碱性成纤维细胞生长因子对脊髓损伤早期保护作用的实验研究

目的　探讨碱性成纤维细胞生长因子（ｂ Ｆ Ｇ Ｆ）对脊髓损伤的早期保护作用。方法　选３４ 只 Ｓ Ｄ 大鼠,随机分为正常组、对照组和治疗组,采用 Ａｌｌｅｎ 氏技术,以１０ ｇ×２．５ ｃｍ 致伤力造成大鼠 Ｔ８ 急性脊髓损伤,并于损伤平面以下蛛网膜下腔置入细塑料管,治疗组给予ｂ Ｆ Ｇ Ｆ治疗,对照组同时注入生理盐水。术后切取损伤区脊髓组织进行形态学观察和生化指标测定。结果受损伤段脊髓组织水含量增多,钙离子水平升高,镁离子水平下降,白质内髓鞘结构紊乱,囊性变严重,而ｂ Ｆ Ｇ Ｆ可明显改变上述变化。结论　ｂ Ｆ Ｇ Ｆ对脊髓损伤早期的继发性损害有保护作用。     

磁刺激和碱性成纤维细胞生长因子对脊髓损伤早期的保护作用

目的探讨脊髓损伤后，应用磁刺激和外源性碱性成纤维细胞生长因子(bFGF)对损伤脊髓组织早期的保护作用。方法实验利用Allen WD(weight drop)技术，以致伤力(砝码质量10g，下落高度2．5cm)制成wistar大鼠T8脊髓损伤模型，治疗组分别于术后即刻、1h、2h、4h、24h分别予0．5HZ、70％输出强度的磁刺激，同时经蛛网膜下腔导管注入20ul bFGF，对照组不做处理。术后2h、6h、24h取治疗组、对照组动物损伤区脊髓组织作以下检测：用干湿法测水含量；用原子吸收光谱法测钙、镁离子含量；伤后5d取损伤脊髓组织，电镜观察脊髓结构。结果损伤区脊髓组织水含量增多，钙离子水平升高，镁离子水平下降，白质内髓鞘结构紊乱，囊性变严重；而应用磁刺激和bFGF可改善上述变化。结论脊髓损伤后应用磁刺激和bFGF可减轻脊髓损伤后的离子失衡，从而对继发性脊髓损伤具有保护作用。     

内皮素受体拮抗剂对损伤脊髓早期保护作用

目的评价非选择性内皮素(ET)受体拮抗剂PD145065对损伤脊髓的保护作用,证实ET参与脊髓损伤(SCI)后继发损伤的假设并探讨其作用机制。方法压迫法致伤大鼠脊髓(50g,1min)。损伤前10min鞘内注射PD145065或生理盐水,观察脊髓血流(SCBF)、丙二醛(MDA)、细胞内钙(［Ca2+］i)、伊文思兰(EB)及水含量变化。结果伤区SCBF在伤后5min即有明显下降,为基线的(75.23±9.21)%,2h降为(57.06±7.35)%;伤区邻近血流下降较慢,伤后30min降为(79.82±7.98)%。伤区及邻近区伤后4h?SCBF都未恢复。伤段脊髓组织中MDA、［Ca2+］i、EB和水含量均高于假手术组(P＜0.05)。PD145065明显改善了伤区SCBF,消除了伤区邻近段SCBF的下降。PD145065预处理组脊髓中MDA、［Ca2+］i、EB和水含量均低于生理盐水组(P＜0.05)。结论PD145065对损伤脊髓早期有明显保护作用,ET及其受体可能通过多种途径参与SCI后的继发损伤。临床应用ET受体拮抗剂对SCI可能有治疗作用。     

脊髓损伤早期FOS蛋白表达变化及三七总皂甙的影响

目的 :探讨脊髓继发性损伤的病理生理机制及三七总皂甙防治该病的作用机理。 方法 :以Wistar大鼠 6 5只为研究对象 ,分为空白组、假手术组、溶媒对照组、三七总皂甙组 ,各实验组按 2h、6h、12h、2 4h时相点观察 ,Allen脊髓损伤模型10g× 10cm致伤脊髓。各组在相应时相点取脊髓组织 ,采取免疫细胞化学方法观察脊髓FOS蛋白的表达变化。 结果 :脊髓FOS蛋白表达 :溶媒对照组 >三七总皂甙组 >假手术组 >空白组。 结论 :c -fos参与了脊髓继发损伤的病理生理机制 ,三七总皂甙可能通过抑制脊髓组织神经元c -fos原癌基因的表达而起保护作用     

