14,15-EET Reduced Brain Injury from Cerebral Ischemia and Reperfusion via Suppressing Neuronal Parthanatos

Area of Science:

• Neuroscience
• Biochemistry
• Pathology

Background:

• Cerebral ischemia and reperfusion (I/R) induce neuronal death through parthanatos, a programmed cell death pathway.
• 14,15-epoxyeicosatrienoic acid (14,15-EET) is known to have neuroprotective effects, but its role in mitigating parthanatos is not fully understood.

Purpose of the Study:

• To investigate the protective effect of 14,15-EET against neuronal parthanatos induced by cerebral I/R.
• To elucidate the underlying mechanisms, including the modulation of reactive oxygen species (ROS) and antioxidant gene expression.

Main Methods:

• Cerebral I/R was simulated using middle cerebral artery occlusion and reperfusion (MCAO/R) in vivo and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro.
• Cerebral infarct volume and neuronal apoptosis were assessed using TTC staining and the Tunel method.
• Western blot, immunofluorescence, Mito SOX, DCFH-DA, and qPCR were employed to detect PARP-1 activation, AIF nuclear translocation, ROS production, and antioxidant gene expression (GSH-Px, HO-1, SOD).

Main Results:

• MCAO/R significantly increased cerebral infarct volume and neuronal apoptosis.
• OGD/R induced ROS generation, PARP-1 cleavage, and AIF nuclear translocation in cortical neurons.
• 14,15-EET pretreatment attenuated infarct volume and apoptosis, enhanced antioxidant gene expression, and reduced ROS production.

Conclusions:

• 14,15-EET inhibits neuronal parthanatos following cerebral I/R.
• The neuroprotective mechanism involves the upregulation of antioxidant genes and the reduction of ROS generation.
• This study provides a scientific basis for developing 14,15-EET-based therapies for cerebral I/R injury.