Differences in cell death between high and low energy brain injury in adult rats

Background  Traumatic brain damage is dependent on energy transfer to the brain at impact. Different injury mechanisms may cause different types of brain injury. It is, however, unknown if the relative distribution between apoptotic cell-death and necrotic cell- death in different populations of brain cells varies depending on energy transfer. Method  Experimental contusions were produced with a modified weight drop onto the exposed dura of rats. Animals were divided into two groups. They received a weight drop from two different heights to vary energy transfer to be higher or lower. Animals were sacrificed at 24 hours post injury (1 DPI) or 6 days (6 DPI); brains were frozen and processed for TUNEL (TdT mediated dUTP nick end labelling), light microscopy and immunochemistry. Findings  The total number of TUNEL positive cells was higher in the higher energy group on the first day after the injury. At the same time point, relatively fewer cells were apoptotic than necrotic, while relatively more glial cells than neurons were TUNEL-positive in higher energy trauma. At 6 day after the injury fewer cells were TUNEL positive and there were no longer significant differences between the high and low energy groups. Conclusions  Increasing energy transfer in a model for brain contusion demonstrated qualitative and quantitative changes in the pattern of cell death. This complexity must be considered when evaluating brain-protection as treatment results may vary depending on which cellular population and which mechanism of cell death is treated under the exact experimental and clinical conditions.     

Significance of the mass-compression effect of postlaminectomy/laminotomy fibrosis on histological changes on the dura mater and nerve root of the cauda equina: an experimental study in rats

Purpose The precise mechanism and pathological role of postlaminectomy/laminotomy fibrosis (PLF) in postoperative neurological deficits have not been established. Many studies use magnetic resonance imaging (MRI) to prove that there is no consistent correlation between PLF and postoperative neurological deficits and back pain (PNDBP). Therefore, we assumed that the direct-compression effect may not be the only factor but that other neurological deficits associated with pathological mechanisms should exist and need more investigation. The purpose of this study was to compare over time the differences and changes in histopathological properties of PLF in rats.Methods We used a rat model with walking-track analysis for neurologic evaluation, grading scale to evaluate PLF, histomorphometric measurements of dura sac diameter, and histological tissue reactions (dura mater and spinal rootlets) juxtaposed to the postlaminectomy/laminotomy defect. The 54 adult Sprague–Dawley rats were divided into laminotomy (n = 18), laminectomy (n = 18), and sham-operation groups (n = 18). All groups were subdivided into three equal subgroups based on different postoperative time points (1, 2, and 3 months). All sections of vertebral column were stained with hematoxylin and eosin and with Masson’s trichrome.Results The results showed that only a slight compression effect reflected by nonsignificant changes in the maximum anterior-posterior diameters within the dura sac, in the walking tract test, and increased grades of PLF over time. In addition, significant pathological inflammatory changes, such as thickening of the dura mater, axonal swelling, and neovascularization, were found in the post-laminectomy/laminotomy groups at each time point.Conclusion Laminectomy-/laminotomy-related inflammation may lead to PLF, and these pathological changes may be the main cause of postoperative neurological deficits. These findings show that research on preventing PLF should include perioperative modulation of inflammatory reactions induced by laminectomy/laminotomy.     

Pharmacological and pathological modulation of cerebral physiology

Anaesthesia for neurosurgery aims to provide optimal surgical conditions whilst maintaining adequate cerebral blood flow in order to supply the brain with appropriate amounts of oxygen and glucose. Most anaesthetic drugs influence the normal cerebral physiology either directly or indirectly. They can cause changes in cerebral blood flow by influencing cerebral blood vessel calibre, by interfering with autoregulatory processes and by modifying cerebral metabolism. The brain's limited ability to store oxygen and glucose means that its supply must be continuous if neuronal damage is to be avoided. Ischaemic cerebral damage is the most important pathological mechanism in patients with stroke, subarachnoid haemorrhage and traumatic brain injury. Significant traumatic brain injury causes widespread derangement of cerebral physiology, including changes in cerebral blood flow, autoregulation and cerebral energy dynamics. This article outlines the effect of anaesthesia on cerebral physiology and reviews the pathophysiology of traumatic brain injury and subarachnoid haemorrhage.     

