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1.
Neurosci Lett ; 708: 134358, 2019 08 24.
Article in English | MEDLINE | ID: mdl-31269465

ABSTRACT

Rodent models of contusion spinal cord injury (SCI) are widely studied for the mechanisms underlying functional deficits after SCI. Yet, how does lesion level affect SCI-induced motor and sensory dysfunctions remains unclear. Using a computer-controlled impactor (Impact One™, Leica) and the same parameters (diameter, 2.0 mm; Speed: 4.0 m/s; Depth: 1.5 mm; Dwell time: 0.1 s), we produced contusions at mid-thoracic (T10) and rostral-lumbar (L2) spinal cord in male rats, and compared locomotor and sensory dysfunctions within the same experimental setting. The time courses of locomotor deficit were comparable between thoracic (n = 8) and lumbar (n = 7) SCI rats, but the severity was greater after thoracic SCI especially during the first week post-injury, as indicated by the lower Basso, Beattle and Bresnahan open-field locomotion scores. Both groups showed similar heightened avoiding response (hyper-reactivity) to mechanical stimulation applied at the hindpaws from day 21-56 post-injury, as indicated by decreased paw withdrawal thresholds. Compared to lumbar SCI, thoracic SCI induced a greater decrease of paw withdrawal latency in hot-plate test from day 28-56 post-injury. In contrast, lumbar SCI rats showed a greater reduction of avoidance threshold to mechanical stimulation at the girdle region, and larger overgroomed area than thoracic SCI rats at day 14 post-injury. Thus, thoracic SCI may induce greater motor deficits and hindpaw heat hyper-reactivity than did lumbar SCI. In contrast, lumbar SCI may elicit greater at-level mechanical hyper-reactivity and overgrooming behavior than thoracic SCI. Future study needs to examine the specific pathological changes underlying different dysfunctions in two SCI models.


Subject(s)
Contusions/physiopathology , Motor Activity , Sensation , Spinal Cord Injuries/physiopathology , Spinal Cord/physiopathology , Animals , Avoidance Learning , Contusions/psychology , Lumbosacral Region , Male , Pain Threshold , Rats, Sprague-Dawley , Spinal Cord Injuries/psychology , Thorax
2.
Appl Neuropsychol Adult ; 24(4): 299-307, 2017.
Article in English | MEDLINE | ID: mdl-27101223

ABSTRACT

Executive dysfunctions are among the most prevalent neurobehavioral sequelae of traumatic brain injuries (TBIs). Using culturally validated tests from the Delis-Kaplan Executive Function System (D-KEFS: Trail Making, Verbal Fluency, Design Fluency, Sorting, Twenty Questions, and Tower) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS: Rule Shift Cards, Key Search, and Modified Six Elements), the current study was the first to examine executive functioning in a group of Iranian TBI patients with focal frontal contusions. Compared with a demographically matched normative sample, the frontal contusion patients showed substantial impairments, with very large effect sizes (p ≤ .003, 1.56 < d < 3.12), on all the executive measures. Controlling for respective lower-level/fundamental conditions, the differences on the highest-level executive (cognitive switching) conditions were still significant. The frontal patients also committed more errors. Patients with lateral prefrontal (LPFC) contusions were qualitatively worst. For example, only the LPFC patients committed perseverative repetition errors. Altogether, our results support the notion that the frontal lobes, specifically the lateral prefrontal regions, play a critical role in cognitive executive functioning, over and above the contributions of respective lower-level cognitive abilities. The results provide clinical evidence for validity of the cross-culturally adapted versions of the tests.


Subject(s)
Brain Injuries, Traumatic/psychology , Cognition Disorders/psychology , Contusions/psychology , Executive Function , Frontal Lobe/diagnostic imaging , Adolescent , Adult , Brain Injuries, Traumatic/complications , Case-Control Studies , Cognition Disorders/complications , Contusions/complications , Humans , Male , Neuropsychological Tests , Young Adult
3.
Exp Neurol ; 279: 261-273, 2016 May.
Article in English | MEDLINE | ID: mdl-26875994

ABSTRACT

Most in vivo spinal cord injury (SCI) experimental models use rodents. Due to the anatomical and functional differences between rodents and humans, reliable large animal models, such as non-human primates, of SCI are critically needed to facilitate translation of laboratory discoveries to clinical applications. Here we report the establishment of a controlled spinal contusion model that produces severity-dependent functional and histological deficits in non-human primates. Six adult male rhesus macaque monkeys underwent mild to moderate contusive SCI using 1.0 and 1.5mm tissue displacement injuries at T9 or sham laminectomy (n=2/group). Multiple assessments including motor-evoked potential (MEP), somatosensory-evoked potential (SSEP), MR imaging, and monkey hindlimb score (MHS) were performed. Monkeys were sacrificed at 6 months post-injury, and the lesion area was examined for cavitation, axons, myelin, and astrocytic responses. The MHS demonstrated that both the 1.0 and 1.5mm displacement injuries created discriminative neurological deficits which were severity-dependent. The MEP response rate was depressed after a 1.0mm injury and was abolished after a 1.5mm injury. The SSEP response rate was slightly decreased following both the 1.0 and 1.5mm SCI. MRI imaging demonstrated an increase in T2 signal at the lesion site at 3 and 6months, and diffusion tensor imaging (DTI) tractography showed interrupted fiber tracts at the lesion site at 4h and at 6 months post-SCI. Histologically, severity-dependent spinal cord atrophy, axonal degeneration, and myelin loss were found after both injury severities. Notably, strong astrocytic gliosis was not observed at the lesion penumbra in the monkey. In summary, we describe the development of a clinically-relevant contusive SCI model that produces severity-dependent anatomical and functional deficits in non-human primates. Such a model may advance the translation of novel SCI repair strategies to the clinic.


Subject(s)
Contusions/pathology , Spinal Cord Injuries/pathology , Animals , Astrocytes/pathology , Atrophy , Axons/pathology , Behavior, Animal , Contusions/psychology , Disease Models, Animal , Evoked Potentials, Motor , Evoked Potentials, Somatosensory , Gliosis/pathology , Hindlimb , Locomotion , Macaca mulatta , Male , Myelin Sheath/pathology , Spinal Cord/pathology , Spinal Cord Injuries/psychology
4.
Metab Brain Dis ; 30(2): 411-26, 2015 Apr.
Article in English | MEDLINE | ID: mdl-24771110

ABSTRACT

Traumatic brain injury (TBI) is accompanied with enhanced matrix metalloproteinase-9 (MMP-9) activity and elevated levels of plasma fibrinogen (Fg), which is a known inflammatory agent. Activation of MMP-9 and increase in blood content of Fg (i.e. hyperfibrinogenemia, HFg) both contribute to cerebrovascular disorders leading to blood brain barrier disruption. It is well-known that activation of MMP-9 contributes to vascular permeability. It has been shown that at an elevated level (i.e. HFg) Fg disrupts blood brain barrier. However, mechanisms of their actions during TBI are not known. Mild TBI was induced in wild type (WT, C57BL/6 J) and MMP-9 gene knockout (Mmp9(-/-)) homozygous, mice. Pial venular permeability to fluorescein isothiocyanate-conjugated bovine serum albumin in pericontusional area was observed 14 days after injury. Mice memory was tested with a novel object recognition test. Increased expression of Fg endothelial receptor intercellular adhesion protein-1 and formation of caveolae were associated with enhanced activity of MMP-9 causing an increase in pial venular permeability. As a result, an enhanced deposition of Fg and cellular prion protein (PrP(C)) were found in pericontusional area. These changes were attenuated in Mmp9(-/-) mice and were associated with lesser loss of short-term memory in these mice than in WT mice. Our data suggest that mild TBI-induced increased cerebrovascular permeability enhances deposition of Fg-PrP(C) and loss of memory, which is ameliorated in the absence of MMP-9 activity. Thus, targeting MMP-9 activity and blood level of Fg can be a possible therapeutic remedy to diminish vasculo-neuronal damage after TBI.


Subject(s)
Brain Injuries/genetics , Brain Injuries/metabolism , Cerebrovascular Circulation/genetics , Fibrinogen/metabolism , Matrix Metalloproteinase 9/genetics , Animals , Blood-Brain Barrier/metabolism , Brain Injuries/psychology , Capillaries/pathology , Cerebral Cortex/injuries , Cerebral Veins/metabolism , Contusions/genetics , Contusions/metabolism , Contusions/psychology , Intercellular Adhesion Molecule-1/biosynthesis , Male , Memory Disorders/etiology , Memory Disorders/genetics , Memory Disorders/psychology , Memory, Short-Term , Mice , Mice, Inbred C57BL , Mice, Knockout , Permeability , PrPC Proteins/metabolism
5.
Brain Res ; 1576: 18-26, 2014 Aug 12.
Article in English | MEDLINE | ID: mdl-24905625

