Secondary White Matter Injury and Therapeutic Targets After Subarachnoid Hemorrhage

Abstract

Aneurysmal subarachnoid hemorrhage (SAH) is one of the special stroke subtypes with high mortality and mobility. Although the mortality of SAH has decreased by 50% over the past two decades due to advances in neurosurgery and management of neurocritical care, more than 70% of survivors suffer from varying degrees of neurological deficits and cognitive impairments, leaving a heavy burden on individuals, families, and the society. Recent studies have shown that white matter is vulnerable to SAH, and white matter injuries may be one of the causes of long-term neurological deficits caused by SAH. Attention has recently focused on the pivotal role of white matter injury in the pathophysiological processes after SAH, mainly related to mechanical damage caused by increased intracerebral pressure and the metabolic damage induced by blood degradation and hypoxia. In the present review, we sought to summarize the pathophysiology processes and mechanisms of white matter injury after SAH, with a view to providing new strategies for the prevention and treatment of long-term cognitive dysfunction after SAH.

Early Brain Injury After Subarachnoid Hemorrhage: Incidence and Mechanisms

“…11,19 Active trials in SAH are still primarily focused on reducing DCI, and neglect therapeutic targets relating to EBI. 23,131 Prospective study targeting EBI will require substantial collaboration between translational scientists, experienced clinical investigators, and funding agencies. However, this is the clear next step to reduce the health care burden of SAH and improve patient outcomes.…”

White Matter Injury: An Emerging Potential Target for Treatment after Subarachnoid Hemorrhage

“…After SAH, WM is massively damaged, which not only causes various dysfunctions or disabilities but also causes dysfunction in the remote nerve projection area. By inhibiting or reducing WMI, it can limit the scope and extent of SAH and reduce clinical symptoms [ 7 ]. Measures to promote WM regeneration and remodeling are beneficial to functional recovery during the rehabilitation period.…”

Lipocalin-2-Mediated Insufficient Oligodendrocyte Progenitor Cell Remyelination for White Matter Injury After Subarachnoid Hemorrhage via SCL22A17 Receptor/Early Growth Response Protein 1 Signaling

“…Although WMIs have distinct etiologies, a shared neuropathological feature involves the failed differentiation of oligodendrocyte precursor cells (OPCs) into myelin-producing oligodendrocytes following injury, causing impaired myelin formation and regeneration (remyelination) [ 5 ]. Nevertheless, the mechanisms underlying this pathology have not been fully elucidated, as a comprehensive understanding of the inhibitory microenvironment that deters oligodendrocyte differentiation and regeneration is lacking; moreover, approved therapies are also lacking [ 6 , 7 ].…”