inducing and monitoring repetitive mild traumatic brain injury (rmtbi) in mice using a modified fluid percussion device

rmTBI-inductie bij muizen via een methode voor gesloten hoofdletsel

Mild TBI, including concussion and sub-concussion, account for the majority of all TBI cases (&#62;80% of all TBI)1. Mild TBI commonly results from falls, traffic accidents, acts of violence, contact sports (e.g., football, boxing, hockey), and military combat2,3. Mild TBI can lead to neurobiological events that affect neurobehavioral functions throughout the patient&#39;s lifetime and increase the risk of neurodegenerative diseases4,5,6. Animal models provide an efficient and controlled means to study mild TBI, with the hope of further enhancing the diagnosis and treatment of mild TBI. Various models for mild TBI have been developed, such as the controlled cortical impact (CCI), weight drop (WD), fluid percussion injury (FPI), and blast-TBI models7,8. No single experimental model can mimic the entire complexity of TBI-induced pathology9,10. The heterogeneity of these models is advantageous for addressing the diverse features associated with mild TBI patients and investigating the corresponding cellular and molecular mechanisms. However, each animal model of TBI has its limitations3, limiting our current knowledge concerning animal mild TBI and their clinical relevance.
The WD and CCI models are utilized to replicate clinical conditions such as cerebral tissue loss, acute subdural hematoma, axonal injury, brain concussion, blood-brain barrier dysfunction, and even coma following TBI3,11,12. The WD model involves inducing brain damage by striking either the dura mater or skull with freely falling weights. The impact of a weighted object upon an intact skull can replicate mixed focal/diffuse injuries; however, this method is associated with poor accuracy and repeatability of the injury site, rebound injury, and a higher mortality rate due to skull fractures3,11,12. The CCI model involves applying air-driven metal to impact the exposed dura mater directly. Compared to the WD model, the CCI model is more accurate and reproducible, but it does not produce diffuse injury due to the small diameter of the impacting tip11. During FPI modelling, the brain tissue is briefly displaced and deformed by percussion. FPI can induce mixed focal/diffuse injury and replicate intracranial hemorrhage, brain swelling and progressive gray matter damage after TBI. However, FPI has a high mortality rate due to brainstem damage and prolonged apnea3,12. The craniotomy involved in conventional WD, CCI, and FPI models can lead to cortical contusion, hemorrhagic lesions, the damage of the blood-brain barrier, immune cell infiltration, glial cell activation, prolonged modeling time, and possible fatal outcomes3,12.
Mild TBI is characterized by a GCS (Glasgow coma scale, GCS) score within the range of 13 to 152. Mild TBI can be either focal or diffuse and is associated with both acute injuries, such as breakdown of cellular homeostasis, excitotoxicity, glucose depletion, mitochondrial dysfunction, blood flow disturbance, and axonal damage, as well as subacute injuries, including axonal damage, neuroinflammation, and gliosis2,3. Despite significant progress in delineating the intricate pathophysiology of TBI, the underlying mechanisms of mild TBI/rmTBI remain elusive and require further investigation9. Given that CHI is the most common type of TBI12, this protocol presents a novel approach to creating a more precisely controlled mouse model of rmTBI using a modified FPI device to perform impact in a thinned-skull window13. By avoiding craniotomy-induced injuries, variable skull thickness and shape-induced inaccuracies, and rebound injury, this approach aims to overcome the main disadvantages associated with the WD, CCI, and FPI models. Applying FPI impact on the thinned-skull window is convenient for evaluating cerebral vessel damage following rmTBI and helps minimize high mortality rates in some models, resulting in a closer resemblance to the clinical features of TBI patients.

Auteur in de schijnwerpers: Optimalisatie van knaagdiermodellen voor het onderzoeken van de mechanismen en revalidatie bij herhaald mild traumatisch hersenletsel

Gemodificeerd muismodel van repetitief mild traumatisch hersenletsel met een verdund schedelvenster en vloeibare percussie

Traumatic brain injury is a significant health issue for the worldwide population. Our main focus is on the mechanism of TBI and the rehabilitation, with a particular focus on the mild TBI and the neuroprotective effects of access. No single animal models can adequately mimic all aspects of the human TBI due to the complexity of a clinical TBI.Each model has its own advantages and the disadvantages when implemented for TBI research. These challenges necessitate the optimization of animal models. The closed-head injury is a common message for making the rodent models of a repeated mTBI.However, this message is susceptible to many factors, including the impact methods used and the anatomy of the rodent scaffold. In our research, we combine the thinned-skull window and the fluid percussion measures to minimize the inflammation due to the craniotomy and the fluid percussion, and produce a more precise model of our repeated mTBI. Overall, the modified closed-head injury associated to repeated mTBI represents a valuable tour for researchers investigating the underlying mechanism that contribute to focal and diffuse pathological changes in repeated mTBI.

Het induceren en monitoren van repetitief mild traumatisch hersenletsel (rmTBI) bij muizen met behulp van een gemodificeerd vloeistofpercussieapparaat

Research

JoVE Journal

Neuroscience

Inducing and Monitoring Repetitive Mild Traumatic Brain Injury (rmTBI) in Mice Using a Modified Fluid Percussion Device

rmTBI Induction in Mice via a Closed-Head Injury Method

Modified Mouse Model of Repetitive Mild Traumatic Brain Injury Incorporating Thinned-Skull Window and Fluid Percussion

Author Spotlight: Optimizing Rodent Models for Investigating the Mechanisms and Rehabilitation in Repeated Mild Traumatic Brain Injury

Mild traumatic brain injury is a clinically highly heterogeneous neurological disorder. Highly reproducible traumatic brain injury (TBI) animal models ...