Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice

Clinical advances in the treatment of intracranial hemorrhage(ICH)are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury.Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases.Our results indicated a significant increase in the level of acrolein after ICH in mouse brain.In primary neurons,acrolein induced an increase in mitochondrial fragmentation,loss of mitochondrial membrane potential,generation of reactive oxidative species,and release of mitochondrial cytochrome c.Mechanistically,acrolein facilitated the translocation of dynaminrelated protein 1(Drpl)from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission.Further studies found that treatment with hydralazine(an acrolein scavenger)significantly reversed Drpl translocation and the morphological damage of mitochondria after ICH.In parallel,the neural apoptosis,brain edema,and neurological functional deficits induced by ICH were also remarkably alleviated.In conclusion,our results identify acrolein as an important contributor to the secondary brain injury following ICH.Meanwhile,we uncovered a novel mechanism by which Drpl-mediated mitochondrial oxidative damage is involved in acroleininduced brain injury.

Time representation of mitochondrial morphology and function after acute spinal cord injury

Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2–24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2–24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na＋-K＋-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged.