The blood–brain barrier and the neurovascular unit in subarachnoid hemorrhage: molecular events and potential treatments

Abstract

The response of the blood–brain barrier (BBB) following a stroke, including subarachnoid hemorrhage (SAH), has been studied extensively. The main components of this reaction are endothelial cells, pericytes, and astrocytes that affect microglia, neurons, and vascular smooth muscle cells. SAH induces alterations in individual BBB cells, leading to brain homeostasis disruption. Recent experiments have uncovered many pathophysiological cascades affecting the BBB following SAH. Targeting some of these pathways is important for restoring brain function following SAH. BBB injury occurs immediately after SAH and has long-lasting consequences, but most changes in the pathophysiological cascades occur in the first few days following SAH. These changes determine the development of early brain injury as well as delayed cerebral ischemia. SAH-induced neuroprotection also plays an important role and weakens the negative impact of SAH. Supporting some of these beneficial cascades while attenuating the major pathophysiological pathways might be decisive in inhibiting the negative impact of bleeding in the subarachnoid space. In this review, we attempt a comprehensive overview of the current knowledge on the molecular and cellular changes in the BBB following SAH and their possible modulation by various drugs and substances.

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

“… 73 Many recent experiments have discovered many pathophysiological mechanisms that deteriorate the BBB after SAH, and alleviating these cascades might be decisive in inhibiting the negative impact of bleeding in the subarachnoid space. 74 Free haem, released through haemolysis, is bound by haemopexin and rapidly scavenged by CD91. It was reported that CSF haemopexin significantly increased and was associated with iron deposition in brain tissue and poorer neurological outcome in SAH patients, and more interestingly, the serum haemopexin level was lower when the BBB was compromised after SAH.…”

Blood-Brain Barrier Alterations and Edema Formation in Different Brain Mass Lesions

“…The main cellular components of BBB are endothelial cells (ECs), astrocytes, and pericytes (Ballabh et al, 2004). Endothelial cells line the vascular lumen and are connected at the molecular level by different junctional protein complexes such as tight junctions (TJ), adherent junctions (AJ), and gap junctions (Begley and Brightman, 2003;Solár et al, 2022). TJs are located between endothelial cells and consist of transmembrane proteins, including occludin, claudin, junctional adhesion molecule (JAM) as well as cytoplasmatic proteins that anchor transmembrane proteins to the cytoskeleton of endothelial cells (Stamatovic et al, 2016).…”

The glymphatic system and subarachnoid hemorrhage: disruption and recovery

“…The drugs covered here represent treatments that have a history of clinical use and have also been found to influence glymphatic function in the context of SAH models. While many drugs have been explored to address the pathology seen in SAH, few have seen clinical use in this context and fewer have been explored for their influence on the GS [ 87 ]. As previously outlined, GS dysfunction seen in SAH is associated with subsequent neurological deficits and therefore is an important target in recovery from SAH.…”