沙鼠脑缺血模型特点及应用的研究进展

脑缺血因其高的发病率而成为近年来研究的热点。用于研究脑缺血的动物模型较多,其中沙鼠因大脑基底动脉环先天性发育不完全而成为脑缺血研究的较理想模型。沙鼠脑缺血模型在研究单侧脑缺血和全脑缺血方面都具有独特的优势,在研究脑缺血后脑区的病理变化、再灌注损伤机制及开发脑保护药方面都得到十分广泛的应用。本文针对不同脑缺血模型尤其是沙鼠模型的制作方法、优缺点及应用领域,将近年来国内外相关研究文献进行较为系统的梳理和综述。     

Administration of mesenchymal stem cells and ziprasidone enhanced amelioration of ischemic brain damage in rats

Ziprasidone is a benzisothiazolyl piperazine derivative that was developed from the chemically related antipsychotic drug tiospirone, and it improves neurological functions of the ischemic brain and is effective in treatment of schizophrenia. Mesenchymal stem cells (MSCs) are considered as a leading candidate for neurological regenerative therapy because of their neural differentiation properties in damaged brain. We investigated whether the transplantation of neural progenitor cells (NPCs) derived from adipose mesenchymal stem cells combined with ziprasidone enhances neuroprotective effects in an animal model of focal cerebral ischemia. In combination therapy groups, significant reduction of infarct volume and improvement of neurological functions were observed at 3 days after middle cerebral artery occlusion (MCAO) compared with monotherapy. Co-administration of ziprasidone and NPCs enhanced the anti-apoptotic effect and reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with the NPCs alone group at 7 days after MCAO. Ziprasidone or the combination of ziprasidone and NPCs induced the expression of endogenous neurotrophic factor gene brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell-derived neurotrophic factor (GDNF). The immunohistochemical investigation revealed that the ziprasidone and NPCs attenuated the increased intensity of microglial marker (Iba-1) in the infarcted cortical area. Moreover, the number of transplanted NPCs on day 7 with combination therapy was significantly higher than with NPCs alone. These effects might be responsible for improved functional behavior and increased survival of NPCs. Our finding indicates that combination therapy of ziprasidone and NPCs enhances neuroprotection against ischemic brain injury.     

InfarctSizer: computing infarct volume from brain images of a stroke animal model

Many computational methods for determining the infarct volume from the image of 2,3,5-triphenyltetrazolium chloride-stained brain slices rely on the discretion of the user to determine the infarct region by visual inspection. Once the user determines the infarct boundary by visual inspection, the methods compute the area within the boundary with the assumption that all the spots within the boundary have been infarcted at the same level. However, in the same brain image, partially infarcted spots often tend to appear pinkish whereas fully or severely infarcted spots appear white. We developed a program called InfarctSizer, which automatically detects the infarct region and computes the infarct volume proportional to infarction levels. Comparison of InfarctSizer with other methods shows that InfarctSizer computes the infarct volume more accurately and efficiently than other methods. InfarctSizer and sample brain images are available at http://wilab.inha.ac.kr/brainimage.     

Action of ERK5 in ischemic tolerance suggests its probable participation in the signaling mechanism

Here we examined the effects of ischemia preconditioning and ketamine, an NMDA receptor antagonist, on the activation and its nucleus translocation of ERK5 in hippocampal CA1 region. Our results showed ERK5 was not activated in rat hippocampus CA1 region. But in cytosol extracts preconditioned with 3 min of sublethal ischaemia, ERK5 activation was enhanced significantly, with two peaks occurring at 3 hr and 3 days, respectively. This activation returned to base level 3 days later. The results lead us to conclude that preconditioning increased the activations of ERK5 during reperfusion after lethal ischemia through NMDA receptor. Preconditioning increased the activation and nucleus translocation of ERK5 during reperfusion after lethal ischemia through the NMDA receptor. These findings might provide some clues to understanding the mechanism underlying ischemia tolerance and to finding clinical therapies for stroke using the endogenous neuroprotection.     

Changes in orientation of attritional wear facets with implications for jaw motion in a mixed longitudinal sample of Propithecus edwardsi from Ranomafana National Park, Madagascar

In many mammalian species, the progressive wearing down of the teeth that occurs over an individual's lifetime has the potential to change dental function, jaw movements, or even feeding habits. The orientation of phase-I wear facets on molars reveals the direction of jaw movement during the power stroke of mastication. We investigated if and how molar wear facets change with increasing wear and/or age by examining a mixed longitudinal dataset of mandibular tooth molds from wild Propithecus edwardsi (N = 32 individuals, 86 samples). Measurements of the verticality of wear facets were obtained from three-dimensional digital models generated from μCT scans. Results show that verticality decreases over the lifetime of P. edwardsi, a change that implies an increasingly lateral translation of the jaw as the teeth move into occlusion. A more transverse phase-I power stroke supports the hypothesis that these animals chew to maximize longevity and functionality of their teeth, minimizing the "waste" of enamel, while maintaining sharp shearing crests. Results of this study indicate that wear facet verticality is more closely correlated with age than overall amount of tooth wear, measured as area of exposed dentin, suggesting that age-related changes in cranial morphology may be more responsible for adjustments in jaw motion over the lifetimes of Propithecus than wear-related changes inthe shape of occluding teeth. Finally, the rate of decrease in wear facet verticality with age is greater in males than in females suggesting differences in development and/or access to resources between the sexes in this species.     

