Ultrasound-Enhanced Protective Effect of Tetramethylpyrazine via the ROS/HIF-1A Signaling Pathway in an in Vitro Cerebral Ischemia/Reperfusion Injury Model

Reactive oxygen species-induced oxidative stress is an important pathophysiological process during cerebral ischemia/reperfusion (I/R) injury. It has been reported that the protective effect of tetramethylpyrazine (TMP) against cerebral I/R injury can be significantly improved by its combination with ultrasound exposure. However, the molecular mechanisms and signaling pathways underlying the synergistic protective effect remain unclear. In the present work, the damage induced by I/R injury was modeled by glutamate-induced toxicity to pheochromocytoma (PC12) cells. The ultrasound-enhanced protective effect of TMP was systemically investigated by measuring variations in cell viability, cell migration and levels of intracellular reactive oxygen species, the oxidative stress-related protein glutathione, apoptosis-related proteins (caspase-8, -9 and -3), as well as expression of related genes (hypoxia-inducible factor-1a, p53, murine double minute2). The results suggest that the ultrasound-enhanced protective effect of TMP against cerebral I/R injury might act via the reactive oxygen species/hypoxia-inducible factor-1a signaling pathway, and an appropriate ultrasound intensity should be selected to achieve an optimal synergistic neuroprotective effect.     

应用瞬时波强负向波面积评估甲状腺功能亢进患者脑循环阻力

目的 探讨应用颈总动脉瞬时波强(WI)参数负向波面积(NA)评估甲状腺功能亢进症(HT)患者脑循环阻力的临床意义。方法 HT患者83例,其中49例游离三碘甲腺原氨酸(FT₃)≤50 pmol/L(HT1组),34例FT₃>50 pmol/L(HT2组);对照组为78名健康志愿者。应用WI技术检测受检者右侧颈总动脉,获得收缩早期正向波(W1)、收缩中期负向波面积(NA)、最大血流速度(U_max)等参数,并记录相关临床资料,对各组资料进行比较。结果 ①HT1组、HT2组W1、U_max明显高于对照组,差异均有统计学意义(P<0.001)。HT2组NA明显高于HT1组和对照组,差异均有统计学意义(P<0.001)。②各组NA值均随W1、U_max、脉压差(PP)的增高而升高(P<0.05),HT1组NA与FT₃呈线性相关(P<0.05);HT2组NA与心率、收缩压(SP)呈线性相关(P<0.05)。③83例HT患者中,18例(21.69%)WI波形于收缩中期出现明显紊乱。结论 WI参数NA可反映HT患者脑循环阻力状态。     

TCD等影像学对蛛网膜下腔出血后继发脑血管痉挛的研究进展

蛛网膜下腔出血后最严重的并发症之一是脑血管痉挛（CVS）,脑血管痉挛是导致患者高死亡率的主要病因之一。本文就各种神经影像学检查对CVS的诊断研究进展作一综述。     

Strain differences and laminar localization of structural neurochemical changes in aging rat

To obtain comparisons of age-related microchemical changes in cerebral cortex of two comonly employed rat strains (Fischer 344 and Sprague-Dawley), neurochemical assays of substances regarded as quantitative indices of structural entities in brain were performed. These included DNA as a marker for cells, lipid sialoganglioside as an index of neuronal membrane mass, and galactocerebroside as an index of myelin. Fischer 344 rats were studied at 3–4 months (young), 14–16 months (middle age) and 25–28 months (old). Sprague-Dawleys were examined at 3–6 months (young), 14–17 months (middle age) and 25–28 months (old). Significant differences in the time courses of changes occurred; Fischer rats increased their brain weight at each aging point, while Sprague-Dawley rats reached stable brain weights by 4 months of age. Neither strain had a significant change in cell packing density of somatosensory cortex as measured by DNA. However, total ganglioside sialic acid declined in both strains, occurring by middle age in the Fischer and not until senescence in the Sprague-Dawley cortex. Cerebroside galactose increased in the Fischer between young and middle age, and was not further elevated in the older group. The Sprague-Dawley had its major increase in this marker between the middle aged and senescent groups. Intralaminar assays of these same markers in young and old Fisher 344 rats again indicated that DNA did not change, and that sialoganglioside was lost from all layers of the cortex in equal amounts. However, the increase in galactocerebroside resulted entirely from increases in the lower lamina of somatosensory cortex (lamina IV and below), suggesting on-going myelination of afferent and efferent axons. The time course of lipid membrane alteration is strain-dependent and selective as to cortical laminar localization. The findings are discussed in reference to human aging change in the same neurochemical indices.     

