Deans' stroke musings: Targeting Ferroptosis for Cerebral Neuroprotection in Ischemic Stroke: Pathophysiological Insights

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.

Friday, May 29, 2026

Targeting Ferroptosis for Cerebral Neuroprotection in Ischemic Stroke: Pathophysiological Insights

With this new and old research your competent? doctor has everything needed to create recovery protocols, right? NO? So, you DON'T have a functioning stroke doctor, do you?

Ferroptosis (12 posts to July 2012)

Targeting Ferroptosis for CerebralNeuroprotection in Ischemic Stroke:Pathophysiological Insights

Authors Song C , Tang S, Huang Y, Xie G, Tang J

Received 27 February 2026

Accepted for publication 16 May 2026

Published 26 May 2026 Volume 2026:19 605531

DOI https://doi.org/10.2147/IJGM.S605531

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Woon-Man Kung

Chong Song,^1,^* Songlin Tang,^2,^* Yongpan Huang,^1,^* Guangdi Xie,³ Jiayu Tang⁴

¹School of Medicine, Changsha Social Work College, Changsha, Hunan, People’s Republic of China; ²Department of Neurology, The First Affiliated Hospital of Shaoyang College, Shaoyang, Hunan, People’s Republic of China; ³Department of Neurology, Huitong People’s Hospital, Huitong, Hunan, People’s Republic of China; ⁴Department of Neurology, Brain Hospital of Hunan Province, Changsha, Hunan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jiayu Tang, Department of Neurology, Brain Hospital of Hunan Province, Changsha, Hunan, People’s Republic of China, Email tangjiayu1978@163.com Yongpan Huang, School of Medicine, Changsha Social Work College, Changsha, Hunan, People’s Republic of China, Email yongpanhuangyxy@163.com

Abstract: Acute ischemic stroke, a leading cause of neurological disability, stemed from cerebral hypoperfusion-induced ischemia/reperfusion (I/R) injury. Ferroptosis, an iron-dependent, lipid peroxidation-driven cell death, has emerged as a key pathological driver. Unlike apoptosis, ferroptosis involves glutathione peroxidase 4 (GPX4) inactivation, iron dysregulation, and lethal lipid peroxides. Its preclinical inhibition reduced neuronal loss, demonstrating therapeutic promise. Ischemic injury activated accidental/regulated cell death pathways, with ferroptosis, apoptosis, and pyroptosis dynamically regulated by ischemia duration/severity. Convergent mechanisms included hypoxia-induced mitochondrial dysfunction, iron/lipid peroxidation disrupting blood-brain barrier integrity, glutamate-ferroptosis oxidative crosstalk, and Ca²⁺ overload via reversed Na⁺/Ca²⁺ exchange and NMDA hyperactivity. Clinically, cerebrospinal ferritin elevation and parenchymal iron deposition predicted poor outcomes, prioritizing iron homeostasis modulation. GPX4 activation, ACSL4/LOX inhibition, and ACSL3-mediated MUFA integration have showed efficacy in preclinical models. Translational barriers included poor blood-brain barrier permeability of inhibitors, unvalidated human pathways, and lack of relevant comorbid models. Advancing therapies required biomarker discovery, human tissue validation, and integrated models to bridge mechanisms and clinical translation. Ferroptosis inhibition emerged as a neuroprotective strategy with transformative therapeutic potential for acute ischemic stroke, offering a novel avenue to mitigate neuronal injury and improve clinical outcomes.