Deans' stroke musings: Inhibition of glial D-serine release rescues synaptic damage after brain injury

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, March 3, 2022

Inhibition of glial D-serine release rescues synaptic damage after brain injury

Now we just need someone to put this together into a protocol and distribute it effectively to all stroke hospitals(meaning the stroke hospital implements the protocol). That will never occur, we have NO leadership that will ensure it gets done.

Inhibition of glial D-serine release rescues synaptic damage after brain injury

1The Miami Project to Cure Paralysis,Department of Neurological Surgery,University of Miami Miller School of Medicine,Miami, Florida, USA2Department of Psychiatry, Harvard MedicalSchool, Boston, Massachusetts, USA3Translational Psychiatry Laboratory, McLeanHospital, Belmont, Massachusetts, USA4Department of Biochemistry, RappaportFaculty of Medicine, Technion-Israel Instituteof Technology, Haifa, IsraelCorrespondenceDaniel J. Liebl, The Miami Project to CureParalysis, The University of Miami, 1095 NW14th Terrace, R-48, Miami, FL 33136, USA.

Abstract

Synaptic damage is one of the most prevalent pathophysiological responses to traumatic CNS injury and underlies much of the associated cognitive dysfunction;however, it is poorly understood. The D-amino acid, D-serine, serves as the primary co-agonist at synaptic NMDA receptors (NDMARs) and is a critical mediator of NMDAR-dependent transmission and synaptic plasticity. In physiological conditions,D-serine is produced and released by neurons from the enzymatic conversion of L-serine by serine racemase (SRR). However, under inflammatory conditions, glial cells become a major source of D-serine. Here, we report that D-serine synthesized by reactive glia plays a critical role in synaptic damage after traumatic brain injury (TBI) and identify the therapeutic potential of inhibiting glial D-serine release though the transporter Slc1a4 (ASCT1). Furthermore, using cell-specific genetic strategies and pharmacology, we demonstrate that TBI-induced synaptic damage and memory impairment requires D-serine synthesis and release from both reactive astrocytes and microglia. Analysis of the murine cortex and acutely resected human TBI brain also show increased SRR and Slc1a4 levels. Together, these findings support a novel role for glial D-serine in acute pathological dysfunction following brain trauma,whereby these reactive cells provide the excess co-agonist levels necessary to initiate NMDAR-mediated synaptic damage.