Idiopathic hypertrophic spinal pachymeningitis

Spinal idiopathic hypertrophic pachymeningitis (IHP) is a rare, chronic, nonspecific, granulomatous inflammatory disorder of the dura with unknown etiology. It can cause a localized or diffuse thickening of the dura mater with compression of the spinal canal and possible myelopathic symptoms. The authors report 3 consecutive cases of spinal IHP with a review of the literature. The diagnosis of spinal IHP was based on biopsy and pathological confirmation. Typical MR imaging findings suggestive of spinal IHP were noted in all cases. The clinical course may be marked by deterioration despite conservative therapy and may require surgical intervention to prevent irreversible neurological damage. Therefore, prompt diagnosis and institution of proper treatment is critical.     

Pathology of synovitis and hemophilic arthropathy

Hemophilia is an X chromosome linked disease characterized by an increased tendency to hemorrhage. Due to recurrent haemarthroses specific changes occur in synovium and cartilage. This process is called haemophilic arthropathy. The pathogenetic mechanisms involved are not precisely known. Current concepts, which are based on experimental in vitro studies and clinical experience, hold that the synovium becomes catabolically active because of the exposure to blood components and as a result induces cartilage destruction. A considerable amount of reports concerning blood induced joint damage suggest that synovial changes have a leading role in the development of the joint damage and therefore precede the changes in cartilage. However, there are also observations that question whether this is the only and the initiating mechanism of joint damage in hemophilia they hold that intra-articular blood has a direct harmful effect on cartilage before synovial changes and suggest that joint damage may occur before synovial inflammation is evident. Primarily there may be damage of articular cartilage with synovitis as a consequence. These studies show that synovitis is involved, but that it is not the only mechanism in the joint damage caused by intra-articular bleeding. These findings do not contradict the current concept of blood-induced cartilage damage in which synovial changes are thought to play an important role. Several pathological processes are possibly involved, some of them occurring in parallel and others sequentially. Possibly intra-articular blood first has an direct effect on cartilage, and then it affects the synovium. Thus, both processes occur in parallel, and while they influence each other they probably do not depend on each other. This concept resembles degenerative joint damage as found in osteoarthritis.     

Models of spinal cord injury: Part 1. Static load technique

Testing of potential therapies for spinal cord injury has been significantly hampered by the unavailability of a standardized, reproducible animal model with predictable outcome at a given force of injury (dose-response). The rat was selected in the development of this model in preference to larger animals for economy and availability; this permits use of large numbers of animals to increase statistical validity. In the experiments reported in this article, a static load method (weight placed gently on cord) of inducing cord injury was evaluated. A total of 198 Sprague-Dawley rats were used. Under general anesthesia, a one-level laminectomy was carried out at T-12 with the dura mater intact. Weights varying from 80 to 150 g were lowered onto the dorsal surface of the intact dura mater for durations of 0 to 300 seconds. Recovery of motor function was assessed for up to 8 weeks using two behavioral tests, a modified Tarlov scale and an inclined plane test of hind limb motor function. A statistically significant relationship was found between force of injury and motor recovery as measured by the Tarlov scale, but this did not correlate with inclined plane performance; the duration that the weight rested on the cord did not influence outcome. Pathologically, there was variation in the extent of damage for a given injury load. A semiquantitative pathological assessment of cord injury showed a statistically significant correlation between pathological score and behavioral deficit as measured by the Tarlov scale, but this did not correlate with inclined plane performance. In view of these deficiencies, the static load technique does not seem to be an ideal model for spinal cord injury research.     

Per- and postoperative changes in the arterio-venous oxygen content difference (AVDO2) in patients subjected to craniotomy for cerebral tumours

Summary Sixteen patients with supratentorial cerebral tumours were subjected to craniotomy under thiopentone, fentanyl, nitrous oxide, halothane anaesthesia during moderate hypocapnia (PaCO₂ level 4.0 kPa). The arterio-venous oxygen content difference (AVDO₂) was measured peroperatively, and repeatedly during the first three hours after extubation.Peroperatively the level of AVDO₂ averaged 8.0 vol% during opening of the dura, and decreased to 7.0 vol% during closure of the dura (P<0.05). Immediately after extubation the AVDO₂ decreased to 4.3 vol% (P<0.05), and during the next 3 hours a gradual increase to 5.8 vol% (P<0.05) was disclosed. In individual cases the postoperative changes in AVDO₂ correlated fairly well with changes in mean arterial blood pressure (MABP), but other factors including duration of the operation, age of the patients, size of the tumour, level of PaCO₂ and adaptation to prolonged hyperventilation during operation are supposed to be responsible for the low levels of AVDO₂ observed in the postoperative period.     

