颅内压低频分析

目的：临床和基础研究发现,颅内压存在波动,本工作通过动物实验模拟颅高压并研究颅内压的波动。实验方法：14条犬安置硬膜外球囊并注液制成颅高压模型,通过改变球囊内液体量来改变颅高压程度和颅内容积,由压力传感器持续记录相应压力。结果：对颅内压、腰区脑脊液压分别进行FFT分析,发现都存在一个约为0．2Hz的波动,该频率既不是心率(3Hz左右)也不是呼吸频率(0．4Hz),记为M波。分析表明：1)正常情况下,M波并不出现;2)实验开始阶段,不出现M波,当颅内压超过一定压力水平时,M波出现。随后的药物干预实验显示,采用迷走神经阻断药阿托品能明显抑制M波,而交感神经阻断药心得安效果不明显,初步说明M波与脑血管的某些调节机制有关。     

长爪沙鼠脑缺血模型近交系的培育及其发病机制研究进展

长爪沙鼠具有脑血管变异缺失的特性,是脑缺血研究良好的模型动物。普通长爪沙鼠群体中模型成功率低,影响研究结果稳定性,不符合实验动物福利要求。我们团队在证实脑血管Willis环(circle of Willis,COW)变异缺失具有遗传性的基础上,首先通过定向选育建立了脑缺血高发群体,进而通过全同胞近亲繁殖的方式,建立了脑缺血模型近交系,其COW缺失率达76.62%,模型成功率达到88.89%。此外,建立了近交系微卫星DNA和生化位点遗传检测方法,分析了长爪沙鼠脑缺血模型近交系动物的生长发育和血液生理生化等指标,为该模型的推广应用奠定了基础。我们还发现,VEGFA基因、AKT/PI3K和Notch信号通路在长爪沙鼠脑血管发育中发挥重要作用。通过抑制消减杂交方法筛选获得4个与长爪沙鼠脑血管发育相关的基因。长爪沙鼠脑缺血模型近交系的培育成功解决了模型发生率低的问题,减少了动物使用量,提高了研究结果可信度和稳定性,促进了相关机制研究。     

非容积依赖性呼吸力学参数估计的敏感度分析

研究呼吸运动过程中呼吸驱动压P(t)、呼吸气体流率V(t)及肺容积V(t)三者间的数量关系,建立相应数学模型,进而估计气道阻力(R_W)、肺顺应性(C_L)等呼吸力学参数,不仅有重要理论意义,并且在临床医学、环境医学等领域也有重要应用价值。一、呼吸力学模型呼吸过程中,胸膜腔压力相对于口腔压力的变化与呼吸气体流率。肺容积之间的关系     

呼吸力学参数的强迫振荡识别方法及其应用

呼吸力学参数包括呼吸气体的压力、流率、胸肺系统的顺应性、气道阻力、惯性阻力以及呼吸功等。测量这些参数可进一步从生物力学角度分析呼吸过程,在理论上与实际上均有一定意义。例如,测量胸内压、各级气道阻力、肺顺应性等,有助于深入了解肺内气体的传输和分布问题;定量研究气道阻力或肺顺应性的改变,对于阐明慢性阻塞性肺疾病(COPD)     

脑Willis环循环分析专用软件研制Ⅰ．软件功能介绍

脑血管疾病是严重危害人类健康的常见病。大量实验及临床研究表明．许多患者在发病前期．其循环动力学状态已有显著变化,因此为了适应于临床检测和大规模人群普查,有必要编制一套基于Win95／Win98平台上的专用软件,用于实时检测与分析脑血管动力学参数,使它成为早期诊断有价值的指标。本文描述了该软件的流程和各模块的功能,有关临床实际应用将在后续文章中叙述。     

