Stroke Flashcards
Ischaemic stroke usually results from
the obstruction of a major cerebral vessel which leads to a decrease in cerebral blood flow, and a subsequent reduction in adenosine triphosphate (ATP).
Na+/K+ ATPase (NKA) is responsible for
maintaining the electrochemical gradient, and hence the membrane potential, of the cell
How do we know that ischaemia causes e.c. K+ accumulation and membrane depolarization?
Cascio et al. (2001) showed that ischaemia causes extracellular K+ accumulation and depolarization of the membrane potential (Vm) (e.g. when [K+ ]o was 14 mM, Vm depolarized by 20 mV after 30 min of ischaemia), resulting in intermittent failure of conduction in coronary perfused rabbit papillary muscle
Who showed that glutamate from the synapse activates mGluR’s?
Porter, 1996
Who showed that increased Ca2+ i leads to a positive feedback cycle?
Filosa et al., 2006
BK
K+ into blood vessels
Raised e.c. K+
What is the major effect of glutamate increase?
Na+/Ca2+ influx from NMDAR’s
What study showed that it was duration not concentration that mediated glutamate induced neuronal death?
Dennis Choi (1987) demonstrated that 5 minutes of exposure to glutamate at 100 micromolar (uM) kills 50% of neurons
What happens when MPTP opens?
increases mitochondrial membrane permeability (Δψm), causes mitochondria to become further depolarised, meaning that Δψm is abolished
What happens when Δψm is lost?
mitochondria can no longer generate ATP and protons and some molecules are able to flow across the outer mitochondrial membrane uninhibited
What does associated accumulation of of free Ca2+ lead to?
rapid and extensive breakdown of phospholipids, proteins and even nucleic acids by the activation of calcium-dependent phospholipases, proteases, and endonucleases
Why do pericytes die in rigour?
It has been found that calcium toxicity leads to death of these pericytes and that they die in rigor because ATP is needed to disengage myosin from actin (Yemisci et al.,2009).
How is the death of pericytes translated clinically in ischaemic stroke patients?
The resulting long-lasting capillary constriction (Hauck et al.,2004) restricts microvascular reperfusion when a thrombus in a culprit upstream artery has been removed, which will contribute to the no-reflow phenomenon after stroke.
What does death of pericytes do to the BBB?
In addition, death of pericytes is expected to result in the loss of their maintenance of the blood–brain barrier (BBB) (Bell et al.,2010)
How do we know that pericyte deficiency leads to higher permeability of the BBB?
Using a set of adult viable pericyte-deficient mouse mutants, Armulik et al., 2010 demonstrated that pericyte deficiency increases permeability of the BBB to water and a range of low-molecular-mass and high-molecular-mass tracers. The increased endothelial transcytosis resulted in oedema and extravasation of plasma proteins in the mouse brain.
Who showed that active relaxation of capillaries requires Ca2+ entry?
Active relaxation of pericytes requires decreased voltage-gated Ca2+ entry (Puro, 2007).
