Izvorni znanstveni članak
https://doi.org/10.3325/cmj.2014.55.366
A proposed role for efflux transporters in the pathogenesis of hydrocephalus
Satish Krishnamurthy
; Department of Neurosurgery, Upstate Medical University, Syracuse, NY, USA
Michael D. Tichenor
; Upstate Medical University, Syracuse, NY, USA
Akhila G. Satish
; Department of Engineering University of Pennsylvania Philadelphia, PA, USA
David B. Lehmann
; Department of Pharmacology Upstate Medical University Syracuse, NY, USA
Sažetak
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.
Ključne riječi
Hrčak ID:
129942
URI
Datum izdavanja:
15.8.2014.
Posjeta: 998 *