How does mannitol decrease intracranial pressure under the no-reabsorption rule?

I was recently asked this excellent question by a neuro-intensivist working in the USA.  I’m confident he knows more about the blood-brain barrier than I do, but here are my own thoughts on the topic.

Firstly, it’s complicated. A nice experiment on six acute brain trauma patients reported in 2012 showed that ICP is well reduced by 1g/ kg BW mannitol with no reduction in cerebral blood volume, so I think we can put that mechanism to one side. (1)

Next, we know that the blood-brain barrier is very impermeable to mannitol (and to sodium), so hyperosmotic/ hypertonic solutions will greatly increase delta pi. But we also know that paracellular Jv is exceedingly low in the continuous capillaries of the central nervous system with plenty of tight junctions but few breaks. Aquaporins are remarkably infrequent, but solutes have to cross the BBB by transcellular transport, and water will invariably travel with them. It seems likely an increased delta pi would favour net outward balance of water that accompanies transcellular solute transport.

Then there is the blood-CSF barrier. The old account of ventricular to cisternal flow may be under suspicion, but the presence of fenestrated (capable of absorption) capillaries adjoining the ependyma in the choroidal plexus makes this a very likely site for raised delta pi to exert its influence on limiting CSF production and enhancing absorption.

Finally, more new stuff. After we were told the brain has no lymph system, it now may have two; the perivascular glymph system and a recently-discovered true lymphatic route to cervical nodes with fenestrated (absorbing) capillaries. (2) Raised delta pi can therefore enhance cerebral interstitial fluid /lymph return.

I hate the trite phrase “more research is needed”, but it seems to be the case in cerebrovascular physiology.

  1. Diringer MN, Scalfani MT, Zazulia AR, Videen TO, Dhar R, Powers WJ. Effect of mannitol on cerebral blood volume in patients with head injury. Neurosurgery. 2012;70:1215-8; discussion 1219.
  2. Aspelund A, Antila S, Proulx ST et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. 2015;212:991-999.

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