Procollagen propeptides in chronic subdural hematoma reveal sustained dural collagen synthesis after head injury

Heula, Anna-Leena; Sajanti, Juha; Majamaa, Kari

doi:10.1007/s00415-009-0048-6

Cited by 18 publications

(14 citation statements)

References 23 publications

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“…High concentrations of type 1 (PICP) and type 3 (PIIINP) procollagen are present in this fluid and suggest a fibro-proliferative process is occurring, similar to that seen in wound healing [16, 17]. This process is likely to be initiated when the dural border cells are separated, and is an attempt at a reparative process.…”

Section: Introductionmentioning

confidence: 78%

“…This process is likely to be initiated when the dural border cells are separated, and is an attempt at a reparative process. However, the collagen synthesis outweighs its breakdown, leading to the continuous formation of a collagen matrix and hence formation of the new membranes [17]. The SMAD signalling pathway is an important mediator of the persistent fibrosis which contributes to membrane development, and is activated by transforming growth factor (TGF-β1), expressed by eosinophils [18].…”

Section: Introductionmentioning

confidence: 99%

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Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy

Edlmann

Giorgi-Coll

Whitfield

et al. 2017

J Neuroinflammation

417

360

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Chronic subdural haematoma (CSDH) is an encapsulated collection of blood and fluid on the surface of the brain. Historically considered a result of head trauma, recent evidence suggests there are more complex processes involved. Trauma may be absent or very minor and does not explain the progressive, chronic course of the condition. This review focuses on several key processes involved in CSDH development: angiogenesis, fibrinolysis and inflammation. The characteristic membrane surrounding the CSDH has been identified as a source of fluid exudation and haemorrhage. Angiogenic stimuli lead to the creation of fragile blood vessels within membrane walls, whilst fibrinolytic processes prevent clot formation resulting in continued haemorrhage. An abundance of inflammatory cells and markers have been identified within the membranes and subdural fluid and are likely to contribute to propagating an inflammatory response which stimulates ongoing membrane growth and fluid accumulation. Currently, the mainstay of treatment for CSDH is surgical drainage, which has associated risks of recurrence requiring repeat surgery. Understanding of the underlying pathophysiological processes has been applied to developing potential drug treatments. Ongoing research is needed to identify if these therapies are successful in controlling the inflammatory and angiogenic disease processes leading to control and resolution of CSDH.

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Section: Introductionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy

Edlmann

Giorgi-Coll

Whitfield

et al. 2017

J Neuroinflammation

417

360

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show abstract

“…subarachnoid hemorrhage) which, in humans, as in the intrathecal mass observed in guinea pig and dog, is composed of Types 1 and 3 collagen. 8,35,36 The mass presents as a progressive expansion from the catheter outwards with less mature (newly created) collagen observed proximal to the catheter and mature collagen present in the outer margins. 8 Sequential MRIs in dogs receiving morphine infusion revealed a time-dependent enlargement of the mass.…”

Section: Intrathecal Massmentioning

confidence: 99%

Mast Cell Degranulation and Fibroblast Activation in the Morphine-induced Spinal Mass

et al. 2019

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Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background As the meningeally derived, fibroblast-rich, mass-produced by intrathecal morphine infusion is not produced by all opiates, but reduced by mast cell stabilizers, the authors hypothesized a role for meningeal mast cell/fibroblast activation. Using the guinea pig, the authors asked: (1) Are intrathecal morphine masses blocked by opiate antagonism?; (2) Do opioid agonists not producing mast cell degranulation or fibroblast activation produce masses?; and (3) Do masses covary with Mas-related G protein-coupled receptor signaling thought to mediate mast cell degranulation? Methods In adult male guinea pigs (N = 66), lumbar intrathecal catheters connected to osmotic minipumps (14 days; 0.5 µl/h) were placed to deliver saline or equianalgesic concentrations of morphine sulfate (33 nmol/h), 2’,6’-dimethyl tyrosine-(Tyr-D-Arg-Phe-Lys-NH2) (abbreviated as DMT-DALDA; 10 pmol/h; μ agonist) or PZM21 (27 nmol/h; biased μ agonist). A second pump delivered subcutaneous naltrexone (25 µg/h) in some animals. After 14 to 16 days, animals were anesthetized and perfusion-fixed. Drug effects on degranulation of human cultured mast cells, mouse embryonic fibroblast activation/migration/collagen formation, and Mas-related G protein-coupled receptor activation (PRESTO-Tango assays) were determined. Results Intrathecal infusion of morphine, DMT-DALDA or PZM21, but not saline, comparably increased thermal thresholds for 7 days. Spinal masses proximal to catheter tip, composed of fibroblast/collagen type I (median: interquartile range, 0 to 4 scale), were produced by morphine (2.3: 2.0 to 3.5) and morphine plus naltrexone (2.5: 1.4 to 3.1), but not vehicle (1.2: 1.1 to 1.5), DMT-DALDA (1.0: 0.6 to 1.3), or PZM21 (0.5: 0.4 to 0.8). Morphine in a naloxone-insensitive fashion, but not PZM21 or DMT-DALDA, resulted in mast cell degranulation and fibroblast proliferation/collagen formation. Morphine-induced fibroblast proliferation, as mast cell degranulation, is blocked by cromolyn. Mas-related G protein-coupled receptor activation was produced by morphine and TAN67 (∂-opioid agonist), but not by PZM21, TRV130 (mu biased ligand), or DMT-DALDA. Conclusions Opiates that activate Mas-related G protein-coupled receptor will degranulate mast cells, activate fibroblasts, and result in intrathecal mass formation. Results suggest a mechanistically rational path forward to safer intrathecal opioid therapeutics.

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“…Hypercoagulative and hyperfibrinolytic activities are enhanced after head injury and this may cause CSDH [11]. Additionally, the levels of TNF-a, IL-1b, IL-6, IL-8, IL-10 and procollagen propeptides are significantly increased during CSDH formation [12][13][14]. The pathological process of SDE and CSDH indicates that local inflammation plays a leading role in the pathogenesis of the evolution and propagation of CSDH [15].…”

Section: Discussionmentioning

confidence: 99%

Surgical management of the patients with chronic subdural haematoma and contralateral subdural effusion: Operation or no-operation?

Wang

Zhao

Li³

et al. 2015

Brain Injury

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Procollagen propeptides in chronic subdural hematoma reveal sustained dural collagen synthesis after head injury

Cited by 18 publications

References 23 publications

Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy

Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy

Mast Cell Degranulation and Fibroblast Activation in the Morphine-induced Spinal Mass

Surgical management of the patients with chronic subdural haematoma and contralateral subdural effusion: Operation or no-operation?

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