The Updated Role of the Blood Brain Barrier in Subarachnoid Hemorrhage: From Basic and Clinical Studies

Abstract

: Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke associated with high mortality and morbidity. The blood-brain-barrier (BBB) is a structure consisting primarily of cerebral microvascular endothelial cells, end feet of astrocytes, extracellular matrix, and pericytes. Post-SAH pathophysiology included early brain injury and delayed cerebral ischemia. BBB disruption was a critical mechanism of early brain injury, and was associated with other pathophysiological events. These pathophysiological events may propel the development of secondary brain injury, known as delayed cerebral ischemia. Imaging advancements to measure BBB after SAH primarily focused on exploring innovative methods to predict clinical outcome, delayed cerebral ischemia, and delayed infarction related to delayed cerebral ischemia in acute periods. These predictions are based on detecting abnormal changes in BBB permeability. The parameters of BBB permeability are described by changes in computed tomography (CT) perfusion and magnetic resonance imaging (MRI). Kep seems to be a stable and sensitive indicator in CT perfusion, whereas Ktrans is a reliable parameter for dynamic contrast-enhanced MRI. Future prediction models that utilize both the volume of BBB disruption and stable parameters of BBB may be a promising direction to develop practical clinical tools. These tools could provide greater accuracy in predicting clinical outcome and risk of deterioration. Therapeutic interventional exploration targeting BBB disruption is also promising, considering the extended duration of post-SAH BBB disruption.

Elevated concentrations of macrophage migration inhibitory factor in serum and cerebral microdialysate are associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

“…Furthermore, we found a significant positive correlation between serum and CSF MIF levels during EP d1−4 (Figure 1B), possibly indicating that intrathecal MIF release could be involved in the acute elevation of circulating MIF after aSAH. Thus, assuming a physiological serum concentration of 6-10 ng/ml (17,28), a pathological CSF concentration of 30 ng/ml, and a 1:10 dilution after CSF flow into venous blood (30), the early serum levels of 12.2 [8.7-16.4] ng/ml we observed could well be accounted for by CSF-related changes of MIF concentrations in blood, especially given that early impairments of blood-brain-and blood-CSF-barrier are well-known features of aSAH (31,32), which could be further aggravated by MIF itself (33). The fact that after stratification based on outcome, a significant correlation was only observed in patients with poor clinical outcome (as shown in the Supplementary material) is in line with this assumption, since early blood-brain-barrier dysfunction has been shown to predict neurological outcomes after aSAH (34).…”

A new perspective on cerebrospinal fluid dynamics after subarachnoid hemorrhage: From normal physiology to pathophysiological changes

“…20 Besides, both acute and chronic pathological changes after SAH are associated with the CSF dynamic disorder that involves CSF production, movement, and drainage. A plethora of studies report pathological impairment found in the choroid plexus, 82 BBB, 83 arachnoid granulations, 84 lymphatic, 85 and glymphatic system, 17 which may be related to post-SAH blood clearance. (Figure 3)…”

Therapeutic Effect of Mitochondrial Division Inhibitor-1 (Mdivi-1) on Hyperglycemia-Exacerbated Early and Delayed Brain Injuries after Experimental Subarachnoid Hemorrhage

“…One of the critical mechanisms of early brain injury is the disruption of the blood-brain barrier (BBB), a structure that primarily consist of cerebral microvascular endothelial cells, astrocytic endfeet, an extracellular matrix, and pericytes [7]. Loss of BBB integrity results in the direct exposure of the brain tissues to neurotoxic blood contents and immune cells, which leads to secondary brain insults, including inflammation and oxidative stress, as well as other cascades [8].…”