malealdehyde and Brain-Injuries

Cardiac arrest (CA) yields poor neurological outcomes. Salubrinal (Sal), an endoplasmic reticulum (ER) stress inhibitor, has been shown to have neuroprotective effects in both in vivo and in vitro brain injury models. This study investigated the neuroprotective mechanisms of Sal in postresuscitation brain damage in a rodent model of CA. In the present study, rats were subjected to 6 min of CA and then successfully resuscitated. Either Sal (1 mg/kg) or vehicle (DMSO) was injected blindly 30 min before the induction of CA. Neurological status was assessed 24 h after CA, and the cortex was collected for analysis. As a result, we observed that, compared with the vehicle-treated animals, the rats pretreated with Sal exhibited markedly improved neurological performance and cortical mitochondrial morphology 24 h after CA. Moreover, Sal pretreatment was associated with the following: (1) upregulation of superoxide dismutase activity and a reduction in maleic dialdehyde content; (2) preserved mitochondrial membrane potential; (3) amelioration of the abnormal distribution of cytochrome C; and (4) an increased Bcl-2/Bax ratio, decreased cleaved caspase 3 upregulation, and enhanced HIF-1

Topics: Aldehydes; Animals; Apoptosis; Brain Injuries; Cardiopulmonary Resuscitation; Caspase 3; Cerebellar Cortex; Cinnamates; Cytochromes c; Endoplasmic Reticulum Stress; Heart Arrest; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Membrane Potential, Mitochondrial; Microscopy, Electron, Transmission; Mitochondria; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Superoxide Dismutase-1; Thiourea

Poor neurological outcome remains a major problem in patients with cardiac arrest. Ghrelin has been shown to be neuroprotective in models of neurologic injury in vitro and in vivo. This study was performed to assess the effects of ghrelin on postresuscitation brain injury in a rat model of cardiac arrest. Sprague-Dawley rats were subjected to 6-min cardiac arrest and resuscitated successfully. Either vehicle (saline) or ghrelin (80 μg/kg) was injected blindly immediately after return of spontaneous circulation (ROSC). A tape removal test was performed to evaluate neurological function at 24, 48, and 72 h after ROSC. Then, brain tissues were harvested and coronal brain sections were analyzed by hematoxylin and eosin (HE) staining for neuronal viability and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining for apoptosis in hippocampal CA1 sectors. In additional groups, rats were sacrificed at 6 h after ROSC, and hippocampal tissues were collected for further analysis. We found that animals treated with ghrelin had improved neurological performances, reduced neuronal injury, and inhibited neuronal apoptosis compared with the vehicle group. Moreover, ghrelin treatment was associated with the following: (1) a decrease in caspase-3 up-regulation and an increased Bcl-2/Bax ratio, (2) a reduction in maleic dialdehyde content and an up-regulation in superoxide dismutase activity, and (3) an increase in uncoupling protein 2 (UCP-2) expression. Our results suggest that ghrelin treatment attenuated postresuscitation brain injury in rats, possibly via regulation of apoptosis, oxidative stress, and mitochondrial UCP-2 expression. Ghrelin may have therapeutic potential when administered after cardiac arrest and cardiopulmonary resuscitation.

Topics: Aldehydes; Animals; Apoptosis; bcl-2-Associated X Protein; Brain Injuries; CA1 Region, Hippocampal; Cardiopulmonary Resuscitation; Caspase 3; Cell Survival; Ghrelin; Heart Arrest; Ion Channels; Mitochondrial Proteins; Neurons; Neuroprotective Agents; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Time Factors; Uncoupling Protein 2; Up-Regulation