Cerebrospinal fluid hypersecretion in pediatric hydrocephalus.
Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis. Here, the authors review the molecular mechanisms of CSF secretion by the choroid plexus epithelium, the most efficient and actively secreting epithelium in the human body, and provide experimental and clinical evidence for the role of increased CSF production in hydrocephalus. Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence. Investigation into the human genetics of developmental hydrocephalus and choroid plexus hyperplasia, and the molecular physiology of the ion channels and transporters responsible for CSF secretion, might yield novel targets that could be exploited for pharmacotherapeutic intervention.
['Karimy|Jason K|JK|', 'Duran|Daniel|D|', 'Hu|Jamie K|JK|', 'Gavankar|Charuta|C|', 'Gaillard|Jonathan R|JR|', 'Bayri|Yasar|Y|', 'Rice|Hunter|H|', 'DiLuna|Michael L|ML|', 'Gerzanich|Volodymyr|V|', 'Marc Simard|J|J|', 'Kahle|Kristopher T|KT|']
D002552:Cerebral Ventricles D065634:Cerebrospinal Fluid Leak D002831:Choroid Plexus D006801:Humans D006849:Hydrocephalus
cerebrospinal fluid pediatric hydrocephalus choroid plexus AE2 = anion exchanger 2 AQP = aquaporin BIF = brain interstitial fluid CA = carbonic anhydrase CPC = choroid plexus cauterization CPE = choroid plexus epithelium CPH = choroid plexus hyperplasia CPP = choroid plexus papilloma ETV = endoscopic third ventriculostomy EVD = external ventricular drain KCC = K+-Cl− cotransporter NBCe2 = Na+-HCO3− cotransporter NCBE = Na+-HCO3− exchanger NKCC1 NKCC1 = Na+-K+-2Cl− cotransporter SPAK = Ste20/SPS1-related proline-alanine-rich protein kinase epithelia ion transport