overpressure air delivery for the induction of indirect traumatic optic neuropathy (iton) in mice

<meta charset="utf8"></head><body>用于在小鼠模型中诱导 CNS 损伤的定制超压空气系统

Closed-system central nervous system (CNS) injuries are injuries that are caused by damage to the brain or spinal cord without causing a break in the skull or spinal column. These injuries include traumatic brain injury (TBI) and spinal cord injury (SCI) and can occur from a variety of incidents, including blunt force injuries (e.g., falls, sports injuries, motor vehicle accidents) and explosive blasts. Closed-system CNS injuries are generally considered less severe compared to penetrating CNS injuries, yet they occur more often. However, similar to penetrating injuries, closed-system CNS injuries can result in long-term and progressive health issues, especially after repeated occurrences1,2,3,4,5,6. Concerningly, emerging evidence suggests that even subclinical closed-system CNS injuries, which fall below the diagnostic criteria for a TBI or SCI after a single occurrence7,8,9,10,11,12,13, may evolve into chronic neurodegenerative diseases after repeated injury6,14,15,16. This underscores the urgent need for a better understanding of the mechanisms and consequences of single and repeated closed-system CNS injuries.&#160; Such knowledge is imperative for improved protective and therapeutic approaches. Crucial to this endeavor are animal models that replicate closed-system CNS injuries.
Current animal models of closed-system CNS injuries have been instrumental in advancing our understanding of the pathophysiology and potential protective and therapeutic interventions for these traumas. Rodents are particularly popular due to their low cost, availability, genetic manipulability, ease of handling, well-established behavioral and physiological assays, and more favorable ethical considerations17. Common methods for inducing closed-system TBI in rodents include weight-drop devices18,19, controlled cortical impact (CCI) devices20, and compression-air-driven shock tubes21. For SCI, blunt trauma models typically require laminectomy22,23 or other surgical techniques24 to access the spinal cord or epidural space directly. However, closed-body SCI blast injury models have been developed using compression-air-driven shock tubes 25. Despite providing valuable insights, each of these models has unique limitations. Weight-drop models can have high variability and limited control of injury location and severity, producing experimental and ethical concerns for causing severe, uncontrolled injury26. CCI devices offer precision but require training to operate, may involve a craniotomy, and can suffer from mechanical variability impacting reproducibility27. Shock tubes are generally less invasive but can be difficult to acquire, complex to set up and operate, and can create unrealistic and highly variable injury conditions due to environmental factors, wave reflections, and complex pressure interactions28.
To better study the mechanisms and effects of single and repeat closed-system CNS injuries and their treatments, this paper presents a modular, user-friendly, cost-effective, and non-invasive method. The primary objective of this approach is to enable precise control and flexible modification of injury parameters, including location, severity, and timing. To support this objective, this manuscript provides a detailed protocol for constructing, calibrating, and troubleshooting an overpressure air system, which addresses some of the limitations of existing closed-system CNS injury devices. This system not only offers cost-effectiveness and minimal setup time, but it highly versatile, providing consistent and reproducible results while minimizing ethical concerns and maximizing clinical relevance. Additionally, the system&#8217;s ability to produce a range of closed-system CNS injuries in murine models is described, along with its potential applications in future studies. Notably, the goal of this manuscript is to provide a framework that enables investigators to easily acquire, adapt, and expand this system for their specific needs, thereby furthering ongoing research in CNS trauma. Representative results demonstrating the system&#8217;s efficacy in inducing axonal trauma are also presented.

<meta charset="utf8"></head><body>作者聚焦：开发精确且临床相关的模型来研究创伤性视神经病变的继发性变性

局灶性、闭路系统中枢神经系统损伤系统

超压空气输送诱导小鼠间接创伤性视神经病变 （ITON）

overpressure-air-delivery-for-induction-indirect-traumatic-optic

Research

JoVE Journal

Neuroscience

Overpressure Air Delivery for the Induction of Indirect Traumatic Optic Neuropathy (ITON) in Mice

256 次观看. 首先，通过评估对脚趾捏没有反应来确认小鼠的麻醉。将鼠标固定在内部动物支架中，其头部和上后肩通过矩形开口露出，同时背侧和下后肢保持屏蔽。在上后肩上贴上手术胶带以固定鼠标。将内部动物支架插入外部支架。打开动物支架内部的二级麻醉管路后，密封支架的末端，以防止麻醉剂从管中泄漏出来，防止实验过程中鼠标移动。将外部...

视频: 超压空气输送诱导小鼠间接创伤性视神经病变 （ITON）

System for Focal, Closed-System Central Nervous System Injury

The prevalence of closed-system central nervous system (CNS) injuries underscores the need for an enhanced understanding of these traumas to improve protective and therapeutic interventions. Crucial to this research are animal models that replicate closed-system CNS injuries. In this context, a custom overpressure air system was engineered to reproduce a range of closed-system CNS injuries in murine models, including ocular, brain, and spinal cord trauma. To date, the system has been used to administer eye-, head-, or spine-directed overpressure air to model anteroposterior pole injury in the eye, indirect traumatic optic neuropathy (ITON), focal traumatic brain injury, and spinal cord injury. This paper provides a detailed protocol outlining the system&#39;s design and operation and shares representative results demonstrating its effectiveness. The robust framework presented here provides a strong foundation for ongoing research in CNS trauma. By leveraging the system&#8217;s flexible attributes, investigators can modify and carefully control the location, severity, and timing of injuries. This allows for comprehensive comparisons of molecular mechanisms and therapeutic efficacy across multiple closed-system CNS injuries.

This protocol describes a custom overpressure air system designed to induce closed-system central nervous system (CNS) injuries in mice, including ocular, brain, and spinal cord traumas. The goal of this protocol is to provide a framework for researchers to easily adapt and expand the system for their unique CNS trauma studies.

The prevalence of closed-system central nervous system (CNS) injuries underscores the need for an enhanced understanding of these traumas to improve ...

超压空气输送诱导小鼠间接创伤性视神经病变 （ITON）

超压空气输送诱导小鼠间接创伤性视神经病变（ITON）