Brain Neuronal Degeneration Caused by Episodic Alcohol Intoxication in Rats: Effects of Nimodipine, 6,7-Dinitro-quinoxaline-2,3-dione, and MK-801

Rats repeatedly intoxicated with alcohol (ethanol, three times daily) over a 4-day period display neuronal degeneration in the dentate gyrus; entorhinal, piriform, insular, orbital, and perirhinal cortices; and in the olfactory nerve fibers and terminals in the olfactory bulb. Postulating a role for excitotoxicity, we have attempted to prevent the degeneration using antagonists that are neuroprotective in this type of brain damage. In an initial study, continuous subcutaneous infusion of a high dose of the glutamate/NMDA receptor antagonist MK-801 (2 mg/kg/day) by itself caused extensive neuronal degeneration in several brain regions and severe behavioral intoxication that precluded survival if combined with high blood alcohol levels (～300 mg/dl). Moreover, the lower, nonneurotoxic blood alcohol levels (～150 mg/dl) that were compatible with survival worsened the MK-801-induced brain damage. In a subsequent experiment, daily intraperitoneal injections of a lower dose of MK-801 (1 mg/kg/day) resulted in no MK-801 toxicity and, when combined with neurotoxic levels of alcohol, no reduction in alcohol-induced neurotoxicity. Nimodipine, a voltage-gated Ca²⁺ channel blocker, reduced the neuronal damage in the dentate gyrus, but greatly increased it in the piriform cortex when administered intragastrically at 600 mg/kg/day; it provided no protection from alcohol-dependent degeneration when given intragastrically at 100 mg/kg/day. Continuous intracere-broventricular delivery of 0.24 to 0.29 mg/day of 6,7-dinitro-quinoxa-line-2,3-dione, a glutamate/α-amino-3-hydroxy-5-methyl-4-isoxazole receptor antagonist, failed to diminish alcohol-dependent neuronal damage in any brain region. We conclude that brain damage from episodic “binge” alcohol intoxication is not primarily mediated by excitotoxic mechanisms, implying that other, nonexcrtotoxic pathophysiological mechanisms, are involved. Furthermore, MK-801, far from protecting from the alcohol-induced damage, at high doses causes widespread neuropathology that is significantly potentiated by alcohol.     

A Rat Model of Striatonigral Degeneration Generated by Simultaneous Injection of 6-Hydroxydopamine into the Medial Forebrain Bundle and Quinolinic Acid into the Striatum

A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson''s disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.     

Prevalence of Disc Degeneration in Asymptomatic Korean Subjects. Part 2 : Cervical Spine

Objective

Similar to back pain, neck pain has recently shown to have increasing prevalence. Magnetic resonance imaging (MRI) is useful in identifying the causes of neck pain. However, MRI shows not only pathological lesions but also physiological changes at the same time, and there are few Korean data. The authors have attempted to analyze the prevalence of disc degeneration in highly selective asymptomatic Korean subjects using MRI.

Methods

We performed 3 T MRI sagittal scans from C2 to T1 on 102 asymptomatic subjects (50 men and 52 women) who visited our hospital between the ages of 14 and 82 years (mean age 46.3 years). All images were read independently by three observers (two neurosurgeons and one neuroradiologist) who were not given any information about the subjects. We classified grading for cervical disc herniation (HN), annular fissure (AF), and nucleus degeneration (ND), using disc degeneration classification.

Results

The prevalence of HN, AF, and ND were 81.0%, 85.9%, and 95.4%, respectively. High prevalence of HN, AF, and ND was shown compared to previous literature.

Conclusion

In asymptomatic Korean subjects, the abnormal findings of 3 T MRI showed a high prevalence in HN, AF, and ND. Several factors might play important roles in these results, such as population-specific characters, MRI field strength, and disc degeneration grading system.     

椎间盘退变模型的研究现状及进展

目的：探讨椎间盘退变模型的研究现状及进展。方法：在Pubmed、中国知网查阅有关椎间盘退变模型研究的文献,进行汇总分析。结果：椎间盘退变模型可以通过体外和体内两种方法构建,前者包括椎间盘细胞模型和椎间盘组织模型,后者包括诱发性椎间盘退变模型和自发性椎间盘退变模型。体外模型适用面较广,但培养要求较高,不能全面模拟体内环境;体内培养干预技术较容易实现,但适用面较窄。结论：人椎间盘退变的影响因素繁多,目前的椎间盘退变模型往往具有一定的局限性,无法全面地模拟出人的椎间盘退变情况。无创、微创构建椎间盘退变模型将是未来的发展趋势。     

骨质疏松症对脊柱小关节退变的影响

骨质疏松症(OP)以骨量减少和骨的微细结构破坏为主要特征,并伴随骨质脆性增加和骨折危险性升高.由于骨的结构破坏,可引发脊柱退行性变,使椎体高度丢失应力改变及使人体成骨、破骨细胞代谢紊乱,发生脊柱尤其是腰椎小关节退变.但由骨质疏松症引起脊柱小关节退变尤其是腰椎小关节退变原因发病机制文献报道较少,目前认为骨质疏松对脊柱小关节退变与成骨,破骨细胞代谢影响,及发生椎体内微骨折,改变椎体高度及软骨下骨血供应微环境,增加小关节应力,减少其血供营养有关.     

