White Matter Injury in Early Brain Injury after Subarachnoid Hemorrhage

Abstract

Subarachnoid hemorrhage (SAH) is a major cause of high morbidity, disability, and mortality in the field of neurovascular disease. Most previous SAH studies have focused on improving cerebral blood flow, reducing cerebral vasospasm, reducing neuronal calcium overload, and other treatments. While these studies showed exciting findings in basic science, therapeutic strategies based on the findings have not significantly improved neurological outcomes in patients with SAH. Currently, the only drug proven to effectively reduce the neurological defects of SAH patients is nimodipine. Current advances in imaging technologies in the field of stroke have confirmed that white matter injury (WMI) plays an important role in the prognosis of types of stroke, and suggests that WMI protection is essential for functional recovery and poststroke rehabilitation. However, WMI injury in relation to SAH has remained obscure until recently. An increasing number of studies suggest that the current limitations for SAH treatment are probably linked to overlooked WMI in previous studies that focused only on neurons and gray matter. In this review, we discuss the biology and functions of white matter in the normal brain, and discuss the potential pathophysiology and mechanisms of early brain injury after SAH. Our review demonstrates that WMI encompasses multiple substrates, and, therefore, more than one pharmacological approach is necessary to preserve WMI and prevent neurobehavioral impairment after SAH. Strategies targeting both neuronal injury and WMI may potentially provide a novel future for SAH knowledge and treatment.

Peroxisomal Dysfunction Contributes to White Matter Injury Following Subarachnoid Hemorrhage in Rats via Thioredoxin-Interacting Protein-Dependent Manner

“…Noteworthy, ROS-generating stimuli may potentiate the TXNIP/NLRP3 pathway by enhancing TXNIP transcription and expression. The underlying mechanisms of ROS-mediated TXNIP elevation may be dependent on MAPK, Forkhead box class O (FOXO), etc., (Nasoohi et al, 2018). Additionally, the accumulation of H 2 O 2 greatly increased the level of TXNIP (Zaragoza-Campillo and Moran, 2017), suggesting the potential association of TXNIP and peroxisome-mediated ROS.…”

“…TXNIP is an endogenous inhibitor of the thioredoxin (TRX) system, a major cellular thiol-reducing and antioxidant system (Xu et al, 2019). Recently, a significant body of literature has supported an essential role of TXNIP in the activation of the NLRP3-inflammasome and its downstream molecules (Nasoohi et al, 2018). Various endogenous and exogenous stimuli control TXNIP expression, including glucose, ER stress, oxidative stress, and AMPK.…”

Melatonin attenuates white matter injury in mice by reducing oligodendrocyte apoptosis after subarachnoid hemorrhage

“…Various pathophysiological changes, such as the mass effect of clot, increasing intracranial pressure, decompensation of cerebral autoregulation, spreading depolarization, BBB breakdown, release of toxic blood components, secondary inflammation, and cell death occur immediately after hemorrhage (13). These injuries contribute to poor neurological outcome(s); however, few studies have focused on WM injury after SAH (22). The effect of WM fiber injury on neurological deficits, consciousness, and memory after SAH may be overlooked due to induction of apoptosis in oligodendrocytes.…”

Irisin Contributes to Neuroprotection by Promoting Mitochondrial Biogenesis After Experimental Subarachnoid Hemorrhage

“…Notably, excessive oxidative stress could also trigger neuronal apoptosis, which is one of the common characteristics of EBI (Mo et al, 2019 ; Pang et al, 2019 ). As our previous study expounded, strategies to block oxidative stress-related pathways could improve the outcomes after SAH (Pang et al, 2018 ).…”