SherlockMS and the Case of the Broken Floodgates

My brother, Sherlock Holmes, hunts pickpockets and husbands with double lives. Charming.
I hunt culprits who make synapses whisper, soften barriers, and recruit cells as accomplices. That isn’t merely detective work—it’s high culture. 

That evening an envelope lay on my table. No wax seal, no drama—just one sentence: “Intractable vomiting. Visual loss. Transverse myelitis symptoms. Please come.” I raised an eyebrow. “Ah,” I said. “A case where the criminals don’t run. They flow.”

The Crime Scene: One Body, Three Alarms

Hospitals smell of disinfectant and premature conclusions. The patient- let’s call her Mrs. P. - looked as if she had wrestled with the world and narrowly lost:

• nausea and vomiting, as if someone had removed the “stop” button from the vomiting center
• painful, dramatic visual disturbance
• leg weakness not explainable by “poor sleep”

A resident said, “Maybe psychosomatic?”

I looked at him as if he’d offered to understand London via postcards. “My dear friend,” I said, “when the brain sounds an alarm, it is rarely theater. It is more often… logistics.”

The First Suspects: Police, Building Authority, Garbage Collection

I begin every case with a simple rule: who keeps the city running?

In the brain, it isn’t only neurons. Neurons are aristocratic speakers: loud, important and dependent.

The real city workers are others:

• Astrocytes: building authority + utilities + border control in one
• Microglia: the police, sometimes helpful, sometimes… temperamental
• Oligodendrocytes: the cable insulators, hardworking, and deeply offended when ignored

And me? I’m the only one who can interrogate them all.

3) The Trace in the Water: AQP4 and the Floodgate Keepers

I went first to where no one likes to look: the brain’s water management.

Astrocytes have specialized equipment, endfeet, little “cuffs” that embrace blood vessels and help keep the blood–brain barrier tight.

And in those endfeet sits a star among water channels: Aquaporin-4 (AQP4). A gatekeeper protein. A professional.

If the floodgates hold, the city runs. If they don’t… you get London at rush hour only with fluid and an immune circus.

I asked, “Any attacks involving the vomiting center? Brainstem?”

“Yes,” the attending said. “Imaging is suspicious in a region that… causes trouble quickly.”

I nodded. “Area postrema.” That’s a place in the brain that is allowed to be a little “leaky,” so it can sense signals in the blood—a natural back entrance.

And back entrances are excellent for criminals.

The Culprit Appears: An Assault on the Floodgates

“So,” I said, “we have visual loss, long spinal cord symptoms, and brainstem/area-postrema drama. This is no ordinary pickpocketing. This is a targeted attack.”

The real question: who attacks whom?

Some diseases are bar fights, general inflammation, everyone against everyone.

But this case smelled like contract work. And then, inevitably, the labs whispered the word I could already taste: AQP4 antibodies.

I smiled thinly. “There you are. The culprit isn’t the neuron. Not even the myelin. The culprit aims directly at… the building authority.” Because once antibodies tag AQP4, the brutal accomplice arrives: complement. Not a subtle investigative agency more a jackhammer.

And when astrocytes die, others often fall after them, not because they’re “also guilty,” but because metabolic support suddenly disappears. Oligodendrocytes collapse, myelin suffers, axons lose their supply.

A biological domino effect. “The vomiting,” I explained, “is no coincidence. If the attack hits regions that are already easier to access, you get exactly these symptoms.”

The resident asked, “Why doesn’t it hit everywhere? AQP4 is everywhere, isn’t it?”

I leaned in. “Because even criminals have preferences and not every roadblock is built the same.”

The Twist: Astrocytes Aren’t Always Victims

Just as everyone relaxed “Aha, diagnosis! Case closed!” another file knocked on the door. A different patient, this time from the MS clinic: “No new relapses, but slow worsening. And a biomarker is abnormal.” I scanned the page. GFAP elevated in blood. I grinned. “Wonderful. Now it becomes literary.”

GFAP is a structural fiber inside astrocytes; something like their internal scaffolding and workwear. When astrocytes react strongly or get injured, GFAP can leak outward. Clinicians call it a clue. I call it a fingerprint at the scene.

And here is the part London teaches too rarely: Astrocytes are not merely construction workers. They are political actors. Depending on the signal, they can:

• stabilize barriers or loosen them
• keep immune cells out or invite them in with chemokines (“Come in, there’s a party!”)
• lose protective functions: disorganized endfeet, reduced glutamate uptake → more neuronal overexcitation
• shift metabolism: less “lactate service” for neurons, more self-preservation (everyone becomes selfish in a fire)
  
• release messengers that recruit and activate immune cells
• and in some contexts even retain a kind of inflammatory “memory” as if noting: “Next time, escalate faster.” 

“That,” I told the team, “is the difference between my brother and me. He asks: Who did it? I ask: Who is the victim today and the accomplice tomorrow?”

A Scene at the Synapse Market: Glutamate Sabotage

To make it clear even for laypeople, I used my favorite image:

“Imagine a synapse as a marketplace. Neurons shout their offers. Astrocytes are the sanitation department and the city administration: they clear excess neurotransmitters, buffer ions, keep the square walkable.”

If astrocytes lose that buffering work, too much “noise” remains in the system. Glutamate can become toxic, not with an immediate explosion, but with a slow fire in the wiring.

And now the truly neuro-detective part:

Astrocytes don’t just sit at vessels. They also sit at synapses with fine perisynaptic processes. They can isolate synapses, modulate them, even tag them so microglia “clean them up.”

“So if you see cognitive symptoms, fatigue, or network instability,” I said, “don’t think only ‘lesion.’ Think city operations. Think supply. Think of the ones who never make it onto the cover image.”

Verdict: Two Cases, One Principle

In the end I wrote two diagnoses on two separate files and yet it was a single crime novel:

1. The floodgate attack
   A targeted assault on AQP4/endfeet → astrocyte injury and death → secondary demyelination and tissue damage → dramatic localization (optic nerve, spinal cord, brainstem regions).
   Astrocytes as victims.
   
2. The quiet propaganda in tissue
   Astrocytes become reactive, lose homeostasis, send signals that amplify inflammation or brake repair, yet sometimes also attempt counter-regulation (barrier repair, inhibitory immune signals).
   Astrocytes as players; sometimes arsonists, sometimes firefighters.
   

“And that,” I said, “is exactly why astrocytes are perfect characters in a detective story: they’re everywhere, networked, context-sensitive and they turn local trouble into a systemic narrative.”

Back to Baker Street

Back in my room I sank into the armchair. London hummed like a distant EEG carpet.  I studied the files and thought with the mild pride of someone who categorizes the world correctly:

“My brother solves cases because humans are bad liars. I solve cases because cells cannot lie at all; they only follow signals. And that, for all its tragedy, is far more elegant.”

I took a sip of tea and smiled. “Most people think the brain is an organ for thinking. How sweet. It is, above all, a city. And tonight, I saved its floodgates.”

Your SherlockMS