Evaluation of hippocampal injury and cognitive function induced by embolization in the rat brain.

Embolism is responsible for at least 20% of all stroke and half of cerebral infarctions. A number of animal models have been developed to mimic thromboembolic stroke. However, little aimed directly at hippocampal damage and cognitive function. In the present study, three sizes of emboli (150-178 µm, 74-124 µm, and 48-74 µm) were employed to induce thromboembolic stroke model in rats. Results showed that the diameter of the particle was critical for animal behavioral and histopathological consequences. Hematoxylin-eosin (HE) staining revealed that CA1 and CA2-3, which are two of the main hippocampal subdivisions were injured seriously, especially induced by emboli(48-74 µm) . At 24 hr, the neurological deficit scores showed that emboli injection could cause significant neurological deficit, and the increase of neurological deficit scores correlated well to the diameter of emboli. At 60 days, emboli(150-178 µm) and emboli(48-74 µm) lead to obvious cognitive impairment, which correlated well to the hippocampal CA1 injury. Our research might be helpful to choose suitable size of emboli to induce animal model to research subcortical ischemia and vascular dementia. However, cognitive alterations and cerebral injury following different sizes of emboli injection in rats remains a topic for future investigation.

Salvianolic acid A protects human SH-SY5Y neuroblastoma cells against H2O2-induced injury by increasing stress tolerance ability.

Salvianolic acid A (Sal A) is a polyphenol extracted from the root of the Salvia miltiorrhiza bunge. Hydrogen peroxide (H(2)O(2)) is a major reactive oxygen species (ROS), which has been implicated in stroke and other neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. In this study, we investigated the neuroprotective effects of Sal A in human SH-SY5Y neuroblastoma cells against H(2)O(2)-induced injury. Our results showed that cells pretreated with Sal A exhibited enhanced neuronal survival and that this protection was associated with an increase in adenosine triphosphate (ATP) and the stabilization of mitochondrial membrane potential. In addition, Sal A markedly decreased the excessive activation AMP-activated protein kinase (AMPK) and the serine-threonine protein kinase, Akt, in SH-SY5Ycells induced by H(2)O(2). In conclusion, our results demonstrated that Sal A protects SH-SY5Y cells against H(2)O(2)-induced oxidative stress and these protective effects are related to stress tolerance and not energy depletion via inhibition of the AMPK and Akt signaling pathway.

[Effect of pinocembrin on brain mitochondrial respiratory function].

There are growing evidences that pinocembrin has better neuroprotective effect. In the present study, the effect of pinocembrin on mitochondrial respiratory function was evaluated in global brain ischemia/ reperfusion (4-vessel occlusion, 4-VO) rats. The results showed that pinocembrin improved the respiratory activity of 4-VO brain mitochondria, through increasing ADP/O, state 3 respiration state (V3), respiration control rate index (RCI) and oxidative phosphorylation rate (OPR). And then, the effect of pinocembrin on brain mitochondria was verified in vitro. The results showed that pinocembrin increased ADP/O, state 3 respiration state, respiration control rate index, oxidative phosphorylation rate in NADH/FADH2 dependent respiratory chain and decreased state 4 respiration state (V4) in NADH dependent respiratory chain. Pinocembrin improved ATP content in brain mitochondria in vitro and in SH-SY5Y cells.

The characteristics of therapeutic effect of pinocembrin in transient global brain ischemia/reperfusion rats.

AIMS: The therapeutic effect of pinocembrin, together with the therapeutic time window, in the transient global cerebral ischemia/reperfusion (I/R) rats was investigated. MAIN METHODS: Adult male Sprague-Dawley rats were subjected to global cerebral ischemia for 20 min by four-vessel occlusion. Pinocembrin (1 and 5mg/kg) was administrated intravenously 30 min before ischemia and 30 min, 2h, 6h after reperfusion, respectively. Neurological scores, brain edema and histological examination by Nissl staining were employed to assess the neuronal injury after ischemia and the neuroprotection by pinocembrin. The activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and the content of malondialdehyde (MDA) in brain tissue were tested by colorimetric assays. Alterations of neurotransmitters were determined by a high performance liquid chromatography-electrochemical method. KEY FINDINGS: Pinocembrin significantly ameliorated neurological deficits and brain edema, and alleviated the degree of hippocampal neuronal loss at 24h after global cerebral I/R with a broad therapeutic time window. It was found that treatment with pinocembrin reduced the compensatory increase of SOD activity and decreased the MDA level and MPO activity in a dose-dependent manner. The metabolic balance between excitatory and inhibitory amino acids was modulated by pinocembrin treatment. SIGNIFICANCE: These findings suggest that pinocembrin provides neuroprotection against global cerebral ischemic injury with a wide therapeutic time window, which may be attributed to its antioxidative, antiinflammatory and antiexcitotoxic effects.

[Effect of metformin on the formation of hepatic fibrosis in type 2 diabetic rats].

The aim of this study is to investigate the effects of the metformin on the formation of hepatic fibrosis in type 2 diabetic rats and discuss its mechanism of liver-protecting activity. After SD rats were fed with high-fat and high-sucrose diet for four weeks, low-dose streptozotocin (STZ) was injected intraperitoneally to make the animal mode of type 2 diabetes. Then, all diabetic rats was fed with the high-fat diet and metformin (ig, 100 mg x kg(-1)) was given orally to metformin group for four months. After the last administration, fasting blood glucose was determined. The livers were removed to calculate the hepatic coefficient and to make HE and Picro acid-Sirius red staining, immunohistochemistry (alpha-SMA and TGFbeta1) and TUNEL staining in order to evaluate the effect of metformin on the hepatic fibrosis. The animal model of type 2 diabetes with hepatic fibrosis was successfully made. Metformin can significantly alleviate the lesions of hepatic steatosis and fibrosis, markedly reduce the expressions of alpha-SMA and TGFbeta1 in liver tissue of type 2 diabetic rats. However, TUNEL staining result suggested that metformin could not reduce apoptosis of hepatocytes. The results suggest that metformin can inhibit the formation of hepatic fibrosis in type 2 diabetes.