脊髓损伤早期三七总皂甙抗氧自由基作用的实验研究

Ｗｉｓｔａｒ大鼠４８只随机分三组，Ａｌｌｅｎ＇ｓ脊髓损伤（ＳＣＩ）模型２５０ｇ·ｃｍ致伤Ｔ_（１３）～Ｌ_１脊髓节段，腹腔注射三七总皂甙（ＰＮＳ），伤后３０ｍｉｎ时１００ｍｇ／ｋｇ，２ｈ及４ｈ各５０ｍｇ／ｋｇ；以二甲亚砜（ＤＭＳＯ）为抗氧自由基阳性对照药物，并设立空白对照。伤后１ｈ及４ｈ取伤区脊髓组织测定丙二醛（ＭＤＡ）及超氧化物歧化酶（ＳＯＤ），发现ＰＮＳ显著减少ＭＤＡ的生成，保护ＳＯＤ活力降低。组织形态学观察到灰质区出血坏死，髓鞘分离及线粒体水肿较轻。提示ＳＣＩ早期ＰＮＳ具有明显的抗氧自由基反应和减轻继发性损害的作用。     

汉防己甲素对大鼠急性脊髓损伤的作用及意义

目的：探讨汉防己甲素（Tet）对急性脊髓损伤（ASCI）的保护作用及作用机制。方法：81只大鼠随机分为三组：生盐水对照组（NS组）、汉防己甲素治疗组（Tet组）和甲基强松龙治疗组（MP组），每组27只，用加速型Allen′s打击法制成脊髓急性损伤模型，监测大鼠ASCI后及用药后的血压变化，测定损伤区脊髓Ca^2 、MDA含量；采用氢清除法测定脊髓伤区血流量（SCBF）的变化；连续观测6周ASCI后运动功能评分情况，ASCI后4h,8h、6周取伤区标本进行组织病理检查，结果：ASCI后10s各组动物的MABP显著升高，1min内迅速降至正常水平，之后Tet组舒张压，平均动脉明显降低（P＜0．05），而收缩压降低不明显（P＞0．05）；ASCI后SCBF下降，但Tet组和MP组的SCBF较NS组高（P＜0．05）；损伤区Ca^2 及MDA含量Tet组和MP组均较NS组低，神经功能评分均较NS组高。结论：Tet能改善微循环，防止SCBF的减少；抗脂质过氧化损伤，减少脂质过氧化物MDA的生成；减轻Ca^2 的局部积聚，防止钙超载，阻断继发性损伤的链式反应，减轻组织继发性损伤。对实验性急性脊髓损伤有保护作用。     

血小板活化因子及其受体拮抗剂对颈髓损伤后血脊髓屏障病理损害的影响

目的 探讨血小板活化因子(PAF)及其受体拮抗剂对猫颈髓损伤后血脊髓屏障损害的作用。方法 采用鞘内注射PAF及静脉注射PAF受体拮抗剂BN52021，观察其对颈髓损伤后脊髓组织PAF含量、血脊髓屏障的影响。结果 颈髓损伤后颈髓伤区及邻近脊髓组织PAF含量、伊文思蓝含量、水含量均明显增加，鞘内注射PAF可使伤后PAF含量、伊文思蓝含量、水含量增加更为显著。BN52021可抑制伤后颈髓组织PAF含量升高，降低颈髓组织伊文思蓝含量及水含量。结论 PAF是导致颈髓损伤后血脊髓屏障损害的重要因子，而BN52021叫可有效减轻血脊髓屏障的病理损害。     