ABSTRACT

Animal models of traumatic brain injury (TBI) are essential for testing novel hypotheses and therapeutic interventions. Unfortunately, due to the broad heterogeneity of TBI in humans, no single model has been able to reproduce the entire spectrum of these injuries. The controlled cortical impact (CCI) model is one of the most commonly used models of contusion TBI. However, behavioral evaluations have revealed transient impairment in motor function after CCI in rats and mice. Here we report a new semicircular CCI (S-CCI) model by increasing the impact tip area to cover both the motor cortex and hippocampal regions in adult mice. Mice were subjected to S-CCI or CCI using an electromagnetic impactor (Impactor One, MyNeuroLab; semicircular tip: 3mm radius; CCI tip diameter: 3mm). We showed that S-CCI, at two injury severities, significantly decreased the neuroscore and produced deficits in performance on a rotarod device for the entire duration of the study. In contrast, the CCI induced motor deficits only at early stages after the injury, suggesting that the S-CCI model produces long-lasting motor deficits. Morris water maze test showed that both CCI and S-CCI produced persisting memory deficits. Furthermore, adhesive removal test showed significant somatosensory and motor deficits only in the S-CCI groups. Histological analysis showed a large extent of cortical contusion lesions, including both the sensory and motor cortex, and hippocampal damage in the S-CCI. These findings collectively suggest that the current model may offer sensitive, reliable, and clinically relevant outcomes for assessments of therapeutic strategies for TBI.


Subject(s)
Brain Injuries/pathology , Cognition Disorders/etiology , Hippocampus/injuries , Models, Animal , Movement Disorders/etiology , Sensorimotor Cortex/injuries , Wounds, Nonpenetrating/pathology , Animals , Brain Injuries/psychology , Cognition Disorders/physiopathology , Contusions/etiology , Contusions/pathology , Contusions/physiopathology , Contusions/psychology , Equipment Design , Female , Hippocampus/pathology , Hippocampus/physiopathology , Learning Disabilities/etiology , Learning Disabilities/physiopathology , Maze Learning , Memory Disorders/etiology , Memory Disorders/physiopathology , Mice , Mice, Inbred C57BL , Movement Disorders/physiopathology , Psychomotor Performance , Reaction Time , Rotarod Performance Test , Sensorimotor Cortex/pathology , Sensorimotor Cortex/physiopathology , Severity of Illness Index , Wounds, Nonpenetrating/psychology
6.
Fortschr Neurol Psychiatr ; 81(9): 511-22, 2013 Sep.
Article in German | MEDLINE | ID: mdl-23986459

ABSTRACT

In 2005, the "Deutsche Gesellschaft für Neurowissenschaftliche Begutachtung" (German Society for Neuroscientific Legal Evaluation) together with other Societies published a guideline for the legal evaluation of patients with closed head injuries. Meanwhile, not only scientific progress in imaging techniques but also in other fields such as neuropsychology has necessitated a revision, which is presented here. In the mean time, the handling of guidelines has been systematised in Germany so that a registration with the Cooperation of German Medical Learned Societies is applied for and publication in the German Guideline Registry is expected.


Subject(s)
Head Injuries, Closed/psychology , Liability, Legal , Brain Injuries/diagnosis , Brain Injuries/psychology , Contusions/diagnosis , Contusions/psychology , Disability Evaluation , Electroencephalography , Forensic Psychiatry , Germany , Head Injuries, Closed/diagnosis , Humans , Legislation, Medical , Mental Processes , Neuroimaging , Neuropsychological Tests
7.
BMC Med Res Methodol ; 11: 59, 2011 Apr 27.
Article in English | MEDLINE | ID: mdl-21524301

