Voditelj:
Prof.dr.sc. Marijan Klarica
Redoviti profesor farmakologije
Šalata 8, 10 000 Zagreb
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Suradnici:
Dr.sc. Darko Orešković
Institut Ruđer Bošković
Dr.sc. Ivana Jurjević
Goran Ivkić, dr.med.

U laboratoriju se odvijaju istraživanja fiziologije i patofiziologije likvora i intrakranijskog tlaka.

U tijeku su sljedeći projekti:
Sudbina moždanih metabolita i lijekova u likvorskom sustavu
Utvrđeno je da cerebralne kapilare djeluju kao glavni put za otklanjanje moždanih metabolita i anionskih lijekova putem aktivnog transporta
Likvorski sustav je zatvoreni sustav koji komunicira s krvi uglavnom preko cerebralnih kapilara, ali ne u smislu cirkulacije i apsorpcije likvora u duralne venske sinuse kako postulira klasična hipoteza o sekreciji likvora, cirkulaciji i apsorpciji

Patofiziologija hidrocefalusa
U novom modelu akutne okluzije Sylvijevog akvadukta u mačaka, veličina izoliranih moždanih komora i promjene tlaka likvora u komorama i subarahnoidnom prostoru istražuju se kako bi se razjasnila patofiziologija akutnog hidrocefalusa
Rezultati pokazuju da za dilataciju izoliranih komora mehanička opstrukcija sama po sebi nije dovoljna

Mehanizam regulacije intrakranijskog tlaka
Po prvi puta registrirano je da se tlak u moždanim komorama, cervikalnom i epiduralnom prostoru te spinalnom i subarahnoidnom prostoru mijenja istodobno tijekom promjena položaja tijela i tijekom infuzija u likvorski sustav

Mehanizam djelovanja osmotskih lijekova na intrakranijsku hipertenziju
Naši rezultati ukazuju da intravenska primjena hiperosmolarnih otopina osmotskih lijekova uzrokuje pad tlaka likvora u intaktnom kraniju smanjenjem volumena likvora u spinalnom dijelu, ali ne dehidracijom moždanog tkiva, smanjenjem intrakranijskog volumena likvora ili smanjenjem sekrecije likvora, kako se općenito pretpostavlja

Head:
Professor Marijan Klarica,
Professor of pharmacology
Šalata 8, 10 000 Zagreb
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Associates:
Darko Orešković, PhD
Institute Ruđer Bošković
Ivana Jurjević, MD, PhD
Goran Ivkić, MD, PhD

Our laboratory is involved in the research about physiology and pathophysiology of the cerebrospinal fluid and intracranial pressure.

Following lines of investigations are currently being persuied:
Fate of the brain metabolites in medications in the cerebrospinal fluid’s system
It has been shown that cerebral capillaries are the main pathway, via active transprort, for the removal of brain metabolites and anionic medications.
Cerebrospinal fluid’s system is a close circuit system which is communicating with the blood mainly through cerebral capillaries. However, this communication is not done by the circulation and absorption of the CSF into sinouses of the dura mater, as postulated by the classical theory of secretion, circulation and absorption of the CSF.

Pathophysiology of the hydrocephalus
We are investigating the size of the isolated brain ventricles and changes in the CSF pressure (within the brain ventricels and subarachnoid space) on the new model of acute occlusion of the cerebral aquaducte (aquaductus Sylvii) in order to elucidated pathophysiology of the hydrocephalus.
Results have shown that mechanical obstruction itself is not sufficient to cause the hydrocephalus.

Regulation mechanisms of the intracranial pressure
For the first time it has been shown that the pressure in the brain ventricles, cervical, epidural and spinal and subarachnoid space change simultaneously during changes in the body posture and application of the infusion in the CSF system.

Effect of osmotic drugs on the intracranial hypertension
Our results have shown that the application of the hyperosmolaric solutions of osmotic drugs causes drop of the intracranial pressure within the intact cranium. However, this effect is not accomplished by the dehydration of the brain tissue, reduction in the intracranial CSF volume, or reduction of CSF secretion, as have been believed before, but through the reduction of the CSF volume in the spinal part of the system.

IZABRANE PUBLIKACIJE / SELECTED PUBLICATIONS:
  • Orešković D, Klarica M, Vukić M. Does the secretion and circulation of the cerebrospinal fluid really exist? Medical Hypotheses 56 (5) 622-624; 2001
  • Zmajević M, Klarica M, Varda R, Kudelić N, Bulat M. Elimination of phenolsulfonphthalein from the cerebrospinal fluid via capillaries in central nervous system by active transport. Neuroscience Letters 321: 123-125; 2002
  • Klarica M, Varda R, Vukić M, Orešković D, Radoš M, Bulat M. Spinal contribution to CSF pressure lowering effect of mannitol in cats. Acta Neurochir 95: 407-410; 2005
  • Orešković D, Vukić M, Klarica M, Bulat M. The investigation of cerebrospinal fluid formation by ventriculo-aqueductal perfusion method in cats. Acta Neurochir 95: 433-436; 2005
  • Klarica M. Radoš M, Draganić P, Erceg G, Orešković D, Maraković J, Bulat M. Effect of head position on cerebrospinal fluid pressure in cats: comparison with artificial model. Croat Med J 47: 233-238; 2006
  • Vladić A, Klarica M, Bulat M. Dynamics of distribution of 3H-inulin between the cerebrospinal fluid compartments. Brain Res 1248: 127-135, 2009
  • Klarica M, Orešković D, Božić B, Vukić M, Butković V, Bulat M. New experimental model of acute aqueductal blockade in cats: Effects on cerebrospinal fluid pressure and the size of brain ventricles. Neuroscience 158: 1397-1405, 2009
  • Orešković D, Klarica M. The formation of cerebrospinal fluid: nearly a hundred years of interpretations and misinterpretations. Brain Res Rev 2010; 64: 241-262;
  • Bulat M, Klarica M. Recent insights into a new hydrodynamics of the cerebrospinal fluid. Brain Res Rev 65: 99-112, 2011;
  • Orešković D, Klarica M. Development of hydrocephalus and classical hypothesis of cerebrospinal fluid hydrodynamics: facts and illusions. Progress in Neurobiology 94: 238-258, 2011.