Cerebral Ischemia-reperfusion Injury Model Research Articles

Protective effects and mechanism of puerarin on learning-memory disorder after global cerebral ischemia-reperfusion injury in rats

To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats, and to explore its mechanism of action. The global cerebral ischemia-reperfusion injury model was established using the modifified Pulsinelli four-vessel occlusion in Sprague-Dawley rats. Rats were intraperitoneally injected with puerarin (100 mg/kg) 1 h before ischemia and once every 6 h afterwards. The learning-memory ability was evaluated by the passive avoidance test. The dynamic changes of the cell counts of apoptosis and positive expression of Bcl-2 in the hippocampus CA1 region were determined by the TUNEL and immunohistochemical methods, respectively. (1) Compared with the reperfusion group, the step through latency (STL) in the passive avoidance test in the puerarin group was prolonged signifificantly (P<0.01). (2) The apoptotic neurons were injured most severely on the 3rd day in the hippocampal CA1 region after global ischemia and reperfusion. In the puerarin group, the number of apoptotic cells decreased at respective time points after ischemia-reperfusion (P<0.01). (3) The level of positive expression of Bcl-2 varied according to the duration of reperfusion and the peak level occurred on day 1 in the hippocampal CA1 region after global cerebral ischemia. Compared with the reperfusion group, the expression of Bcl-2 in the puerarin group was up-regulated at the respective time points after ischemia reperfusion (P<0.01), reaching the peak on day 1. Puerarin could improve the learning-memory ability after global cerebral ischemia and reperfusion in rats. The protective mechanism might be related to the effect of inhibiting or delaying the cell apoptosis through up-regulating the expression of Bcl-2 after ischemia and reperfusion.

Nanoparticle‐mediated delivery of superoxide dismutase to the brain: an effective strategy to reduce ischemia‐reperfusion injury

Excessive production of reactive oxygen species (ROS) after cerebral ischemia and reperfusion is implicated in brain damage through different cellular and molecular mechanisms, and it is further aggravated by impaired cellular antioxidant defense systems under ischemic conditions. Therapeutic strategies based on exogenous delivery of the native form of superoxide dismutase (SOD), a free radical scavenger, are limited because of its short half-life (approximately 6 min) in vivo and poor permeability across the blood-brain-barrier (BBB). We encapsulated SOD in biodegradable poly(D,L-lactide co-glycolide) nanoparticles (SOD-NPs) and tested their efficacy in a rat focal cerebral ischemia-reperfusion injury model. We hypothesized that localized brain delivery of SOD-NPs would sustain the protective effect of SOD by neutralizing the deleterious effects of ROS formed following ischemia-reperfusion. SOD-NPs were administered at the time of reperfusion via the intracarotid route to maximize their localization in the brain. Animals receiving SOD-NPs (10,000 U of SOD/kg) demonstrated a 65% reduction in infarct volume, whereas an equivalent dose of SOD in solution (SOD-Sol) increased it by 25% over saline control (P<0.001; data at 6 h following reperfusion). Control NPs alone or mixed with SOD-Sol were ineffective in reducing infract volume, with results similar to saline control, indicating the protective effect of the encapsulated enzyme. SOD-NPs maintained BBB integrity, thereby preventing edema, reduced the level of ROS formed following reperfusion, and protected neurons from undergoing apoptosis. Animals treated with SOD-NPs demonstrated greater survival than those with saline control (75% vs. 0% at 28 days) and later regained most vital neurological functions. SOD-NPs may be an effective treatment option in conjunction with a thrombolytic agent for stroke patients.

Effects of Qingkailing Injection on Transforming Growth Factor-β1 Expression in Cerebral Ischemia-reperfusion Injury in Rats

Abstract Objective To explore the effects of Qingkailing injection (QKL) on transforming growth factor-β1 (TGF-β1) expression in the rats with cerebral ischemia-reperfusion injury. Methods Healthy Wistar rats were randomly divided into 3 groups: normal group, model group, and QKL-treated group. Model of cerebral ischemia-reperfusion injury was copied by repeated occlusion of common carotid arteries (CCA) on both sides. The expression of glial fibrillary acidic protein (GFAP) and TGF-β1 in brain tissue was observed at different time intervals, using immunity histochemistry staining method. Results At different time intervals after cerebral ischemia-reperfusion injury, the expression of GFAP and TGF-β1 in brain tissue increased by different degrees, whereas QKL decreased them by different degrees. Conclusion QKL could probably reduce the expression of TGF-β1 by restraining the activity of astrocytes (AST).

Effect of pretreatment with penehyclidine hydrochloride on cerebral infarction volume and neuronal apoptosis in murine models of cerebral ischemia-reperfusion injury

乙酰胆碱(Ach)是脑内经典的兴奋性递质,作用于M型和N型胆碱受体,与大脑的多种高级神经功能有关.研究发现,脑缺血时Ach释放异常增加,若干胆碱酯酶抑制剂对神经元有损害作用[1].也有研究表明Ach可加强谷氨酸(Glu)诱导的培养海马神经元变性,且这种作用是通过M型胆碱受体来实现的.Glu和Ach可能在缺血性脑损伤中有放大的协同作用[2].脑内突触前N型胆碱受体激活后也能够增加包括Glu在内的多种递质的释放[3].本实验选用对M型和N型胆碱受体都有阻滞作用的新型胆碱能受体阻滞剂盐酸戊乙奎醚为研究药,以东莨菪碱为阳性对照药,通过观察脑缺血/再灌注损伤大鼠的脑梗死体积和神经元凋亡的变化,探讨盐酸戊乙奎醚的脑保护作用及其机制。

Cardioprotective actions of transforming growth factor-β

Transforming growth factor-beta (TGF-β) has been shown to have protective effects in experimental models of myocardial, mesenteric, and cerebral ischemia-reperfusion injury. These effects are mediated by its ability to block adhesion of neutrophils to endothelium and to preserve endothelial function in terms of physiologic release of nitric oxide (NO). TGF-β also maintains the rhythmicity of cultured cardiac myocytes and blocks the suppressive effects of interleukin-1 on their beating rate by antagonizing the pathologic induction of NO synthase. These data suggest that TGF-β will be useful clinically in treatment of both reperfusion injury and inflammatory diseases of the heart.

Blood to Brain Transport after Newborn Cerebral Ischemia/Reperfusion Injury

These experiments examine the transfer of urea, sodium, and sucrose from blood to brain in an animal model of newborn cerebral ischemia-reperfusion injury. Cerebral ischemia (20 min) was produced in anesthetized, ventilated piglets by increasing intracranial pressure above mean arterial blood pressure, thereby reducing cerebral perfusion pressure to zero. The blood to brain transfer of urea, sodium, and sucrose was then measured in sham control piglets and at 30 min and 2 hr of reperfusion following ischemia. At 30 min of reperfusion, urea and sodium transfer were increased while sucrose transfer was unchanged. However, at 2 hr of reperfusion, transfer of all three tracers was elevated. The difference in the time course of increased transport of these substances into the brain following ischemia cannot be explained by size differences, indicating that changes in the blood-brain barrier following ischemia are more complex than merely opening junctions between cells and creating leaky sites. Alterations in blood-brain barrier transport could participate in altered neuronal function after ischemia-reperfusion injury.