title: Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications.
abstract: Focal cerebral ischaemia and post-ischaemic reperfusion cause cerebral capillary dysfunction, resulting in oedema formation and haemorrhagic conversion. There are substantial gaps in understanding the pathophysiology, especially regarding early molecular participants. Here, we review physiological and molecular mechanisms involved. We reaffirm the central role of Starling's principle, which states that oedema formation is determined by the driving force and the capillary "permeability pore". We emphasise that the movement of fluids is largely driven without new expenditure of energy by the ischaemic brain. We organise the progressive changes in osmotic and hydrostatic conductivity of abnormal capillaries into three phases: formation of ionic oedema, formation of vasogenic oedema, and catastrophic failure with haemorrhagic conversion. We suggest a new theory suggesting that ischaemia-induced capillary dysfunction can be attributed to de novo synthesis of a specific ensemble of proteins that determine osmotic and hydraulic conductivity in Starling's equation, and whose expression is driven by a distinct transcriptional program.
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA. msimard@smail.umaryland.edu
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kent
authors.forename: Mingkui
authors.initials: M
authors.lastname: Chen
authors.forename: Kirill V
authors.initials: KV
authors.lastname: Tarasov
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Gerzanich
mesh_terms: D001929:Brain Edema / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D002543:Cerebral Hemorrhage / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000503:physiopathology*; D014158:Transcription, Genetic