Type of research: basic Duration from: 01/01/91. to 12/15/95. Papers on project (total): 30
Papers on project quoted in Current Contents: 4
Institution name: Medicinski fakultet, Zagreb (108) Department/Institute: Department for Pharmacology Address: Šalata 11, 10000 Zagreb, Croatia City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0)1-4566-839
Fax: 385 (0)1-424-001
Summary: According to classical hypothesis the hydrocephalus is
caused by obstruction of the cerebrospinal fluid (CSF) circulation, while
according to our working hypothesis the hydrocephalus could be due to
increased osmolality of CSF in brain ventricles during pathological
processes (i.e. meningitis) or disturbed hydrodynamics of CSF. Using CT
technique in acute experiments in dogs we have shown that application of
hyperosmolal sucrose in the lateral ventricle leads to dilatation of
ventricles (and increase of CSF pressure) within 5 min without
development of periventricular edema. This suggest that hyperosmolal CSF
in ventricles can lead to development of hydrocephalus. In another
series of experiments in cats it was shown that 3 weeks after
implantation of acrylic screw in aqueduct of Sylvii a significant
hydrocephalus is developed without obstruction of CSF communication
between ventricles and subarachnoid spaces; only hydrodinamics of this
communication was disturbed. This means that disturbed hydrodinamics of
CSF pulsation can cause hydrocephalus. According to our hypothesis CSF
does not circulate but only pulsates to-and-fro so that distribution of
substances will be limited by the rate of their disappearance from CSF,
i.e. their half-lifes in CSF. We have shown that 3H-benzylpenicillin
after application in the lateral ventricle of dogs is much better
ditributed between CSF compartments when its active transport is blocked
by probenecid than under control conditions when its half-life is two
times shorter. This active transport enables development of concentration
gradients of endogenous substances between CSF compartments. On the
other hand 3H-inulin, which is not actively transported and has long
half-life, after its application in the lateral ventricle is well
distributed into all CSF compartments.
Research goals: According to the classical hypothesis the CSF is
secreted in brain ventricles, it circulates through ventricles and
subarachnoid spaces to be absorbed across arachnoid villi into cerebral
venous sinuses. Furthermore, hydrocephalus is developed because of
obstruction of CSF circulation, accumulation of CSF in ventricles and
their widening. According to our working hypothesis CSF does not circulate
unidirectionally but CSF pulsates forward-backward due to
sistolic-diastolic changes of blood volume in the cranial vault, while
volume of CSF is regulated by hydrostatic and osmotic pressures between
bloodstream and CSF (and not by secretion and absorption of CSF). In our
view hydrocephalus could develop due to increase of CSF osmolality or
changes in hydrodynamics (to-and-fro movements) of CSF. Aim of these
investigations is to explore whether incresae of CSF osmolality in
ventricles lead to their widening accompanied by an increase of CSF
pressure, and whether disturbance of CSF hydrodinamics obtained by
placement of an acrylic screw in aqueduct of Sylvii, leads to
hydrocephalus. Furthermore, we plan to investigate how pulsations of CSF
affects distribution of substances in CSF, and whether active transport
contributes to development of concentration gradients of substances
between CSF compartments. Other information about the project.