TY - JOUR
T1 - Brain oedema in focal ischaemia
T2 - molecular pathophysiology and theoretical implications
AU - Simard, J. Marc
AU - Kent, Thomas A.
AU - Chen, Mingkui
AU - Tarasov, Kirill V.
AU - Gerzanich, Volodymyr
N1 - Funding Information:
This work was supported by grants to JMS from the National Heart, Lung and Blood Institute (HL051932, HL082517), the National Institute of Neurological Disorders and Stroke (NS048260), the Veterans Affairs (Baltimore VA, Baltimore, MD), and the Christopher Reeves Paralysis Foundation; to TAK from the National Institute of Child Health and Human Development (HD039833); to VG from the National Institute on Drug Abuse (DA018329) and the American Heart Association (0455634U).
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
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U2 - 10.1016/S1474-4422(07)70055-8
DO - 10.1016/S1474-4422(07)70055-8
M3 - Review article
C2 - 17303532
AN - SCOPUS:33846882646
SN - 1474-4422
VL - 6
SP - 258
EP - 268
JO - Lancet Neurology
JF - Lancet Neurology
IS - 3
ER -