NDRG4 protein-deficient mice exhibit spatial learning deficits and vulnerabilities to cerebral ischemia

The N-myc downstream-regulated gene (NDRG) family consists of four related proteins, NDRG1-NDRG4, in mammals. We previously generated NDRG1-deficient mice that were unable to maintain myelin sheaths in peripheral nerves. This condition was consistent with human hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease type 4D, caused by a nonsense mutation of NDRG1. In contrast, the effects of genetic defects of the other NDRG members remain unknown. In this study, we focused on NDRG4, which is specifically expressed in the brain and heart. In situ mRNA hybridization on the brain revealed that NDRG4 was expressed in neurons of various areas. We generated NDRG4-deficient mice that were born normally with the expected Mendelian frequency. Immunochemical analysis demonstrated that the cortex of the NDRG4-deficient mice contained decreased levels of brain-derived neurotrophic factor (BDNF) and normal levels of glial cell line-derived neurotrophic factor, NGF, neurotrophin-3, and TGF-β1. Consistent with BDNF reduction, NDRG4-deficient mice had impaired spatial learning and memory but normal motor function in the Morris water maze test. When temporary focal ischemia of the brain was induced, the sizes of the infarct lesions were larger, and the neurological deficits were more severe in NDRG4-deficient mice compared with the control mice. These findings indicate that NDRG4 contributes to the maintenance of intracerebral BDNF levels within the normal range, which is necessary for the preservation of spatial learning and the resistance to neuronal cell death caused by ischemic stress.     

Oral health‐related quality of life in hospitalised stroke patients

doi:10.1111/j.1741‐2358.2009.00330.x
Oral health‐related quality of life in hospitalised stroke patients Objective: The aim of this study was to test the hypothesis that impairment of orofacial function following stroke affects the patients’ oral health‐related quality of life (OHRQoL). Material and methods: From the University Hospitals of Geneva, 31 stroke patients (18 men, 13 women, mean age 69.0 ± 12.7 years) with unilateral facial and limb palsy were recruited (patient group, PG). In the study, the Oral Health Impact Profile (OHIP)‐EDENT was utilised to assess OHRQoL. Further examinations comprised a test of masticatory efficiency and lip force, stroke severity National Institute of Health Stroke Scale and dental state. The control group (CG) consisted of 24 subjects with similar age, gender and dental state. Results: The PG mean OHIP‐EDENT sum score was 18.8 ± 15.5 and proved higher than one of the CG, indicating a lower OHRQoL in the PG (p < 0.01). The score of the sub‐domains ‘functional limitation’ and ‘physical pain’ were significantly higher in PG (p < 0.03 and p < 0.02, respectively). The masticatory efficiency was significantly lower in the PG (p < 0.0001) and was associated with the OHIP‐EDENT sum score and its sub‐domains, except for ‘physical disability’. This effect was not present in the CG. Conclusion: The OHRQoL is significantly reduced in hospitalised stroke patients whereby functional impairment seems predominant when compared with psychological and psycho‐social aspects.     

Space availability influence laterality in donkeys (Equus asinus)

Cerebral lateralization is the portioning of the cognitive functions between the two cerebral hemispheres. Several factors, like embryological manipulations, light exposure, health conditions, sex and age can influence the left-right brain asymmetries and contribute to increasing the variability in the strength and direction of laterality within most species. We investigated the influence of an environmental constraint, namely space availability, as a new source of variation on laterality in an adult vertebrate model, the donkey. In a baseline condition we tested whether donkeys show a motor lateralization bias at population level, while in an experimental condition we manipulated space availability to verify if a reduction in this parameter could represent a new source of variation in laterality. Results show that donkeys are lateralized at population level with a strong bias to standing with the right forelimb advanced over the left and that a reduction of space availability is an important source of variation in the laterality strength and direction within this species. The comparative analysis of the environmental and developmental factors that give origin to neural and behavioural laterality in animal models will be very important for a better understanding of the evolutionary origin of such multifaceted phenomenon.     

老年高血压患者踝肱指数及其与冠心病、脑卒中相关性的研究

目的:了解老年高血压患者外周动脉性疾病(PAD)患病率及其特点,重点研究踝肱指数(ABI)与冠心病、脑卒中相关性的临床意义.方法:入选我院和安贞医院门诊及住院老年男性高血压患者,无损伤周围血管检查仪测定患者踝肱指数、标准问卷调查及各项指标测量确定患者身体基线状况;任一侧肢体ABI≤0.9诊断为PAD,1.01-1.30...