enalapril and Cognitive-Dysfunction

We previously reported that apoptosis is responsible for cognitive impairment in rats with myocardial infarction (MI). Acute administration of an apoptosis inhibitor (Z-vad) effectively reduced brain inflammation in rats with cardiac ischemia/reperfusion injury. However, the beneficial effects of Z-vad on cognitive function, brain inflammation, mitochondrial function, cell death pathways, and neurogenesis in MI rats have not been investigated. Male rats were divided into sham or MI groups (left anterior descending coronary ligation). A successful MI was determined by a reduction of ejection fraction <50 %. Then, MI rats were allocated to receive vehicle, enalapril (10 mg/kg, a positive control), and Z-vad (1 mg/kg) for 4 weeks. Cardiac function, cognitive function, and molecular analysis were investigated. MI rats exhibited cardiac dysfunction, cognitive impairment, blood brain barrier (BBB) breakdown, dendritic spine loss, which were accompanied by an upregulation of oxidative stress, mitochondrial dysfunction, and apoptosis. Chronic treatment with Z-vad attenuated cardiac dysfunction following MI to the same extent as enalapril. Z-vad successfully improved cognitive function and restored dendritic spine density in MI rats through a reduction of systemic oxidative stress and brain mitochondrial dysfunction similar to enalapril. Moreover, Z-vad provided greater efficacy than enalapril in enhancing mitophagy, neurogenesis, synaptic proteins and reducing apoptosis in hippocampus of MI rats. Nevertheless, neither Z-vad nor enalapril increased BBB tight junction protein. In conclusion, treatment with an apoptosis inhibitor reduced cognitive impairment in MI rats via reducing oxidative stress, mitochondrial dysfunction, apoptosis, and restoring dendritic spine density, together with enhancing mitophagy and neurogenesis.

Topics: Animals; Apoptosis; Cognitive Dysfunction; Enalapril; Encephalitis; Male; Myocardial Infarction; Rats

Topics: Child, Preschool; Cognitive Dysfunction; Edema; Enalapril; Female; Growth Disorders; Human Growth Hormone; Humans; Hypertension; Nephrotic Syndrome; Severity of Illness Index

Topics: Arteriosclerosis; Bone Marrow Transplantation; Child, Preschool; Cognitive Dysfunction; Diagnosis, Differential; DNA Helicases; DNA Mutational Analysis; Enalapril; Female; Granulocyte Colony-Stimulating Factor; Growth Disorders; Human Growth Hormone; Humans; Kidney Transplantation; Mutation; Nephrotic Syndrome; Osteochondrodysplasias; Primary Immunodeficiency Diseases; Pulmonary Embolism