三种麻醉药在大鼠脑外科实验中麻醉效果的比较

动物实验中麻醉占有重要地位 ,神经外科动物实验需要维持稳定的颅内压、血压以及呼吸等重要指标 ,对麻醉药物提出更高要求。戊巴比妥钠、复方氯胺酮及乌拉坦是动物实验中常用麻醉剂 ,效果肯定。但目前尚无文献对这 3种药物在脑外科实验中的麻醉效果进行评价。我们在制备帕金森病大鼠模型时应用以上药物 ,对麻醉效果进行了初步比较 ,以期选择合适的麻醉剂 ,保证手术过程顺利 ,提高动物术后成活率。1　材料与方法1 1　实验动物及分组　雄性一级Ｗｉｓｔａｒ大鼠 4 5只 ,由军事医学科学院动物实验中心提供 ,体重 2 4 0～2 70 ｇ ,2 4小时人工…     

多聚环氧化合物预处理异体移植静脉顺应性实验研究

目的研究多聚环氧化合物(polyepoxy compound,PC)预处理的人离体大隐静脉的顺应性。方法PC与戊二醛(Glutaradehyde,GA)分别对人的离体大隐静脉预处理,并记录三种静脉随内压变化的投影几何参数(面积、周长、长轴和短轴),通过对三种静脉的投影几何参数在不同内压下的变化进行研究,比较两种方法处理的血管顺应性的差异,新鲜静脉(Fresh)作为对照。结果三种静脉在相同内压变化时的投影几何参数变化,各组之间的差异无统计学意义(P>0.05)。结论PC不影响血管的顺应性。     

新水缸潜水模型在斑马鱼焦虑及应激行为研究中的进展

新水缸潜水实验(novel tank diving test)是专门针对模式动物斑马鱼或其他小型鱼类的焦虑行为研究设计的评价范式,是介于活体和细胞测定之间的药物筛选模型。该模型从小鼠迷宫实验模型发展而来,在行为测试的便捷性上具有一定优势。斑马鱼与人类具有较高的基因同源性,药物介导的斑马鱼焦虑和攻击行为与其内分泌系统中下丘脑-垂体-肾间腺(HPI)轴密切相关,类似于人体下丘脑-垂体-肾上腺(HPA)轴的作用。因此该模式对人类焦虑行为的研究具有重要的指导意义。总的来说,新水缸潜水实验是一种高效、可靠的高通量行为筛选模型,主要应用于动物社会性、成瘾性、睡眠、学习与记忆等研究领域。本文综述了过去15年间,新水缸潜水模型从形成雏形到不断完善,最后广泛应用于各种场景,从模型起源、测定参数、用途、存在问题和未来发展趋势等5个方面进行综述,并与明/暗水缸实验进行比较分析,以期扩宽斑马鱼焦虑及应激行为评价实验的研究范畴和应用范围。     

旱獭在生物医学中的应用

旱獭,又名土拨鼠,属于啮齿目,松鼠科,旱獭属动物。它是使用最广的野生哺乳动物之一,同时它又是一冬眠动物,具有冬眠动物的特性,在内分泌与代谢机能、食欲、活动量和体重等方面每年都发生周期性的变化。旱獭已广泛应用于肥胖症与能量平衡、内分泌与代谢机能、中枢神经系统调控机制以及心血管疾病、脑血管疾病和瘤形成等方面的研究。自从1978年发现旱獭病毒(WHV)以来,该病毒以及它的宿主———旱獭已被当作研究人乙型肝炎病毒(HBV)感染的最理想模型。由于WHV与HBV在形态学、基因组结构、基因产物、复制、流行病学、感染过程及其病程甚至…     

第十一届中国实验动物科学年会（2014，重庆）顺利召开

科技日报讯：6月26～27日,第十一届中国实验动物科学年会在重庆举行,本次会议参会代表近五百名,包括从事实验动物和动物实验以及相关学科的科研技术人员、教学人员、管理人员、科技产品研发人员等。〈br〉 本次大会包括院士报告、特邀报告、科普讲堂、专题研讨、热点论坛、学术沙龙等内容。会议颁发了中国实验动物学会科学技术奖与国际青年科学家奖。随后的院士报告、特邀报告围绕中国实验动物学科的发展,以及生物医药研究对实验动物专业的迫切需求等展开。同时,会议对实验动物在生命科学及医学研究中的应用进行了科普讲座。此外,会议还针对实验动物资源和实验动物设备研制、实验动物国家标准、疾病模型研制、以及药物的临床前研究等领域设置了专题讲座和研讨。     

