The neuroprotective effects of grape seed proanthocyanidin on rat brain injury caused by chronic intermittent hypoxia

Chronic intermitted hypoxia including sleep breathing disorder leads to brain injury. This study explores the potential therapeutic effects of grape seed proanthocyanidin as a neuroprotective agent. A rat model of chronic intermittent hypoxia was employed, and the animals were given low or high doses of grape seed proanthocyanidin. The ultrastructure changes in the brain, the biochemical components, and the animal behavior were examined. The results showed that with hypoxia exposure, neuronal mitochondria exhibited injuries at ultrastructural level, with increased malondialdehyde (MDA) content and reduced superoxide dismutase (SOD) activity. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining revealed increased cell apoptosis in hippocampus. In Morris water maze the animals showed decreased learning abilities, when compared to normal control. The administration of grape seed proanthocyanidin treatment reversed all these observed changes, and improved the learning behavior. We concluded that grape seed proanthocyanidin could alleviate the brain injury caused by hypoxia from sleep breathing disorder. Neurology Asia 2014; 19(4) : 399 – 403 Address correspondence to: Dr. Hong-Yang WANG; School of rehabilitation, Hebei Lianhe University, Tangshan, China; email: [email protected] INTRODUCTION Sleep breathing disorder, especially obstructive sleep apnea syndrome (OSA), leads to hypoxia in the circulation, with possible brain injury, , grey matter loss, hippocampus shrinkage, and cognition impairment. It is believed that the brain injury is caused by oxidative stress and activation of a series of signaling pathways such as c-Jun N-terminal kinase (JNK). Therefore targeting the oxidative stress may be helpful in treatment against the associated brain injuries caused by chronic hypoxia. Grape seed proanthocyanidin is a bioactive compound extracted from grape seed. It has been previously found to have strong anti-oxidation effect in treatments of different diseases, especially the cardiovascular diseases. Whether grape seed proanthocyanidin is also effective in protecting brain injury caused by hypoxia, is however not been previously investigated. Here we test the hypothesis in a rat model of chronic intermitted hypoxia, to determine whether the grape seed proanthocyanidin is able to protect against such brain disorders, and possibly other brain degenerative diseases. METHODS Animals and the hypoxia exposure Eighty male Sprague Dawley (SD) rats (Beijing Weitong Lihua Co.) (Animal license: SCXK(Jing)2002-003) (Weighted 310-350 g) were used in this study. The animals were randomly assigned to four groups with 20 animals each: control, hypoxia (50 ml/L oxygen), hypoxia with low dose proanthocyanidin (orally fed 100mg/kg) and hypoxia with high dose proanthocyanidin (orally fed 200mg/kg). For intermitted hypoxia, the animals were kept in intermittent hypoxia room from 8:00 am to 4:00 pm (8 hours) every day for 2 or 6 weeks (10 animals for each duration). N 2 and O 2 air were delivered to the intermittent hypoxia room in controlled manner. In the hypoxia group, the N 2 was given for 30 seconds, with lowest O 2 concentration at 5% (50 ml/L). Then the O 2 concentration was allowed to recover to 21% (210 ml/L). The cycle was repeated every 2 minutes. In the control group, compressed air was given. Neurology Asia December 2014 400 Morris water maze The Morris water maze was performed as previously described. The animal was trained five times in the morning, tested six times at noon and six times in the afternoon. The time the animal took to find the hidden platform, and the time the animal spent in the area of hidden platform after the platform was removed were recorded.