Enhanced Phosphodiestric Breakdown of Phosphatidylinositol Bisphosphate After Experimental Brain Injury

Abstract: Regional levels of lactate and inositol 1,4,5-trisphosphate (IP₃), a cellular second messenger of the excitatory neurotransmitter system, were measured after lateral fluid percussion (FP) brain injury in rats. At 5 min postinjury, tissue lactate concentrations were significantly elevated in the cortices and hippocampi of both the ipsilateral and contralateral hemispheres. By 20 min postinjury, lactate concentrations were elevated only in the cortices and hippocampus of the ipsilateral hemisphere. Whereas the IP₃ concentrations were elevated in the hippocampi of the ipsilateral and contralateral hemisphere and in the cortex of ipsilateral hemisphere at 5 min postinjury, no elevation in these sites was found at 20 min postinjury. Histologic analysis revealed neuronal damage in the cortex and CA3 regions of hippocampus ipsilateral to the injury at 24 h postinjury. The present results suggest activation of the phosphoinositide signal transduction pathway at the onset of injury and of a possible requirement of early persistent metabolic dysfunction (>20 min) such as the lactate accumulation in the delayed neuronal damage.     

Development of Prolonged Focal Cerebral Edema and Regional Cation Changes Following Experimental Brain Injury in the Rat

The present study examined the formation of regional cerebral edema in adult rats subjected to lateral (parasagittal) experimental fluid-percussion brain injury. Animals receiving fluid-percussion brain injury of moderate severity over the left parietal cortex were assayed for brain water content at 6 h, 24 h, and 2, 3, 5, and 7 days post injury. Regional sodium and potassium concentrations were measured in a separate group of animals at 10 min, 1 h, 6 h, and 24 h following fluid-percussion injury. Injured parietal cortex demonstrated significant edema, beginning at 6 h post injury (p less than 0.05) and persisting up to 5 days post injury. In the hippocampus ipsilateral to the site of cortical injury, significant edema occurred as early as 1 h post injury (p less than 0.05), with resolution of water accumulation beginning at 3 days. Sodium concentrations significantly increased in both injured cortex (1 h post injury, p less than 0.05) and injured hippocampus (10 min post injury, p less than 0.05). Potassium concentrations fell significantly 1 h post injury within the injured cortex (p less than 0.05), whereas significant decreases were not observed until 24 h post injury within the injured hippocampus. Cation alterations persisted throughout the 24-h post injury period. These results demonstrate that regional brain edema and cation deregulation occur in rats subjected to lateral fluid-percussion brain injury and that these changes may persist for a prolonged period after brain injury.     

液压脑损伤大鼠大脑皮质突触素的动态变化

目的:探讨液压脑损伤后突触素在皮质区表达的动态变化.方法:应用液压脑损伤复制脑损伤动物模型,应用免疫组织化学和计算机图像分析技术定量分析皮质受损区突触素表达的动态变化.结果:突触素在皮质受伤区表达呈现两次高峰:分别为3～12h和15～30d,90d表达接近正常.结论:突触素在皮质受伤区第2次表达增高可能与脑的结构和功能恢复有关.急性期表达增高则可能与脑的直接损伤有关.     

Infant brain subjected to oscillatory loading: material differentiation,properties, and interface conditions

Past research into brain injury biomechanics has focussed on short duration impulsive events as opposed to the oscillatory loadings associated with Shaken Baby Syndrome (SBS). A series of 2D finite element models of an axial slice of the infant head were created to provide qualitative information on the behaviour of the brain during shaking. The test series explored variations in subarachnoid cerebrospinal fluid (CSF) representation, brain matter stiffness, dissipation, and nonlinearity, and differentiation of brain matter type. A new method of CSF modelling based on Reynolds lubrication theory was included to provide a more realistic brain–CSF interaction. The results indicate that solid CSF representation for this load regime misrepresents the phase lag of displacement, and that the volume of subarachnoid CSF, and inclusion of thickness variations due to gyri, are important to the resultant behavior. Stress concentrations in the deep brain are reduced by fluid redistribution and gyral contact, while inclusion of the pia mater significantly reduces cortex contact strains. These results provide direction for future modelling of SBS.     

丙泊酚用于颅脑损伤手术患者的麻醉效果及对血清SOD、颅内压的影响

目的:分析丙泊酚用于颅脑损伤手术患者的麻醉效果及对血清超氧化物歧化酶(SOD)、颅内压的影响.方法:选择2017年3月-2019年3月我院收治的颅脑损伤手术患者100例纳入本次研究,根据麻醉方式分为观察组(n=51)和对照组(n=49).对照组使用七氟烷进行麻醉诱导,观察组采用丙泊酚进行麻醉诱导.比较两组患者呼吸恢复时...     

