An Assessment of Early Platelet Activity in Experimental Subarachnoid Hemorrhage and Middle Cerebral Artery Thrombosis in the Cat

Denton, Ira C.; Robertson, James T.; Dugdale, Marion

doi:10.1161/01.str.2.3.268

Cited by 25 publications

(5 citation statements)

References 13 publications

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“…Experimental and clinical studies indicate that platelets activate early after aSAH (Clower et al , 1988; Denton et al , 1971; Haining et al , 1988; Hirashima et al , 2005; Ishikawa et al , 2009; Sehba et al , 2005; Stein et al , 2006a). Reduction in venous jugular platelet counts and shape change indicating sequestration and activation is observed 5 minutes after experimental (Denton et al , 1971), and 48 hours after clinical aSAH (Hirashima et al , 2005).…”

Section: Early Events After Asahmentioning

confidence: 99%

“…Reduction in venous jugular platelet counts and shape change indicating sequestration and activation is observed 5 minutes after experimental (Denton et al , 1971), and 48 hours after clinical aSAH (Hirashima et al , 2005). Moreover, platelet aggregates are found lodged in major cerebral arteries at 2 hours (Clower et al , 1988; Haining et al , 1988), and in the parenchymal vessels 10 minutes after experimental aSAH (Ishikawa et al , 2009; Sehba et al , 2005).…”

Section: Early Events After Asahmentioning

confidence: 99%

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The importance of early brain injury after subarachnoid hemorrhage

Sehba

Hou

Pluta

et al. 2012

Progress in Neurobiology

492

392

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Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency that accounts for 5% of all stroke cases. Individuals affected are typically in the prime of their lives (mean age 50 years). Approximately 12% of patients die before receiving medical attention, 33% within 48 hours and 50% within 30 days of aSAH. Of the survivors 50% suffer from permanent disability with an estimated lifetime cost more than double that of an ischemic stroke. Traditionally, spasm that develops in large cerebral arteries 3-7 days after aneurysm rupture is considered the most important determinant of brain injury and outcome after aSAH. However, recent studies show that prevention of delayed vasospasm does not improve outcome in aSAH patients. This finding has finally brought in focus the influence of early brain injury on outcome of aSAH. A substantial amount of evidence indicates that brain injury begins at the aneurysm rupture, evolves with time and plays an important role in patients’ outcome. In this manuscript we review early brain injury after aSAH. Due to the early nature, most of the information on this injury comes from animals and few only from autopsy of patients who died within days after aSAH. Consequently, we began with a review of animal models of early brain injury, next we review the mechanisms of brain injury according to the sequence of their temporal appearance and finally we discuss the failure of clinical translation of therapies successful in animal models of aSAH.

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Section: Early Events After Asahmentioning

confidence: 99%

Section: Early Events After Asahmentioning

confidence: 99%

The importance of early brain injury after subarachnoid hemorrhage

Sehba

Hou

Pluta

et al. 2012

Progress in Neurobiology

492

392

View full text Add to dashboard Cite

show abstract

“…A reduction in venous jugular platelet count and shape change indicating sequestration and activation is observed 5 min after SAH in animals and 48 h after ictus in SAH patients [91, 92]. Furthermore, platelet aggregates in the lumen of small cerebral vessels are found within 10 min after SAH in animals [62] and within 2 days after SAH in human autopsy studies [8].…”

Section: Early Brain Injury By Sahmentioning

confidence: 99%

Metamorphosis of Subarachnoid Hemorrhage Research: from Delayed Vasospasm to Early Brain Injury

2010

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Delayed vasospasm that develops 3–7 days after aneurysmal subarachnoid hemorrhage (SAH) has traditionally been considered the most important determinant of delayed ischemic injury and poor outcome. Consequently, most therapies against delayed ischemic injury are directed towards reducing the incidence of vasospasm. The clinical trials based on this strategy, however, have so far claimed limited success; the incidence of vasospasm is reduced without reduction in delayed ischemic injury or improvement in the long-term outcome. This fact has shifted research interest to the early brain injury (first 72 h) evoked by SAH. In recent years, several pathological mechanisms that activate within minutes after the initial bleed and lead to early brain injury are identified. In addition, it is found that many of these mechanisms evolve with time and participate in the pathogenesis of delayed ischemic injury and poor outcome. Therefore, a therapy or therapies focused on these early mechanisms may not only prevent the early brain injury but may also help reduce the intensity of later developing neurological complications. This manuscript reviews the pathological mechanisms of early brain injury after SAH and summarizes the status of current therapies.

