Neurovascular events after subarachnoid hemorrhage: focusing on subcellular organelles

Abstract

Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Early brain injury (EBI) and cerebral vasospasm (CVS) are the two most important pathophysiological mechanisms for brain injury and poor outcomes for patients with SAH. CVS has traditionally been considered the sole cause of delayed ischemic neurological deficits after SAH. However, the failure of antivasospastic therapy in patients with SAH supported changing the research target from CVS to other mechanisms. Currently, more attention has been focused on global brain injury within 3 days after ictus, designated as EBI. The dysfunction of subcellular organelles, such as endoplasmic reticulum stress, mitochondrial failure, and autophagy-lysosomal system activation, has developed during EBI and delayed brain injury after SAH. To our knowledge, there is a lack of review articles addressing the direction of organelle dysfunction after SAH. In this review, we discuss the roles of organelle dysfunction in the pathogenesis of SAH and present the opportunity to develop novel therapeutic strategies of SAH via modulating the functions of organelles.

Fig. 1

The functional disturbance of organelles in the pathogenesis of SAH. The components of the vascular neural network of the brain, including neurons, glia, endothelium, pericytes, vascular smooth muscle cells, and perivascular nerves, all suffer from SAH-induced injuries. The dysfunctions/functional alterations of the organelles that take place are in the transcription factors (e.g., Nrf2, NF-κB, and HIF-1), mitochondrial dysfunction, endoplasmic reticulum stress, and the autophagy–lysosomal system. These pathophysiologic cascades play a critical role in inflammation, apoptosis, necrosis, and autophagy in brain parenchyma after SAH