Journal of neurotrauma
-
Journal of neurotrauma · Nov 2020
ReviewImproving Understanding and Outcomes of Traumatic Brain Injury Using Bidirectional Translational Research.
Recent clinical trials in traumatic brain injury (TBI) have failed to demonstrate therapeutic effects even when there appears to be good evidence for efficacy in one or more appropriate pre-clinical models. While existing animal models mimic the injury, difficulties in translating promising therapeutics are exacerbated by the lack of alignment of discrete measures of the underlying injury pathology between the animal models and human subjects. To address this mismatch, we have incorporated reverse translation of bedside experience to inform pre-clinical studies in a large animal (pig) model of TBI that mirror practical clinical assessments. ⋯ The cerebral effects of these clinically commonly used vasoactive agents are not known. This review will emphasize pediatric work and will describe bidirectional translational studies using a more human-like animal model of TBI to identify better therapeutic strategies to improve outcome post-injury. These studies in addition investigated the mechanism(s) involved in improvement of outcome in the setting of TBI.
-
Journal of neurotrauma · Nov 2020
ReviewIntracranial Pressure Monitoring in Experimental Traumatic Brain Injury: Implications for Clinical Management.
Traumatic brain injury (TBI) is often associated with long-term disability and chronic neurological sequelae. One common contributor to unfavorable outcomes is secondary brain injury, which is potentially treatable and preventable through appropriate management of patients in the neurosurgical intensive care unit. Intracranial pressure (ICP) is currently the predominant neurological-specific physiological parameter used to direct the care of severe TBI (sTBI) patients. ⋯ The detailed cellular and molecular derangements associated with intracranial hypertension (IC-HTN) and their relationship to injury phenotype and neurological outcomes are not completely understood. Various animal models of TBI have been developed, but the clinical applicability of ICP monitoring in the pre-clinical setting has not been well-characterized. Linking basic mechanistic studies in translational TBI models with investigation of ICP monitoring that more faithfully replicates the clinical setting will provide clinical investigators with a more informed understanding of the pathophysiology of IC-HTN, thus facilitating development of improved therapies for sTBI patients.
-
Journal of neurotrauma · Nov 2020
Mechanism of dysphagia after acute traumatic cervical spinal cord injury.
Swallowing dysfunction, which may cause aspiration pneumonia, is one of the most important complications of treatment of traumatic cervical spinal cord injury (CSCI); however, the mechanism of dysphagia is not well understood. No previous studies have reported the association between morphological changes of the soft tissue and dysphagia. We aimed to determine the factors associated with severity of dysphagia after CSCI and elucidate its mechanism. ⋯ The multiple regression analysis revealed that age, motor score, tracheostomy, and retropharyngeal space were significantly associated with DSS. Severe paresis, tracheostomy, old age, and swelling of the retropharyngeal space were significantly affected by dysphagia after CSCI. Morphological changes in the pharynx, situated right behind the larynx, after the injury affects the mechanism of dysphagia.
-
Yucatan miniature pigs (YMPs) are similar to humans in spinal cord size as well as physiological and neuroanatomical features, making them a useful model for human spinal cord injury. However, little is known regarding pig gait kinematics, especially on a treadmill. In this study, 12 healthy YMPs were assessed during bipedal and/or quadrupedal stepping on a treadmill at six speeds (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 km/h). ⋯ This study establishes a methodology for bipedal and quadrupedal treadmill-based kinematic testing in healthy YMPs. The treadmill approach used was effective in recruiting primarily the spinal circuitry responsible for the basic stepping patterns as has been shown in cats. We recommend 2.5 km/h (0.7 m/sec) as a target walking gait for pre-clinical studies using YMPs, which is similar to that used in cats.