The density of nociceptive SP- and CGRP-immunopositive nerve fibers in the dura mater lumbalis of rats is enhanced after laminectomy,even after application of autologous fat grafts

A considerable number of patients complain about pain after lumbar surgery. The spinal dura mater has been debated as a possible source of this pain. However, there is no information if laminectomy influences the nociceptive sensory innervation of the dura. Therefore, we quantitatively evaluated the density of SP- and CGRP-immunopositive nerve fibers in the dura mater lumbalis in an animal model of laminectomy. Twelve adult Lewis rats underwent laminectomy, in six of them the exposed dura was covered by an autologous fat graft. Further six animals without surgical treatment served as controls. Six weeks after surgery, the animals were perfused and the lumbar dura was processed immunohistochemically for the detection of CGRP- and SP-containing nerve fibers. In controls, the peptidergic nerve fibers were found predominantly in the ventral but rarely in the dorsal dura mater lumbalis. After laminectomy, the density of SP- and CGRP-immunopositive neurons significantly increased in ventral as well as in dorsal parts of the dura. Axonal spines could be observed in some cases at the site of laminectomy. The application of autologous fat grafts failed to inhibit the significant increase in the density of peptidergic afferents. Thus, we have provided the first evidence that laminectomies induce an increase in the density of putative nociceptive SP- and CGRP-immunopositive neurons in the lumbar dura mater ascribable to an axonal sprouting of fine nerve fibers. This effect was not prevented by using autologous fat grafts. It is conceivable that the neuronal outgrowth of nociceptive afferents is a cause of low back pain observed after lumbar surgery.     

硬膜外腔注入镇痛复合药后硬膜神经脊髓细胞超微结构的变化

２６只健康杂种犬分别于Ｌ４～５硬膜外腔注入醋酸确炎舒松一Ａ、盐酸利多卡因、地塞米松、维生素Ｂ１、维生素Ｂ１２、６５４－２配制成的复合液，在注药不同次数后３天、７天分别取局部硬膜、神经根、脊髓组织作光镜和电镜观察，并与正常组织对照。在硬膜外腔注入复合药液后的标本，光镜观察未发现组织细胞学的病理性改变，亦未发现炎性反应。电镜观察发现硬膜组织间皮细胞及纤维细胞胞浆基质浓缩，内有空泡．部分胶原纤维排列疏松，周期性横纹消失，毛细血管内皮细胞粗面内质同扩张，基底膜不完整。神经根和脊髓组织细胞无明显改变。这种改变在一周内可恢复正常。     

A simple and effective method for obtaining stable in vivo whole-cell recordings from visual cortical neurons

We describe a simple and effective method for obtaining stable in vivo whole-cell recordings in cat visual cortex. The core of the new approach is to prevent brain pulsation by retaining the dura mater. After being treated with an enzyme (collagenase), the dura became soft enough to allow easy penetration by a patch-clamp electrode with negligible damage to the tip. The procedure is as simple as those used for extracellular recordings, and all the intricate steps required for conventional techniques are no longer necessary. The reliability of this approach is demonstrated by stable and sustained intracellular recordings and high-quality intracellular staining. The method is especially effective for studying small neurons in the superficial layers immediately below the dura.     

选择性颈段脊神经后根部分切断术治疗脑性瘫引起的上肢痉挛型瘫

目的：采用双开门术式选择性颈段脊神经后根部分切断术治疗脑性瘫引起的上肢痉挛型瘫。方法：颈椎椎板两侧行上宽下窄骨槽,内板不切断,切除棘突、切断椎弓,轻轻将椎板向两侧翻开,暴露硬膜、脊髓及神经后根,选择性按比例将部分神经后根切断。缝合硬膜,将椎板回置解剖位。结果：经５个月～３年对３０例病人的术后观察,上肢痉挛解除彻底,功能得到明显改善。Ｘ光片示椎板愈合,骨折线区密度均匀,椎板结构正常,无颈椎不稳。结论：该术式创伤小,损伤轻,颈椎后部结构破坏小,椎管的完整性得到保护,痉挛解除彻底。是目前治疗脑性瘫最佳术式与方法。     

