Deans' stroke musings: Hypoxia Limits Inhibitory Effects of Zn2+ on Spreading Depolarizations

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, November 27, 2013

Hypoxia Limits Inhibitory Effects of Zn2+ on Spreading Depolarizations

This sounds like something your doctor and researchers should be working on to generate a protocol.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0075739

Isamu Aiba, C. William Shuttleworth: Department of Neurosciences, University of New Mexico, Albuquerque, New Mexico, United States of America

Corresponding Author

Email: bshuttleworth@salud.unm.edu

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: IA CWS. Performed the experiments: IA. Analyzed the data: IA. Wrote the manuscript: IA CWS.

Abstract

Spreading depolarizations (SDs) are coordinated depolarizations of brain tissue that have been well-characterized in animal models and more recently implicated in the progression of stroke injury. We previously showed that extracellular Zn²⁺ accumulation can inhibit the propagation of SD events. In that prior work, Zn²⁺ was tested in normoxic conditions, where SD was generated by localized KCl pulses in oxygenated tissue. The current study examined the extent to which Zn²⁺ effects are modified by hypoxia, to assess potential implications for stroke studies. The present studies examined SD generated in brain slices acutely prepared from mice, and recordings were made from the hippocampal CA1 region. SDs were generated by either local potassium injection (K-SD), exposure to the Na⁺/K⁺-ATPase inhibitor ouabain (ouabain-SD) or superfusion with modified ACSF with reduced oxygen and glucose concentrations (oxygen glucose deprivation: OGD-SD). Extracellular Zn²⁺ exposures (100 µM ZnCl₂) effectively decreased SD propagation rates and significantly increased the initiation threshold for K-SD generated in oxygenated ACSF (95% O₂). In contrast, ZnCl₂ did not inhibit propagation of OGD-SD or ouabain-SD generated in hypoxic conditions. Zn²⁺ sensitivity in 0% O₂ was restored by exposure to the protein oxidizer DTNB, suggesting that redox modulation may contribute to resistance to Zn²⁺ in hypoxic conditions. DTNB pretreatment also significantly potentiated the inhibitory effects of competitive (D-AP5) or allosteric (Ro25-6981) NMDA receptor antagonists on OGD-SD. Finally, Zn²⁺ inhibition of isolated NMDAR currents was potentiated by DTNB.

Together, these results suggest that hypoxia-induced redox modulation can influence the sensitivity of SD to Zn²⁺ as well as to other NMDAR antagonists. Such a mechanism may limit inhibitory effects of endogenous Zn²⁺ accumulation in hypoxic regions close to ischemic infarcts.