Cytokine Concentrations in the Cerebrospinal Fluid of Great Danes with Cervical Spondylomyelopathy

Background

Chronic inflammation is involved in the pathogenesis of human cervical spondylotic myelopathy and could also play a role in cervical spondylomyelopathy (CSM) in dogs.

Hypothesis/Objectives

That cerebrospinal fluid (CSF) cytokine concentrations would differ between clinically normal (control) and CSM‐affected Great Danes (GDs), with affected GDs showing higher levels of inflammatory cytokines, such as interleukin (IL)‐6 and monocyte chemoattractant protein‐1/chemokine ligand 2 (MCP‐1/CCL2).

Animals

Client‐owned GDs: 15 control, 15 CSM‐affected.

Methods

Prospective study. Dogs underwent cervical vertebral column magnetic resonance imaging and collection of CSF from the cerebellomedullary cistern. Cytokine concentrations were measured using a commercially available canine multiplex immunoassay. Cytokine concentrations were compared between groups. Associations with the administration of anti‐inflammatory medications, disease duration and severity, severity of spinal cord (SC) compression, and SC signal changes were investigated in affected GDs.

Results

Affected GDs had significantly lower MCP‐1/CCL2 (mean 138.03 pg/mL, 95% confidence interval [CI] = 114.85–161.20) than control GDs (212.89 pg/mL, 95% CI = 165.68–260.11, P = .028). In affected GDs, MCP‐1/CCL2 concentrations correlated inversely with the severity of SC compression. There were no associations with administration of anti‐inflammatory medications, disease duration, or disease severity. IL‐6 concentrations were significantly higher (2.20 pg/mL, 95% CI = 1.92–2.47, P < .001) in GDs with SC signal changes.

Conclusions and Clinical Importance

Lower MCP‐1/CCL2 in CSM‐affected GDs might compromise clearance of axonal and myelin debris, delay axon regeneration, and affect recovery. Higher IL‐6 in CSM‐affected GDs with SC signal changes suggests more severe inflammation in this group.     

Current Concepts in the Management of Acute Spinal Cord Injury

Acute injury to the spinal cord initiates a sequence of vascular, biochemical, and inflammatory events that result in the development of secondary tissue damage. Experimental studies and clinical trials in humans have demonstrated that the extent of this secondary tissue damage can be limited by pharmacologic intervention at appropriate intervals after injury. High doses of methylprednisolone sodium succinate (MPSS) improve the outcome of acute spinal cord injury in humans if treatment is initiated within 8 hours of injury. Starting therapy more than 8 hours after injury is detrimental to outcome. The clinical efficacy of methylprednisolone in improving the outcome of canine spinal cord injuries has not yet been demonstrated and its use by veterinarians is controversial. Many dogs are not seen by a veterinarian within the 8-hour window after injury, and these dogs frequently are treated with nonsteroidal anti-inflammatory drugs or large doses of dexamethasone or prednisone before methylprednisolone treatment can be initiated, thus increasing the risk of severe adverse effects. Other drugs that may provide safer and more effective alternatives to methylprednisolone include thyrotropin-releasing hormone (TRH), the 21-aminosteroids, and kappa opioid agonists. Recent studies suggest that modulation of the influx of inflammatory cells and activation of endogenous microglial cells may provide another means of improving the outcome of acute spinal cord injuries. Many drugs being developed to treat acute spinal cord injury have shown promising results when evaluated experimentally. However, any proposed therapeutic strategy should be evaluated in prospective blinded clinical trials before being adopted in clinics.     

Ultrasonographic assessment of the reticular motility in cows after administration of different doses of metoclopramide and neostigmine

The aim of the present study was to use of ultrasonography for assessment of reticular motility after administration of various doses of metclopramide and neostigmine in cows. A total of ten Holstein cows were used in six trials in each one single dose of each drug was used. Metoclopramide was used at 0.1, 0.2 and 0.3 mg/kg intramuscularly, whereas neostigmine was used at 0.02, 0.03, and 0.04 mg/kg subcutaneously. Reticular motility was assessed using 3.5 MHz transducer just before drugs administration and every 20 minutes after administration with total time of two hours. At twenty minutes postadministration, metoclopramide at a dose rate of 0.3 mg kg significantly (P<0.01) produced shortening of the interval time between the two biphasic reticular contractions by 25% and significantly (P<0.05) increased the amplitude of the first reticular contraction by 42%, but with mild neurological signs. Neostigmine produced non-significant increase in reticular contraction rate and strength. The results of the present study indicate that metoclopramide and neostigmine at selected doses are not clinically useful agents for increasing reticular contraction rate and strength. The findings of this study in healthy animals may not be extrapolatable to findings in cattle with reticuloruminal hypomotility.     

Oxytocin Content of the Cerebrospinal Fluid of Dogs and Its Relationship to Pain Induced by Spinal Cord Compression

Objectives —To determine whether oxytocin exists in the cerebrospinal fluid (CSF) of dogs and whether the amount of oxytocin in the CSF of dogs with neck or back pain caused by spinal cord compression is significantly different than that in the CSF of clinically normal dogs.
Study Design —Prospective controlled study.
Animal Population —A total of 15 purpose-bred beagles and 17 client-owned dogs.
Methods —CSF was collected by needle puncture of the cerebellar medullary cistern after induction of general anesthesia. Oxytocin levels within the samples were determined through radioimmunoassay.
Results —Dogs with spinal cord compression had significantly more oxytocin in their CSF than the clinically normal dogs (13.76 ± 2.0 pg/mL and 3.61 ± 0.63 pg/mL, respectively; P < .0001). Dogs with chronic signs (>7 days) had significantly more oxytocin in their CSF than dogs with acute signs (<7 days) (21.60 ± 0.86 pg/mL and 6.80 ± 0.81 pg/mL, respectively; P < .0001). Both acutely and chronically affected dogs had significantly more oxytocin in their CSF than the controls ( P < .005 and P < .0001 respectively).
Conclusions —Dogs with neck and back pain caused by spinal cord compression have significantly more oxytocin in their CSF than clinically normal dogs. Dogs with chronic clinical signs have significantly more oxytocin in their CSF than dogs with acute clinical signs.
Clinical Relevance —In humans, intrathecal injection of oxytocin is effective in treating low back pain for up to 5 hours. Intrathecal oxytocin may be a logical choice for perioperative analgesia in dogs undergoing myelography because the intrathecal space is accessed for injection of contrast agent.     