低剂量他克莫司治疗大鼠急性脊髓损伤的实验研究

目的：探讨低剂量他克莫司（tacrolimus，又名FK506）对大鼠急性脊髓损伤是否具有神经保护作用。方法：雄性Wistar大鼠72只，随机分为假手术组（12只）、损伤组（30只）和FK506治疗组（30只）。采用Allen’s打击法致伤大鼠T10脊髓，假手术组仅做椎板切除术。FK506治疗组在脊髓损伤后5min一次性经尾静脉注射FK5060．3mg／kg，其余两组以相同方法给予等量生理盐水。致伤后30min、6h、24h、48h、72h取伤段脊髓组织行病理观察及原位末端标记法（TUNEL）检测神经细胞凋亡，伤后1、3、7、14、21d行脊髓功能BBB评分和斜板实验。结果：伤后3、7、14、21d，FK506治疗组斜板实验和BBB评分明显优于损伤组，两组间比较差异有显著性（P〈0．05）；伤后各时间点FK506治疗组脊髓损伤区出血坏死较损伤组轻；伤后6、24、48、72h神经细胞凋亡FK506治疗组较损伤组明显减少，两组间比较差异有显著性（P〈0．05）。结论：在大鼠急性脊髓损伤后早期应用低剂量他克莫司（0．3mg/kg）治疗对神经具有保护作用，可减少神经细胞凋亡，减轻脊髓继发性损伤，促进脊髓功能恢复。     

硫酸镁对继发性脊髓损伤保护作用的实验研究

目的：探讨硫酸镁对继发性脊髓损伤的保护作用及其作用机制。方法：选健康新西兰大白兔36只，随机分为3组：A组为正常组，仅行L1～L3椎板减压；B组和C组分别为对照组和治疗组，行L1～L3椎板减压后采用Allen’s重物打击法致伤脊髓．伤后30min时B组经腹腔注射蒸馏水600mg／kg，C组经腹腔注射硫酸镁600mg／kg。48h后切取伤段脊髓组织分别测定水、钙、镁含量，观察局部组织病理学改变、超微结构变化及单位面积凋亡细胞数。结果：与A组比较，B、C组伤段脊髓组织水、钙含量增多，镁含量减少，组织病理学改变及超微结构破坏严重，细胞凋亡数上升，且C组较对B组轻。结论：早期应用硫酸镁治疗可减轻脊髓损伤后的继发性损伤。     

大剂量甲基强的松龙对大鼠急性脊髓半切损伤的早期神经保护作用

目的研究大剂量甲基强的松龙（methylprednisolone,MP）对大鼠急性脊髓半切损伤的早期神经保护作用。方法 50只SD大鼠随机取10只仅行椎板切除,作为对照组。其余40只随机分为2组,脊髓半切损伤组及MP治疗组各20只。各组动物再随机平分为2个小组,分别在脊髓半切损伤后1d、7d进行BBB法神经功能评分、脊髓组织形态学观察、神经中丝（neurofilament NF）和胶质纤维酸性蛋白（glial fibrillary acidic protein,GFAP）免疫组化测定。结果脊髓半切损伤后立即使用大剂量MP明显提高了伤后7d时MP治疗组的BBB评分;对损伤脊髓的组织形态学有明显改善;明显提高了NF的表达,抑制了GFAP的表达。结论早期大剂量使用MP对大鼠急性脊髓半切损伤有神经保护作用。     

Analysis of spinal cord evoked potential and locomotor function during acute spinal cord compression in cats.

The aim of this study was to investigate whether or not conductive spinal cord evoked potentials and spinal cord function change correspondingly with each other. The relationship between conductive spinal cord evoked potentials and locomotor function during acute spinal cord compression in animals was investigated. In decerebrate cats, controlled locomotion can be induced by electrical stimuli in the mesencephalic locomotor region. Conductive spinal cord evoked potentials were recorded at the L3 level of the spinal cord and stimuli were given at the T4 segment. The locomotor function was evaluated through electromyograms of the hind limbs. By compressing the spinal cord at L1, both the conductive spinal cord evoked potentials and the locomotor function gradually decreased. When the first negative potential amplitude of conductive spinal cord evoked potentials was decreased to half the level found in normal cats, locomotor function was injured irreversibly. These results showed that changes in the conductive spinal cord evoked potentials were related to changes in locomotor function. The 50% level of the first negative potential amplitude was considered to be the critical level at which irreversible spinal cord paralysis occurred in the cats.     