大鼠外伤后癫痫动物模型研制方法的探讨

目的:探讨大鼠外伤后癫痫(PTE)动物模型模型的制作方法和稳定性。方法:将50只成年雄性SD大鼠随机分为2组,液压损伤组40只,手术对照组10只。液压损伤组的大鼠在清醒状态下给予液压打击造成其重度颅脑外伤,于致伤后6个月内观察大鼠的行为、脑电图改变,并进行组织病理学分析。结果:液压损伤组在致伤后约有42.86%的大鼠出现典型的癫痫发作症状和脑电图上痫样放电。病理检查见伤侧脑皮质有局部挫伤,蛛网膜下腔及脑实质有出血灶和胶质结节形成等改变。液压损伤组其发作形式、脑电图特征和病理学改变与人类的PTE特征基本一致。结论:颅脑液压冲击伤可建立起清醒状态下大鼠的PTE动物模型,操作简单、稳定性及可靠性较好,有望为PTE的深入研究提供一种更为有效的实验动物模型。     

介入栓塞对颅内动脉瘤患者动脉瘤破裂、神经及脑损伤相关因子的影响

目的:探讨介入栓塞对颅内动脉瘤患者动脉瘤破裂、神经及脑损伤相关因子的影响。方法:选择我院收治的98例颅内动脉瘤患者,随机分为观察组50例以及对照组48例。观察组应用血管内介入手术,对照组应用显微外科夹闭手术。观察比较两组治疗前后血清胱抑素C(Cys-C)、含半胱氨酸的天冬氨酸蛋白水解酶3(Caspase3)、神经元特异性烯醇化酶(NSE)、星形胶质源性蛋白(S100β)、白介素-6(IL-6)、内皮素-1(ET-1)及基质金属蛋白酶-9(MMP-9)水平的变化。结果:治疗前,两组各项指标水平无显著变化(P0.05);治疗后,两组血清Cys-C、Caspase3、IL-6、ET-1、MMP-9水平均较治疗前显著降低(P0.05),且观察组以上指标水平显著低于对照组(P0.05);而组间及组内前后血清NSE及S100β水平比较差异均无明显统计学意义(P0.05)。结论:采用介入栓塞治疗颅内动脉瘤患者可能会降低颅内动脉瘤发生破裂的可能性,降低脑损伤程度,且对中枢神经系统影响不大。     

厄贝沙坦对脑损伤大鼠神经细胞凋亡的影响

目的:研究血管紧张素I受体(AT1)抑制剂厄贝沙坦对侧位液压脑损伤模型大鼠神经细胞凋亡的影响。方法:利用改良的侧位液压损伤装置建立大鼠颅脑损伤(TBI)模型,术前及术后给予厄贝沙坦治疗,用激光多普勒测定局部脑区血流(r CBF)的变化,术前及术后1、3、5和7d利用神经功能评分评估大鼠神经功能损伤,利用TUNEL染色检测大鼠脑细胞凋亡情况,利用Western Blot检测大鼠脑组织损伤周围区域活性caspase 3的表达。结果:与正常值相比,TBI手术后损伤局部脑区r CBF下降至30%(P0.05),神经功能评分显著降低(P0.05),损伤区周围脑组织TUNEL阳性细胞明显增多,活性caspase 3的表达显著增加(P0.05)。厄贝沙坦治疗组大鼠r CBF显著高于单纯TBI组,梗死区面积显著缩小,神经功能得到明显改善,损伤区周围脑组织TUNEL阳性细胞和活性caspase 3表达下降(P均0.05)。结论:厄贝沙坦预处理能够通过抑制凋亡发挥神经保护作用。     

Alterations in Ionized and Total Blood Magnesium After Experimental Traumatic Brain Injury

Experimental evidence suggests that magnesium plays a role in the pathophysiological sequelae of brain injury. The present study examined the variation of blood ionized and total magnesium, as well as potassium, sodium, and ionized calcium, after experimental fluid percussion brain injury in rats. Blood ionized magnesium concentration significantly declined from 0.45 +/- 0.02 to 0.32 +/- 0.02 mM by 30 min postinjury and stayed depressed for the 24-h study period in vehicle-treated rats. Blood total magnesium concentration was 0.59 +/- 0.01 mM and remained stable over time in brain-injured vehicle-treated animals. When magnesium chloride (125 micromol/rat) was administered 1 h postinjury, ionized magnesium levels were restored by 2 h postinjury and remained at normal values up to 24 h following brain trauma. Magnesium treatment also significantly reduced posttraumatic neuromotor impairments 1 and 2 weeks after the insult, but failed to attenuate spatial learning deficits. A significant positive and linear correlation could be established between ionized magnesium levels measured 24 h postinjury and neuromotor outcome at 1 and 2 weeks. We conclude that acute ionized magnesium measurement may be a predictor of long-term neurobehavioral outcome following head injury and that delayed administration of magnesium chloride can restore blood magnesium concentration and attenuate neurological motor deficits in brain-injured rats.     