Cerebral hemodynamics during arterial and CO(2) pressure changes: in vivo prediction by a mathematical model

The aim of this work was to analyze changes in cerebral hemodynamics and intracranial pressure (ICP) evoked by mean systemic arterial pressure (SAP) and arterial CO(2) pressure (Pa(CO(2))) challenges in patients with acute brain damage. The study was performed by means of a new simple mathematical model of intracranial hemodynamics, particularly aimed at routine clinical investigation. The model was validated by comparing its results with data from transcranial Doppler velocity in the middle cerebral artery (V(MCA)) and ICP measured in 44 tracings on 13 different patients during mean SAP and Pa(CO(2)) challenges. The validation consisted of individual identification of 6 parameters in all 44 tracings by means of a best fitting algorithm. The parameters chosen for the identification summarize the main aspects of intracranial dynamics, i.e., cerebrospinal fluid circulation, intracranial elastance, and cerebrovascular control. The results suggest that the model is able to reproduce the measured time patterns of V(MCA) and ICP in all 44 tracings by using values for the parameters that lie within the ranges reported in the pathophysiological literature. The meaning of parameter estimates is discussed, and comments on the main virtues and limitations of the present approach are offered.     

A simple mathematical model of the interaction between intracranial pressure and cerebral hemodynamics

Ursino, Mauro, and Carlo Alberto Lodi. A simplemathematical model of the interaction between intracranial pressure andcerebral hemodynamics. J. Appl.Physiol. 82(4): 1256-1269, 1997.A simplemathematical model of intracranial pressure (ICP) dynamics oriented toclinical practice is presented. It includes the hemodynamics of thearterial-arteriolar cerebrovascular bed, cerebrospinal fluid (CSF)production and reabsorption processes, the nonlinear pressure-volumerelationship of the craniospinal compartment, and a Starling resistormechanism for the cerebral veins. Moreover, arterioles are controlledby cerebral autoregulation mechanisms, which are simulated by means ofa time constant and a sigmoidal static characteristic. The model isused to simulate interactions between ICP, cerebral blood volume, andautoregulation. Three different related phenomena are analyzed: thegeneration of plateau waves, the effect of acute arterial hypotensionon ICP, and the role of cerebral hemodynamics during pressure-volume index (PVI) tests. Simulation results suggest the following:1) ICP dynamics may become unstablein patients with elevated CSF outflow resistance and decreasedintracranial compliance, provided cerebral autoregulation is efficient.Instability manifests itself with the occurrence of self-sustainedplateau waves. 2) Moderate acutearterial hypotension may have completely different effects on ICP,depending on the value of model parameters. If physiological compensatory mechanisms (CSF circulation and intracranial storage capacity) are efficient, acute hypotension has only negligible effectson ICP and cerebral blood flow (CBF). If these compensatory mechanismsare poor, even modest hypotension may induce a large transient increasein ICP and a significant transient reduction in CBF, with risks ofsecondary brain damage. 3) The ICPresponse to a bolus injection (PVI test) is sharply affected, viacerebral blood volume changes, by cerebral hemodynamics andautoregulation. We suggest that PVI tests may be used to extractinformation not only on intracranial compliance and CSF circulation,but also on the status of mechanisms controlling CBF.

