Low-Molecular-Weight Fucoidan Attenuates Mitochondrial Dysfunction and Improves Neurological Outcome After Traumatic Brain Injury in Aged Mice: Involvement of Sirt3.

摘要: Traumatic brain injury (TBI) is a leading cause of death and long-term disability. Fucoidan, sulfated polysaccharide extracted from brown algae, possesses potent anti-oxidative anti-inflammatory effects. Considering TBI happens frequently in adults, especially aged individuals, we herein sought to define the protective effects low-molecular-weight fucoidan (LMWF) mice. 16- 18-month-old mice administered with LMWF (1-50 mg/kg) or vehicle were subjected using controlled cortical impact (CCI) model. at doses 10 50 mg/kg significantly reduced both hippocampal lesion volume. This protection was associated neuronal apoptosis, as evidenced by TUNEL staining. Importantly, effective even when up 4 h after TBI. Treatment improved neurobehavioral outcomes, including sensorimotor function, hippocampus-associated spatial learning memory. In addition, suppressed protein carbonyl, lipid peroxidation, reactive oxygen species (ROS) generation, well mitochondrial dysfunction, which cytochrome c release collapse membrane potential (MMP). To evaluate underlying molecular mechanisms, expression sirtuin 3 (Sirt3) detected RT-PCR Western blot. The results showed that increased Sirt3, further elevated treatment. Knockdown Sirt3 intracerebroventricular injection small interfering RNA (siRNA) partially prevented therapeutic LMWF. Collectively, these findings demonstrated exerts neuroprotection against brain, may be attenuation dysfunction through activation.