Deans' stroke musings: Knockdown of BNIP3 death gene family protects neurons from oxygenand- glucose-deprivation (OGD)-induced cell death

Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Wednesday, January 25, 2012

Knockdown of BNIP3 death gene family protects neurons from oxygenand- glucose-deprivation (OGD)-induced cell death

If the Canadians can produce all these wonderful papers maybe we should outsource our research needs to them. From the 2011 Canadian Stroke Congress.
page 99 here:
http://www.strokecongress.org/2011/wp-content/uploads/2011/12/CSC_Abstracts.pdf

Background: The BNIP3 family is a group of death-inducing mitochondrial proteins that includes BNIP3, NIX (also called BNIP3L) and BNIP3h. Previously, we reported that BNIP3 was upregulated and played a role in delayed neuronal death in in vivo and in vitro models of hypoxia and experimental stroke. Here, we tested the protective effects of inhibiting the BNIP3 gene family on primary neurons against oxygen and glucose deprivation (OGD) followed by reperfusion (RP). Methods: We developed lentiviral vectors for BNIP3 subfamily knockdown. We performed RNA interference, immunohistochemistry, Western blot, subcellular fractionation, cell death and mitochondrial function measurements to reveal the roles of the BNIP3 gene family on neuronal death in experimental stroke. Results: BNIP3 and NIX were highly upregulated after OGD/RP. Knockdown of BNIP3 or NIX alone protected about 15 - 23% of neurons from OGD-induced cell death. Combined use of the two vectors to knockdown the BNIP3 family (BNIP3, BNIP3L and BNIP3h) reduced neuronal death by 40% afterODG for 6 hours and reperfusion for 72 hours. Mitochondrial membrane potential loss, permeability transition pore opening and ROS production were all significantly attenuated by BNIP3 and/or NIX inhibition. Further,we show that AIF was released from mitochondria and translocated into nuclei in neurons treated with OGD/RP, while inhibition of BNIP3 by RNA interference blocked AIF translocation and prevented neuronal death.
Over-expression of BNIP3 and BNIP3L caused AIF translocation and subsequent neuronal death. Conclusion: Our results indicate that the BNIP3 death gene family is one of the regulators of caspase-independent neuronal death in the OGD model of stroke.