Docosahexaenoic Acid Alleviates Oxidative Stress-Based Apoptosis Via Improving Mitochondrial Dynamics in Early Brain Injury After Subarachnoid Hemorrhage

• Published in: Cellular and molecular neurobiology 2018-10, Vol.38 (7), p.1413-1423
• Main Authors: Zhang, Tongyu, Wu, Pei, Zhang, John H., Li, Yuchen, Xu, Shancai, Wang, Chunlei, Wang, Ligang, Zhang, Guang, Dai, Jiaxing, Zhu, Shiyi, Liu, Yao, Liu, Binbing, Reis, Cesar, Shi, Huaizhang
• Format: Article
• Language: English
• Subjects: Aneurysms; Animals; Apoptosis; Apoptosis - drug effects; Atrophy; Bax protein; Bcl-x protein; Biomedical and Life Sciences; Biomedicine; Brain Injuries - drug therapy; Brain Injuries - etiology; Brain Injuries - metabolism; Brain Injuries - pathology; Brain injury; Cardiovascular system; Caspase; Caspase-3; Cell Biology; Cells, Cultured; Docosahexaenoic acid; Docosahexaenoic Acids - pharmacology; Docosahexaenoic Acids - therapeutic use; Dynamin; Edema; Embryo, Mammalian; Fusion protein; Male; Malondialdehyde; Mitochondria; Mitochondria - drug effects; Mitochondria - physiology; Mitochondrial Dynamics - drug effects; Molecular modelling; Neurobiology; Neurological diseases; Neurons - drug effects; Neurons - pathology; Neuroprotection; Neuroprotection - drug effects; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Optic atrophy; Original Research; Oxidative stress; Oxidative Stress - drug effects; Primary Cell Culture; Proteins; Rats; Rats, Wistar; Reactive oxygen species; Reactive Oxygen Species - metabolism; Serine; Subarachnoid hemorrhage; Subarachnoid Hemorrhage - complications; Subarachnoid Hemorrhage - drug therapy; Subarachnoid Hemorrhage - metabolism; Subarachnoid Hemorrhage - pathology; Superoxide dismutase; Therapeutic applications; Traumatic brain injury
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-018-0608-3

Mitochondrial dysfunction is considered a crucial therapeutic target for early brain injury following subarachnoid hemorrhage (SAH). Emerging evidence indicates that docosahexaenoic acid (DHA), an essential omega-3 fatty acid, protects mitochondria in various chronic diseases. This study aimed to investigate the neuroprotective effects of DHA on mitochondrial dynamic dysfunction after EBI using in vivo and in vitro approaches. For in vivo experiments, the rat endovascular perforation SAH model was performed, whereby DHA was administered intravenously 1 h after induction of SAH. Primary cultured neurons treated with oxyhemoglobin (OxyHb) for 24 h were used to mimic SAH in vitro. Our results demonstrated that DHA improved neurological deficits and reduced brain edema in rats with SAH, and attenuated OxyHb-induced neuronal death in primary cultured cells. DHA reduced the amount of reactive oxygen species-positive cells and improved cell viability when compared to the SAH + vehicle group in vitro. DHA attenuated malondialdehyde levels and superoxide dismutase stress, increased Bcl2 and Bcl-xl, and decreased Bax and cleaved caspase-3 in vivo. Additionally, DHA ameliorated mitochondrial dysfunction, upregulated the mitochondrial fusion-related protein Optic Atrophy 1, and downregulated the mitochondrial fission-related protein Dynamin-Related-Protein 1 (Drp1) and Serine 616 phosphorylated Drp1 after SAH both in vitro and in vivo. Taken together, our current study demonstrates that DHA might prevent oxidative stress-based apoptosis after SAH. The characterization of the underlying molecular mechanisms may further improve mitochondrial dynamics-related signaling pathways.