| Communicating hydrocephalus (CH) occurs frequently in both
children and adults, but research on this important type of
hydrocephalus has been impeded by the lack of a suitable animal
model. Several attempts have been made in the past 20 years
to induce CH in dogs and rats, but the methods used do not produce
the disorder consistently and the site of obstruction has not
been determined unequivocally. While congenital models of CH
exist in mice, these animals are too small for comprehensive
investigations that employ diagnostic imaging and cerebrospinal
fluid (CSF) shunting. Therefore, we intend to perfect a rat
model of CH that will be reliable, clearly impair CSF absorption
at the arachnoid granulations, and cost effective. Furthermore,
we propose to share this model with Dr. Egnor’s group
in order to test his pioneering work on the Windkessel Effect
and its importance in hydrocephalus.
Our plan comprises two phases. First, in Dr. McAllister’s
laboratory at the Wayne State University School of Medicine
we will develop the appropriate methodology for creating CH
in adult rats. We will test the efficacy of several substances
(kaolin, silicone oil, and methyl-methacrylate) to induce
CH via microsurgical infusions into the subarachnoid space
overlying the cerebral hemispheres. CH will be confirmed preliminarily
using anatomic magnetic resonance imaging. Second, after shipping
animals with CH to Dr. Egnor’s laboratory at the State
University of New York at Stony Brook, comprehensive CSF flow
and pressure studies will be performed using MRI.
Once the model has been developed successfully, we anticipate
at least 18 months of experimental manipulations to completely
test Dr. Egnor’s mathematical modeling, including studies
of shunt malfunction. Therefore, a two-year budget has been
proposed.
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