液压打击损伤后海马CA1区神经元兴奋性变化的研究

为考察脑损伤对海马CA1区锥体神经元电活动的影响并研究大黄素对神经元的超兴奋性和突触传递的作用,应用液压打击大鼠脑损伤模型和细胞外记录方法提取诱发的海马CA1区场兴奋性突触后电位(fPSP)和群峰电位(PS),进行相关的数据处理和分析。发现损伤侧比非损伤侧的fPSP斜率明显升高,PS波峰个教显著增加,而PS潜伏期明显减小;在灌流液中施加大黄素,CA1区诱发场电位明显减弱。研究结果表明：颅脑损伤可造成海马CA1区锥体神经元的迟发性过度兴奋;大黄素对神经元的兴奋性有抑制作用,可能对颅脑损伤后的中枢神经系统具有保护功能。     

Regional Activities of Phospholipase C after Experimental Brain Injury in the Rat

Regional activities of phosphoinositide-specific phospholipase C (PLC) were measured after lateral fluid percussion (FP) brain injury in rats. The activity of PLC on phosphatidylinositol 4,5-bisphosphate (PIP₂) in the rat cortex required calcium, and at 45 M concentration it increased PLC activity by about ten-fold. The activity of PLC was significantly increased in the cytosol fraction in the injured (left) cortex (IC) at 5 min, 30 min and 120 min after brain injury. However, in the same site, increases were observed in the membrane fraction only at 5 min after brain injury. In both the contralateral (right) cortex (CC) and ipsilateral hippocampus (IH), the activity of PLC was increased in the cytosol only at 5 min after brain injury. These results suggest that increased activity of PLC may contribute to increases in levels of cellular diacylglycerol and inositol trisphosphate in the IC (the greatest site of injury), and to a smaller extent in the IH and CC, after lateral FP brain injury. It is likely that this increased PLC activity is caused by alteration in either the levels or activities of one or more of its isozymes (PLC, PLC, and PLC) after FP brain injury.     

Reconstructed bone end loads on the canine forelimb during gait

The objective of this work was to determine bone loading conditions that, when applied to a finite element model, would best reproduce the in vivo strain field as measured by surface-mounted strain rosettes. The present study adopts the basic mathematical approach to load reconstruction introduced by Weinans and Blankevoort (J. Biomech. 28 (1995) 739) who determined the relationship between applied loads and bone strain distribution using ex vivo calibration testing. Our method eliminates the need for subsequent ex vivo calibration tests by instead substituting a computational calibration procedure. This first application of the method is with in vivo strains on the canine forelimb during gait (Coleman et al., J. Biomech. 35 (2002) 1677), but with further refinements the method could be used to reconstruct the in vivo loading conditions in living subjects.     

Regional and Temporal Alterations in DNA Fragmentation Factor (DFF)-Like Proteins Following Experimental Brain Trauma in the Rat

DNA fragmentation, an early event in neuronal death following traumatic brain injury, may be triggered by the 40-kDa subunit of DNA fragmentation factor (DFF40). DFF40 is typically bound to the 45-kDa subunit of DFF (DFF45), and activation of DFF40 may occur as a result of caspase-3-mediated cleavage of DFF45 into 30- and 11-kDa fragments. In this study, the intracellular distribution of DFF45 and DFF40 was examined following lateral fluid percussion brain injury of moderate severity (2.4-2.7 atm) in male Sprague-Dawley rats. In the cytosolic fraction (S1) of the injured cortex at 2 and 24 h postinjury, significant decreases in the intensities of DFF45-like proteins at 45- and 32-kDa bands and a concomitant increase in the 11-kDa bands were observed (p < 0.05 vs. uninjured controls). A significant decrease in the intensities of the 32-kDa band in the nuclear (P1) fraction of the injured cortex was observed at 30 min and 2 h postinjury (p < 0.01). Concomitantly, a decrease in DFF40 was observed in the cortical S1 fraction at 2 and 24 h (p < 0.05) and in the P1 fraction at 30 min and 2 h postinjury (p < 0.01). In the hippocampus, DFF45 decreased at 30 min in the P1 and 2 h in the S1 fraction (p < 0.05) and recovered by 24 h postinjury, whereas DFF40 was significantly decreased in the S1 and increased in the P1 fraction at both 2 and 24 h (p < 0.01), which indicated a translocation of DFF40 from cytosol to nucleus. These data are the first to demonstrate that changes in DFF proteins occur after brain trauma and suggest that these changes may play a role in apoptotic cell death via caspase-3-DFF45/DFF40-DNA cleavage observed following traumatic brain injury.     

