Effects of traumatic brain injury of different severities on emotional, cognitive, and oxidative stress-related parameters in mice.
ABSTRACT Cognitive deficits and psychiatric disorders are significant sequelae of traumatic brain injury (TBI). Animal models have been widely employed in TBI research, but few studies have addressed the effects of experimental TBI of different severities on emotional and cognitive parameters. In this study, mice were subjected to weight-drop TBI to induce mild, intermediate, or severe TBI. After neurological assessment, the mice recovered for 10 days, and were then subjected to a battery of behavioral tests, which included open-field, elevated plus-maze, forced swimming, tail suspension, and step-down inhibitory avoidance tests. Oxidative stress-related parameters (nonprotein thiols [NPSH], glutathione peroxidase [GPx], glutathione reductase [GR], and thiobarbituric acid reactive species [TBARS]) were quantified in the cortex and hippocampus at 2 and 24 h and 14 days after TBI, and histopathological analysis was performed 15 days after TBI. Mice subjected to mild TBI showed increased anxiety and depressive-like behaviors, while intermediate and severe TBI induced robust memory deficits. The severe TBI group also displayed increased locomotor activity. Intermediate and severe TBI caused extensive macroscopic and microscopic brain damage, while mild TBI typically had no histological abnormalities. Moreover, a significant increase in TBARS in the ipsilateral cortex and GPx in the ipsilateral hippocampus was observed at 24 h and 14 days, respectively, following intermediate TBI. The current experimental TBI model induced emotional and cognitive changes comparable to sequelae seen in human TBI, and it might therefore represent a useful approach to the study of mechanisms of and new treatments for TBI and related disorders.
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ABSTRACT: Each year in the US, ∼1.5 million people sustain a traumatic brain injury (TBI). Victims of TBI can suffer from chronic post-TBI symptoms, such as sensory and motor deficits, cognitive impairments including problems with memory, learning, and attention, and neuropsychiatric symptoms such as depression, anxiety, irritability, aggression, and suicidal rumination. Although partially associated with the site and severity of injury, the biological mechanisms associated with many of these symptoms - and why some patients experience differing assortments of persistent maladies - are largely unknown. The use of animal models is a promising strategy for elucidation of the mechanisms of impairment and treatment, and learning, memory, sensory, and motor tests have widespread utility in rodent models of TBI and psychopharmacology. Comparatively, behavioral tests for the evaluation of neuropsychiatric symptomatology are rarely employed in animal models of TBI and, as determined in this review, the results have been inconsistent. Animal behavioral studies contribute to the understanding of the biological mechanisms by which TBI is associated with neurobehavioral symptoms and offer a powerful means for pre-clinical treatment validation. Therefore, further exploration of the utility of animal behavioral tests for the study of injury mechanisms and therapeutic strategies for the alleviation of emotional symptoms are relevant and essential.Frontiers in Neurology 01/2013; 4:157.
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ABSTRACT: Traumatic brain injury (TBI) is a worldwide phenomenon that affects all ages and socioeconomic classes and results in varying degrees of immediate and delayed motor, cognitive, and emotional deficiencies. A plethora of pharmacologic interventions that target recognized initiators and propagators of pathology are being investigated in an attempt to ameliorate secondary injury processes that follow primary injury. Diazoxide (DZ), a KATP channel activator, has been shown to provide short- and long-term protective effects in a variety of in vitro and in vivo cerebral ischemia models. However, the effects of DZ on behavioral outcome following TBI have not been investigated. TBI was induced in male C57Bl/6J mice by controlled cortical impact (CCI) and followed by intraperitoneal administration of either normal saline, dimethyl sufoxide (DMSO), or 2.5 mg/kg DZ in DMSO, 30-minutes post-injury and daily for three days. Open field and beam walk performances were used to assess motor and behavioral function 1, 7, and 14 days following injury. Spatial learning and memory was assessed three weeks following injury using the Morris water maze. Injured mice were significantly impaired on the beam-walk and Morris water maze tasks, and were hyperactive and anxious in an open field environment. On post-injury days 1 and 14, mice treated with DMSO exhibited an increase in the amount of time required to perform the beam walk task. In addition, animals exposed to DMSO or DZ + DMSO exhibited slower swimming speed in the Morris water maze on the final day of testing. There was no therapeutic effect, however, of the treatment or vehicle on open field behavior or learning and memory function in the Morris water maze. In summary, CCI produced significant long-term impairment of motor, memory, and behavioral performance measures, and DZ administration, under the conditions used, provided no functional benefits following injury.Pharmacology Biochemistry and Behavior 04/2013; · 2.82 Impact Factor
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ABSTRACT: Traumatic brain injury (TBI) is a major cause of death and disability and impairs health-related quality of life (HRQOL). Psychiatric disorders have been recognized as major components of TBI morbidity, yet few studies have addressed the relationship between these outcomes. Sample size, selection bias, and retrospective design, are methodological limitations for TBI-related psychiatric studies. For this study, 33 patients with severe TBI were evaluated prospectively regarding demographic, clinical, radiological, neurosurgical, laboratory, and psychosocial characteristics, as well as psychiatric manifestations and HRQOL, 18 months after hospitalization. Psychiatric manifestations were assessed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), the Hospital Anxiety and Depression Scale (HADS), the Brief Psychiatric Rating Scale (BPRS), and the Apathy Evaluation Scale (AES). HRQOL was determined using the Medical Outcomes Study's 36-item Short-Form Health Survey (SF-36). Following TBI, a significant increase in the prevalence of major depressive disorder (MDD) and generalized anxiety disorder (p=0.02), and a significant decrease in the prevalence of alcohol and cannabinoid abuse (p=0.001) were observed. The most frequent psychiatric disorders following severe TBI were found to be MDD (30.3%), and personality changes (33.3%). In comparison to patients without personality changes, patients with personality changes experienced a decline in general health and impairments in physical and social functioning. Patients with MDD showed impairment in all SF-36 domains compared to non-depressed patients. This prospective TBI-related psychiatric study is the first to demonstrate a significant association between MDD, personality changes, and HRQOL, following severe TBI in a well-defined sample of patients.Journal of neurotrauma 11/2011; 29(6):1029-37. · 4.25 Impact Factor