Methods in molecular biology
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Fluid percussion was first conceptualized in the 1940s and has evolved into one of the leading laboratory methods for studying experimental traumatic brain injury (TBI). Over the decades, fluid percussion has been used in numerous species and today is predominantly applied to the rat. The fluid percussion technique rapidly injects a small volume of fluid, such as isotonic saline, through a circular craniotomy onto the intact dura overlying the brain cortex. ⋯ The fluid enters the cranium, producing a compression and displacement of the brain parenchyma resulting in a sharp, high magnitude elevation of intracranial pressure that is propagated diffusely through the brain. This results in an immediate and transient period of traumatic unconsciousness as well as a combination of focal and diffuse damage to the brain, which is evident upon histological and behavioral analysis. Numerous studies have demonstrated that the rat fluid percussion model reproduces a wide range of pathological features associated with human TBI.
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Weight drop models in rodents have been used for several decades to advance our understanding of the pathophysiology of traumatic brain injury. Weight drop models have been used to replicate focal cerebral contusion as well as diffuse brain injury characterized by axonal damage. More recently, closed head injury models with free head rotation have been developed to model sports concussions, which feature functional disturbances in the absence of overt brain damage assessed by conventional imaging techniques. ⋯ In the second part, we describe the development of our own weight drop closed head injury model that features impact plus rapid downward head rotation, no structural brain injury, and long-term cognitive deficits in the case of multiple injuries. This rodent model was developed to reproduce key aspects of sports concussion so that a mechanistic understanding of how long-term cognitive deficits might develop will eventually follow. Such knowledge is hoped to impact athletes and war fighters and others who suffer concussive head injuries by leading to targeted therapies aimed at preventing cognitive and other neurological sequelae in these high-risk groups.
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Despite prodigious advances in TBI neurobiology research and a broad arsenal of animal models mimicking different aspects of human brain injury, this field has repeatedly experienced collective failures to translate from animals to humans, particularly in the area of therapeutics. This lack of success stems from variability and inconsistent standardization across models and laboratories, as well as insufficient objective and quantifiable diagnostic measures (biomarkers, high-resolution imaging), understanding of the vast clinical heterogeneity, and clinically centered conception of the TBI animal models. Significant progress has been made by establishing well-defined standards for reporting animal studies with "preclinical common data elements" (CDE), and for the reliability and reproducibility in preclinical TBI therapeutic research with the Operation Brain Trauma Therapy (OBTT) consortium. However, to break the chain of failures and achieve a therapeutic breakthrough in TBI will probably require the use of higher species models, specific mechanism-based injury models by which to theranostically targeted treatment portfolios are tested, more creative concepts of therapy intervention including combination therapy and regeneration neurobiology strategies, and the adoption of dosing regimens based upon pharmacokinetic-pharmacodynamic (PK-PD) studies and guided by the injury severity and TBI recovery process.
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Animal models play a critical role in understanding the biomechanical, pathophysiological, and behavioral consequences of traumatic brain injury (TBI). In preclinical studies, cognitive impairment induced by TBI is often assessed using the Morris water maze (MWM). ⋯ We include a theoretical framework for examining deficits in discrete stages of cognitive function and offer suggestions for how to make inferences regarding the specific nature of TBI-induced cognitive impairment. The ultimate goal is more precise modeling of the animal equivalents of the cognitive deficits seen in human TBI.
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The growth and development of plants during spaceflight have important implications for both basic and applied research supported by NASA and other international space agencies. While there have been many reviews of plant space biology, the present chapter attempts to fill a gap in the literature on the actual process and methods of performing plant research in the spaceflight environment. The author has been a principal investigator on six spaceflight projects and has another two space experiments in development. ⋯ Additional issues considered are working at NASA centers, hardware development, safety concerns, and the engineering versus science culture in space agencies. The difficulties of publishing the results from spaceflight research based on such factors as the lack of controls, limited sample size, and the indirect effects of the spaceflight environment also are summarized. Finally, lessons learned from these spaceflight experiences are discussed in the context of improvements for future space-based research projects with plants.