High Serum Levels of Growth Factors Are Associated with Good Outcome in Intracerebral Hemorrhage

Sobrino, Tomás; Arias, Susana; Rodríguez-González, Raquel; Brea, David; Silva, Yolanda; Ossa, Natàlia Pérez de la; Agulla, Jesús; Blanco, María del Pilar; Pumar, J.M.; Serena, Joaquı́n; Dávalos, Antoni; Castillo, José

doi:10.1038/jcbfm.2009.182

Cited by 46 publications

(48 citation statements)

References 25 publications

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“…[18][19][20] In a clinical ICH study, high levels of VEGF and Ang-1 at 72 hours after symptom onset were associated with good functional outcome and reduced lesion volume. 11 In our study, neither VEGF nor Ang-1 were associated with PHE or clinical outcome. This could be a result of the different time points of GFs assessment.…”

Section: March 2013mentioning

confidence: 81%

“…3 The impact of PHE on clinical outcome is still under debate. [4][5][6][7] Matrix metalloproteinase (MMP)-3 and MMP-9, [8][9][10] as well as growth factors (GFs) such as vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1), 11 are expressed in abnormally high concentrations in brain and peripheral blood in ICH patients. In ICH animal models, elevated MMP-9 and MMP-3 contribute to blood-brain barrier (BBB) disruption, 12,13 brain edema, 14,15 and neuronal cell death.…”

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confidence: 99%

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Association of Molecular Markers With Perihematomal Edema and Clinical Outcome in Intracerebral Hemorrhage

Liu

et al. 2013

Stroke

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Background and Purpose-Perihematomal edema contributes to secondary brain injury in intracerebral hemorrhage (ICH). Increase of matrix metalloproteinases (MMPs) and growth factors is considerably involved in blood-brain barrier disruption and neuronal cell death in ICH models. We therefore hypothesized that increased levels of these molecular markers are associated with perihematomal edema and clinical outcome in ICH patients. Methods-Fifty-nine patients with spontaneous ICH admitted within 24 hours of symptom onset were prospectively investigated. Noncontrast CT was performed on admission for diagnosis of ICH and quantification of initial hematoma volume. MRI was performed on day 3 to evaluate perihematomal edema. Concentrations of MMP-3, MMP-9, as well as vascular endothelial growth factor and angiopoietin-1 on admission were determined by enzyme-linked immunosorbent assays. Clinical outcome was assessed by modified Rankin Scale at 90 days. Results-Increased MMP-3 levels were independently associated with perihematomal edema volume (P<0.05). Cytotoxic edema surrounding the hematoma was seen in 36 (61%) cases on 3-day MRI. Cytotoxic edema did not correlate with the level of any of the biomarkers studied. Levels of MMP-3 ≥12.4 ng/mL and MMP-9 ≥192.4 ng/mL but not vascular endothelial growth factor and angiopoietin-1 predicted poor clinical outcome at 90 days (modified Rankin Scale >3) independent of stroke severity and hematoma volume at baseline (odds ratio, 25.3, P=0.035; odds ratio, 68.9, P=0.023; respectively). Conclusions-MMPs 3 and 9 seem to be significantly involved in secondary brain injury and outcome after primary ICH in humans, and thus should be further evaluated as targets for therapeutic strategies in this devastating disorder. (Stroke. 2013;44:658-663.)

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Section: March 2013mentioning

confidence: 81%

mentioning

confidence: 99%

Association of Molecular Markers With Perihematomal Edema and Clinical Outcome in Intracerebral Hemorrhage

Liu

et al. 2013

Stroke

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“…A prospective study on primary ICH patients has demonstrated that high serum levels of growth factors such as vascular endothelial growth factor, glanulocytecolony stimulating factor (G-CSF), and angiopoietin 1 are associated with good functional outcome and reduced lesion volume (62). With regard to G-CSF, daily intraperitoneal injection of this cytokine from 2 h after induction of ICH by collagenase in rats resulted in improved recovery from neurological deficits.…”

Section: Growth Factors and Cytokinesmentioning

confidence: 99%

Exploring Neuroprotective Drug Therapies for Intracerebral Hemorrhage

Katsuki

2010

J Pharmacol Sci

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Abstract. Intracerebral hemorrhage (ICH) is a devastating neurological disorder with high mortality and poor prognosis, for which virtually no effective drug therapies are available at present. Experimental animal models, based on intrastriatal injection of collagenase or autologous blood, have enabled great advances in elucidation of cellular/molecular events contributing to brain pathogenesis associated with ICH. Many lines of evidence indicate that blood constituents, including hemoglobin-derived products as well as proteases such as thrombin, play important roles in the pathogenic events. Inflammatory reactions involving neutrophils, activated microglia, and production of proinflammatory cytokines also constitute a critical aspect of pathology leading to neurodegeneration and tissue damage. Efforts are continuing to find drugs that potentially alleviate pathologi cal and neurological outcomes of ICH. Various drugs that possess antioxidative, antiinflammatory or neurotrophic/neuroprotective properties have been demonstrated to produce therapeutic effects on ICH animal models. Drugs already in clinical use such as minocycline, statins, and several nuclear receptor ligands are among the list of effective drugs, but whether they also show therapeutic efficacy in human ICH patients remains unproven. Here, current knowledge of ICH pathogenesis and problems arising with respect to exploration of new drug candidates are discussed.

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“…G-CSF was the only cytokine of 23 measured whose serum levels were elevated after traumatic brain injury in a murine model (Dohi et al, 2014). High levels of G-CSF are associated with better functional outcome and reduced lesion volume in intracranial hemorrhage (Sobrino et al, 2009). G-CSF is elevated 2 h after controlled cortical injury, but not at later time points in mice, which may make it useful in determining the timing of injury (Dohi et al, 2014).…”

Section: Granulocyte Colony Stimulating Factor (G-csf)mentioning

confidence: 98%

Blood biomarkers for evaluation of perinatal encephalopathy: state of the art

Graham

Everett

Delpech

et al. 2018

Current Opinion in Pediatrics

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Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products, and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the "liquid brain biopsy." A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.

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High Serum Levels of Growth Factors Are Associated with Good Outcome in Intracerebral Hemorrhage

Cited by 46 publications

References 25 publications

Association of Molecular Markers With Perihematomal Edema and Clinical Outcome in Intracerebral Hemorrhage

Association of Molecular Markers With Perihematomal Edema and Clinical Outcome in Intracerebral Hemorrhage

Exploring Neuroprotective Drug Therapies for Intracerebral Hemorrhage

Blood biomarkers for evaluation of perinatal encephalopathy: state of the art

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