A proposed role for efflux transporters in the pathogenesis of hydrocephalusReport as inadecuate

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Croatian medical journal, Vol.55 No.4 August 2014. -

Hydrocephalus is a common brain disorder that is treated

only with surgery. The basis for surgical treatment rests on

the circulation theory. However, clinical and experimental

data to substantiate circulation theory have remained inconclusive.

In brain tissue and in the ventricles, we see that

osmotic gradients drive water diffusion in water-permeable

tissue. As the osmolarity of ventricular CSF increases

within the cerebral ventricles, water movement into the

ventricles increases and causes hydrocephalus. Macromolecular

clearance from the ventricles is a mechanism to

establish the normal CSF osmolarity, and therefore ventricular

volume. Efflux transporters, p-glycoprotein, are

located along the blood brain barrier and play an important

role in the clearance of macromolecules endobiotics

and xenobiotics from the brain to the blood. There is clinical

and experimental data to show that macromolecules

are cleared out of the brain in normal and hydrocephalic

brains. This article summarizes the existing evidence to

support the role of efflux transporters in the pathogenesis

of hydrocephalus. The location of p-gp along the pathways

of macromolecular clearance and the broad substrate

specificity of this abundant transporter to a variety of different

macromolecules are reviewed. Involvement of p-gp

in the transport of amyloid beta in Alzheimer disease and

its relation to normal pressure hydrocephalus is reviewed.

Finally, individual variability of p-gp expression might explain

the variability in the development of hydrocephalus

following intraventricular hemorrhage.

Author: Satish Krishnamurthy - ; Department of Neurosurgery, Upstate Medical University, Syracuse, NY, USA Michael D. Tichenor - ; Upstat

Source: http://hrcak.srce.hr/


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