ferroptosis in brain stroke

1. FERROPTOSIS PHENOMENON IN BRAIN ISCHEMIC STROKE
NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH
HYDERABAD
Presented by
Y. Veekshith
PC/2021/217
Pharmacology&toxicology
Under the guidance of
Dr Manoj Dandekar

2. Ferroptosis
is a new type of PCD characterized by iron dependent accumulation of lipid peroxides
• Brent Stockwell and Scott J.Dixon coined the term ferroptosis in 2012
• Lipid peroxides is marker for ferroptosis
• Glutathione peroxidase-4 - master regulator of ferroptosis
FERROPTOSIS
SCOTT J.DIXON
BRENT STOCKWELL
Fe CYTOPLASAM
FENTON
REACTION
FORMATION
OF ROS
INCREASE IN
LIPID
PEROXIDES
FERROPTOSIS

3. Biochemical changes :
Caspases Caspases GPX-4
Morphological changes :
Cell shrink Cell swelling Cell swelling Cell are normal
CM intact CM Damage CM damage CM Intact & normal
Nucleus changes :
Chromatin condensation Pyknosis & karyolysis Pyknosis & Karyolysis Normal
Mitochondrial damage
1- small size
2- om – rupture
3- im – dense thick
4- cristae – reduced /absent
PROGRAMMED CELL DEATH
APOPTOSIS PYROPTOSIS NECROPTOSIS

4. STROKE
According to American stroke association,
Stroke occurs when blood vessel that carries oxygen and nutrients to brain is either blocked by clot or burst
STROKE
HEMORRHAGIC
ISCHEMIC
A blockage of the blood vessel in the brain Caused by burst or leaking blood vessel in the brain

5. Core and Penumbra
• Ischemic penumbra is used to define ischemic but
still viable cerebral tissue.
• In the core zone, which is area of severe ischemia
(blood flow below 10-25%), the loss of oxygen and
glucose results in rapid depletion of energy stores.
• Severe ischemia can results in necrosis of neurons
and also of supporting cellular elements (glial cells)
within the severely ischemic area.
• The penumbra is where pharmacological
intervention are mostly likely to be effective.

6. Shen, Lesang et al.
Mechanism of ferroptosis

7. FERROPTOSIS ASSOCIATED MECHANISIM AND POTENTIAL THERAPY IN ACUTE CNS INJURY

8. Possible targets and molecular mechanisms of the crosstalk between oxidative stress and ferroptosis in
ischemic stroke
Jia-Xin Ren et

9. Potential regulatory mechanism of ferroptosis in ischemic stroke
She X, Lan B, Tian H and Tang B(2020)

10. POTENTIAL AND EMERGING THERAPY TAGETTING FERROPTOSIS IN STROKE

11. • Diabetic patient has poor stroke outcome
• Study focus on DFX effect on cerebral
vascularization & functional outcomes
• By taking BMEC, they measure vascular
indices , neurovascular remodelling ,
microglial activation
• DFX improve APP4 Polarity & BBB
permeability , prevent Vasoregression
and microglial activation
• Results : HT impact on post stroke
vascularization & recovery response in
diabetes ,Treatment of iron chelators has
differential outcomes in comorbid
diseases, Iron chelator and inhibition of
ferroptosis may provide a novel disease
modifying therapy in prevention of post
stroke cognitive impairment in diabetes

13. Conclusion
Cerebral ischemia can induces ferroptosis and in turn ferroptosis aggravates
cerebral ischemic injury, inhibiting ferroptosis can alleviate this injury.
Regulatory mechanism involved with ferroptosis in stroke including iron overload and
regulatory mechanism upstream of GPX4,12/15LOX and Nrf2 ,remain unclear in
particular, whether ferroptosis causes cell death or by other means requires further
investigation.
Relationship between ferroptosis and other cell death mechanisms such as apoptosis
etc in stroke is an imp direction for future research.
The resolution of these obstacles will provide crucial support for the development of
ferroptosis as a target in stroke intervention and an imp direction for the study of
pathological mechanisms involved in cerebral ischemia.

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