三七总皂甙对鼠脊髓损伤早期病理变化影响的观察

Allen氏法250g·cm致伤60只Wistar大鼠T13～L1脊髓节段。伤后30min、2h、4h、第二及第三个24h分别腹腔注射三七总皂甙（PNS）100mg／kg及50mg／kg体重；另设二甲亚砜对照组及空白对照组。伤后30min、2h、6h、24h、1周及6周各取伤区脊髓组织送光、电镜检查。结果显示PNS治疗组脊髓灰质出血坏死较轻，周围白质大部存留，髓鞘残留，大量毛细血管和少突胶质细胞增生。提示PNS可减轻脊髓损伤后的灰质坏死，调节微循环和减轻继发性病理损害，为白质存活创造条件。     

Effect of lidocaine treatment on acute spinal cord injury

The effect of continuous infusion of lidocaine on acute spinal cord trauma in cats was studied. Intravenous and subarachnoid administration of lidocaine did not alter generation and conduction of the spinal evoked responses (SERs) in intact animals. The cortical somatosensory evoked responses and SERs were abolished after weight drop injuries of 120 and 400 g-cm. No return of the evoked responses occurred within 4 hours after trauma in either the lidocaine- or the saline-treated groups. Loss of SERs and appearance of an evoked injury potential were sensitive determinants of spinal cord injury. We concluded that lidocaine treatment did not facilitate the return of spinal cord function in this model of acute spinal cord injury.     

The influence of spine distraction on cat spinal cord blood flow and evoked potentials

The changes of spinal cord blood flow (SCBF) and spinal cord evoked potential (SCEP) due to spine distraction were analyzed in 30 cats. Spine distraction was performed at L1/2 level at which spinal bodies were separated surgically. SCBF was measured by means of a microsphere technique before, during and after spine distraction and SCEP elicited by spinal cord electrical stimulation was recorded simultaneously. With slight spine distraction (SCEP amplitude 80-100%), SCBF was increased significantly over normal value. SCBF was decreased significantly by further distraction (SCEP 50-80%), but was recovered over normal value after the release of distraction. When severe distraction (SCEP less than 50%) was applied, decreased SCBF around L1 level was irreversible. These results suggested that the disorder of SCBF regulating system due to spine distraction could be expected by analyzing changes of the SCEP.     

Comparison of spinal cord evoked potentials and peripheral nerve evoked potentials by electric stimulation of the spinal cord under acute spinal cord compression in cats

STUDY DESIGN: Spinal cord evoked potentials and peripheral nerve evoked potentials after spinal cord stimulation were recorded under acute spinal cord compression in 19 cats. OBJECTIVES: To investigate the effects of acute compression upon grey matter and white matter by comparing both potentials. METHODS: We compared peripheral nerve evoked potentials, recorded at the biceps brachii branch of the musculocutaneous nerve, with descending spinal cord evoked potentials, recorded from the lumbar spinal cord, by stimulation to the C2 level, under compression of the C6 segment. RESULTS: The amplitude of both potentials decreased with increased compression. The second wave of peripheral nerve evoked potentials, which are motor fibre action potentials, decreased sooner than those of the spinal cord evoked potentials. CONCLUSION: These findings indicate that peripheral nerve evoked potentials are sensitive to acute damage of the segmented compression. This suggests that grey matter is more vulnerable to compression than white matter.     