重型颅脑损伤后颅内高压的治疗研究进展

重型颅脑损伤后颅内压增高预示着不良的神经功能预后和极高的死亡率,一直是临床治疗中的研究热点,可采取高渗性脱水,亚低温疗法,巴比妥昏迷治疗及外科手术干预等治疗措施控制颅内压。由于亚低温治疗会增加患者发生肺炎的风险,巴比妥类药物副作用较大,现均已少用。近来研究发现,监测颅内压、脑灌注压、脑组织氧分压并指导临床治疗,可降低死亡率与改善预后。也有研究发现去骨瓣减压术治疗顽固性颅内高压与神经功能预后较差有关。目前关于颅内高压治疗的最佳方案仍存在争议,未来还需根据患者病情,为其制定规范化与个体化的治疗方案,预防继发性颅脑损伤,降低颅内压。本文就近年来重型颅脑损伤后颅内高压的治疗进展进行阐述。     

大鼠侧位液压冲击脑损伤动物模型的病理生理学观察

目的：建立一种重复性好的大鼠分级侧位液压冲击脑损伤模型,为进一步研究外伤性脑损伤的分子机制提供物质基础。方法：雄性ＳＤ大鼠,随机分为正常对照组,手术对照组和损伤组损作组接冲击力大小分为轻（１００ｋＰａ）、中（２００ｋＰａ）、重（３００ｋＰａ）３个亚组。实验中由计算机记录冲击时脑承受的压力曲线并描记大鼠血压和心率变化。结果：脑承受的压力曲线与冲击气压呈直线正相关（ｒ＝０．９８５）,损伤组大鼠在冲击后     

腰大池持续引流术对老年重型颅脑损伤患者颅内压和并发症及预后的影响

目的:探讨腰大池持续引流术对老年重型颅脑损伤患者颅内压、并发症和预后的影响。方法:选取2014年8月～2018年8月期间成都医学院第一附属医院收治的老年重型颅脑损伤患者60例为研究对象。根据随机数字表法将患者分为对照组(n=30)与研究组(n=30),其中对照组术后给予常规的脱水对症治疗,研究组则在此基础上给予腰大池持续引流术。比较两组术后临床疗效以及并发症,术后3d、5d、7d颅内压,随访半年,观察两组患者预后。结果:研究组治疗后总有效率为90.00%,显著高于对照组患者的66.67%(P0.05)。两组患者术后3d、5d、7d颅内压均较术前降低,且研究组低于对照组(P0.05)。研究组脑梗死、脑水肿、硬膜下积液、癫痫、纵裂积液等并发症发生率均低于对照组(P0.05),而颅内感染比较差异无统计学意义(P0.05)。研究组良好例数高于对照组,而重残以及死亡例数均低于对照组,差异有统计学意义(P0.05);而两组轻残、植物生存例数比较差异无统计学意义(P0.05)。结论:腰大池持续引流术治疗老年重型颅脑损伤患者,疗效满意,可显著改善患者颅内压,减少并发症发生率,改善患者预后,适于临床推广。     

神经电生理在颅内动脉瘤夹闭术中联合颅内压、脑灌注压监测的应用效果研究

摘要 目的：探讨神经电生理在颅内动脉瘤夹闭术中联合颅内压（ICP）、脑灌注压（CPP）监测的应用效果。方法：选取2018年12月～2020年1月我院进行开颅手术治疗的颅内动脉瘤患者60例,采用简单随机化分组方法分为两组,每组30例。对照组实施颅内动脉瘤夹闭手术,观察组在对照组基础上,术中应用神经电生理、ICP、CPP监测。比较两组动脉瘤夹闭情况,术后第1 d新发神经功能缺损情况,术前、术后1 d、术后3个月格拉斯哥昏迷评分（GCS）、美国国立卫生研究院脑卒中量表（NIHSS）评分及术后3个月预后优良率。结果：两组动脉瘤均完全夹闭,观察组术后第1 d新发神经功能缺损率6.67%（2/30）低于对照组的26.67%（8/30）（P＜0.05）;术后1 d观察组GCS评分高于对照组,NIHSS评分低于对照组（P＜0.05）;排除失访病例后,观察组术后3个月GOS分级、mRS分级优良率分别为88.89%、88.89%,与对照组的88.00%、84.00%比较,差异无统计学意义（P＞0.05）。结论：采用神经电生理联合ICP、CPP监测,能够实时掌握颅内动脉瘤夹闭术患者脑组织血流情况,根据监测结果及时采取相应干预措施,可预防不可逆的脑缺血改变,改善术后早期患者意识状态,减少术后早期神经功能缺损的发生。