Selective age-related changes in neuronal markers and smooth muscle reactivity in cerebrovascular beds of Fischer 344 rats

Choline accumulation, choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) activities were measured simultaneously in various cerebrovascular beds and brain areas from Fischer 344 rats aged 4.5 and 22 months. A slight (25%) but not significant decrease in choline accumulation was observed concomitantly with a significant increase (187%, p<0.05) in ChAT activity in the major cerebral arteries of the 22-month-old rats. In small cortical pial vessels and selected brain regions, cholinergic and GABAergic biochemical markers remain unaltered in aged rats. The vasomotor reactivity of the basilar artery was investigated in rats of 4.5, 12, 22 and 30 months of age. In the 22-month-old rats, maximal responses to 5-hydroxytryptamine (−25%, not significant) and prostaglandin F₂ (−30%, p<0.05 by ANOVA) were less intense as compared to other age-groups despite preserved contractile responses to dopamine, uridine triphosphate or a depolarizing concentration of K⁺. Relaxations induced by histamine, acetylcholine, noradrenaline, adenosine and somatostatin were strictly comparable among the different age-groups. The sensitivity of the basilar artery to all vasoactive agents failed to demonstrate any correlation with age. Our study suggests that cerebrovascular cholinergic and GABAergic markers undergo minor and selective changes with increasing age. Further, basilar artery vasomotor functions appeared relatively spared by the aging process despite age-related selective decreases in contractile responses to 5-hydroxytryptamine and prostaglandin F₂.     

Effects of sympathetic stimulation on cerebral and ocular blood flow Modification by hypertension,hypercapnia, acetazolamide,PGI2 and papaverine

The effect of unilateral, electrical stimulatio of the cervical sympathetic chain in rabbits anesthetized with pentobarbital sodium and vasodilated by hypercapnia, acetazolamide, papaverine or PGI₂ was investigated to determine to what extent the sympathetic nerves to the brain and the eye cause vasoconstriction and prevent overperfusion in previously vasodilated animals. Evans blue was given as a tracer for protein leakage. Blood flow determinations were made with the labelled microsphere method during normotension and acute arterial hypertension. Hypertension was induced by ligation of the thoracic aorta and in some animals metaraminol or angiotensin was also used. Acetazolamide caused a two to threefold increase in cerebral blood flow (CBF) and hypercapnia resulted in a fivefold increase. CBF was not markedly affected by papaverine or PGI₂. In the choroid plexus, the ciliary body and choroid, papaverine and hypercapnia caused significant blood flow increases on the control side. Sympathetic stimulation induced a 12 % blood flow reduction in the brain in normotensive, hypercapnic animals. Marked effects of sympathetic stimulation at normotension were obtained under all conditions in the eye. In the hypertensive state the CBF reduction during sympathetic stimulation was moderate, but highly significant in hypercapnic or papaverine-treated animals as well as in controls. Leakage of Evans blue was more frequently seen on the nonstimulated side of the brain. In the eye there was leakage only on the control side except in PGI₂-treated animals where 2 rabbits had bilateral leakage. The effect of sympathetic stimulation on the blood flow in the cerebrum and cerebellum in vasodilated animals seems to be small or absent if the blood pressure is normal. In the eye pronounced vasoconstriction occurs under these conditions. In acute arterial hypertension sympathetic stimulation protects both the cerebral and ocular barriers even under conditions of marked vasodilation.     

经颅重复磁刺激对人脑皮层兴奋性的影响

目的　研究经颅重复磁刺激（rTMS）对人脑运动皮层兴奋性的影响。方法　5Hz×30次或15Hz×30次rTMS,以相当于120%静止运动阈值的强度,作用于12名青壮年志愿者,并利用成对的条件-检测刺激方法检验rTMS对皮层内抑制（ICI）及皮层内易化（ICF）的影响。结果　15HzrTMS显著抑制ICI达3.4min,兴奋ICF达1.5min,而运动阈值仅被降低约30s。5HzrTMS仅显著抑制ICI30s,而对ICF及运动阈值无影响。结论　高频阈上rTMS能一过性抑制皮层内抑制环路并提高皮层内兴奋性环路的活动。