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Objective Endothelial regeneration is an essential process for the prevention of excessive neointimal formation following endothelial denudation. Beclin 1, a mammalian autophagy gene, is a link between autophagy and apoptosis. We hypothesized that the interference of Beclin 1 can influence re-endothelialization and ultimately affect neointimal formation by regulating autophagy and apoptosis. Methods A rat carotid injury model of endothelial denudation was used, and small interfering RNA of Beclin 1 was perivascularly administered. Neointima was evaluated by morphological analysis. von Willebrand factor, Beclin 1, LC3, autophagic substrate p62 and caspase-3 levels were detected by immunofluorescence or Western blotting. Terminal deoxynucleotidyl transferase-mediated digoxigenin–dUTP–biotin nick-end labeling assay was performed to evaluate apoptosis. Results Carotid injury induced an upregulation of Beclin 1 protein which was down regulated by more than 50% with small RNA interference. Beclin 1 knockdown significantly retarded re-endothelialization 7 days after injury and subsequently augmented neointima by more than 2 folds at 14 and 21 days. Autophagy and apoptosis were detected to reveal the regulatory effect of Beclin 1. The injury-activated autophagy, shown by the increased levels of punctate LC3 and LC3II as well as decreased p62 expression, was significantly inhibited by Beclin 1 knockdown. Meanwhile, the apoptotic endothelial cell number was increased and caspase-3 was up-regulated, though the expression of truncated BID was not significantly influenced. Conclusion Beclin 1 knockdown exacerbated neointimal formation after rat carotid injury, associated with retarded re-endothelialization due to enhanced apoptosis, while simultaneously prohibiting autophagic activation. The data suggested an essential role of Beclin 1 as a regulator between autophagy and apoptosis in the setting of neointimal formation. [ABSTRACT FROM AUTHOR]

Aß40-induced vascular dysfunction has been implicated in the pathogenesis of Alzheimer׳s disease (AD). In the present study, we investigated the possible protective effects of puerarin against Aß40-induced vascular damage and impairment to angiogenesis in transgenic TG (fli1:EGFP) zebrafish and human endothelial cells. Aß40 peptides at 5μM caused an obvious reduction of vessel branches in the subintestinal vein basket, induced NADPH oxidase-derived reactive oxygen species and impaired vascular endothelial growth factor (VEGF)-dependent angiogenesis. Pretreatment with puerarin attenuated Aβ40-induced vessel reduction and impairment to angiogenesis in a dose-dependent manner. In addition, Aß40 decreased VEGF-dependent phosphorylation of Akt and eNOS, whereas puerarin treatment attenuated these detrimental effects. Furthermore, the restoration of Aß40-induced-angiogenesis impairment by puerarin was abolished by either the PI3 kinase inhibitor LY294002 (10μM) or eNOS inhibitor L-NAME. The present study suggests that puerarin exerts its protective action probably through reduction of NADPH oxidase-derived reactive oxygen species overproduction and activation of the PI3K/Akt/eNOS pathways. [ABSTRACT FROM AUTHOR]

Abstract: Focal cerebral infarction causes secondary damage in the ipsilateral ventroposterior thalamic nucleus (VPN). Chondroitin sulfate proteoglycans (CSPGs) are a family of putative inhibitory components, and its degradation by chondroitinase ABC (ChABC) promotes post-injury neurogenesis. This study investigated the role of ChABC in the primary and secondary injury post stroke in hypertension. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO), and were subjected to continuous intra-infarct infusion of ChABC (0.12U/d for 7 days) 24h later. Neurological function was evaluated by a modified neurologic severity score. Neurons were counted in the peri-infarct region and the ipsilateral VPN 8 and 14 days after MCAO by Nissl staining and NeuN labeling. The expressions of CSPGs, growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were detected with immunofluorescence or Western blotting. The intra-infarct infusion of ChABC, by degrading accumulated CSPGs, rescued neuronal loss and increased the levels of GAP-43 and SYN in both the ipsilateral cortex and VPN, indicating enhancd neuron survival as well as augmented axonal growth and synaptic plasticity, eventually improving overall neurological function. The study demonstrated that intra-infarct ChABC infusion could salvage the brain from both primary and secondary injury by the intervention on the neuroinhibitory environment post focal cerebral infarction. [Copyright &y& Elsevier]