The effect of anesthetic agents on descending spinal cord evoked potential and the compound muscle action potentials elicited by stimulation at the cerebral motor cortex and the spinal cord]

Recently, intraoperative monitoring of the motor tract by descending spinal cord motor evoked potentials (MEP) and compound muscle action potentials (CMAP) has been applied in clinical testing. Since several reports have mentioned the vulnerability of these potentials to anesthetic agents, experimental studies were carried out on the relationship between these potentials and anesthesia using 41 adult cats. The effects of anesthesia on changes in amplitude of the direct wave (D wave) and indirect wave (I wave) of the MEP and CMAPs were investigated. These potentials were generated by stimulation of the spinal cord and the motor cortex, respectively. Enflurane (2%), halothane (1%) and isoflurane (1.5%) with pure oxygen decreased the amplitude of the I wave to less than 50% of the control level. The CMAP after stimulation of the spinal cord was degraded to less than 30%, and the CMAP after cortical stimulation vanished completely. Only the D wave was stable against inhalational anesthetic agents. Sixty-seven percent nitrous oxide with the above concentrations of these inhalational anesthetic agents decreased the amplitude of the I wave to less than 30% and the CMAP evoked by spinal cord stimulation vanished. The effect of modified NLA (diazepam and pentazocine) on these potentials was weaker than that of the inhalational anesthetic agents.     

Megadose corticosteroid therapy following experimental traumatic spinal injury

Corticosteroids are frequently used in the treatment of spinal trauma, although neither experimental nor clinical evidence to support their use is persuasive. Recently there have been claims that extremely high doses ("megadoses") of corticosteroids (equivalent to 15 to 30 mg/kg of methylprednisolone) improve neurological recovery compared to results with traditional steroid doses. The authors have compared the effect of megadose dexamethasone and methylprednisolone therapy to that of saline treatment following traumatic cervical spinal injury in the cat. During 6 weeks postinjury, neurological recovery did not differ significantly in corticosteroid-treated and saline-treated animals. Moreover, histopathological changes in the spinal cord were similar in methylprednisolone- and saline-treated cats. Corticosteroid-treated animals had a higher mortality rate than did control animals, with the predominant cause of death being neurogenic pulmonary edema. It is concluded that megadose corticosteroid treatment does not improve neurological recovery in this experimental model of spinal injury, and is associated with increased mortality.     

Effects of deep barbiturate coma on acute spinal cord injury in the cat

The effects of barbiturate administration on experimental balloon-induced spinal cord injury were tested in cats. Somatosensory evoked potentials from sciatic nerve stimulation were obtained before trauma and every 60 minutes after it up to the sixth hour, when the animals were killed. Eight cats received no barbiturate treatment. On histologic examination the traumatic lesion was found to be extensive (mean, 72.8% of total cross section of the cord area), sparing dorsal columns only in six cats. Somatosensory evoked potentials were absent in two cats and profoundly modified (that is, the late waves were absent) in six cats at the sixth hour. Eight cats were given a continuous infusion for 1 hour of intravenous thiopental sodium (total dose, 65-90 mg/kg) starting 30 minutes after trauma. In these eight cats, the extent of the traumatic lesion was significantly reduced (8.8% of the cord area). Among them, three animals presented with unaltered somatosensory evoked potentials (that is, with the presence of both primary components and late waves) at the sixth hour. It was concluded that thiopental sodium improves the response of the spinal cord to trauma, both at an anatomic and at a functional level.     

Acute phase histopathological study of spinally administered midazolam in cats.

Midazolam may be a useful analgesic when administered intrathecally. However, neurotoxicity must be excluded. The purpose of this study was to investigate whether spinally administered midazolam induces acute-phase histopathological or inflammatory reactions of the spinal cord. A lumbar laminectomy was performed on 40 cats, and their spinal cords were exposed. Midazolam 10 mg (2 mL, n = 20 cats) or saline 2 mL (20 cats) was administered directly to the spinal cord. At 1, 2, 4, or 6 h after the administration, cats were killed, and the lumbar spinal cord was removed and fixed in 10% formalin. Histology was examined using light microscopy with hematoxylin and eosin staining. Both groups showed slight to moderate changes in the spinal cord, but no severe damage was observed. Inflammatory reactions were seen in only one cat in the saline group with slight neutrophil infiltration. These changes were not different between the midazolam group and the saline group. In conclusion, up to 6 h after direct exposure to midazolam, no acute histological damage or inflammatory reaction of the spinal cord was seen in cats. IMPLICATIONS: Spinally administered midazolam, even in large doses, does not cause acute neurotoxicity or inflammation of the spinal cord.