This is a shocking finding. Sun Lien was stunned for a long time and didn't speak, his mind was full of Liu Tangchun's original sentence "A bag of mannitol is just ......"

If there was a time machine, Sun Lien would definitely have traveled back two days and slapped himself in the face. Mannitol is your illegitimate child? Do you feel that you owe it all the time? Do you have to use it?

In all fairness, Sun Lien certainly did not foresee that mannitol would have an adverse effect on Tang Min's condition. It would have been impossible for any doctor to foresee this. But...... If he could have been more cautious in dealing with his condition, maybe he wouldn't have used mannitol on Tang Min's body.

Sun Lien was busy condemning himself for not being cautious in his heart, while Zhou Ce frowned and asked Yuan Ping'an, "You mean, it was only after the AQP4 protein was inhibited that it caused her disease to progress?"

This is a possible corollary. Yuan Ping'an also appeared cautious on this issue, "But...... I've never heard of a ...... where inhibition of AQP4 protein can lead to disease."

"So according to this 'possible inference'......" Zhou Ce accentuated the pronunciation of the five words "possible inference", "can we think that many of the low-signal areas in her brain are caused by the inhibition of AQP4?"

Yuan Ping'an thought about it again and again, and finally shook his head, "I'm not sure about this." ”

AQP4 protein is a highly sensitive aquaporin that does more than just pump water molecules into glial cells. It is also able to pump out the water molecules inside the glial cells. From this mechanism analysis, the conclusion of the paper itself seems to contradict reality to some extent: mannitol creates an intracranial osmotic gradient after crossing the cerebral blood barrier, thereby promoting the water molecules in neurons and glial cells to enter the blood vessels.

However, if mannitol inhibits AQP4 protein expression...... What about the dilated hyposignal shadow, which uses the osmotic gradient to pump water molecules out of the cell and inhibits the aquaporins, which expands the range of edema?

"The AQP4 protein not only pumps water molecules into the interstitial cells during the acute phase of cerebral edema, but also slowly pumps out water molecules after the acute phase – you can think of this process as the peak regulation of water in many reservoirs when heavy rains come. Yuan Ping'an explained Zhou Ce's problem in the simplest way and said, "AQP4 is the sluice gate for rapid storage of water into the reservoir, and the interstitial cells are the reservoir itself - mannitol is more like the evaporation of water in the reservoir itself, but its rate is much stronger than that of solar radiation alone." ”

The analogy is easier to understand. Sun Lien frowned and said, "So...... After the reservoir evaporated rapidly, the water level rose?"

"It's not intuitive, but it's the status quo. Yuan Ping'an nodded, "If you only consider the reservoir, then after ruling out all other possibilities, the change can only come from the upstream water." ”

Sun Lien was planning to continue to extend on this issue, but ...... It seemed that because of Zhou Ce's words to Brune, a somewhat strange thought suddenly popped up in his mind.

"How can you be sure that we have all the possibilities?" he asked rhetorically, with the intention of raising the bar, "could it be something else?"

"Other issues don't explain why the water level is rising. Yuan Ping'an glanced at Sun Lien a little strangely, as if the question was not the deputy leader of his own diagnosis team, but a poor child with congenital stupidity. "Nothing else can conjure water molecules out of thin air, can they?"

"There's an idiom called 'open source and reduce expenditure'. Sun Lien shook his head and said, "Upstream water, this is open source." What if there's a throttling problem?"

"What do you mean......" Yuan Ping'an said with some hesitation, while Sun Lien rushed ahead of him and added, "If this reservoir ...... Didn't you have a gate in the first place?"

"It's not that there is something wrong with her AQP4 protein being inhibited, she is born with insufficient AQP4 protein expression!" Speaking of which, Sun Lien finally made his own diagnosis for the first time, although there is not enough evidence, but he intuitively believes that the probability of this is very high, "That's why mannitol will cause such obvious changes!"

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Tang Min's condition can be said to be very complicated, but if the concept of AQP4 protein underexpression is introduced, all the problems suddenly have a common solution.

Why is her first symptom of vision loss? Because the AQP4 protein is most distributed in the optic nerve, which is also most sensitive to interstitium and synapses. Symptoms occur due to insufficient expression of the AQP4 protein and a rapid increase in water content in the optic nerve.

Why did she later develop hydrocephalus that was difficult to correct? Because the AQP4 protein is not expressed enough, it is difficult for the interstitial cells in the brain to regulate water levels. However, due to the large number of AQP protein family members, other AQP proteins compensate for the AQP4 protein to a certain extent. As a result, only refractory hydrocephalus and slight microscopic stromal cell edema appeared.

Why is it that after the development of hydrocephalus, her other neurological functions are not affected in a way? Because the low expression of AQP4 protein inhibits the occurrence of cytotoxic edema - the interstitial cells cannot play the role of water storage, and the other nerves are unable to receive excess water. So she had brain herniation, but it didn't damage much neurological function. But at the same time, she also developed an inexplicable, stubborn increase in intracranial pressure.

At the same time, the lack of expression of AQP4 protein may even explain the current "worsening of symptoms after mannitol".

Prior to mannitol, cerebrospinal fluid (CSF) and plasma osmolality in the human body were identical. After mannitol, the plasma osmolality in the human body rises rapidly, resulting in the physical phenomenon of water transfer from cerebrospinal fluid (brain tissue) to plasma. This phenomenon tends to rebound rapidly after mannitol is discontinued—plasma osmolality returns rapidly after mannitol is stopped, while cerebrospinal fluid (CSF) inevitably increases osmolality due to dehydration. Sometimes there is even an inverse osmotic gradient in which the cerebrospinal fluid osmolality is greater than the plasma osmolality.

Because mannitol inhibits AQP4 protein expression, and Tang Min herself is in a state of insufficient AQP4 protein expression, her body is unable to balance the pressure difference between cerebrospinal fluid and plasma through this specific water channel system. This has led to the current situation of "enlargement of the area of intracranial edema after the use of mannitol".

"So...... These areas of hypointensity are indeed edema. And Tang Min's problem is not a tumor or an autoimmune disease. She has a genetic problem. "It's not that she can't produce AQP4 protein at all, it's that her body can't produce enough AQP4 protein." That's why this problem arises – at the end of the day, her symptoms are chronic, irreversible and interstitial cell edema. ”