Fluid metabolic pathways after subarachnoid hemorrhage

Abstract

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating cerebrovascular disease with high mortality and morbidity. In recent years, a large number of studies have focused on the mechanism of early brain injury (EBI) and delayed cerebral ischemia (DCI), including vasospasm, neurotoxicity of hematoma and neuroinflammatory storm, after aSAH. Despite considerable efforts, no novel drugs have significantly improved the prognosis of patients in phase III clinical trials, indicating the need to further re‐examine the multifactorial pathophysiological process that occurs after aSAH. The complex pathogenesis is reflected by the destruction of the dynamic balance of the energy metabolism in the nervous system after aSAH, which prevents the maintenance of normal neural function. This review focuses on the fluid metabolic pathways of the central nervous system (CNS), starting with ruptured aneurysms, and discusses the dysfunction of blood circulation, cerebrospinal fluid (CSF) circulation and the glymphatic system during disease progression. It also proposes a hypothesis on the metabolic disorder mechanism and potential therapeutic targets for aSAH patients. Cover Image for this issue: https://doi.org/10.1111/jnc.15384.

Treatment effect of DNA framework nucleic acids on diffuse microvascular endothelial cell injury after subarachnoid hemorrhage

“… 2 , 3 The monolayer endothelial cells of the cerebral arterioles, also known as brain microvascular endothelial cells (BMECs), are vulnerable to injury due to the presence of anatomically weak vessel structures that lack elastic intima and smooth muscles in the media layer. 4 , 5 Studies have revealed that diffuse injury to the BMECs induced by cytotoxic metabolites of erythrocytes in the CSF is an important pathological change after SAH. 6 As a trigger of “secondary brain injury” after SAH, diffuse BMEC injury is related to dysfunction of the BBB, an increased risk of cerebral vasospasm and delayed cerebral ischemia, which lead to poor prognosis in patients with SAH.…”

“…Generally caused by intracranial aneurysm (IA) rupture, SAH is characterized by diffuse distribution of blood in the subarachnoid space, in which the cerebral microvascular bed is immersed in cerebrospinal fluid (CSF) containing cytotoxic metabolites of blood components 2,3 . The monolayer endothelial cells of the cerebral arterioles, also known as brain microvascular endothelial cells (BMECs), are vulnerable to injury due to the presence of anatomically weak vessel structures that lack elastic intima and smooth muscles in the media layer 4,5 . Studies have revealed that diffuse injury to the BMECs induced by cytotoxic metabolites of erythrocytes in the CSF is an important pathological change after SAH 6 .…”

“Atypical” Mild Clinical Presentation in Elderly Patients With Ruptured Intracranial Aneurysm: Causes and Clinical Characteristics

“…For patients with brain atrophy, we believe due to decreased adhesion connecting lesions to surrounding tissues and the surrounding lower intracranial pressure (ICP) (25), aneurysms might be more prone to rupture with a sudden fluctuation of blood pressure. In addition, the enlarged subarachnoid space and lower ICP outside the lesion make formation of a localized hematoma difficult, which could be an important factor related to the hemostatic effect in the acute phase after SAH (26). Moreover, due to brain atrophy, bleeding is more likely to spread diffusely in the subarachnoid space on the surface of brain tissues, which could be a major contributor to the high Fisher grade after aneurysm rupture in this age group (27).…”

Rethinking the initial changes in subarachnoid haemorrhage: Focusing on real-time metabolism during early brain injury

“…As we previously proposed and reviewed, 19 there are three steps of microcirculation disturbance after SAH: microcirculation compensation, decompensation and irreversible phases. After microvasospasms in the compensation period, platelet aggregation 20 and leukocyte plugging 21 in capillaries cause microcirculatory dysfunction in the decompensation phase.…”

“…16 In addition, free iron (Fe 3+ ) released from haemolytic red blood cells is also involved in arteriolar and capillary microvasospasms after SAH in mice, 17 while iron deposits in the cortex have been reported to be associated with cognitive outcomes in SAH patients. 18 As we previously proposed and reviewed, 19 there are three steps of microcirculation disturbance after SAH: microcirculation compensation, decompensation and irreversible phases. After microvasospasms in the compensation period, platelet aggregation 20 and leukocyte plugging 21 in capillaries cause microcirculatory dysfunction in the decompensation phase.…”