Human cellular inflammation in the pathology of acute cerebral ischaemia

Price, Catherine J.; Warburton, Elizabeth A.; Menon, David

doi:10.1136/jnnp.74.11.1476

Cited by 54 publications

(41 citation statements)

References 78 publications

(56 reference statements)

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“…Theoretically, adding blood into the parenchyma and thereby increasing tissue pressure may reduce the hydrostatic driving force, but it does so at an untenable cost to the organ by: adding mass that contributes to increased intracranial pressure; adding the toxic oxidant, haemoglobin; and by inciting a robust inflammatory response, all of which contribute adversely to the outcome. [88][89][90] Implications for clinical management are similar to those for the previous stage, but optimising parameters to achieve the conflicting goals is now more difficult.…”

Section: Permeability Poresmentioning

confidence: 97%

Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications

Simard

Kent

Chen

et al. 2007

The Lancet Neurology

685

619

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Focal cerebral ischaemia and post-ischaemic reperfusion cause cerebral capillary dysfunction, resulting in oedema formation and haemorrhagic conversion. There are substantial gaps in understanding the pathophysiology, especially regarding early molecular participants. Here, we review physiological and molecular mechanisms involved. We reaffirm the central role of Starling's principle, which states that oedema formation is determined by the driving force and the capillary "permeability pore". We emphasise that the movement of fluids is largely driven without new expenditure of energy by the ischaemic brain. We organise the progressive changes in osmotic and hydrostatic conductivity of abnormal capillaries into three phases: formation of ionic oedema, formation of vasogenic oedema, and catastrophic failure with haemorrhagic conversion. We suggest a new theory suggesting that ischaemia-induced capillary dysfunction can be attributed to de novo synthesis of a specific ensemble of proteins that determine osmotic and hydraulic conductivity in Starling's equation, and whose expression is driven by a distinct transcriptional program.Correspondence to: Dr J Marc Simard, Department of Neurosurgery, 22 S. Greene St., Suite 12SD, Baltimore, MD 21201−1595, USA msimard@smail.umaryland.edu. Contributors JMS originated the overall concept for this review and wrote the first and second drafts. TAK contributed to and helped edit the first and second drafts, and supplied important citations. MC participated in the original work on the sections on the NC Ca-ATP channel and contributed to the first draft. KVT did the computer analysis of the gene promoter regions. VG engaged in numerous intellectual exchanges with JMS during formulation of concepts for this review.Conflict of interest JMS and MC have applied for a US patent, "A novel non-selective cation channel in neural cells and methods for treating brain swelling" (application number 10/391,561). NIH Public Access

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Section: Permeability Poresmentioning

confidence: 97%

Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications

Simard

Kent

Chen

et al. 2007

The Lancet Neurology

685

619

View full text Add to dashboard Cite

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“…1,7,45 A rapid activation of resident microglial cells and infiltration of peripheral inflammatory monocytes has 2048 Choi et al AJP October 2011, Vol. 179, No.…”

Section: Discussionmentioning

confidence: 99%

“…7,47 In most previous studies, A3AR agonists were administered before or immediately after stroke. 15,17,18 The present study is the first to demonstrate anti-ischemic protection achieved by postischemic treatment (ie, at 2 and 7 hours after the onset of ischemia) of the A3AR agonist LJ529.…”

Section: Discussionmentioning

confidence: 99%

“…In this context, much attention has been paid to inflammation, which starts after excitotoxicity and lasts for up to several days and even weeks, as an attractive therapeutic target to prevent the evolution of massive tissue damage in ischemia. 7 The A3 adenosine receptor, one of the four adenosine receptor subtypes (A1, A2A, A2B, and A3), is widely distributed in human and rat brain. 8,9 Expression of A3AR is reported to increase in activated inflammatory cells and modulate their activities 10,11 Moreover, the A3AR agonists are known to have anti-inflammatory effects in various animal models.…”

mentioning

confidence: 99%

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A3 Adenosine Receptor Agonist Reduces Brain Ischemic Injury and Inhibits Inflammatory Cell Migration in Rats

