High CSF transforming growth factor   levels after subarachnoid haemorrhage: association with chronic communicating hydrocephalus

Douglas, Michael E.; Daniel, Matija; Lagord, Catherine; Akinwunmi, James; Jackowski, A.; Cooper, Caroline; Berry, Martin; Logan, Ann

doi:10.1136/jnnp.2008.155671

Cited by 59 publications

(44 citation statements)

References 40 publications

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“…Interestingly, elevated levels of TGF-β 1 in the CSF of patients with SAH have already been reported in the literature [16,17,18], and are in line with our observations in the peripheral blood. Moreover, high CSF concentrations of TGF-β 1 were significantly associated with the development of chronic communicating hydrocephalus [16,17,18].…”

Section: Discussionsupporting

confidence: 81%

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Soluble Endoglin and Transforming Growth Factor-β<sub>1</sub> and the Development of Vasospasm after Spontaneous Subarachnoid Hemorrhage: A Pilot Study

et al. 2011

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Background:Cerebral vasospasm (CVS) and cerebral infarction due to vasospasm (CIV) are major complications after spontaneous subarachnoid hemorrhage (SAH). Alteration of vasomotor tone has been postulated as an important factor in the pathogenesis of CVS. Members of the transforming growth factor-β (TGF-β) family and their receptors have been implicated in the regulation of vascular tone. Methods:Serum levels of soluble endoglin (sEng) and plasma levels of TGF-β₁ of 20 consecutive SAH patients were analyzed within 15 days after SAH using ELISA and correlated with CVS, CIV and outcome. Twenty voluntary age- and sex-matched blood donors served as healthy controls (HCs). Results:SAH patients showed significantly lower sEng serum levels and higher TGF-β₁ plasma levels compared to HCs. Patients who developed Doppler sonographic CVS (dCVS) had significantly higher TGF-β₁ levels. Patients with CIV and patients with hydrocephalus showed significantly lower sEng levels. On day 3, pSAH sEng levels below 3.88 ng/ml or TGF-β₁ levels higher than 7.2 ng/ml had a predictive value for the development of CIV. Low mean sEng levels over the study period were highly predictive of poor long-term functional outcome (modified Rankin Scale ≧2) at 6 months after SAH. Conclusions:Concentrations of the vasoactive factors sEng in serum and TGF-β₁ in plasma are significantly altered in SAH patients compared to HCs. The results of this pilot study indicate that sEng could represent a novel prognostic biomarker for the onset of secondary complications and long-term functional outcome after SAH.

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Section: Discussionsupporting

confidence: 81%

“…Moreover, high CSF concentrations of TGF-β 1 were significantly associated with the development of chronic communicating hydrocephalus [16,17,18]. In our study, no association was found for development of hydrocephalus and TGF-β 1 values.…”

Section: Discussioncontrasting

confidence: 51%

Soluble Endoglin and Transforming Growth Factor-β<sub>1</sub> and the Development of Vasospasm after Spontaneous Subarachnoid Hemorrhage: A Pilot Study

et al. 2011

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“…In our experiment, TGF-b1 was not observed in the CSF in any of the four patient groups. Our results differ from previous serial analyses of TGF-b1 in patients after SAH [17,30]. These differences may be related to sampling time after SAH.…”

Section: Cytokines and Growth Factorscontrasting

confidence: 85%

Cytokine and Growth Factor Concentration in Cerebrospinal Fluid from Patients with Hydrocephalus Following Endovascular Embolization of Unruptured Aneurysms in Comparison with Other Types of Hydrocephalus

et al. 2010

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To better understand the development of hydrocephalus of different origins, we evaluated cytokine and growth factor concentration in cerebrospinal fluid from patients with hydrocephalus. CSF was collected from patients developing hydrocephalus following hemorrhage (n = 15), patients with normal pressure hydrocephalus (n = 10), and following the embolization of unruptured intracranial aneurysms (n = 9). Myelography patients (n = 15) served as controls. Quantification of 11 molecules relating angiogenesis, inflammation, and wound healing in the CSF was performed using ELISA. All three hydrocephalus groups had decreased concentration of TIMP-4 compared to the normal group. The hemorrhage group showed increased concentration of IL-6, IL-8, MCP-1, MMP-9, and TIMP-1 compared to the control group. The unruptured aneurysm group had increased concentration of IL-6 and decreased concentration of TIMP-2 compared to the control group. Compared to the normal patients, increased concentrations of wound healing molecules were evident in all three groups. Increased inflammation was evident in the hemorrhage and unruptured aneurysm groups.

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“…BMP7 [24], TGFb1 and 2 [25][26][27][28][29], PDGF-BB [30], NGF [31] FGF-2 [32,33] and TGF-a [34] have all been identified. Only in a few circumstances are their effects on leptomeningeal cells known.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3

et al. 2011

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The role of cerebrospinal fluid (CSF) in the pathogenesis of meningiomas is unknown. Cell cultures from three human leptomeninges, five WHO grade I and seven grade II meningiomas were treated with remnant CSF from 22 patients with no central nervous system disease and normal cell indices. Cells were evaluated by CyQUANT for DNA synthesis/cell proliferation and by western blots for phosphorylation/activation of growth regulatory pathways activated in meningiomas including JAK1-STAT3, MEK1-p44/42MAPK, Akt-mTOR and Rb. Analysis of Caspase 3 activation and survivin was also performed. Finally, the effects of PDGF neutralizing antibody and cucurbitacin, a STAT3 inhibitor on CSF stimulation were tested. Compared to controls and the mitogen PDGF-BB, various CSF samples significantly stimulated DNA synthesis/cell proliferation in 20 and 22 week leptomeningeal cultures and all of the grade I and II meningioma cells tested. Collectively CSF samples, from multiple different patients, stimulated DNA synthesis in tests of 23 of 32 grade I and 18 of 28 grade II meningioma cells. CSF stimulated phosphorylation/activation of STAT3 and reduced p44/42 MAPK in the leptomeningeal, all three grade I and 1 of three grade II meningioma cells. CSF did not affect Caspase 3 activity or survivin levels. PDGF neutralizing antibody had no effect on CSF stimulation but cucurbitacin blocked PDGF and CSF stimulation. While there are limitations to the CSF available since they were not from "normal" volunteers, the studies suggest that, in some settings, CSF is potentially mitogenic to leptomeningeal and meningioma cells and may act, in part, via activation of STAT3.

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High CSF transforming growth factor levels after subarachnoid haemorrhage: association with chronic communicating hydrocephalus

Abstract: Acutely measured levels of TGFbeta1/beta2 in the CSF of patients with subarachnoid haemorrhage are thus potential prognostic biomarkers for the subsequent development of chronic communicating hydrocephalus, indicating likely dependency on CSF shunting.

Cited by 59 publications

References 40 publications

Soluble Endoglin and Transforming Growth Factor-β<sub>1</sub> and the Development of Vasospasm after Spontaneous Subarachnoid Hemorrhage: A Pilot Study

Soluble Endoglin and Transforming Growth Factor-β<sub>1</sub> and the Development of Vasospasm after Spontaneous Subarachnoid Hemorrhage: A Pilot Study

Cytokine and Growth Factor Concentration in Cerebrospinal Fluid from Patients with Hydrocephalus Following Endovascular Embolization of Unruptured Aneurysms in Comparison with Other Types of Hydrocephalus

Cerebrospinal fluid stimulates leptomeningeal and meningioma cell proliferation and activation of STAT3

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