noninvasive-in-pen-approach-test-for-laboratory-housed-pigs

Noninvasive, In-pen Approach Test for Laboratory-housed Pigs

Traumatic brain injury (TBI) incidences have increased in both civilian and military populations, and many researchers are adopting a porcine model for ...

Virginia Polytechnic Institute and State University

Recent military combat has heightened awareness to the complexity of blast-related traumatic brain injuries (bTBI). Experiments using animal, cadaver, or biofidelic physical models remain the primary measures to investigate injury biomechanics as well as validate computational simulations, medical diagnostics and therapies, or protection technologies. However, blast injury research has seen a range of irregular and inconsistent experimental methods for simulating blast insults generating results which may be misleading, cannot be cross-correlated between laboratories, or referenced to any standard for exposure. Both the US Army Medical Research and Materiel Command and the National Institutes of Health have noted that there is a lack of standardized preclinical models of TBI. It is recommended that the blast injury research community converge on a consistent set of experimental procedures and reporting of blast test conditions. This chapter describes the blast conditions which can be recreated within a laboratory setting and methodology for testing in vivo models within the appropriate environment.

Bridging the Gap of Standardized Animals Models for Blast Neurotrauma: Methodology for Appropriate Experimental Testing.

Blast-induced neurotrauma (BINT) has increased in incidence over the past decades and can result in cognitive issues that have debilitating consequences. The exact primary and secondary mechanisms of injury have not been elucidated and appearance of cellular injury can vary based on many factors, such as blast overpressure magnitude and duration. Many methodologies to study blast neurotrauma have been employed, ranging from open-field explosives to experimental shock tubes for producing free-field blast waves. While there are benefits to the various methods, certain specifications need to be accounted for in order to properly examine BINT. Primary cell injury mechanisms, occurring as a direct result of the blast wave, have been identified in several studies and include cerebral vascular damage, blood-brain barrier disruption, axonal injury, and cytoskeletal damage. Secondary cell injury mechanisms, triggered subsequent to the initial insult, result in the activation of several molecular cascades and can include, but are not limited to, neuroinflammation and oxidative stress. The collective result of these secondary injuries can lead to functional deficits. Behavioral measures examining motor function, anxiety traits, and cognition/memory problems have been utilized to determine the level of injury severity. While cellular injury mechanisms have been identified following blast exposure, the various experimental models present both concurrent and conflicting results. Furthermore, the temporal response and progression of pathology after blast exposure have yet to be detailed and remain unclear due to limited resemblance of methodologies. This chapter summarizes the current state of blast neuropathology and emphasizes the need for a standardized preclinical model of blast neurotrauma.

Cellular Mechanisms and Behavioral Outcomes in Blast-Induced Neurotrauma: Comparing Experimental Setups.

Explosions account for 79% of combat related injuries and often lead to polytrauma, a majority of which include blast-induced traumatic brain injuries (bTBI). These injuries lead to internal bleeding in multiple organs and, in the case of bTBI, long term neurological deficits. Currently, there are no treatments for internal bleeding beyond fluid resuscitation and surgery. There is also a dearth of treatments for TBI. We have developed a novel approach using hemostatic nanoparticles that encapsulate an anti-inflammatory, dexamethasone, to stop the bleeding and reduce inflammation after injury. We hypothesize that this will improve not only survival but long term functional outcomes after blast polytrauma. Poly(lactic-co-glycolic acid) hemostatic nanoparticles encapsulating dexamethasone (hDNPs) were fabricated and tested following injury along with appropriate controls. Rats were exposed to a single blast wave using an Advanced Blast Simulator, inducing primary blast lung and bTBI. Survival was elevated in the hDNPs group compared to controls. Elevated anxiety parameters were found in the controls, compared to hDNPs. Histological analysis indicated that apoptosis and blood-brain barrier disruption in the amygdala were significantly increased in the controls compared to the hDNPs and sham groups. Immediate intervention is crucial to mitigate injury mechanisms that contribute to emotional deficits.

Article	Year
Bridging the Gap of Standardized Animals Models for Blast Neurotrauma: Methodology for Appropriate Experimental Testing. Methods in molecular biology (Clifton, N.J.)\| PubMed ID: 27604715	2016
Cellular Mechanisms and Behavioral Outcomes in Blast-Induced Neurotrauma: Comparing Experimental Setups. Methods in molecular biology (Clifton, N.J.)\| PubMed ID: 27604716	2016
Hemostatic nanoparticles increase survival, mitigate neuropathology and alleviate anxiety in a rodent blast trauma model. Scientific reports\| PubMed ID: 30006635	2018

Pamela J. Vandevord

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