ABSTRACT

BACKGROUND: Ambulatory blood pressure monitoring (ABPM) is increasingly used to measure blood pressure (BP) in research studies. We examined ease of use, comfort, degree of disturbance, reported adverse effects, factors associated with poor tolerability, and association of poor tolerability with data acquisition of 24-hour ABPM using the Oscar 2 monitor in the research setting. METHODS: Sixty adults participating in a research study of people with a history of borderline clinic BP reported on their experience with ABPM on two occasions one week apart. Poor tolerability was operationalized as an overall score at or above the 75th percentile using responses to questions adapted from a previously developed questionnaire. In addition to descriptive statistics (means for responses to Likert-scaled "0 to 10" questions and proportions for Yes/No questions), we examined reproducibility of poor tolerability as well as associations with poor tolerability and whether poor tolerability was associated with removal of the monitor or inadequate number of BP measurements. RESULTS: The mean ambulatory BP of participants by an initial ABPM session was 148/87 mm Hg. After wearing the monitor the first time, the degree to which the monitor was felt to be cumbersome ranged from a mean of 3.0 to 3.8, depending on whether at work, home, driving, or other times. The most bother was interference with normal sleeping pattern (mean 4.2). Wearers found the monitor straightforward to use (mean 7.5). Nearly 67% reported that the monitor woke them after falling asleep, and 8.6% removed it at some point during the night. Reported adverse effects included pain (32%), skin irritation (37%), and bruising (7%). Those categorized as having poor tolerability (kappa = 0.5 between sessions, p = 0.0003) were more likely to report being in fair/poor health (75% vs 22%, p = 0.01) and have elevated 24-hour BP average (systolic: 28% vs 17%, p = 0.56; diastolic: 30% vs 17%, p = 0.37). They were also more likely to remove the monitor and have inadequate numbers of measurements. CONCLUSIONS: The Oscar 2 ABPM device is straightforward to use but can interfere with sleep. Commonly reported adverse effects include pain, skin irritation, and bruising. Those who tolerate the monitor poorly are more likely to report being in fair or poor health and to remove it, particularly at night.


Subject(s)
Blood Pressure Monitoring, Ambulatory/statistics & numerical data , Blood Pressure/physiology , Hypertension/diagnosis , Oscillometry/statistics & numerical data , Research Subjects/psychology , Adult , Blood Pressure Determination , Blood Pressure Monitoring, Ambulatory/adverse effects , Blood Pressure Monitoring, Ambulatory/psychology , Contusions/complications , Contusions/psychology , Cross-Sectional Studies , Exanthema/complications , Exanthema/psychology , Female , Health Status Indicators , Humans , Hypertension/ethnology , Hypertension/physiopathology , Male , Middle Aged , Models, Statistical , Oscillometry/adverse effects , Oscillometry/psychology , Pain/complications , Pain/psychology , Reproducibility of Results , Research Design , Self Report , Sleep Wake Disorders/complications , Socioeconomic Factors , Surveys and Questionnaires , Time Factors
8.
J Neurotrauma ; 27(11): 2091-106, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21087156

ABSTRACT

Most experimental models of spinal cord injury (SCI) in rodents induce damage in the thoracic cord and subsequently examine hindlimb function as an indicator of recovery. In these models, functional recovery is most attributable to white-matter preservation and is less influenced by grey-matter sparing. In contrast, most clinical cases of SCI occur at the lower cervical levels, a region in which both grey-matter and white-matter sparing contribute to functional motor recovery. Thus experimental cervical SCI models are beginning to be developed and used to assess protective and pharmacological interventions following SCI. The objective of this study was to characterize a model of graded cervical hemicontusion SCI with regard to several histological and behavioral outcome measures, including novel forelimb behavioral tasks. Using a commercially available rodent spinal cord impactor, adult male rats received hemicontusion SCI at vertebral level C5 at 100, 200, or 300 kdyn force, to produce mild, moderate, or severe injury severities. Tests of skilled and unskilled forelimb and locomotor function were employed to assess functional recovery, and spinal cord tissue was collected to assess lesion severity. Deficits in skilled and unskilled forelimb function and locomotion relating to injury severity were observed, as well as decreases in neuronal numbers, white-matter area, and white-matter gliosis. Significant correlations were observed between behavioral and histological data. Taken together, these data suggest that the forelimb functional and locomotor assessments employed here are sensitive enough to measure functional changes, and that this hemicontusion model can be used to evaluate potential protective and regenerative therapeutic strategies.


Subject(s)
Contusions/pathology , Contusions/psychology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/psychology , Animals , Benzoxazines , Cell Count , Disease Models, Animal , Fluorescence , Forelimb/physiology , Functional Laterality/physiology , Glial Fibrillary Acidic Protein/metabolism , Gliosis/pathology , Health , Immunohistochemistry , Locomotion/physiology , Male , Motor Skills/physiology , Myelin Basic Protein/metabolism , Neuroglia/metabolism , Neurons/pathology , Oxazines , Psychomotor Performance/physiology , Rats , Rats, Sprague-Dawley , Recovery of Function , Spinal Cord/pathology
10.
Neurochem Res ; 32(12): 2046-53, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17476592

