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The enteric nervous system (ENS) is located outside the blood-brain barrier.

The ENS is embedded within the walls of the gastrointestinal tract, spanning from the esophagus to the anus. It consists of two main plexuses:

• Myenteric plexus (Auerbach's plexus) - between the longitudinal and circular muscle layers
• Submucosal plexus (Meissner's plexus) - in the submucosa

Since the ENS is part of the peripheral nervous system and resides in the gut wall, it's separated from the central nervous system by the blood-brain barrier. This anatomical separation is actually functionally important - it allows the ENS to operate with significant autonomy from the brain and spinal cord, earning it the nickname "the second brain."

The ENS can function independently to control gut motility, secretion, and blood flow, though it does communicate with the CNS via the vagus nerve and other autonomic pathways that cross the blood-brain barrier at specific regulated points.