单纯前路与前后联合入路治疗退变性多节段脊髓型颈椎病的对比研究

目的 比较前路多节段（≥3）颈椎间盘切除椎管减压植骨融合内固定（ACDF）与后路单开门椎管扩大成形（ELAP）联合ACDF治疗伴颈椎后凸、巨大椎间盘突出的退变性多节段脊髓型颈椎病的疗效。方法 回顾性分析2014年1月至2019年1月于我院接受多节段ACDF或ELAP联合ACDF治疗的41例合并颈椎后凸畸形、巨大椎间盘突出的退变性多节段脊髓型颈椎病病人的临床资料,根据手术方式分为单纯前路组（21例）和前后联合入路组（20例）,单纯前路组21例,男10例,女11例,年龄为（52.10±5.96）岁。前后联合入路组20例,男12例,女8例,年龄为（53.23±5.12）岁。记录病人手术时间、术中出血量、住院时间、疼痛视觉模拟量表（visual analogue scale,VAS）评分、日本骨科协会（Japanese Orthopedic Association,JOA）评分、Nurick评分、C_2-7 Cobb角、局部后凸角（RK）、C_2-7矢状面垂直轴（SVA）。结果 前后联合入路组手术时间、出血量大于单纯前路组（P＜0.05）。两组住院时间的差异无统计学意义（P＞0.05）。末次随访,两组VAS评分、Nurick评分均小于术前,JOA评分大于术前,差异均有统计学意义（P＜0.05）;前后联合入路组VAS评分、Nurick评分小于单纯前路组,JOA评分、JOA改善率大于单纯前路组,差异均有统计学意义（P＜0.05）。两组C_2-7 Cobb角、RK均大于术前（P＜0.05）,C_2-7 SVA与术前比较,差异无统计学意义（P＞0.05）。两组C_2-7 Cobb角、RK、C_2-7 SVA比较,差异无统计学意义（P＞0.05）。结论 多节段ACDF、ELAP联合ACDF治疗合并颈椎后凸畸形、巨大椎间盘突出的退变性多节段脊髓型颈椎病均可显著改善病人的临床症状及颈椎曲度。与多节段ACDF比较,ELAP联合ACDF虽然手术创伤大但术式更安全,病人的临床症状效果改善更好。     

The Effects of Platelet‐Rich Plasma on Halting the Progression in Porcine Intervertebral Disc Degeneration

Disc degeneration and the subsequent herniation and/or rupture of the intervertebral disc (IVD) are due to a failure of the extracellular matrix of the annulus to contain the contents of the nucleus. This results from inadequate maintenance of the matrix components as well as the proteolytic activity of matrix metalloproteinases (MMPs) that degrade matrix molecules. Arresting progression of disc degeneration in the annulus holds greater clinical potential at this point than prevention of its onset in the nucleus. Therefore, in this study, we have therapeutic aims that would decrease levels of the cytokines and growth factors that indirectly lead to disc degeneration via stimulating MMP and increase levels of several beneficial growth factors, such as transforming growth factor‐β, with the addition of platelet‐rich plasma (PRP) that would stimulate cell growth and matrix synthesis. For this study, we attempted to address these imbalances of metabolism by using tumor necrosis factor‐α treated annulus fibrosus cells isolated from porcine IVD tissue and incubating the cells in a growth factor rich environment with PRP. These results indicate that the PRP in vitro increased the production of the major matrix components (type II collagen and aggrecan) and decreased the inhibitory collagenase MMP‐1. This application will address a therapeutic approach for intervening early in the degenerative process.     

Effect of radiofrequency microtenotomy on degeneration of tendons: An experimental study on rabbits

IntroductionRadiofrequency microtenotomy is used to enhance healing by increasing vascularity in the degenerated tendon. In the present study, the effect of radiofrequency microtenotomy (Rf-mt) treatment on tendon degeneration was investigated.Materials and methodsA total of 32 New Zealand rabbits were enrolled in the current study. Experimental degeneration was performed by injecting prostaglandin E1 (PGE1) into the bilateral Achilles tendons of rabbits. After excluding 4 rabbits with an infection on the injection site, 4 other rabbits were sacrificed to define the histopathologic changes in the tendons. The remaining 24 rabbits were divided into 2 groups: the control group and the Rf-mt group. In the control group, the Rf-mt device was only applied to the Achilles tendon without running the device. In the Rf-mt group, the Rf-mt device was applied bilaterally at the fourth energy level for 500 ms to an area within 2 cm proximal to the insertion site at 0.5 cm intervals in order to form a grid. Six rabbits from each group were sacrificed at 6 and 12 weeks. The Achilles tendons were evaluated histopathologically by a modified Movin scale and by immunohistopathologic staining for vascular endothelial growth factor and type 4 collagen.ResultsAfter the PGE1 injection, findings similar to chronic degenerative tendinopathy were observed. The Rf-mt group showed significant improvement in vascularity in the histopathological and immunohistochemical examination (P < 0.05). However, there was no significant difference in healing between the control and Rf-mt groups (P > 0.05).ConclusionsRf-mt treatment increases vascularity in degenerated tendons but does not create difference to facilitate the healing process comparing control group.     

The lumbar intervertebral disc: From embryonic development to degeneration

Lumbar intervertebral discs (IVDs) are prone to degeneration upon skeletal maturity. In fact, this process could explain approximately 40% of the cases of low back pain in humans. Despite the efficiency of pain-relieving treatments, the scientific community seeks to develop innovative therapeutic approaches that might limit the use of invasive surgical procedures (e.g., spine fusion and arthroplasty). As a prerequisite to the development of these strategies, we must improve our fundamental knowledge regarding IVD pathophysiology. Recently, several studies have demonstrated that there is a singular phenotype associated with Nucleus pulposus (NP) cells, which is distinct from that of articular chondrocytes. In parallel, recent studies concerning the origin and development of NP cells, as well as their role in intervertebral tissue homeostasis, have yielded new insights into the complex mechanisms involved in disc degeneration. This review summarizes our current understanding of IVD physiology and the complex cell-mediated processes that contribute to IVD degeneration. Collectively, these recent advances could inspire the scientific community to explore new biotherapeutic strategies.