Glymphatic system and intracerebral hemorrhage: Identifying molecular targets for future therapeutic advancements

Abstract

The glymphatic system is an essential component in modulating brain health and clearing out toxins from the central nervous system (CNS). The glymphatic system, especially the perivascular space, undergoes significant alterations during CNS inflammation. Various cerebrovascular disorders have implicated glymphatic dysfunction as the major contributing factor for cerebral edema, neuroinflammation, as well as damage to the blood-brain barrier (BBB). Intracerebral hemorrhage (ICH) is a major life-threatening stroke subtype with limited therapies available. ICH results from the rupture of cerebral arteries, accumulation of the blood and hematoma formation in the brain parenchyma. The toxic degradation components from the hematoma further exacerbates the oxidative stress, inflammatory response and cerebral edema, worsening the BBB disruption as well as the neurological outcomes post-ICH. Thus, making it imperative to understand the underlying mechanisms of secondary brain injury (SBI) and create targeted therapeutic strategies to improve patient recovery. Owing to the involvement of the glymphatic system in clearing out debris, it may contribute in alleviating SBI following ICH. In this review we intend to gain a better understanding of the glymphatic system’s role in mitigating SBI as well as potential therapeutic approaches that target this system to improve patient recovery and reduce damage post-ICH.