ABSTRACT

Following contusive spinal cord injury (SCI), calpain activity is dramatically increased and remains elevated for days to weeks. Although calpain inhibition has previously been demonstrated to be neuroprotective following spinal cord injury, most studies administered the calpain inhibitor at a single time point. We hypothesized that sustained calpain inhibition would improve functional and pathological outcomes, as compared to the results obtained with a single postinjury administration of the calpain inhibitor. Contusion SCI was produced in female Long-Evans rats using the Infinite Horizon spinal cord injury impactor at the 200 kdyn force setting. Open-field locomotor function was evaluated until 6 weeks postinjury. Histological assessment of lesion volume and tissue sparing was performed at 6 weeks after SCI. Calpain inhibitor MDL28170 administered as a single postinjury i.v. bolus (20 mg/kg) or as a daily i.p. dose (1 mg/kg) improved locomotor function, but did not increase tissue sparing. Combined i.v. and daily i.p. MDL28170 administration resulted in significant improvement in both functional and pathological outcome measures, supporting the calpain theory of SCI proposed by Dr. Banik and colleagues.


Subject(s)
Calpain/antagonists & inhibitors , Contusions/drug therapy , Contusions/pathology , Cysteine Proteinase Inhibitors/therapeutic use , Dipeptides/therapeutic use , Locomotion/physiology , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/pathology , Animals , Contusions/psychology , Dipeptides/administration & dosage , Female , Injections, Intraperitoneal , Injections, Intravenous , Locomotion/drug effects , Rats , Rats, Long-Evans , Spinal Cord/pathology , Spinal Cord Injuries/psychology
11.
J Neurotrauma ; 24(4): 674-89, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17439350

ABSTRACT

This study characterized the Infinite Horizon (IH) Impactor for use in mouse models of contusion spinal cord injury (SCI), and investigated the feasibility and reliability of using magnetic resonance imaging (MRI) as a method to accurately measure lesion volume after mouse contusion SCI. Eight-week-old female C57Bl/6 mice received a mild (30 kilodyne), moderate (50 kilodyne), or severe (70 kilodyne) contusion injury at the T9 vertebral level. Uninjured control mice received a T9 laminectomy only. Functional recovery was assessed using the Basso, Beattie, Bresnahan (BBB) and Basso Mouse Scale (BMS) open-field locomotor rating scales. Next, 4% paraformaldehyde-perfused spinal cords were collected between the T6 and T12 spinal roots, and stored in phosphate-buffered saline (PBS) at 4 degrees C until MRI analysis. MRI lesion volumes were determined using T1-weighted images on a 7-Tesla MRI. Histology was performed on 20-microm polyester wax-embedded sections processed from the same spinal cords for stereological determination of fibronectin lesion volume and myelin basic protein spared white matter volume. Area of spared white matter at the epicenter was also analyzed. The results demonstrated that the IH Impactor produced precise, graded contusion SCI in mice. Lesion volumes were positively correlated with force of impact, and negatively correlated with spared white matter and functional recovery. Additionally, similar lesion volumes were detected using fibronectin staining and MRI analysis, although MRI may be more sensitive for milder injuries. These results give researchers more options in how to analyze spinal cord injuries in animal models.


Subject(s)
Behavior, Animal/physiology , Contusions/pathology , Contusions/psychology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/psychology , Animals , Brain/pathology , Female , Fibronectins/metabolism , Image Processing, Computer-Assisted , Locomotion/physiology , Magnetic Resonance Imaging , Mice , Mice, Inbred C57BL , Myelin Basic Protein/metabolism , Plastic Embedding , Reproducibility of Results
12.
Unfallchirurg ; 109(12): 1109-16, 2006 Dec.
Article in German | MEDLINE | ID: mdl-17180383

ABSTRACT

In the literature, the association between chronic pain syndromes of the spine and sustained "trifle trauma" is a matter of controversy. "Trifle trauma" is identified as a contusion, compression and/or sprain without a definite, acute imaging sign of injury to the bone, the disk or the ligaments of the spine. Most of the time, striking isolated changes to the intervertebral disks are interpreted as preexisting without relevance to an acute injury. However, complex chronic pain syndromes causing permanent and significant functional limitations in daily life and work may occur. Besides the diagnostic and therapeutic challenge for the treating physician, the expert confronted with compensation claims very often has to answer questions as to whether "trifle trauma" of the spine may lead to significant and permanent functional limitations or loss with chronic pain syndromes, and what the importance of possible isolated changes in intervertebral disks is. The data from literature dealing with this topic is contradictory and deficient. In this article, we critically examine the causality between "trifle trauma" to the spine and possible permanent chronic complaints based on currently available data from the literature in order to support the process of decision making in questions of litigation and controversial compensation claims.


