in stroke patients.

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“…Infection or high levels of proinflammatory biomarkers indicate significantly increased risk of ischemic stroke, especially in the elderly. [8][9][10] The onset or worsening of a stroke in these patients could be caused either by direct damage of the CoVs on the nervous system and/or by an activation of the mechanisms of COVID-19 inflammation induced as well coagulation disorders. As the disease spreads and new evidence emerges, we need to identify the existence of additional pathophysiological mechanisms of stroke in COVID-19 patients.…”

mentioning

confidence: 99%