Choi

Lee

et al. 2011

The American Journal of Pathology

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A3 adenosine receptor (A3AR) is recognized as a novel therapeutic target for ischemic injury; however, the mechanism underlying anti-ischemic protection by the A3AR agonist remains unclear. Here, we report that 2-chloro-N 6 -(3-iodobenzyl)-5=-N-methylcarbamoyl-4=-thioadenosine (LJ529), a selective A3AR agonist, reduces inflammatory responses that may contribute to ischemic cerebral injury. Postischemic treatment with LJ529 markedly reduced cerebral ischemic injury caused by 1.5-hour middle cerebral artery occlusion, followed by 24-hour reperfusion in rats. This effect was abolished by the simultaneous administration of the A3AR antagonist MRS1523, but not the A2AAR antagonist SCH58261. LJ529 prevented the infiltration/migration of microglia and monocytes occurring after middle cerebral artery occlusion and reperfusion, and also after injection of lipopolysaccharides into the corpus callosum. The reduced migration of microglia by LJ529 could be related with direct inhibition of chemotaxis and down-regulation of spatiotemporal expression of Rho GTPases (including Rac, Cdc42, and Rho), rather than by biologically relevant inhibition of inflammatory cytokine/chemokine release ( Excitotoxicity, peri-infarct depolarization, oxidative stress, apoptosis, and inflammation contribute to the development of cerebral injury after ischemia.1 To develop effective therapeutic strategies for postischemic brain injury, it is crucial to understand the highly diverse temporal profiles (eg, onset and duration) of these individual factors and to interrupt their pathophysiological cascades. The N-methyl-D-aspartate (NMDA) receptor blocker MK-801 markedly reduces ischemic brain injury; however, MK-801 has a brief therapeutic time window: the neuroprotective effect of MK-801 is obtained only when therapy is given within at most 1 hour after the onset of focal ischemia in rats and gerbils.2,3 Furthermore, MK-801 only postpones postischemic neuronal death; it does not improve either neurological recovery or endpoint cell survival at weeks after treatment. 4,5 Similarly, ␣-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists also did not significantly protect neuronal loss at 28 days after middle cerebral artery occlusion (MCAO).6 This short therapeutic window and lack of long-term effect of NMDA or AMPA receptor antagonists suggests that these receptors play only a transient role in the early ischemic cascade. Thus, some pathophysiological

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“…The local inflammatory response in the brain is well established as a contributor to ischaemic brain damage, and there is increasing evidence that peripheral inflammatory processes and immune alterations are also important (McColl et al, 2007;Offner et al, 2006;Price et al, 2003). Clinically, immune cell mobilisation is accompanied by an acute-phase response (APR), and the upregulation of circulating cytokines and chemokines (Emsley and Tyrrell, 2002).…”

Section: Introductionmentioning

confidence: 99%

A Rapid and Transient Peripheral Inflammatory Response Precedes Brain Inflammation after Experimental Stroke

Chapman

Dale

Dénes

et al. 2009

J Cereb Blood Flow Metab

116

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Increasing evidence suggests that peripheral inflammatory responses to stroke and other brain injuries have an important role in determining neurological outcome. The mediators of this response and the temporal relationships between peripheral and central inflammatory alterations are poorly understood. In this study, we show that experimental stroke in mice induces a peripheral inflammatory response that peaks 4 h after stroke, and precedes the peak in brain inflammation 24 h after stroke. This peripheral response is dominated by the induction of the chemokine CXCL-1 and the proinflammatory cytokine interleukin-6 and could serve as an accessible target for therapy and as a source of biomarkers predictive of prognosis.

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Human cellular inflammation in the pathology of acute cerebral ischaemia

Cited by 54 publications

References 78 publications

Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications

Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications

A3 Adenosine Receptor Agonist Reduces Brain Ischemic Injury and Inhibits Inflammatory Cell Migration in Rats

A Rapid and Transient Peripheral Inflammatory Response Precedes Brain Inflammation after Experimental Stroke

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