     

Pressure-dependent outflow resistance in cerebrospinal fluid dynamics: evaluation a calculation model for diagnosis of normal pressure hydrocephalus in an animal experiment with H-Tx rats]

The internationally accepted methods of calculating cerebrospinal fluid dynamics proceed from the assumption of a pressure-independent resistance to CSF outflow. Our new model focusses on the pressure-dependency of this resistance. In it, we monitor the entire pressure course over time, p(t) during and after infusion. A comparison of the pressure rise, On(p), during infusion, and the decrease, Off(p), to the same pressure level, permits the creation of all the formulas for C(p) and R(p). The simultaneous measurement of resistance and compliance during a single intervention allows us to minimize patient exertion. In contrast to the classical methods, it is not necessary for the ICP to reach a plateau. Our mathematical model differs from the static examination model by describing a pressure-dependent slope of the function for the resistance. This has been demonstrated in a study using H-Tx rats. In this way, we are able to take the non-linearity of the CSF resorption into consideration.     

The effect of ventricular volume increase in the amplitude of intracranial pressure

We study the impact of vascular pulse in the cerebrospinal fluid (CSF) pressure measured on the lateral cerebral ventricles, as well as its sensitivity with respect to ventricular volume change. Recent studies have addressed the importance of the compliance capacity in the brain and its relation to arterial pulse abortion in communicating hydrocephalus. Nevertheless, this mechanism is not fully understood. We propose a fluid-structure interaction (FSI) model on a 3?D idealized geometry based on realistic physiological and morphological parameters. The computational model describes the pulsatile deformation of the third ventricle due to arterial pulse and the resulting CSF dynamics inside brain pathways. The results show that when the volume of lateral ventricles increases up to 3.5 times, the amplitudes of both average and maximum pressure values, computed on the lateral ventricles surface, substantially decrease. This indicates that the lateral ventricles expansion leads to a dumping effect on the pressure exerted on the walls of the ventricles. These results strengthen the possibility that communicant hydrocephalus may, in fact, be a natural response to reduce abnormal high intracranial pressure (ICP) amplitude. This conclusion is in accordance with recent hypotheses suggesting that communicant hydrocephalus is related to a disequilibrium in brain compliance capacity.     

A Novel Rat Model to Study the Role of Intracranial Pressure Modulation on Optic Neuropathies

Reduced intracranial pressure is considered a risk factor for glaucomatous optic neuropathies. All current data supporting intracranial pressure as a glaucoma risk factor comes from retrospective and prospective studies. Unfortunately, there are no relevant animal models for investigating this link experimentally. Here we report a novel rat model that can be used to study the role of intracranial pressure modulation on optic neuropathies. Stainless steel cannulae were inserted into the cisterna magna or the lateral ventricle of Sprague-Dawley and Brown Norway rats. The cannula was attached to a pressure transducer connected to a computer that recorded intracranial pressure in real-time. Intracranial pressure was modulated manually by adjusting the height of a column filled with artificial cerebrospinal fluid in relation to the animal’s head. After data collection the morphological appearance of the brain tissue was analyzed. Based on ease of surgery and ability to retain the cannula, Brown Norway rats with the cannula implanted in the lateral ventricle were selected for further studies. Baseline intracranial pressure for rats was 5.5±1.5 cm water (n=5). Lowering of the artificial cerebrospinal fluid column by 2 cm and 4 cm below head level reduced ICP to 3.7±1.0 cm water (n=5) and 1.5±0.6 cm water (n=4), a reduction of 33.0% and 72.7% below baseline. Raising the cerebrospinal fluid column by 4 cm increased ICP to 7.5±1.4 cm water (n=2) corresponding to a 38.3% increase in intracranial pressure. Histological studies confirmed correct cannula placement and indicated minimal invasive damage to brain tissues. Our data suggests that the intraventricular cannula model is a unique and viable model that can be used to study the effect of altered intracranial pressure on glaucomatous optic neuropathies.     

