Brinker et al. Our results suggest that efflux transport at the capillary endothelium is much more important for brain homeostasis than the removal of potential toxic brain metabolites by CSF “circulation” [8, 10]. may be criticized since they are surgically invasive and therefore results should be interpreted cautiously”. The BBB is formed by the endothelial cells lining the brain microvessels, under the inductive influence of neighbouring cell types within the 'neurovascular unit' (NVU) including astrocytes and pericytes. PubMed Central Alperin N, Hushek SG, Lee SH, Sivaramakrishman A, Lichtor T: MRI study of cerebral blood flow and CSF flow dynamics in upright posture: the effect of posture on the intracranial compliance and pressure. J Clin Invest. J Clin Invest. Orešković D, Klarica M, Vukić M: The formation and circulation of cerebrospinal fluid inside the cat brain ventricles: a fact or an illusion?. For example, our findings as well as some clinical data and experimental results obtained from different animal species, do not support unidirectional CSF circulation but strongly suggest that there are cardiac cycle-dependent systolic-diastolic to-and-fro cranio-spinal CSF movements. Journal: Fluids and Barriers of the CNS. However, CSF/water volume is slowly carried bidirectionally along all CSF spaces by the systolic-diastolic to-and-fro displacement [3, 10]. That kind of complex CSF movement could explain the observed distribution of many different substances in all directions along the CSF system and within central nervous system tissue. 2014, 25: 39-43. The authors declare that they have no competing interest. concur with our long-standing argument for developing new approaches to CSF physiology, they, unfortunately, failed to correctly interpret some of our published results. However, when the active transport was blocked in animals by probenecid, the concentration of monitored substances in parenchyma and in “peripheral” CSF compartments [8, 10] was significantly increased (during the same period of time) in comparison to control animals. So it was observed that the lumbar space can be significantly altered in different physiological states (hyperventilation, hypoventilation, pressure applied to the abdomen) . 10.1002/jmri.20427. 10.1016/0006-8993(85)91383-6. ScienceOpen on TwitterScienceOpen on YouTubeScienceOpen on LinkedInScienceOpen on Google+ScienceOpen on Facebook. PubMed However, when the active transport was blocked in animals by probenecid, the concentration of monitored substances in parenchyma and in “peripheral” CSF compartments [8, 10] was significantly increased (during the same period of time) in comparison to control animals. Acta Physiol Scand. 10.1002/jmri.20427. 2002, 321: 123-125. 0095229. This means that CSF is being permanently produced and absorbed inside the entire CSF system, as a consequence of water filtration and reabsorption through the capillary walls into the interstitial fluid (ISF) of the surrounding brain tissue, which was thoroughly explained in our paper [5, 6, 12]. extensively reviewed recent findings about CSF circulation in a recent article: “A new look at cerebrospinal circulation”, but did not analyze some important available data in sufficient detail. Cite this article. 10.1016/S0304-3940(02)00395-6. Google Scholar. between blood, interstitial fluid, and CSF. Neurosci. For many of these diseases it is still not clear how best to deliver appropriate drugs to the CNS, and a concerted approach using a variety of models and methods can give critical insights and indicate practical solutions. 10.1136/jnnp.35.4.468. 2009, 158: 1397-1405. a pulsatile to and fro movement throughout the entire brain with local fluid exchange Article 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. 2014, 11: 10-10.1186/2045-8118-11-10. NeuroReport. Brain Res. According to our hypothesis, CSF is not being actively produced predominantly by choroid plexuses, and does not flow unidirectionally to cortical SAS to be passively absorbed through arachnoid villi. Quite the opposite: we developed several original experimental models in both cats and dogs to test the basic tenets of the “classic” CSF hypothesis [3–10]. This does not support the traditional CSF “circulation” along the cranio-spinal CSF space because CSF can only flow from a region of higher to a region of lower CSF pressure .