Poly-IC Preconditioning Protects against Cerebral and Renal Ischemia-Reperfusion Injury

Packard, Amy E.B.; Hedges, Jason C.; Bahjat, Frances R.; Stevens, Susan L.; Conlin, Michael J.; Salazar, Andrés M.; Stenzel-Poore, Mary P.

doi:10.1038/jcbfm.2011.160

Cited by 40 publications

(45 citation statements)

References 15 publications

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“…Moreover, the protective effects of poly(I:C) were abolished in the TLR3 2/2 mouse MCAO model, suggesting that the protective effects of poly(I:C) are mediated via TLR3. It has been reported that poly(I:C) preconditioning could reduce I/R injury (17,18), and our results demonstrated that poly(I:C) treatment 3 h after ischemia had therapeutic effects on cerebral I/R injury. However, a recent study has reported that TRL3 activation increased the susceptibility of neonatal brain to hypoxia and ischemia (36).…”

Section: Discussionsupporting

confidence: 59%

“…Ischemia preconditioning can reduce cerebral I/R injury (35), and recent reports have shown that poly(I:C) preconditioning protects against cerebral I/R injury (17,18). However, it has not been determined whether postischemia poly(I:C) treatment would also be effective in protecting against cerebral I/R injury.…”

Section: Discussionmentioning

confidence: 99%

“…TLR3-deficient mice do not exhibit reduced cerebral infarct volumes after cerebral I/R compared with wild-type mice (16). However, recent reports have shown that polyinosinic-polycytidylic acid (poly(I:C)) preconditioning protects against cerebral I/R injury (17,18). However, it is unclear whether poly(I:C) treatment after cerebral I/R injury is also effective.…”

mentioning

confidence: 90%

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Polyinosinic-Polycytidylic Acid Has Therapeutic Effects against Cerebral Ischemia/Reperfusion Injury through the Downregulation of TLR4 Signaling via TLR3

Wang

Huang

Chen

et al. 2014

The Journal of Immunology

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Recent reports have shown that preconditioning with the TLR3 ligand polyinosinic-polycytidylic acid (poly(I:C)) protects against cerebral ischemia/reperfusion (I/R) injury. However, it is unclear whether poly(I:C) treatment after cerebral I/R injury is also effective. We used mouse/rat middle cerebral artery occlusion and cell oxygen-glucose deprivation models to evaluate the therapeutic effects and mechanisms of poly(I:C) treatment. Poly(I:C) was i.p. injected 3 h after ischemia (treatment group). Cerebral infarct volumes and brain edemas were significantly reduced, and neurologic scores were significantly increased. TNF-α and IL-1β levels were markedly decreased, whereas IFN-β levels were greatly increased, in the ischemic brain tissues, cerebral spinal fluid, and serum. Injuries to hippocampal neurons and mitochondria were greatly reduced. The numbers of TUNEL-positive and Fluoro-Jade B+ cells also decreased significantly in the ischemic brain tissues. Poly(I:C) treatment increased the levels of Hsp27, Hsp70, and Bcl2 and decreased the level of Bax in the ischemic brain tissues. Moreover, poly(I:C) treatment attenuated the levels of TNF-α and IL-1β in serum and cerebral spinal fluid of mice stimulated by LPS. However, the protective effects of poly(I:C) against cerebral ischemia were abolished in TLR3−/− and TLR4−/−mice. Poly(I:C) downregulated TLR4 signaling via TLR3. Poly(I:C) treatment exhibited obvious protective effects 14 d after ischemia and was also effective in the rat permanent middle cerebral artery occlusion model. The results suggest that poly(I:C) exerts therapeutic effects against cerebral I/R injury through the downregulation of TLR4 signaling via TLR3. Poly(I:C) is a promising new drug candidate for the treatment of cerebral infarcts.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 90%

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Polyinosinic-Polycytidylic Acid Has Therapeutic Effects against Cerebral Ischemia/Reperfusion Injury through the Downregulation of TLR4 Signaling via TLR3

Wang

Huang

Chen

et al. 2014

The Journal of Immunology

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“…TLR agonists may also act directly on BBB at the interface between blood and brain resulting in increased BBB stabilization following ischemia. Adapted from [ 125 ] conventional pharmacotherapy (e.g., thrombolytics and clot removal devices) or enhance the effi cacy of existing partially effective therapeutics. As with many human conditions, brain injury is multifactorial; thus, a single therapeutic, a so-called magic bullet, is not likely to exist for stroke or other brain injuries.…”

Section: Resultsmentioning

confidence: 99%

Toll-Like Receptors in Ischemic Stroke and Other Acute Brain Injuries

Bahjat

Gesuete

Stenzel-Poore

2013

Immunological Mechanisms and Therapies in Brain Injuries and Stroke

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Each year a substantial number of Americans suffer from hypoxic injury to the brain due to diminished blood fl ow and few effective treatments are available. A fruitful area of current investigation involves toll-like receptors (TLRs), which are a family of highly conserved receptors that play a key role in the pathology of brain injury. Studies in animals defi cient in specifi c TLRs as well as genetic data from patients with altered TLR biology suggest that the activation of TLRs exacerbates damage in the setting of ischemia. Paradoxically, the stimulation of TLRs prior to injury is known to induce a state of tolerance to subsequent ischemic injury or "preconditioning". Such preconditioning results in a profound neuroprotective effect and the mechanisms involved are under intense investigation. Understanding these divergent roles of TLRs in brain injury and neuroprotection offers great promise in the discovery of new therapeutic targets and the mitigation of ischemic brain injury in "at risk" patients through the use of prophylactic TLR stimulation as a therapeutic strategy. This chapter focuses on these two divergent roles of TLRsone role that promotes and another that prevents ischemic injury in the brain in the context of stroke and other acute brain injuries.

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“…Interestingly, Cole et al [52] demonstrated an unexpected beneficial role for TLR3 in the arterial wall upon systemic administration of poly(I:C). Further, Packard et al [53] found poly(I:C) administration to be protective against cerebral ischemia-reperfusion injury. Since MSCs are widely present in vivo and their perivascular origin in multiple human organs appears certain [5,10] , it is possible that these prophylactic benefits of poly(I:C) may be mediated through its trophic stimulatory effect on the endogenous MSC niches.…”

Section: Competencementioning

confidence: 99%

Enhancing the efficacy of mesenchymal stem cell therapy

Mastri

Lin

Lee

2014

WJSC

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Mesenchymal stem cell (MSC) therapy is entering a challenging phase after completion of many preclinical and clinical trials. Among the major hurdles encountered in MSC therapy are inconsistent stem cell potency, poor cell engraftment and survival, and age/ disease-related host tissue impairment. The recognition that MSCs primarily mediate therapeutic benefits through paracrine mechanisms independent of cell differentiation provides a promising framework for enhancing stem cell potency and therapeutic benefits. Several MSC priming approaches are highlighted, which will likely allow us to harness the full potential of adult stem cells for their future routine clinical use.

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Poly-IC Preconditioning Protects against Cerebral and Renal Ischemia-Reperfusion Injury

Cited by 40 publications

References 15 publications

Polyinosinic-Polycytidylic Acid Has Therapeutic Effects against Cerebral Ischemia/Reperfusion Injury through the Downregulation of TLR4 Signaling via TLR3

Polyinosinic-Polycytidylic Acid Has Therapeutic Effects against Cerebral Ischemia/Reperfusion Injury through the Downregulation of TLR4 Signaling via TLR3

Toll-Like Receptors in Ischemic Stroke and Other Acute Brain Injuries

Enhancing the efficacy of mesenchymal stem cell therapy

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