SVIBOR - Project code: 3-01-325


Strossmayerov trg 4, HR - 10000 ZAGREB
tel.: +385 1 459 44 44, fax: +385 1 459 44 69


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Project code: 3-01-325

Pathophysiology of the Cerebrospinal Fluid

Main researcher: BULAT, MARIN (6133)

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
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.

Keywords: cerebrospinal fluid, hydrocephalus, cerebrospinal fluid hydrodynamics, intracranial pressure,osmolality, drug distribution, half-life

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.

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Last update: 10/09/95