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      Cystometric Measurements in Rats with an Experimentally Induced Traumatic Brain Injury and Voiding Dysfunction: A Time-Course Study

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          Abstract

          Traumatic brain injuries (TBIs) are a serious public health issue worldwide with increased mortality as well as severe disabilities and injuries caused by falls and road accidents. Unfortunately, there is no approved therapy for TBIs, and bladder dysfunction is a striking symptom. Accordingly, we attempted to analyze bladder dysfunction and voiding efficiency in rats with a TBI at different time-course intervals. Time-dependent analyses were scheduled from the next day until four weeks after a TBI. Experimental animals were grouped and analyzed under the above conditions. Cystometric measurements were used for this analysis and were further elaborated as external urethral sphincter electromyographic (EUS-EMG) activity and cystometrogram (CMG) measurements. Moreover, magnetic resonance imaging (MRI) studies were conducted to investigate secondary injury progression in TBI rats, and results were compared to normal control (NC) rats. Results of EUS-EMG revealed that the burst period, active period, and silent period in TBI rats were drastically reduced compared to NC rats, but they increased later and reached a stagnant phase. Likewise, in CMG measurements, bladder function, the voided volume, and voiding efficiency decreased immediately after the TBI, and other parameters like the volume threshold, inter-contraction interval, and residual volume drastically increased. Later, those levels changed, and all observed results were compared to NC rats. MRI results revealed the prevalence of cerebral edema and the progression of secondary injury. All of the above-stated results of the experiments were extensively substantiated. Thus, these innovative findings of our study model will surely pave the way for new therapeutic interventions for TBI treatment and prominently highlight their applications in the field of neuroscience in the future.

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          Most cited references23

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          A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics.

          This report describes the development of an experimental head injury model capable of producing diffuse brain injury in the rodent. A total of 161 anesthetized adult rats were injured utilizing a simple weight-drop device consisting of a segmented brass weight free-falling through a Plexiglas guide tube. Skull fracture was prevented by cementing a small stainless-steel disc on the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to establish fracture threshold; and Group 2, consisting of 107 animals, to determine the primary cause of death at severe injury levels. Data from Group 1 animals showed that a 450-gm weight falling from a 2-m height (0.9 kg-m) resulted in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact was followed by apnea, convulsions, and moderate hypertension. The surviving rats developed decortication flexion deformity of the forelimbs, with behavioral depression and loss of muscle tone. Data from Group 2 animals suggested that the cause of death was due to central respiratory depression; the mortality rate decreased markedly in animals mechanically ventilated during the impact. Analysis of mathematical models showed that this mass-height combination resulted in a brain acceleration of 900 G and a brain compression gradient of 0.28 mm. It is concluded that this simple model is capable of producing a graded brain injury in the rodent without a massive hypertensive surge or excessive brain-stem damage.
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            A controlled cortical impact model of traumatic brain injury in the rat.

            Controlled cortical impact models produce brain injury by using a pneumatic impactor to impact exposed brain. This study systematically examined the effects of varying magnitudes of controlled cortical impact to the rat brain on neurological, cardiovascular, and histopathological variables. As the magnitude of injury increased, the duration of suppression of somatomotor reflexes and the duration of chronic vestibular motor deficits increased. The blood pressure response was observed to depend on injury levels; a moderate injury level produced a hypotensive response while a high injury level produced an immediate brief hypertensive response followed by hypotension. Low injury levels produced no significant macroscopic or microscopic change, but higher injury levels produced cortical contusion and intraparenchymal hemorrhage which, with increasing survival time, evolved into necrotic changes and cavitation underlying the injury site. Also with high levels of injury, axonal injury was found throughout the brain-stem with the greatest concentration of injured axons occurring in the cerebellar peduncles and pontomedullary junction. These data demonstrate that controlled cortical impact in the rat reproduces many of the features observed in other experimental animal models. This model allows independent control of many mechanical loading parameters associated with traumatic brain injury. The controlled cortical impact rat model should be an effective experimental tool to investigators of traumatic brain injury.
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              A fluid percussion model of experimental brain injury in the rat.

              Fluid percussion models produce brain injury by rapidly injecting fluid volumes into the cranial cavity. The authors have systematically examined the effects of varying magnitudes of fluid percussion injury in the rat on neurological, systemic physiological, and histopathological changes. Acute neurological experiments showed that fluid percussion injury in 53 rats produced either irreversible apnea and death or transient apnea (lasting 54 seconds or less) and reversible suppression of postural and nonpostural function (lasting 60 minutes or less). As the magnitude if injury increased, the mortality rate and the duration of suppression of somatomotor reflexes increased. Unlike other rat models in which concussive brain injury is produced by impact, convulsions were observed in only 13% of survivors. Transient apnea was probably not associated with a significant hypoxic insult to animals that survived. Ten rats that sustained a moderate magnitude of injury (2.9 atm) exhibited chronic locomotor deficits that persisted for 4 to 8 days. Systemic physiological experiments in 20 rats demonstrated that all levels of injury studied produced acute systemic hypertension, bradycardia, and increased plasma glucose levels. Hypertension with subsequent hypotension resulted from higher magnitudes of injury. The durations of hypertension and suppression of amplitude on electroencephalography were related to the magnitudes of injury. While low levels of injury produced no significant histopathological alterations, higher magnitudes produced subarachnoid and intraparenchymal hemorrhage and, with increasing survival, necrotic change and cavitation. These data demonstrate that fluid percussion injury in the rat reproduces many of the features of head injury observed in other models and species. Thus, this animal model could represent a useful experimental approach to studies of pathological changes similar to those seen in human head injury.
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                Author and article information

                Journal
                Brain Sci
                Brain Sci
                brainsci
                Brain Sciences
                MDPI
                2076-3425
                14 November 2019
                November 2019
                : 9
                : 11
                : 325
                Affiliations
                [1 ]School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei-11031, Taiwan
                [2 ]Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, Taipei-11031, Taiwan
                [3 ]Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei-11031, Taiwan
                [4 ]Department of Physical Therapy and Graduate Institute of Rehabilitation Science, College of Medicine, Chang Gung University, Taoyuan-33302, Taiwan
                [5 ]Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou-33305, Taiwan
                [6 ]Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei-11031, Taiwan
                [7 ]Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei-11031, Taiwan
                [8 ]Research Center of Biomedical Device, Taipei Medical University, Taipei-11031, Taiwan
                Author notes
                [* ]Correspondence: cwpeng@ 123456tmu.edu.tw ; Tel./Fax: +886-2-2736-1661 (ext. 3070)
                Author information
                https://orcid.org/0000-0002-5305-0357
                https://orcid.org/0000-0002-1794-7941
                https://orcid.org/0000-0001-9744-4094
                Article
                brainsci-09-00325
                10.3390/brainsci9110325
                6895874
                31739594
                1cdbd806-c1cb-47de-a6ec-405335f5fb32
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 25 October 2019
                : 12 November 2019
                Categories
                Article

                traumatic brain injury,cystometric measurements,time-course analysis,external urethral sphincter electromyographic activity

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