Microvascular platelet aggregation and thrombosis after subarachnoid hemorrhage: A review and synthesis

Clarke, Julian V.; Suggs, Julia M; Diwan, Deepti; Lee, Jin Vivian; Lipsey, Kim; Vellimana, Ananth K.; Zipfel, Gregory J.

doi:10.1177/0271678x20921974

Cited by 39 publications

(39 citation statements)

References 84 publications

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“…Some clinical evidence shows that the increase of neutrophils in CSF indicates vascular injury and may be an independent predictor of vasospasm, indicating the risk of DCI ( 33 , 34 ). Further studies have found additional pathogenic mechanisms, such as EBI and apoptosis, destruction of the BBB ( 35 ), micro thromboembolism ( 36 ), and cortical diffuse depolarization ( 37 ), which are more or less linked to inflammation.…”

Section: Pathophysiological Mechanismmentioning

confidence: 99%

The Role of the Blood Neutrophil-to-Lymphocyte Ratio in Aneurysmal Subarachnoid Hemorrhage

et al. 2021

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Aneurysmal subarachnoid hemorrhage (aSAH) is an important type of stroke with the highest rates of mortality and disability. Recent evidence indicates that neuroinflammation plays a critical role in both early brain injury and delayed neural deterioration after aSAH, contributing to unfavorable outcomes. The neutrophil-to-lymphocyte ratio (NLR) is a peripheral biomarker that conveys information about the inflammatory burden in terms of both innate and adaptive immunity. This review summarizes relevant studies that associate the NLR with aSAH to evaluate whether the NLR can predict outcomes and serve as an effective biomarker for clinical management. We found that increased NLR is valuable in predicting the clinical outcome of aSAH patients and is related to the risk of complications such as delayed cerebral ischemia (DCI) or rebleeding. Combined with other indicators, the NLR provides improved accuracy for predicting prognosis to stratify patients into different risk categories. The underlying pathophysiology is highlighted to identify new potential targets for neuroprotection and to develop novel therapeutic strategies.

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Section: Pathophysiological Mechanismmentioning

confidence: 99%

The Role of the Blood Neutrophil-to-Lymphocyte Ratio in Aneurysmal Subarachnoid Hemorrhage

et al. 2021

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“…Multiple neurovascular features have been implicated in DCI pathophysiology [4,5]. Relative to large-vessel vasospasm, the phenomenon of microvascular thrombus formation has been a recent addition to our understanding of DCI [37]. While a protective role against microvessel thrombosis in a DCI-specific setting has been proposed for isoflurane conditioning [12,15], our findings with sevoflurane and desflurane provide novel evidence that inhalational anesthetics as a class might be able to protect against DCI-associated microvessel thrombosis.…”

Section: Anesthetic Conditioning and Microvessel Thrombosismentioning

confidence: 66%

“…While a protective role against microvessel thrombosis in a DCI-specific setting has been proposed for isoflurane conditioning [12,15], our findings with sevoflurane and desflurane provide novel evidence that inhalational anesthetics as a class might be able to protect against DCI-associated microvessel thrombosis. While multiple features of the thrombus-forming cascade have been identified and proposed [37], it remains unclear as to how these inhalational anesthetics might be exerting their effects on the cerebral microvasculature. Further preclinical studies aiming to elucidate how the different anesthetic agents are acting at the molecular level will enable the discovery of novel targets for DCI therapeutics and enable a more practical understanding of microvessel thrombosis.…”

Section: Anesthetic Conditioning and Microvessel Thrombosismentioning

confidence: 99%

Sevoflurane and Desflurane Exposures Following Aneurysmal Subarachnoid Hemorrhage Confer Multifaceted Protection against Delayed Cerebral Ischemia

et al. 2021

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Numerous studies have demonstrated the ability of isoflurane conditioning to provide multifaceted protection against aneurysmal subarachnoid hemorrhage (SAH)-associated delayed cerebral ischemia (DCI); however, preclinical studies have not yet examined whether other commonly used inhalational anesthetics in neurological patients such as sevoflurane or desflurane are also protective against SAH-induced neurovascular deficits. We therefore sought to identify the potential for sevoflurane and desflurane conditioning to protect against DCI in an endovascular perforation mouse model of SAH. Neurological function was assessed daily via neuroscore. Large artery vasospasm and microvessel thrombosis were assessed three days after SAH or sham surgery. Four groups were examined: Sham, SAH + room air, SAH + 2% Sevoflurane, and SAH + 6% Desflurane. For the SAH groups, one hour after surgery, mice received 2% sevoflurane, 6% desflurane, or room air for one hour. We found that conditioning with sevoflurane or desflurane attenuated large artery vasospasm, reduced microvessel thrombosis, and improved neurologic function. Given their frequent clinical use and strong safety profile in patients (including those with SAH), these data strongly support further studies to validate these findings in preclinical and clinical studies and to elucidate the mechanisms by which these agents might be acting.

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“…Microvascular thrombi formation has been found in autopsy studies in the brain of SAH patients [131,132] and experimental animal models of SAH [133,134]. Microthrombi are defined as histological finding of platelet plugs with fibrinogen/fibrin deposition with the arterioles and capillaries of brain [135], which begin to form just 10 min after SAH [136]. By 24 h after rats' SAH induction, ventricular dilation and white matter injury are found on MRI [134].…”

Section: Thrombin In Subarachnoid Hemorrhagementioning

confidence: 99%

The Role of Thrombin in Brain Injury After Hemorrhagic and Ischemic Stroke

Garton

Hua

et al. 2020

Transl. Stroke Res.

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Thrombin is increased in the brain after hemorrhagic and ischemic stroke primarily due to the prothrombin entry from blood either with a hemorrhage or following blood-brain barrier disruption. Increasing evidence indicates that thrombin and its receptors (protease-activated receptors (PARs)) play a major role in brain pathology following ischemic and hemorrhagic stroke (including intracerebral, intraventricular, and subarachnoid hemorrhage). Thrombin and PARs affect brain injury via multiple mechanisms that can be detrimental or protective. The cleavage of prothrombin into thrombin is the key step of hemostasis and thrombosis which takes place in every stroke and subsequent brain injury. The extravascular effects and direct cellular interactions of thrombin are mediated by PARs (PAR-1, PAR-3, and PAR-4) and their downstream signaling in multiple brain cell types. Such effects include inducing blood-brain-barrier disruption, brain edema, neuroinflammation, and neuronal death, although low thrombin concentrations can promote cell survival. Also, thrombin directly links the coagulation system to the immune system by activating interleukin-1α. Such effects of thrombin can result in both short-term brain injury and longterm functional deficits, making extravascular thrombin an understudied therapeutic target for stroke. This review examines the role of thrombin and PARs in brain injury following hemorrhagic and ischemic stroke and the potential treatment strategies which are complicated by their role in both hemostasis and brain.

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Microvascular platelet aggregation and thrombosis after subarachnoid hemorrhage: A review and synthesis

Cited by 39 publications

References 84 publications

The Role of the Blood Neutrophil-to-Lymphocyte Ratio in Aneurysmal Subarachnoid Hemorrhage

The Role of the Blood Neutrophil-to-Lymphocyte Ratio in Aneurysmal Subarachnoid Hemorrhage

Sevoflurane and Desflurane Exposures Following Aneurysmal Subarachnoid Hemorrhage Confer Multifaceted Protection against Delayed Cerebral Ischemia

The Role of Thrombin in Brain Injury After Hemorrhagic and Ischemic Stroke

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