Abstract: High blood pressure is a main risk factor for both initial and recurrent stroke. Compared to the poststroke situation in normotension, the brain lesion is larger in hypertension, and the treatments may not be as effective. Thus, the results from healthy individuals may not be directly applied to the hypertensive. In fact, the high prevalence of hypertension in stroke patients and its devastating effect urge the necessity to integrate arterial hypertension in the study of stroke in order to better mimic the clinical situations. The first step to do so is to have an appropriate hypertensive animal model for stroke studies. Stroke-prone renovascular hypertensive rat (RHRSP) introduced in 1998, is an animal model with acquired hypertension independent of genetic deficiency. The blood pressure begins to increase during the first week after constriction of bilateral renal arteries, and becomes sustained since around the 3rdmonth. Because the morphological and physiological changes of cerebral arteries are similar to those in hypertensive patients, the rats represent a higher than 60% incidence of spontaneous stroke. The animal model has several advantages: one hundred percent development of hypertension without gene modification, high similarity to human hypertension in cerebrovascular pathology and physiology, and easy establishment with low cost. Thus, the model has been extensively used in the investigation of ischemic stroke, and has been shown as a reliable animal model. This paper reviewed the features of RHRSP and its applications in the treatment and prevention of stroke, as well as the investigations of secondary lesions postischemic stroke. [Copyright &y& Elsevier]

Abstract: The aim of present study was to validate the assessment of lower limit of cerebral autoregulation (LLCA) as derived from mean artery blood pressure (MABP) and cerebral zero flow pressure (ZFP) by means of transcranial Doppler (TCD) and to determine the accurate relationship between LLCA and MABP in stroke-prone renovascular hypertensive rats (RHRSP). We studied two groups of rats: RHRSP and normal controls. Blood flow velocity of middle cerebral artery was monitored by TCD and arterial blood pressure was recorded in right femoral artery to compute the ZFP. The value of LLCA was determined as the difference between MABP and ZFP and validated by the value determined by blood withdrawal-induced cerebral autoregulation. In normal rats, the LLCA derived from the new method was 69.8 ± 8.7 mm Hg, from the change of blood velocity was 69.4 ± 9.8 mmHg and from blood volume flow after blood withdrawal was 68.8 ± 9.7 mmHg. In the RHRSP group, the corresponding values of LLCA were 109.1 ± 17.2 mm Hg, 110.0 ± 18.0 mm Hg and 109.0 ± 19.3 mm Hg, respectively. In each group, there was no statistically significant difference among the three values. LLCA in RHRSP began to increase 6 weeks after hypertension-induced operation, significantly higher than controls (p < 0.05), and stabilized at 110 mm Hg, 10 weeks after operation. The increase of LLCA was positively correlated with MABP, following an “S” curve, demonstrating that the change of LLCA was more obvious in the middle range of MABP in RHRSP (R2 = 0.8848, p < 0.05). In conclusion, TCD is a valid and noninvasive method for determination of LLCA compared with the classic method in rats. Our data demonstrated that the change of LLCA may be correlated with MABP, following an “S” curve relationship. [Copyright &y& Elsevier]

Abstract: The disability of visuospatial attention can lead to poor volitional movement and functional recovery in patients with brain lesions. However, the accurate clinical method to assess visuospatial attention is limited. The frontoparietal network including the posterior parietal cortex and the frontal eye fields has been shown to involve in visuospatial attention. The Attention Network Test provided measures for three different components of visuospatial attention: alerting, orienting and executive control. This study was to probe the deficit and relationship of visuospatial attention using Attention Network Test paradigm in patients with frontoparietal network lesions. During this task, patients responded significantly slower on each cue condition and target type than controls, and showed deficits in the alerting and orienting networks. The efficiency of resolving conflict was decreased in patients with frontal lesions whereas this was increased in patients with parietal lesions. These findings suggest that the frontoparietal network is involved in the alerting and orienting attentional function and the executive function is possibly selectively associated with the frontal lobe. The Attention Network Test paradigm produces sensitive, valid and reliable subject estimates of visuospatial attention function in patients with brain lesions, and may be useful for clinical rehabilitation strategy selection for patients with the frontoparietal network lesions. [Copyright &y& Elsevier]

Abstract: Appropriate restoration of blood flow via angiogenesis is critical for the recovery from ischemic stroke. Previously, we reported that treatment with dl-3n-butylphthalide (NBP) increases the number of local potent cerebral microvessels. However, the underlying mechanism remained unclear. The present study was conducted to test whether NBP enhances post-ischemic cerebral angiogenesis via vascular endothelial growth factor (VEGF) and hypoxia induced factor-1α (HIF-1α). Stroke-prone renovascular hypertensive rats (RHRSP) were used to create middle cerebral artery occlusion (MCAO) model. NBP was given 80 mg/kg per d for 10 consecutive days, starting 12, 24, 48 and 72 h respectively after MCAO. Neurological function was assessed daily and infarct volume as well as the expressions of CD31, VEGF, HIF-1α and bFGF was detected 13 days after MCAO. The administration of NBP starting within 24 h after MCAO enhanced recovery of neurobehavioral function, reduced infarct volume, increased the quantity of CD31 positive vessels, and up-regulated expressions of VEGF and HIF-1α. These findings suggest that treatment with NBP within 24 h post-ischemic stroke rescues brain tissue by enhancing angiogenesis associated with up-regulation of VEGF and HIF-1α expressions. [Copyright &y& Elsevier]