Deans' stroke musings: Involvement of Proteasome and Endoplasmic Reticulum Stress in Neurodegeneration after Global Brain Ischemia

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.

Thursday, October 27, 2022

Involvement of Proteasome and Endoplasmic Reticulum Stress in Neurodegeneration after Global Brain Ischemia

No clue.

Involvement of Proteasome and Endoplasmic Reticulum Stress in Neurodegeneration after Global Brain Ischemia

Preprint from Research Square, 21 Oct 2022
DOI: 10.21203/rs.3.rs-2174277/v1 PPR: PPR560802

Preprint

This article is a preprint. It may not have been peer reviewed.

Abstract

A brief period of transient global brain ischemia leads to a selective ischemic neurodegeneration associated with death of hippocampal CA1 pyramidal neurons days after reperfusion. The mechanism of such selective and delayed neurodegeneration is still uncertain. The aim of our work was to study an involvement of proteasome and endoplasmic reticulum (ER) stress in ischemic neurodegeneration. We have performed laser scanning confocal microscopy analysis of brain slices from control and experimental animals that underwent global brain ischemia in duration of 15 minutes and varying times of reperfusion. We have focused on ubiquitin, PUMA that is proapoptotic protein of Bcl-2 family overexpressed in response to both proteasome and ER stress, and p53 that controls expression of PUMA. We have also examined expression of HRD1, E3 ubiquitin ligase that was shown to be overexpressed after ER stress. Using cellular models of both proteasome and ER stress, we have examined possible crosstalk between proteasome and ER stress. We demonstrate that global brain ischemia is associated with an appearance of distinct immunoreactivity of ubiquitin, PUMA and p53 in pyramidal neurons of CA1 layer of hippocampus 72 hours after ischemic insults. Such changes corelate with a delay and selectivity of ischemic neurodegeneration. Immunoreactivity of HRD1 observed in all investigated regions of rat brain was transiently absent in both CA1 and CA3 neurones 24 hours after ischemia in hippocampus that does not correlate with a delay and selectivity of ischemic neurodegeneration. We do not document significant crosstalk between proteasome and ER stress. Our results are in favour of dysfunction of ubiquitin proteasome system and consequent p53-induced expression of PUMA as the main mechanisms responsible for selective and delayed degeneration of pyramidal neurons of hippocampal CA1 layer in response to global brain ischemia.