Subject(s)
Back Pain/etiology , Expert Testimony/legislation & jurisprudence , Intervertebral Disc/injuries , Spinal Injuries/diagnosis , Back Pain/psychology , Compensation and Redress/legislation & jurisprudence , Contusions/diagnosis , Contusions/psychology , Disability Evaluation , Humans , Spinal Injuries/psychology , Sprains and Strains/diagnosis , Sprains and Strains/psychology , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/psychology
13.
Transfusion ; 46(8): 1374-9, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16934074

ABSTRACT

BACKGROUND: Some blood donation-related adverse events (AEs) can negatively impact the blood donor return rate (BDRR) and decrease donor retention. STUDY DESIGN AND METHODS: One-thousand randomly selected whole-blood donors were interviewed 3 weeks after a 525-mL index whole-blood donation for seven AEs. The number of return visits and duration of follow-up were recorded for each of the 1000 donors. A negative binomial regression analysis was used to determine the contribution of the four most common AEs to the BDRR, and interactions between these AEs were also evaluated. RESULTS: The four most common AEs were bruise alone (15.1%), sore arm "alone" (7.0%), fatigue "alone" (5.1%), and donor reaction "alone" (4.2%), where "alone" is defined to also include donors who had a bruise but no other AE. The estimated BDRR for donations without AEs was 1.32 visits per year. The estimated BDRRs for the four most common AEs were: bruise alone, 1.32 visits per year; sore arm alone, 1.30 visits per year (2% reduction in BDRR); fatigue alone, 1.06 visits per year (20% reduction in BDRR); and donor reaction alone, 0.87 visits per year (34% reduction in BDRR). The BDRR for donor reaction, fatigue, and sore arm together was 0.20 visits per year (85% reduction in BDRR). CONCLUSION: Donor reaction had the most negative impact on the BDRR. There appears to be a synergistic effect between donor reaction, fatigue, and sore arm. Theoretically, amelioration of some AEs has the potential to improve BDRRs.


Subject(s)
Blood Donors , Contusions , Pain , Blood Donors/psychology , Blood Transfusion/psychology , Contusions/etiology , Contusions/psychology , Fatigue/etiology , Fatigue/psychology , Humans , Interviews as Topic , Pain/etiology , Pain/psychology , Time Factors
14.
Rev Med Interne ; 26(9): 744-7, 2005 Sep.
Article in French | MEDLINE | ID: mdl-16023271

ABSTRACT

INTRODUCTION: Painful bruising syndrome was described by Gardner and Diamond in 1955. It is marked by spontaneous bruising, without any biological abnormality, affecting young women with pathological mental context. EXEGESIS: We report three observations with painful bruising syndrome. In a patient, psychotherapy induced improvement in dermatological and articular manifestations. In other case, placebotherapy made clinical symptoms go away for a prolonged period. CONCLUSION: Some etiological hypotheses have been postulated for Gardner and Diamond syndrome. However, published cases speak in favour of psychogenic hypothesis. Somatic and psychological approach must be offered to these patients.


Subject(s)
Contusions/psychology , Psychotherapy , Adolescent , Adult , Contusions/physiopathology , Contusions/therapy , Female , Humans , Pain , Placebos , Syndrome
15.
J Neurotrauma ; 18(4): 409-23, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11336442

ABSTRACT

Spinal cord injury (SCI) results in loss of locomotor function and development of abnormal chronic pain syndromes (mechanical allodynia, thermal hyperalgesia). Following injury, secondary mechanisms including release of excitatory amino acids, inflammation and lipid peroxidation damage neural cells through release of cytotoxic free radicals. We hypothesized that selective inhibition of cyclooxygenase-2 (COX-2), an inducible inflammatory mediator, would decrease tissue damage and subsequently reduce locomotor deficits and development of chronic central pain syndromes after injury. Fifteen minutes prior to receiving T13 spinal segment spinal cord contusion injury, 200-225-g male Sprague-Dawley rats received either vehicle (0.5 ml 1:1 v/v DMSO/saline, i.p., n = 20) or the selective COX-2 inhibitor NS-398 (5 mg/kg in DMSO/saline v/v, i.p., n = 20). Locomotor function via the BBB scale, and nociceptive behaviors measured by paw withdrawals to von Frey filaments and radiant heat stimuli were tested for 4 weeks postinjury. Histological examination and volumetric analysis of spinal cord tissue were performed concomitantly. Spinally contused animals receiving NS-398 demonstrated significantly (p < 0.05) reduced locomotor alteration and reductions in both fore- and hindlimb mechanical allodynia and thermal hyperalgesia when compared to vehicle controls. Histological examination of spinal segments at the lesion segment demonstrated reduced lesion extent and increased viable tissue when compared to vehicle controls. Prostaglandin E2 levels were significantly lowered in NS-398-treated but not vehicle-treated animals 12 h after injury. These results support the role of COX-2 in reducing pathological and behavioral deficits after spinal cord injury.