我国肉牛生产发展之管见

本文通过对目前我国肉牛生产发展概况的介绍并与世界主要国家和地区情况的对比，阐述了自己对核问题的看法。对存在问题的原因进行了初步分析，并提出了建设性意见。     

神经生长因子及其受体TrKA在山羊脊髓发育中的表达特点

运用免疫组织化学超敏 SP法对山羊胎儿脊髓发育中神经生长因子 (nerve growth factor,NGF)及其高亲和力受体 Tr KA的表达及其功能进行了系统的研究和探讨。结果显示 ,山羊胎儿脊髓灰质中存在 NGF及其受体 Tr KA,于 6周龄胚就可检测到 ,随胚龄增加 ,其表达范围及免疫反应着色程度逐渐增强。 NGF主要分布于腹角和背角的神经细胞 ,反应产物主要定位于胞质和突起 ;Tr KA的分布主要以腹角及胶状质为主 ,反应产物主要定位于胞核 ,后期胞质及突起也可见到阳性反应。在山羊胎儿脊髓白质中也可观察到 NGF及 Tr KA免疫阳性反应 ,其发育后期更为显著 ,阳性反应主要分布于神经胶质细胞核、神经纤维的轴索及雪旺氏细胞。结果提示 ,NGF不仅对交感和感觉神经元的发育起作用 ,而且还与腹角运动神经元的发育有关     

A Morphological and Stereological Study on Cervical Segment of Spinal Cord of Quails

In this study, volume densities of white and grey matters of cervical segments of spinal cords of quail were investigated stereologically. In both sexes, mature, six quails were used as material of this study. All animals were fixed by perfusing in 10% buffered formalin. Tissue specimens were obtained from cervical spinal cords. These tissue specimens were cut every fiftieth section at 5 μm thickness by a microtome. And mean six or seven sections were examined from every block by this method at microscope. After that, these sections were stained by haematoxylin eosin and photographed. Densities of volumes of all tissues of cervical segments of whole spinal cords and white and grey matters were calculated with principle of Cavalieri. As a result, total volume of spinal cord, volumes of white and grey matters of cervical segment and volume rates of white and grey matters were calculated.     

北京鸭迷走背核向脊髓的直接投射——HRP法研究

采用HRP逆行追踪法,对25例北京鸭迷走背核直接投射到脊髓的传导通路的起始部位进行了研究。乌拉坦(Urethane)静脉注射麻醉动物,分别在脊髓的颈中部(C7)、颈膨大部和腰膨大部注时30～50％HRP,灌流固定,取脑做冰冻连续切片,蓝色反应显色,中性红复染,镜检。实验结果:单侧脊髓注射HRP后,在延髓的闩后部分,双侧的迷走背核内发现了标记细胞,对侧的标记细胞数量多于同侧。此外,双侧的疑核和孤束核也有一些标记细胞。在颈中部脊髓引入HRP后,出现的标记细胞较多;在颈膨大部引入HRP后,出现的标记细胞较少;在腰膨大部引入HRP后,迷走背核内不出现标记细胞,而疑核和孤束核仍有少量标记细胞。本文对禽类迷走背核和疑核至脊髓的直接传导通路,结合哺乳类的有关资料进行了讨论。     

出生前山羊颈段脊髓运动神经元的发育

应用HE染色和超薄切片技术研究第6周到出生前山羊脊髓腹角运动神经元胞体的发育变化。结果表明：1．出生前山羊脊髓腹角运动神经细胞发育包括未分化期、不成熟期、发育成熟期和成熟期4个阶段。2．发育过程中，山羊脊髓运动神经元细胞核的体积持续增长；常染色质增加，异染色质减少且趋边分布；核仁数量减少，中央核仁在第8周形成，以后逐渐发育成熟；核膜渐趋成熟。3．山羊脊髓运动神经元胞体内膜系统的发育变化的规律与神经元的发育阶段相适应。     

嗅鞘细胞生物学特性及其在脊髓再生中应用的研究

近年来研究证明嗅球及嗅神经组织可以分离出嗅神经鞘细胞(olfactory ensheathing cells,OECs)，OECs具有中枢神经系统（CNS）星形胶质细胞和外周雪旺式细胞的特性，移植后的OCEs能够在宿主损伤的脊髓组织进行迁移，能够引导支持损伤的神经元突起再生、生长、延伸。而且还可以通过转基因技术使其携带某些促进神经元再生的外源性基因，表达一些促神经再生的分子，从而改善神经损伤的内环境，诱导损伤的脊髓神经元再生，使得受损脊髓再生的潜力得以发挥，达到脊髓再生和功能恢复的目的。本文就OECs的生物学特性及其在脊髓损伤和CNS的基因治疗进行综述。     

Bulbo-Pons-Mesencephalic Projections to the Lumbo-Sacral Spinal Cord in Healthy and Spastic Paresis-Affected Cattle: A Comparative Investigation

Veterinary Research Communications -