Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasospasm (VS) and delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) are thought to greatly affect prognosis. Haptoglobin (Hp) is a hemoglobin-binding protein expressed by a genetic polymorphism (1-1, 2-1, and 2-2). Our objects were to investigate whether the Hp phenotype could predict the incidence of cerebral infarction, favorable outcome, clinical deterioration by DCI, and angiographical VS after aneurysmal SAH. Ninety-five consecutive patients who underwent clipping or coil embolization were studied. Favorable functional outcome was defined as a modified Rankin Scale score of 0-2 at 3 months. Angiographical VS was diagnosed based on cerebral angiography findings performed between days 7 and 10 after SAH. The Hp 2-2 group had a significantly greater risk of angiographical VS than that of Hp 2-1 and 1-1 groups combined on univariate (odds ratio [OR]: 3.60, confidence interval [CI]: 1.49-8.67, P = .003) and multivariate logistic regression analyses after being adjusted for age, sex, Fisher groups, and other risk factors (OR: 3.75, CI: 1.54-9.16, P = .004). The Hp 2-2 group also showed the tendency of a greater risk of clinical deterioration by DCI with marginal significance on univariate and age- and sex-adjusted analyses (univariate OR: 2.46, CI: .90-6.74, P = .080; age- and sex-adjusted OR: 2.46, CI: .89-6.82, P = .080) but not after being adjusted for other multiple risk factors. The Hp 2-2 group was not associated with the favorable 3-month outcome and cerebral infarction (univariate: P = .867, P = .209; multivariate: P = .905, P = .292). The Hp phenotype seems to be associated with a higher rate of angiographical VS and clinical deterioration by DCI but does not affect the incidence of cerebral infarction and favorable outcome.
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PMID:Haptoglobin phenotype predicts cerebral vasospasm and clinical deterioration after aneurysmal subarachnoid hemorrhage. 2349 76

Cerebral vasospasm (CV) and the resulting delayed cerebral ischemia (DCI) significantly contribute to poor outcomes following aneurysmal subarachnoid hemorrhage (aSAH). Free hemoglobin (Hb) within the subarachnoid space has been implicated in the pathogenesis of CV. Haptoglobin (Hp) binds free pro-oxidant Hb, thereby modulating its harmful effects. Humans can be of three Hp phenotypes: Hp1-1, Hp2-1, or Hp2-2. In several disease states, the Hp2-2 protein has been associated with reduced ability to protect against toxic free Hb. We hypothesized that individuals with the Hp2-2 phenotype would have more CV, DCI, mortality, and worse functional outcomes after aSAH. In a sample of 74 aSAH patients, Hp2-2 phenotype was significantly associated with increased focal moderate (P = 0.014) and severe (P = 0.008) CV and more global CV (P = 0.014) after controlling for covariates. Strong trends toward increased mortality (P = 0.079) and worse functional outcomes were seen for the Hp2-2 patients with modified Rankin scale at 6 wk (P = 0.076) and at 1 y (P = 0.051) and with Glasgow Outcome Scale Extended at discharge (P = 0.091) and at 1 y (P = 0.055). In conclusion, Hp2-2 phenotype is an independent risk factor for the development of both focal and global CV and also predicts poor functional outcomes and mortality after aSAH. Hp phenotyping may serve as a clinically useful tool in the critical care management of aSAH patients by allowing for early prediction of those patients who require increased vigilance due to their inherent genetic risk for the development of CV and resulting DCI and poor outcomes.
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PMID:Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage. 2558 72

Haptoglobin (Hp) is a plasma protein involved in clearing extracellular haemoglobin and regulating inflammation; it exists as two genetic variants (Hp1 and Hp2). In a meta-analysis of six published studies, we confirm that Hp genotype affects short-term outcome (cerebral vasospasm and/or delayed cerebral ischemia) after subarachnoid haemorrhage (SAH) but not long-term outcome (Glasgow Outcome Score and modified Rankin Scale between one and three months). A closer examination of the heterozygous group revealed that the short-term outcome of Hp2-1 individuals clustered with that of Hp1-1 and not Hp2-2, suggesting that the presence of one Hp1 allele was sufficient to confer protection. Since the presence of the Hp dimer is the only common feature between Hp1-1 and Hp2-1 individuals, the absence of this Hp moiety is most likely to underlie vasospasm in Hp2-2 individuals. These results have implications for prognosis after SAH and will inform further research into Hp-based mechanism of action and treatment.
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PMID:Haptoglobin Genotype and Outcome after Subarachnoid Haemorrhage: New Insights from a Meta-Analysis. 3005 87

Survivors of cerebral aneurysm rupture are at risk for significant morbidity and neurological deficits. Much of this is related to the effects of blood in the subarachnoid space which induces an inflammatory cascade with numerous downstream consequences. Recent clinical trials have not been able to reduce the toxic effects of free hemoglobin or improve clinical outcome. One reason for this may be the inability to identify patients at high risk for neurologic decline. Recently, haptoglobin genotype has been identified as a pertinent factor in diabetes, sickle cell, and cardiovascular disease, with the Hp 2-2 genotype contributing to increased complications. Haptoglobin is a protein synthesized by the liver that binds free hemoglobin following red blood cell lysis, and in doing so, prevents hemoglobin induced toxicity and facilitates clearance. Clinical studies in patients with subarachnoid hemorrhage indicate that Hp 2-2 patients may be a high-risk group for hemorrhage related complications and poor outcome. We review the relevance of haptoglobin in subarachnoid hemorrhage and discuss the effects of genotype and expression levels on the known mechanisms of early brain injury (EBI) and cerebral ischemia after aneurysm rupture. A better understanding of haptoglobin and its role in preventing hemoglobin related toxicity should lead to novel therapeutic avenues.
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PMID:Unique Contribution of Haptoglobin and Haptoglobin Genotype in Aneurysmal Subarachnoid Hemorrhage. 2990 50

Delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a major cause of mortality and morbidity. The pathophysiology of DCI after aSAH is thought to involve toxic mediators released from lysis of red blood cells within the subarachnoid space, including free haemoglobin and haem. Haptoglobin and hemopexin are endogenously produced acute phase proteins that are involved in the clearance of these toxic mediators. The aim of this review is to investigate the pathophysiological mechanisms involved in DCI and the role of both endogenous as well as exogenously administered haptoglobin and hemopexin in the prevention of DCI.
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PMID:The role of haptoglobin and hemopexin in the prevention of delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage: a review of current literature. 3149 61