Early heparin administration after traumatic brain injury

Nagata, Katsuhiro; Browne, Kevin D.; Suto, Yujin; Kumasaka, Kenichiro; Cognetti, John S.; Johnson, Victoria E.; Marks, Joshua A.; Smith, Douglas H.; Pascual, José L.

doi:10.1097/ta.0000000000001590

Cited by 14 publications

(5 citation statements)

References 35 publications

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“…Nagata et al has shown that early administration of heparin is associated with a significant decrease in post-TBI inflammation and preservation of cognitive outcomes. These results were further supported by prior studies investigating the role of low-molecular weight fractionated heparin, enoxaparin ( 2 , 23 , 33 – 35 ). Human studies investigated the role of enoxaparin (low-molecular weight fractionated heparin) in aneurysmal SAH with mixed results ( 36 , 37 ).…”

Section: Neuroprotective Effects Of Heparin In Subarachnoid Hemorrhagsupporting

confidence: 76%

“…The accepted mechanism of action of leukocyte extravasation is through interaction of cell glycoproteins with the selectin family of proteins, generally expressed on endothelial cells ( 22 ). Heparin has been shown to specifically decrease the number of leukocytes participating in the inflammatory response to any insult to the central nervous system ( 23 , 24 ).…”

Section: Profile: Characteristics and Mechanism Of Actionmentioning

confidence: 99%

“…In addition to the transient ischemia state associated with SAH, significant vasogenic edema and blood–brain barrier dysfunction plague this patient population and represent a dismal prognostic factor ( 39 ). Heparin has been shown to counter cerebral edema in general in various pathological states including but not limited to TBI, meningitis, ischemia, and intracerebral hemorrhages ( 23 , 40 – 43 ). Various interactions in animal models have been reported between heparin and molecules specifically associated with cerebral edema (VEGF, bradykinin, etc.)…”

Section: Neuroprotective Effects Of Heparin In Subarachnoid Hemorrhagmentioning

confidence: 99%

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Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?

Khattar

James

2018

Front. Neurol.

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Various neurological diseases have recently been associated with neuroinflammation and worsening outcomes. Subarachnoid hemorrhage has been shown to generate a potent neuroinflammatory response. Heparin is a potential effective anti-inflammatory agent to prevent initial injury as well as delayed neurological decline. Different mechanisms of action for heparin have been proposed including, but not limited to the binding and neutralization of oxyhemoglobin, decreased transcription and signal transduction of endothelin-1, inhibition of binding to vessel wall selectins and vascular leakage into the subarachnoid space as well as direct binding and neutralization of inflammatory molecules. With a reasonably safe side-effect profile, heparin has shown significant promise in small series in human studies of aneurysmal subarachnoid hemorrhage in decreasing both initial and delayed neurological injury. Further studies are needed to validate various neuroprotective features of heparin in subarachnoid hemorrhage as well as other disease states.

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Section: Neuroprotective Effects Of Heparin In Subarachnoid Hemorrhagsupporting

confidence: 76%

Section: Profile: Characteristics and Mechanism Of Actionmentioning

confidence: 99%

Section: Neuroprotective Effects Of Heparin In Subarachnoid Hemorrhagmentioning

confidence: 99%

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Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?

Khattar

James

2018

Front. Neurol.

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“…In addition, increased expression of chemokines and chemokine receptors following TBI, including CXCL2, CXCR2, CCL2, CXCR4, and chemokine-like factor 1 (CKLF1), has been shown to further permeabilize the BBB [ 261 – 264 ] and attract neutrophils [ 265 , 266 ]. This causes a significant influx of peripheral immune cells into the brain following TBI, which has been found to worsen edema and neuronal damage [ 267 – 269 ].…”

Section: Acute Damage To the Brain Triggers Inflammation And Increasementioning

confidence: 99%

Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease

Newcombe

Camats-Perna

Silva

et al. 2018

J Neuroinflammation

423

302

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Alzheimer’s disease (AD) is a neurodegenerative disorder, most cases of which lack a clear causative event. This has made the disease difficult to characterize and, thus, diagnose. Although some cases are genetically linked, there are many diseases and lifestyle factors that can lead to an increased risk of developing AD, including traumatic brain injury, diabetes, hypertension, obesity, and other metabolic syndromes, in addition to aging. Identifying common factors and trends between these conditions could enhance our understanding of AD and lead to the development of more effective treatments. Although the immune system is one of the body’s key defense mechanisms, chronic inflammation has been increasingly linked with several age-related diseases. Moreover, it is now well accepted that chronic inflammation has an important role in the onset and progression of AD. In this review, the different inflammatory signals associated with AD and its risk factors will be outlined to demonstrate how chronic inflammation may be influencing individual susceptibility to AD. Our goal is to bring attention to potential shared signals presented by the immune system during different conditions that could lead to the development of successful treatments.

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“…Therefore, heparin has direct anti-inflammatory properties [158,159] linked to the binding of proinflammatory factors [160,161]. Heparin has been shown to specifically decrease the number of leukocytes participating in the inflammatory response to any insult occurring within the CNS [162,163]. In fact, UFH is a potent inhibitor of the adhesion molecules such as both leukocytes and endothelial cell selectins [164].…”

Section: Heparin and Sahmentioning

confidence: 99%

Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An “Heparin Oriented” Systematic Review

Tartara

Montalbetti

Crobeddu

et al. 2023

IJMS

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Subarachnoid hemorrhage (SAH) represents a severe acute event with high morbidity and mortality due to the development of early brain injury (EBI), secondary delayed cerebral ischemia (DCI), and shunt-related hydrocephalus. Secondary events (SSE) such as neuroinflammation, vasospasm, excitotoxicity, blood-brain barrier disruption, oxidative cascade, and neuronal apoptosis are related to DCI. Despite improvement in management strategies and therapeutic protocols, surviving patients frequently present neurological deficits with neurocognitive impairment. The aim of this paper is to offer to clinicians a practical review of the actually documented pathophysiological events following subarachnoid hemorrhage. To reach our goal we performed a literature review analyzing reported studies regarding the mediators involved in the pathophysiological events following SAH occurring in the cerebrospinal fluid (CSF) (hemoglobin degradation products, platelets, complement, cytokines, chemokines, leucocytes, endothelin-1, NO-synthase, osteopontin, matricellular proteins, blood-brain barrier disruption, microglia polarization). The cascade of pathophysiological events secondary to SAH is very complex and involves several interconnected, but also distinct pathways. The identification of single therapeutical targets or specific pharmacological agents may be a limited strategy able to block only selective pathophysiological paths, but not the global evolution of SAH-related events. We report furthermore on the role of heparin in SAH management and discuss the rationale for use of intrathecal heparin as a pleiotropic therapeutical agent. The combination of the anticoagulant effect and the ability to interfere with SSE theoretically make heparin a very interesting molecule for SAH management.

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Early heparin administration after traumatic brain injury

Cited by 14 publications

References 35 publications

Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?

Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?

Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease

Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An “Heparin Oriented” Systematic Review

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