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“…Markers of hypercoagulation, (Antovic et al, 2002; Peltonen et al, 1997) and platelet activation (Denton et al, 1971; Ishikawa et al, 2009; Juvela et al, 1991) rapidly increase following aneurysm rupture; values are higher in the CSF and jugular blood compared to systemic levels, suggesting a cerebral origin (Hirashima et al, 1997; Kasuya et al, 1998; Suzuki et al, 1999). In addition, several autopsy studies have detected the presence of small intra-vascular blood clots, termed microclots, and have demonstrated a correlation between microclot density and the location and severity of histological evidence of ischemia (Stein et al, 2006b) or radiographic evidence of infarction (Suzuki et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Microthrombosis after experimental subarachnoid hemorrhage: Time course and effect of red blood cell-bound thrombin-activated pro-urokinase and clazosentan

Pisapia

Kelly

et al. 2012

Experimental Neurology

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Delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality for patients surviving the rupture of an intracranial aneurysm. Despite an association between vasospasm and DCI, thrombosis and thromboembolism may also contribute to DCI. In this study we investigate the time course of intravascular microclot formation after experimental subarachnoid hemorrhage (SAH) and assess the effects of the following two drugs on microclot burden: mutant thrombin-activated urokinase-type plasminogen activator (scFv/uPA-T), which is bound to red blood cells for use as a thromboprophylactic agent, and clazosentan, an endothelin antagonist. In the first study, adult male C57BL/6 mice were sacrificed at 24 (n=5), 48 (n=6), 72 (n=8), and 96 (n=3) hours after SAH induced by filament perforation of the anterior cerebral artery. Sham animals (n=5) underwent filament insertion without puncture. In the second study, animals received scFv/uPA-T (n=5) 3 hours after hemorrhage, clazosentan (n=5) by bolus and subcutaneous pump after SAH just prior to skin closure, or a combination of scFv/uPA-T and clazosentan (n=4). Control (n=6) and sham (n=5) animals received saline alone. All animals were sacrificed at 48 hours and underwent intra-cardiac perfusion with 4% paraformaldehyde. The brains were then extracted and sliced coronally on a cryostat and processed for immunohistochemistry. An antibody recognizing thrombin–anti-thrombin complexes was used to detect microclots on coronal slices. Microclot burden was calculated for each animal and compared among groups. Following SAH, positive anti-thrombin staining was detected bilaterally in the following brain regions, in order of decreasing frequency: cortex; hippocampus; hypothalamus; basal ganglia. Few microclots were found in the shams. Microclot burden peaked at 48 hours and then decreased gradually. Animals receiving scFv/uPA-T and scFv/uPA-T+clazosentan had a lower microclot burden than controls, whereas animals receiving clazosentan alone had a higher microclot burden (p<0.005). The overall mortality rate in the time course study was 40%; mortality was highest among control animals in the second study. Intravascular microclots form in a delayed fashion after experimental SAH. Microclots may be safely reduced using a novel form of thromboprophylaxis provided by RBC-targeted scFv/uPA-T and represent a potential target for therapeutic intervention in the treatment of DCI.

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An Assessment of Early Platelet Activity in Experimental Subarachnoid Hemorrhage and Middle Cerebral Artery Thrombosis in the Cat

Cited by 25 publications

References 13 publications

The importance of early brain injury after subarachnoid hemorrhage

The importance of early brain injury after subarachnoid hemorrhage

Metamorphosis of Subarachnoid Hemorrhage Research: from Delayed Vasospasm to Early Brain Injury

Microthrombosis after experimental subarachnoid hemorrhage: Time course and effect of red blood cell-bound thrombin-activated pro-urokinase and clazosentan

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