Definition: 'Interstitial Fluid Volume' refers to the total volume of fluid occupying the 'extracellular space' between cells within a tissue. In the central nervous system (CNS), it is the fluid that lies between neurons, glia, and capillaries—distinct from cerebrospinal fluid (CSF) and intracellular fluid.

Physiological Role:

• Serves as a medium for:
  1. Nutrient transport
  2. Waste removal
  3. Ion exchange
  4. Intercellular signaling
• Provides mechanical support and maintains the extracellular matrix (ECM) environment.
• Interfaces dynamically with CSF through the glymphatic system and perivascular pathways.

Brain-Specific Characteristics:

• Estimated to occupy ~15–20% of total brain tissue volume under physiological conditions.
• Closely regulated by:
  1. Capillary filtration through the blood–brain barrier (BBB)
  2. Aquaporin-4 channels on astrocytic endfeet
  3. Arterial pulsatility and sleep-wake cycles (via glymphatic function)

Alterations in ISF Volume: ↑ ISF Volume:

• Idiopathic normal pressure hydrocephalus (iNPH)
• Vasogenic edema
• Aging-related extracellular matrix degradation

↓ ISF Volume:

• Cytotoxic edema (e.g., ischemic stroke)
• Cellular swelling or inflammation

Measurement Techniques:

• Spectral diffusion analysis (→ F_int)
• Diffusion MRI (indirect estimation via ADC)
• Tracer-based imaging in experimental models
• Optical or microdialysis methods in animal studies

Distinction from Related Terms:

• Interstitial fluid volume fraction (F_int):

Dimensionless ratio of ISF volume to total tissue volume.

• CSF volume: Located in ventricles and subarachnoid space; not part of ISF.
• Extracellular volume: Includes ISF + CSF + intravascular space (context-dependent).

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