Subject(s)
Behavior, Animal/drug effects , Contusions/pathology , Contusions/psychology , Cyclooxygenase Inhibitors/pharmacology , Isoenzymes/antagonists & inhibitors , Nitrobenzenes/pharmacology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/psychology , Sulfonamides/pharmacology , Animals , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Dinoprostone/metabolism , Hot Temperature , Hypesthesia/etiology , Hypesthesia/physiopathology , Immunohistochemistry , Male , Motor Activity/drug effects , Physical Stimulation , Prostaglandin-Endoperoxide Synthases , Rats , Rats, Sprague-Dawley , Spinal Cord Injuries/complications , Spinal Cord Injuries/physiopathology
16.
J Neurotrauma ; 17(12): 1205-17, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11186233

ABSTRACT

Spinal cord injury (SCI) often results in abnormal pain syndromes in patients. We present a recently developed SCI mammalian model of chronic central pain in which the spinal cord is contused at T8 using the NYU impactor device (10-g rod, 2.0-mm diameter, 12.5-mm drop height), an injury which is characterized behaviorally as moderate. Recovery of locomotor function was assessed with an open field test and scored using the open field test scale (BBB scale). Somatosensory tests of paw withdrawal responses accompanied by supraspinal responses to both mechanical punctate (von Frey hairs) and nonpunctate (4 mm diameter blunt probe) as well as thermal (radiant heat) peripheral stimuli were performed. Comparisons at the level of the individual animal between precontusion and postcontusion responses indicated significant increases in reactions to low threshold punctate mechanical stimuli, non-punctate stimuli and thermal stimuli (p < 0.05). To demonstrate the validity of this model as a central pain model, gabapentin, an agent used clinically for central pain, was given i.p. at 10 or 30 mg/kg. Gabapentin treatment significantly and reversibly changed the responses, consistent with the attenuation of the abnormal sensory behavior, and the attenuated responses lasted for the duration of the drug effect (up to 6 h). These results support the use of the spinal contusion model in the study of chronic central pain after SCI.


Subject(s)
Acetates/therapeutic use , Amines , Analgesics/therapeutic use , Contusions/drug therapy , Contusions/physiopathology , Cyclohexanecarboxylic Acids , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/physiopathology , gamma-Aminobutyric Acid , Animals , Behavior, Animal/drug effects , Chronic Disease , Contusions/psychology , Gabapentin , Hot Temperature , Male , Motor Activity , Pain/drug therapy , Pain/physiopathology , Pain Measurement , Pain Threshold/drug effects , Physical Stimulation , Rats , Rats, Sprague-Dawley , Reaction Time/drug effects , Spinal Cord Injuries/psychology , Time Factors
17.
Vet Rec ; 145(6): 160-5, 1999 Aug 07.
Article in English | MEDLINE | ID: mdl-10466773

ABSTRACT

A total of 356 piglets from one farm were examined for foot and skin lesions every day for the first 10 days after birth, and then on alternate days until they were weaned. Over a period of 24 days 100 per cent of the piglets examined developed sole bruising, and 49.1 per cent developed sole erosions. Sole bruising lasted for an average of 13 days and sole erosions for seven days. At the beginning of the study, a higher proportion of piglets had mild sole bruising; from three to nine days of age piglets had moderate sole bruising but from days 10 to 20 mild bruising was again observed more frequently. Skin lesions were observed on the carpal aspect of the front limbs; 60.9 per cent of the piglets developed skin abrasions, 70.7 per cent developed healed wounds and 90 per cent developed hairless patches. The skin abrasions lasted on average for six days, the healed wounds for five days and the hairless patches for eight days. Piglets which developed sole bruising and/or sole erosions on the first day of life were significantly heavier than those which did not. Continuous observations of the piglets' behaviour during the first six days of life showed that sole bruising increased as the total time spent in the creep area or lying near the sow on the solid floor increased. During the first three days of life skin abrasions increased as the total time spent lying in the creep area increased. There was a positive correlation between the total time piglets spent suckling and the incidence of carpal skin abrasions between four and six days of age. Piglets with sole bruising, sole erosions or carpal skin abrasions spent less time during the day in 'other' activities such as walking, playing or fighting.


