Glymphatic system function in patients with ischemic stroke evaluated by the DTI-ALPS method: a comprehensive review

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 Glymphatic system function in patients with ischemic stroke evaluated by the DTI-ALPS method: a comprehensive review

Lichuan Zeng^1,2,3†Zihan Yin^1†Wei Li^3†Xiao Wang¹Yaodan Zhang⁴Mingguo Xie^2*Ling Zhao^1*

• ¹Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
• ²Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
• ³Department of Radiology, Deyang Hospital Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Deyang, China
• ⁴Department of Neurology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China

The glymphatic system is a glial-dependent waste clearance pathway in the central nervous system (CNS) of vertebrates that exploits the perivascular compartment between the vascular basement membrane (outermost wall of blood vessels) and astrocytic vascular endfeet to facilitate exchange between cerebrospinal fluid and interstitial solutes throughout the brain. This intricate network plays a vital role in the efficient elimination of metabolic waste and the regulation of water transport within the brain. Ischemic stroke, characterized by interrupted or reduced blood supply to a specific region of the brain, is a major cause of disability and mortality. Impairment of the glymphatic system is implicated in the pathophysiological process of stroke, including disruption of the blood–brain barrier, formation of cerebral edema, induction of neuroinflammation, and accumulation of neurotoxic factors. Various studies have demonstrated asymmetry and impairment of glymphatic function during ischemic stroke. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) using diffusion magnetic resonance imaging is an effective method for evaluating glymphatic system function by examining interstitial fluid dynamics within the human brain. In this study, we provide an overview of putative mechanisms mediating the role of the glymphatic system in ischemic stroke pathophysiology, with a strong focus on discussing DTI-ALPS applications in assessing changes in glymphatic function following an ischemic stroke.(The goal here is to create EXACT PROTOCOLS THAT WILL CLEAR THIS WASTE! And you didn't know that? Assessing does nothing for recovery!)

1 Introduction

Stroke, clinically classified into ischemic or hemorrhagic subtypes, is one of the most common causes of mortality and disability globally, with rising incidence in developing countries (1). Acute ischemic stroke (AIS) is responsible for about 71% of all strokes globally (2) and is predominantly caused by cerebrovascular obstruction (3, 4). Uncontrolled hypertension, cardiac diseases, and large artery atherosclerosis have been established as the primary etiologies of ischemic stroke (5–7), with small vessel disease being another significant contributor to stroke (8). In recent years, there has been a growing focus on elucidating the physiological roles of the glymphatic system (9–12). The intricate network of the glymphatic system facilitates cerebrospinal fluid (CSF) transport via perivascular channels within the brain and is believed to play a crucial role in metabolic waste clearance. In addition to its role in waste clearance, the glymphatic system may also facilitate the distribution of essential substances, such as glucose, lipids, amino acids, and neurotransmitters, throughout the brain. The discovery of the glymphatic system produced a shift in perspective regarding the pathology of neurodegenerative diseases and acute neurological disorders such as stroke (13, 14). Studies of the glymphatic system have largely been conducted using tracer methodologies, with gadolinium-based contrast agent (GBCA) administration via the intrathecal route considered the gold standard for tracer investigations using magnetic resonance imaging (MRI) in human studies. However, the GBCA-enhanced MRI technique is invasive and lacks regulatory approval. In contrast, diffusion tensor image analysis along the perivascular space (DTI-ALPS) offers a noninvasive approach to investigating the human glymphatic system and has recently been applied in Alzheimer’s disease, cerebral small vessel disease, and sleep-related diseases (15–18). The DTI-ALPS has been proposed as an index for quantifying water diffusivity patterns along the deep medullary vein at the level of the lateral ventricular body. In this review, we discuss the physiology of the glymphatic system and the related mechanisms involved in post ischemic injury, which could provide a new direction for research on ischemic stroke. Furthermore, we discuss DTI-ALPS as an index for assessing glymphatic system function in patients who have experienced ischemic stroke.

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