Heme Oxygenase 1 in Cerebrospinal Fluid from Infants and Children after Severe Traumatic Brain Injury

Cousar, J’mir L.; Lai, Yi‐Chen; Marco, Christina D.; Bayır, Hülya; Adelson, P. David; Janesko‐Feldman, Keri; Kochanek, Patrick M.; Clark, Robert S. B.

doi:10.1159/000094160

Cited by 35 publications

(27 citation statements)

References 74 publications

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“…11 The serum levels of direct bilirubin and total bilirubin were increased after acute ischemic stroke, which linked to the severity of stroke.…”

Section: Discussionmentioning

confidence: 99%

“…10 Increased HO-1 concentration was described to be associated with the severity of injury and unfavorable neurologic outcome. 11 Even HO activity protects astrocytes from heme-mediated injury, but paradoxically increases neuronal injury. 13 However, in our study, it is hard to tell the protective or harmful effects of serum HO-1 to our patients.…”

Section: Discussionmentioning

confidence: 99%

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Higher Level of Serum Heme Oxygenase-1 in Patients With Intracerebral Hemorrhage

Li-chun

et al. 2015

International Surgery

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The objective of this paper was to investigate the association of the serum level of heme oxygenase-1 in patients with intracerebral hemorrhage (ICH) with the risk of ICH. Heme oxygenase-1(HO-1) metabolizes heme into biliverdin, bilirubin, carbon monoxide, and iron, our recent study showed that serum level of HO-1 was increased in stroke patients, yet the association of HO-1 level with risk of intracerebral hemorrhage (ICH) is poorly known. Forty patients with ICH and another 40 patients without ICH were recruited. The serum level of HO-1, total, and direct bilirubin were measured. The level of HO-1, serum total bilirubin, and direct bilirubin, as well as blood pressure were increased in ICH group than in control group (P , 0.001). The level of HO-1, both systolic and diastolic blood pressure had a significant difference between subgroups (P , 0.05). Multivariate regression analysis showed that poor compliance to medicine for hypertension, the serum level of HO-1, and systolic blood pressure were associated with the prevalence of ICH. Blood pressure, serum HO-1, serum total bilirubin, and direct bilirubin were raised in patients with ICH who did not take medicine for hypertension compared with those who did, and increased in ICH patients in comparison with control group. Further investigation in multiple medical centers with large number of cohorts is warranted to verify these results. Key words: Heme oxygenase-1 -Intracerebral hemorrhage -Bilirubin -Hypertension H eme oxygenase (HO) presents in several mammalian tissues, catalyzes the rate-limiting step in heme degradation, regulates heme protein turnover, and cleaves the heme ring to form biliverdin that is subsequently converted to bilirubin.1,2,3 There are 3 known HO isoforms: HO-1, HO-2, and HO-3. HO-1, a 32-kDa heat shock protein, is inducible by several stress factors such as oxidative stress, hypoxia, heavy metals, etc. In humans, the ho-1 gene (HMOX1) is located on chromosome 22q12 and contains 4 introns and 5 exons. HO-1 enzymes have been characterized as endoplasmic reticulum associated proteins due to the abundant detection of HO activity in microsomal fractions. HO-2 is a constitutive isoform that is expressed under homeostatic conditions. Both HO-1 and HO-2 are ubiquitously expressed and catalytically active. HO-3 is not catalytically active, there are no functional HO-3 genes at least in rats. 4 Expression of HO-1 has been described in microglia, astrocytes, and neurons in many experimental models such as subarachnoid hemorrhage, ischemia and traumatic brain injury, as well as in human neurodegenerative diseases.1 HO-1 has been reported to be associated with prevalence of stroke.5 Our recent study showed that HO-1 level was higher in patients with stroke than with TIA. 6 The stroke can be caused by ischemic infarction or intracerebral hemorrhage (ICH), which is one of the most prominent conditions leading to high morbidity and mortality.7 Bilirubin, a powerful antioxidant, is induced after hemorrhagic stroke, and is significantly elevated in patie...

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“…11 The serum levels of direct bilirubin and total bilirubin were increased after acute ischemic stroke, which linked to the severity of stroke.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Higher Level of Serum Heme Oxygenase-1 in Patients With Intracerebral Hemorrhage

Li-chun

et al. 2015

International Surgery

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“…13). HO-1 increases appeared more prominent in cerebrospinal fluid from infants compared with older children after traumatic brain injury (Cousar et al, 2006). Increased HO-1 concentration was associated with increased injury severity and unfavorable neuro- and NOS/NO systems may shed light on the pathogenic development of memory deficits associated with vascular dementia .…”

Section: P Aging Parkinson's Disease and Alzheimer's Diseasementioning

confidence: 94%

Pharmacological and Clinical Aspects of Heme Oxygenase

Abraham

Kappas²

2008

Pharmacol Rev

1,012

988

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“…Based on the present and our previous study reporting increased CSF-inducible hsp70 after pediatric TBI [Lai et al, 2004], and a study also published in this special issue of Developmental Neuroscience reporting increased CSF heme oxygenase 1 (hsp32) [Cousar et al, 2006], it appears clear that the stress response is induced in infants and children after TBI. However, the response of individual stress proteins appears to vary after pediatric TBI.…”

Section: Discussionmentioning

confidence: 64%

Mitochondrial Heat Shock Protein 60 Is Increased in Cerebrospinal Fluid following Pediatric Traumatic Brain Injury

Lai¹,

Stange²,

Wisniewski³

et al. 2006

Dev Neurosci

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Mitochondrial dysfunction occurs after traumatic brain injury (TBI) and contributes significantly to subsequent cell death. Heat shock protein 60 (hsp60) is a predominantly mitochondrial protein with important homeostatic functions. Induction of hsp60 has been demonstrated in cerebral ischemia models, possibly reflecting mitochondrial stress. We measured hsp60 concentration in the cerebrospinal fluid (CSF) of 34 infants and children after severe TBI and of 7 control patients by ELISA. Peak CSF hsp60 concentration was increased in TBI patients versus controls (0.84 ng/ml, range 0–44.59, vs. 0.0 ng/ml, range 0–0.48; p < 0.05). Induction of hsp60 occurred early after the injury. Peak hsp60 concentration was independently associated with the severity of injury, defined as the admission Glasgow Coma Scale score. These data suggest that increased hsp60 in CSF might reflect the severity of early mitochondrial stress or damage after TBI.

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Heme Oxygenase 1 in Cerebrospinal Fluid from Infants and Children after Severe Traumatic Brain Injury

Cited by 35 publications

References 74 publications

Higher Level of Serum Heme Oxygenase-1 in Patients With Intracerebral Hemorrhage

Higher Level of Serum Heme Oxygenase-1 in Patients With Intracerebral Hemorrhage

Pharmacological and Clinical Aspects of Heme Oxygenase

Mitochondrial Heat Shock Protein 60 Is Increased in Cerebrospinal Fluid following Pediatric Traumatic Brain Injury

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