Brain swelling and brain oedema in acute head injury

Summary Chronological changes in diffuse brain swelling and brain oedema were studied in repeated CT studies following a closed head injury. These findings were compared with changes in intracranial pressure (ICP). The grades of diffuse brain swelling were classified into mild, moderate and marked according to the CT findings. Planimetry of low density areas of brain oedema was carried out on repeated CT images. Diffuse brain swelling was recognized in 71 of patients shortly after the head injury and subsided within days 3–5. Brain oedema first appeared 24 hours post injury and did not reach its maximum size and distribution before days 5–8. Thus, these two events can be clearly separated. The intracranial pressure reflected the course of the brain swelling and was not very high during the presence of maximum oedema.     

An assessment of the Cerebrotrac 2500 for continuous monitoring of cerebral function in the intensive care unit

Experience of the use of the Cerebrotrac 2500 EEG monitor in 17 patients subjected to artificial ventilation in an intensive care unit is reported; seven were receiving continuous sedation with morphine, midazolam and propofol singly or in combination and 10 received both sedation and the neuromuscular blocking agent, atracurium. The processed EEG patterns could not be precisely correlated with a standard clinical scoring system but were useful in determining the adequacy of sedation, particularly when a muscle relaxant was used. The monitor also shows considerable promise in the management of the paralysed patient with widespread convulsive activity in whom ischaemic brain damage may be occurring from epileptiform activity in the absence of any clinical manifestation. The ability to detect cerebral irritability or isolated epileptiform discharges using this apparatus is, however, questionable. The equipment was easy to use and robust; the running costs were 9.5p per hour.     

神经补片在去骨瓣减压术中的作用

目的探讨神经补片在去骨瓣减压术中的作用。方法回顾性研究,治疗组的78例患者在标准去骨瓣减压时使用神经补片修补硬脑膜,对照组的36例患者在标准去骨瓣减压时使用自体筋膜修补硬脑膜。术后对比两组患者的癫痫发生率;在二期的修补治疗中对比两组患者的手术时间、术中出血量及硬脑膜破损率。结果治疗组和对照组的癫痫发生率分别为6.4%和22.2%,差异显著(χ2=6.095,P=0.014),在二期的颅骨缺损修补中,治疗组和对照组的手术时间分别为(121.9±18.6)min vs.(156.1±14.6)min,出血量分别为(108.1±42.3)ml vs.(181.9±46.5)ml,硬脑膜破损率为3.8%vs.25%;差异均有统计学意义(P0.05)。结论在标准去骨瓣减压时使用神经补片修补硬脑膜能降低患者术后的癫痫发生率,同时有利于患者二期进行的颅骨缺损修补手术,能减少修补手术中的出血量及手术时间,减少副损伤。     

Pathogenetic role of circulatory factors in brain edema development

Sufficient experimental evidence has been accumulated at present, proving that changes in cerebral blood circulation are largely involved in brain edema development. On the one hand, they might be an immediate cause of edema, e.g., a significant rise of the systemic arterial pressure surpassing the limits of cerebral blood flow autoregulation, or cerebral ischemia damaging brain tissue and the bloodbrain barrier. On the other hand, circulatory changes, e.g., systemic arterial and venous pressure variations, as well as changes in cerebrovascular resistance or in the microcirculation of cerebral tissue, might be the factors which affect in different ways the development of edema of various etiologies. The effects of these circulatory changes may have dual implications, being either malignant, i.e., aggravating edema development, or compensatory, i.e., restricting or in some cases even eliminating brain edema. Knowledge of the circulatory changes is an essential tool in neurosurgical practice, providing for effective treatment of this severe pathological process in the brain.     

The influence of intermittent versus continuous brain retractor pressure on regional cerebral blood flow and neuropathology in the rat

Summary To evaluate the possible advantage of intermittent versus continuous brain retractor pressure (BRP) both regional cerebral blood flow (rCBF) measurements and neuromorphological studies have been conducted in the rat. In the same rat model as used in this study it has previously been demonstrated that BRP of 30–40 mm Hg for 15 minutes or more caused severe decrease of rCBF and produced brain damage. In this study a BRP of 40 mm Hg intermittent for 5 and 7 minutes with intervals of 1 minute without BRP for a total of 29 and 31 minutes respectively did not produce brain damage. After BRP for 10 minutes brain damage has been observed. Concerning the rCBF it was demonstrated that a sufficient recirculation after BRP of 30 mm Hg was re-established within 1 minute (70–90 ml/ 100 g/min) and no significant changes of rCBF were observed in the first 10 minutes after discontinuation of the BRP. Judging from these results intermittent BRP has to be preferred to continuous BRP and the time threshold of the BRP is approximately 7 minutes. Sufficient rCBF is re-established quickly after ischaemia so only short intervals between BRP application periods are necessary.     