A coupled hydrodynamic model of the cardiovascular and cerebrospinal fluid system

Coupling of the cardiovascular and cerebrospinal fluid (CSF) system is considered to be important to understand the pathophysiology of cerebrovascular and craniospinal disease and intrathecal drug delivery. A coupled cardiovascular and CSF system model was designed to examine the relation of spinal cord (SC) blood flow (SCBF) and CSF pulsations along the spinal subarachnoid space (SSS). A one-dimensional (1-D) cardiovascular tree model was constructed including a simplified SC arterial network. Connection between the cardiovascular and CSF system was accomplished by a transfer function based on in vivo measurements of CSF and cerebral blood flow. A 1-D tube model of the SSS was constructed based on in vivo measurements in the literature. Pressure and flow throughout the cardiovascular and CSF system were determined for different values of craniospinal compliance. SCBF results indicated that the cervical, thoracic, and lumbar SC each had a signature waveform shape. The cerebral blood flow to CSF transfer function reproduced an in vivo-like CSF flow waveform. The 1-D tube model of the SSS resulted in a distribution of CSF pressure and flow and a wave speed that were similar to those in vivo. The SCBF to CSF pulse delay was found to vary a great degree along the spine depending on craniospinal compliance and vascular anatomy. The properties and anatomy of the SC arterial network and SSS were found to have an important impact on pressure and flow and perivascular fluid movement to the SC. Overall, the coupled model provides predictions about the flow and pressure environment in the SC and SSS. More detailed measurements are needed to fully validate the model.     

Interhemisphere asymmetry of the CSF dynamics and biomechanical properties of the skull

This investigation shows that both intracranial liquor circulation and skull biomechanical properties evaluated by its pliability (compliance) to intracranial pressure are characterised by marked interhemisphere asymmetry. The interhemisphere differences of cerebrospinal fluid mobility were evaluated by means of asymmetry coefficient (right/left ratio of liquor mobility) which was found to be 1.25-1.45 in healthy middle-age persons. For the skull pliability (compliance) the coefficient of hemispheric asymmetry was 0.75-0.95. These two hemisphere asymmetry coefficients are characterized by reciprocal relationships. These coefficients demonstrated no dominancy related to right/left hemisphere as well as no correlation with neurophysiological parameter. Functional tests (apnoea, hyperventilation, Stookey test) gave rise to significant changes of these coefficient values. At ageing, the magnitudes of these coefficients decreased. The spectral analysis of pulse waves of dopplerogram and rheoencephalogram reveals hemisphere asymmetry, too. It should be suggested that the interhemisphere asymmetry of the CSF dynamics and skull biomechanical properties is a special mechanism which contributes in the process of circulatory-metabolic support of brain activity.     

Method of intracranial pressure monitoring and cerebrospinal fluid sampling in swine

Cerebral oedema and encephalopathy have been noted to occur frequently in patients severely ill or dying after trauma, ischaemia, infections or even metabolic disorders. The objective of the present study was to establish continuous monitoring of the intracranial pressure (ICP) and sampling of cerebrospinal fluid (CSF) for further investigations in swine. ICP monitoring was established in eight pigs by using a ventricular drainage system, implemented after paramedian trepanation of the os frontale. CSF and serum samples were taken for measurement of the levels of glucose and protein. Operating time was 21+/-8 min for the trepanation until ICP monitoring was performed. No complications occurred during surgery. Continuous monitoring of ICP and CSF sampling was easy to perform, and without any side-effects in any animal. At autopsy, no iatrogenic lesions were found and monitoring catheters were still in place. For several types of research requiring ICP monitoring and sampling of CSF, this method can be used successfully.     

