Definition: 'ISF dynamics' refers to the movement, exchange, and clearance of interstitial fluid within the brain parenchyma. ISF plays a critical role in transporting nutrients, removing waste products, and maintaining homeostasis in the central nervous system (CNS).

Unlike blood or cerebrospinal fluid (CSF), ISF resides in the extracellular space between neurons and glial cells.

Key Components of ISF Dynamics:

• Production:

ISF is derived from blood plasma through the blood–brain barrier (BBB), as well as from metabolic activity within brain tissue.

• Movement pathways:

– Passive diffusion (Brownian motion)

  – Bulk flow along [[perivascular spaces]]  
  – Exchange with [[cerebrospinal fluid]] (CSF) via the [[glymphatic system]]

• Clearance:

– Paravenous drainage

  – Lymphatic-like pathways (e.g., meningeal lymphatics)  
  – Transport through aquaporin-4 (AQP4) channels on astrocytic endfeet

Clinical Relevance: Altered ISF dynamics are implicated in various neurological conditions, including:

• Idiopathic normal pressure hydrocephalus (iNPH)
• Alzheimer’s disease
• Cerebral edema
• Traumatic brain injury

Disruption in ISF movement may lead to accumulation of neurotoxic waste (e.g., beta-amyloid, tau), impaired clearance of inflammatory mediators, and altered brain compliance.

Measurement Techniques:

• Diffusion-weighted MRI
• Spectral diffusion analysis (→ estimates of F_int and D_int)
• Dynamic contrast-enhanced imaging
• Tracer-based imaging in animal models

Related terms:

• Interstitial Fluid Volume Fraction (F_int)
• Interstitial Diffusivity (D_int)
• Glymphatic system
• Aquaporin-4
• Extracellular space