Nonalcoholic steatohepatitis and insulin resistance in children

Various pathological conditions can cause fatty liver in children. Nonalcoholic steatohepatitis (NASH) in children has been known since 1983. However, NASH diagnosed in childhood does not have a favorable outcome. The pathological characteristics of NASH are significantly different between children and adults. Nonalcoholic fatty liver disease (NAFLD)/NASH is accompanied by insulin resistance, which plays a pivotal role in its pathophysiology in both children and adults. In NASH, a “two-hit” model involving triglyceride accumulation (first hit) and liver damage (second hit) has been accepted. Insulin resistance was found to correlate with changes in fat levels; however, it did not correlate with fibrosis or NAFLD activity score in children. Therefore, insulin resistance may be important in the first hit. Because there is obvious familial clustering in NASH, genetic predisposition as well as environmental factors including diet might be the second hit of NAFLD/NASH.     

脊髓纵裂神经损伤的病理因素与治疗

目的 探讨脊髓纵裂病理因素及其神经损伤机制，选择合理的治疗方法。方法 根据70例脊髓纵裂患者的影像学资料，手术观察，尸解和临床表现，结合治疗方法与效果，研究其导致神经损伤的病理改变。结果 脊髓纵裂病理因素有5个方面；（1）先天性神经发育不良；（2）骨嵴与双管状硬脊膜；（3）脊髓水囊肿；（4）严重脊柱侧弯和异常神经根；（5）终丝及骶等肿瘤，结论 5种病理因素通过先天性缺陷，栓系和压迫机制导致脊髓发生病理变化，影响脊髓功能，应当选择切除骨嵴，硬脊膜成型，终丝切断，囊肿内引流和先天性脊柱侧弯矫形等治疗方法。     

The anterior surgical approach to the cervical spine for intervertebral disc disease

THE ANTERIOR SURGICAL APPROACH to the cervical spine in patients with discogenic compressive pathological findings causing radiculopathy or myelopathy is a commonly performed operation with several technical variations. We describe the normal and pathological anatomy and the techniques of surgical decompression of the dura with autograft fusion, which we have used for the past 35 years.     

转化生长因子-β和碱性成纤维细胞因子在儿童原发性局灶节段性肾小球硬化肾组织中的表达

目的：通过检测转化生长因子-β（TGF-β）和碱性成纤维细胞生长因子（bFGF）在儿童原发性局灶节段性肾小球硬化（FSGS）肾组织中的表达情况,并分析其与肾小管间质病理变化的关系,以了解TGF-β与bFGF在原发性FSGS发生发展中的作用。方法：选择肾活检明确诊断为原发性FSGS患儿的肾组织共43例,其中不伴有肾小管间质病变的FSGS肾组织共16例,设为实验1组;伴有肾小管间质病变的FSGS肾组织共27例,为实验2组。另将同期因孤立性血尿入院肾活检证实为非FSGS、病理改变较轻的肾组织作为对照组,共17例。采用免疫组化法检测细胞/生长因子TGF-β、bFGF在各组中的表达。通过方差分析（ANOVA）和相关分析法分析细胞/生长因子的表达与FSGS肾组织病理变化的关系以及细胞/生长因子之间的相互作用关系。结果：TGF-β、bFGF在各组肾组织中均有表达,表达量在对照组、实验1组和实验2组中依次升高,各组间的差异均具有统计学意义（P〈0.05）;且TGF-β和bFGF的表达与肾小管间质指数呈正相关,相关系数依次为0.763和0.661。此外,TGF-β和bFGF两者的表达量经相关分析也显示呈正相关,相关系数为0.587。结论：TGF-β和bFGF在原发性FSGS患儿肾组织中高表达;随着FSGS的发展,它们在肾组织中表达量不断增加,促使肾小管间质向纤维化发展,而且两者在促进肾脏纤维化具有一定的协同作用。