Mechanisms of the Anti-Ischemic Effect of Angiotensin II AT( 1 ) Receptor Antagonists in the Brain

1. Circulating and locally formed Angiotensin II regulates the cerebral circulation through stimulation of AT(1) receptors located in cerebrovascular endothelial cells and in brain centers controlling cerebrovascular flow. 2. The cerebrovascular autoregulation is designed to maintain a constant blood flow to the brain, by vasodilatation when blood pressure decreases and vasoconstriction when blood pressure increases. 3. During hypertension, there is a shift in the cerebrovascular autoregulation to the right, in the direction of higher blood pressures, as a consequence of decreased cerebrovascular compliance resulting from vasoconstriction and pathological growth. In hypertension, when perfusion pressure decreases as a consequence of blockade of a cerebral artery, reduced cerebrovascular compliance results in more frequent and more severe strokes with a larger area of injured tissue. 4. There is a cerebrovascular angiotensinergic overdrive in genetically hypertensive rats, manifested as an increased expression of cerebrovascular AT(1) receptors and increased activity of the brain Angiotensin II system. Excess AT(1) receptor stimulation is a main factor in the cerebrovascular pathological growth and decreased compliance, the alteration of the cerebrovascular eNOS/iNOS ratio, and in the inflammatory reaction characteristic of cerebral blood vessels in genetic hypertension. All these factors increase vulnerability to brain ischemia and stroke. 5. Sustained blockade of AT(1) receptors with peripheral and centrally active AT(1) receptor antagonists (ARBs) reverses the cerebrovascular pathological growth and inflammation, increases cerebrovascular compliance, restores the eNOS/iNOS ratio and decreases cerebrovascular inflammation. These effects result in a reduction of the vulnerability to brain ischemia, revealed, when an experimental stroke is produced, in protection of the blood flow in the zone of penumbra and substantial reduction in neuronal injury. 6. The protection against ischemia resulting is related to inhibition of the Renin-Angiotensin System and not directly related to the decrease in blood pressure produced by these compounds. A similar decrease in blood pressure as a result of the administration of beta-adrenergic receptor and calcium channel blockers does not protect from brain ischemia. 7. In addition, sustained AT(1) receptor inhibition enhances AT(2) receptor expression, associated with increased eNOS activity and NO formation followed by enhanced vasodilatation. Direct AT(1) inhibition and indirect AT(2) receptor stimulation are associated factors normalizing cerebrovascular compliance, reducing cerebrovascular inflammation and decreasing the vulnerability to brain ischemia.8. These results strongly suggest that inhibition of AT(1) receptors should be considered as a preventive therapeutic measure to protect the brain from ischemia, and as a possible novel therapy of inflammatory conditions of the brain.     

A severe vicious cycle in uncontrolled subarachnoid hemorrhage: the effects on cerebral blood flow and hemodynamic responses upon intracranial hypertension

In subarachnoid hemorrhage (SAH), Cushing postulated that the increase in systemic arterial pressure (SAP) in response to elevation of intracranial pressure (ICP) was beneficial to cerebral perfusion. However, in uncontrolled SAH, the increased SAP may cause more bleeding into the subarachnoid space and further increase the ICP. We created an animal model to simulate SAH by connecting a femoral arterial catheter to the subarachnoid space. The global cerebral blood flow (CBF) was measured with a venous outflow method. The purposes were to observe the CBF change under the simulated SAH, and to evaluate the effects of an adrenergic blocker and a vasodilator. In addition, spectral analysis of the aortic pressure and flow was employed for the analysis of hemodynamic changes at various ICP levels. When the femoral arterial blood was allowed to flow into the subarachnoid space, the ICP was elevated. The Cushing response to increased ICP caused an increase in SAP. A vicious cycle was generated between ICP and SAP. The CBF under the vicious cycle was greatly depressed. The dog developed pulmonary edema (PE) within 5 mins. An alpha-adrenergic blocker (phentolamine) and a vasodilator (nitroprusside) were beneficial to the reduction of SAP and ICP, improvement of CBF, and prevention of PE. Hemodynamic analysis revealed that graded increases in ICP caused increases in SAP, total peripheral resistance, arterial impedance, and pulse reflection with decreases in stroke volume, cardiac output and arterial compliance. The hemodynamic changes may contribute to acute left ventricular failure that leads to pressure and volume loading in the lung circulation, and finally acute PE.