The Central Fluid Percussion Brain Injury in a Gyrencephalic Pig Brain: Scalable Diffuse Injury and Tissue Viability for Glial Cell Immunolabeling following Long-Term Refrigerated Storage

Abstract

Traumatic brain injury (TBI) affects millions of people annually; however, our knowledge of the diffuse pathologies associated with TBI is limited. As diffuse pathologies, including axonal injury and neuroinflammatory changes, are difficult to visualize in the clinical population, animal models are used. In the current study, we used the central fluid percussion injury (CFPI) model in a micro pig to study the potential scalability of these diffuse pathologies in a gyrencephalic brain of a species with inflammatory systems very similar to humans. We found that both axonal injury and microglia activation within the thalamus and corpus callosum are positively correlated with the weight-normalized pressure pulse, while subtle changes in blood gas and mean arterial blood pressure are not. We also found that the majority of tissue generated up to 10 years previously is viable for immunofluorescent labeling after long-term refrigeration storage. This study indicates that a micro pig CFPI model could allow for specific investigations of various degrees of diffuse pathological burdens following TBI.

A strike to the head: Parallels between the pediatric and adult human and the rodent in traumatic brain injury

“…There are several different TBI models that utilize gyrencephalic subjects such as ferrets (Krieg et al., 2023; Schwerin et al., 2017, 2023; Whyte et al., 2019), swine (Kinder et al., 2019; Lafrenaye et al., 2015; Pavlichenko & Lafrenaye, 2023), sheep (Sharkey et al., 2023), and non‐human primates, among other species (Osier & Dixon, 2016; Vink, 2018). Common models that use gyrencephalic subjects are variations of CCI (Schwerin et al., 2017), FPI (Brodhun et al., 2001; Pavlichenko & Lafrenaye, 2023), and the CHIMERA (Krieg et al., 2023; Schwerin et al., 2023; Whyte et al., 2019). Further, another widely used large animal model is an acceleration injury model that produces DAI (Vink, 2018).…”

Porcine Models of Neurotrauma and Neurological Disorders

“…Beyond the papers featuring rotational acceleration injury, Dr. Shin and colleagues in the Kilbaugh laboratory reported on the efficacy of a promising biological approach targeting phosphorylated tau and reducing pathology after a controlled cortical impact (CCI) in pigs [6]. Additionally, Pavlichenko and Lafrenaye employed central fluid percussion injury (CFPI) in pigs and found that while cellular signs of pathology and inflammation correlated with the pressure pulse, blood gasses and mean arterial pressure did not; furthermore, they reported that preserved, refrigerated pig brain tissue was histologically viable after 10 years [7]. We also received papers detailing new tools for use in pig neurotrauma studies.…”