Subject(s)
Animals, Suckling/injuries , Behavior, Animal , Carpus, Animal/injuries , Contusions/veterinary , Foot Injuries/veterinary , Swine Diseases/epidemiology , Animals , Animals, Newborn , Animals, Suckling/psychology , Cohort Studies , Contusions/epidemiology , Contusions/psychology , England/epidemiology , Female , Foot Injuries/epidemiology , Foot Injuries/psychology , Incidence , Lactation/psychology , Swine , Swine Diseases/psychology
18.
J Neurotrauma ; 15(3): 199-216, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9528920

ABSTRACT

Cognitive deficits are the most enduring and disabling sequelae of human traumatic brain injury (TBI), but quantifying the magnitude, duration, and pattern of cognitive deficits produced by different types of TBI has received little emphasis in preclinical animal models. The objective of the present study was to use a battery of behavioral tests to determine if different impact sites produce different patterns of behavioral deficits and to determine how long behavioral deficits can be detected after TBI. Prior to surgery, rats were trained to criteria on delayed nonmatching to position, radial arm maze, and rotarod tasks. Rats received sham surgery (controls), midline frontal contusions (frontal TBI, 2.25 m/sec impact), or unilateral sensorimotor cortex contusions (lateral TBI, 3.22 m/sec impact) at 12 months of age and were tested throughout the next 12 months. Cognitive deficits were more robust and more enduring than sensorimotor deficits for both lateral TBI and frontal TBI groups. Lateral TBI rats exhibited transient deficits in the forelimb placing and in the rotarod test of motor/ambulatory function, but cognitive deficits were apparent throughout the 12-month postsurgery period on tests of spatial learning and memory including: (1)reacquisition of a working memory version of the radial arm maze 6-7 months post-TBI, (2) performance in water maze probe trials 8 months post-TBI, and (3) repeated acquisition of the Morris water maze 8 and 11 months post-TBI. Frontal TBI rats exhibited a different pattern of deficits, with the most robust deficits in tests of attention/orientation such as: (1) the delayed nonmatching to position task (even with no delays) 1-11 weeks post-TBI, (2) the repeated acquisition version of the water maze--especially on the first "information" trial 8 months post-TBI, (3) a test of sensorimotor neglect or inattention 8.5 months post-TBI, and (4) a DRL20 test of timing and/or sustained attention 11 months after surgery. These results suggest that long-term behavioral deficits can be detected in rodent models of TBI, that cognitive deficits seem to be more robust than sensorimotor deficits, and that different TBI impact sites produce dissociable patterns of cognitive deficits in rats.


Subject(s)
Brain Injuries/psychology , Cognition Disorders/psychology , Contusions/psychology , Frontal Lobe/injuries , Motor Cortex/injuries , Somatosensory Cortex/injuries , Animals , Brain Injuries/complications , Cognition Disorders/etiology , Cues , Male , Maze Learning/physiology , Postural Balance/physiology , Rats , Rats, Sprague-Dawley
19.
J Neurotrauma ; 5(2): 151-60, 1988.
Article in English | MEDLINE | ID: mdl-3225858

ABSTRACT

A weight-drop technique was used to produce mild, moderate, or severe spinal cord contusive injury in rats. At 4 weeks after injury, somatosensory evoked potentials (SEPs) were recorded with silver ball electrodes placed over the somatosensory cortex of anesthetized rats to measure the response to sciatic nerve stimulation. Both SEP area and amplitude were measured and were highly correlated with each other. Both indices of the SEP correlated inversely with the height of the weight drop and directly with the degree of residual function assessed at 4 weeks after injury. Measures of residual function consisted of a motor score, inclined plane test, and a combined behavioral score based on several neurologic functions. No correlation between latency of the SEP with degrees of contusive injury was observed. The data indicate that the SEP can be used as one criterion in the assessment of the severity of a lesion in a rat model of a graded spinal cord injury.


Subject(s)
Contusions/physiopathology , Evoked Potentials, Somatosensory , Spinal Cord Injuries/physiopathology , Animals , Behavior, Animal/physiology , Contusions/pathology , Contusions/psychology , Female , Male , Rats , Rats, Inbred Strains , Regression Analysis , Spinal Cord Injuries/pathology , Spinal Cord Injuries/psychology
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