Saturday, February 15, 2020

Targeted Myosin-2 Inhibition Improves Brain Regeneration After Stroke by Relaxing Hypoxia-Induced Vasoconstriction in Capillaries

So this seems to solve 1 of 5 neuronal cascade of death issues.  What the fuck is your hospital doing to solve the other 4? What research are they initiating? Or supporting?

Capillaries that don't open due to pericytes

The 5 causes of the neuronal cascade of death in the first week.

 

Targeted Myosin-2 Inhibition Improves Brain Regeneration After Stroke by Relaxing Hypoxia-Induced Vasoconstriction in Capillaries





    Smooth muscle myosin-2 (SMM) is the key regulator of capillary blood flow in the brain tissue. Pre-capillary contractile pericytes (smooth muscle cells, SMCs) block the entrance of brain capillaries in answer to hypoxia during ischemic stroke. One of the major obstacles in stroke therapies is that SMCs remain permanently contracted even after removing the blood clot from large arteries, which hinders healthy blood reperfusion of the infarcted brain regions. Thus, SMM could be an optimal target to improve brain regeneration after clinical interventions. Therefore, we developed an intra-arterial catheter mediated targeted administration of SMM inhibitors into the ischemic brain regions and tested their effects on cerebral blood flow (CBF) after transient middle cerebral artery occlusion (tMCAO) on rats. SPECT and MRI analyses confirmed that different types of SMM inhibitors (e.g. MPH-222) could drastically improve CBF in the ischemic brain areas. We also corroborated this vasodilatation effect on ex vivo human arterioles, where SMM inhibitors could fully relax contracted vessels even in the presence of upstream vasonstrictor signals. Moreover, MPH-222 could also induce neurite outgrowth in different types of neurons through its effect on the non-muscle myosin-2 (NM2) isoforms. These results suggest that targeted, non-selective myosin-2 inhibition is a conceptually new therapeutic way in stroke interventions, which could be combined with current blood clot removing methods (thrombectomy and thrombolysis).




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