Rat Model of Closed-Head Mild Traumatic Injury and its Validation

Summary

Here, we present a closed-head mild traumatic brain injury (mTBI) rat model and its validation exhibiting remarkable similarity to human mTBI concerning behavioral manifestations during the acute and subacute stages.

Abstract

Animal models are crucial for advancing our understanding of mild traumatic brain injury (mTBI) and guiding clinical research. To achieve meaningful insights, developing a stable and reproducible animal model is essential. In this study, we report a detailed description of a closed-head mTBI model and a representative validation method using Sprague-Dawley rats to verify the modeling effect. The model involves dropping a 550 g mass weight from a height of 100 cm directly onto the head of a rat on a destructible surface, followed by a 180-degree turn. To assess the injury, rats underwent a series of neurobehavioral assessments 10 min post-injury, including time of loss of consciousness, first seeking-behavior time, escape ability, and beam balance ability test. During the acute and subacute stages following the injury, behavioral tests were conducted to assess motor coordination ability (Beam task), anxiety (Open Field test), and learning and memory abilities (Morris Water Maze test). The closed-head mTBI model produced a consistent injury response with minimal mortality and replicated real-life situations. The validation method effectively verified the model development and ensured the stability and consistency of the model.

Introduction

Mild traumatic brain injury (mTBI), or concussion, is the most prevalent type of injury and can lead to various short-term and chronic symptoms¹. These symptoms may include dizziness, headaches, depression, and anhedonia, among others, leading to significant suffering for individuals affected by mTBI². Since most mTBIs are caused by blunt force trauma³, it becomes imperative to develop animal models that accurately mimic such injuries. These models are essential for gaining a better understanding of the injury and its underlying mechanisms, offering a controlled environment with reduced variabilit....

Protocol

Animal experiments were approved by the Central South University Animal Care and Use Committee. All studies were conducted in line with the welfare and ethical principles of laboratory animals.

1. Animal feeding and anesthetization procedure

1. Group house 280-320 g Sprague-Dawley male rats and maintain them on a 12 h/12 h light/dark cycle with access to food and water ad libitum. Perform the study after the rats acclimatize for 6 days.
2. Anesthetize the rat with 3% i.......

Discussion

This model successfully simulates a closed-head mTBI without the need for scalp incision or skull opening, providing a more accurate representation of the impact scenario observed in human cases. The avoidance of scalp incision helps prevent inflammatory responses that may not align with the actual situation. Compared to Richelle Mychasiuk's pediatric model¹², the model used in this study is specifically tailored for adult rats weighing between 280-320 g, enabling us to obtain valuable insights in.......

Materials

Name	Company	Catalog Number	Comments
Acrylic box	In-house	N/A	15 cm x 22 cm x 43 cm
Anesthesia Machine	RWD Life Science Co.	R540 Mice & Rat Animal Anesthesia Machine
Helmet	In-house	N/A	Stainless-steel disk measuring 10 mm in diameter and 3 mm in thickness
Morris water maze	RWD Life Science Co.		Diameter 150 cm, height 50 cm,platform diameter 35 cm
Open field	RWD Life Science Co.	63007	Width100 cm, height 40 cm
Panlab SMART V3.0	RWD Life Science Co.	SMART v3.0
Perforated weight	In-house	N/A	Weight of 550 g and diameter of 18 mm
Pillow	In-house	N/A	Wedge-shaped sponge to place beneath the rat's head