To investigate the role of the myelin-associated protein Nogo-A on axon sprouting and regeneration in the adult central nervous system (CNS), we generated Nogo-A-deficient mice. Nogo-A knockout (KO) mice were viable, fertile, and not obviously afflicted by major developmental or neurological disturbances. The shorter splice form Nogo-B was strongly upregulated in the CNS. The inhibitory effect of spinal cord extract for growing neurites was decreased in the KO mice. Two weeks following adult dorsal hemisection of the thoracic spinal cord, Nogo-A KO mice displayed more corticospinal tract (CST) fibers growing toward and into the lesion compared to their wild-type littermates. CST fibers caudal to the lesion-regenerating and/or sprouting from spared intact fibers-were also found to be more frequent in Nogo-A-deficient animals.
deficits [1]. Small injuries can result in transient impairments, but the mechanisms of recovery are poorly understood [2]. At the cortical level, rearrangements of the sensory and motor representation maps often parallel recovery [3, 4]. Results and discussion In the sensory system, studies have shown thatAdult female Lewis rats were anesthetized, and their left cortical and subcortical mechanisms contribute to motor cortex was exposed and stimulated by a tungsten map rearrangements [5, 6], but for the motor system microelectrode as described in the supplemental materials the situation is less clear. Here we show that large-section, with the aim to identify an area that yields consisscale structural changes in the spared rostral part tent and exclusive hind-limb (HL) responses. Consistent of the spinal cord occur simultaneously with shifts with previous studies [8, 9], this was found to be the case of a hind-limb motor cortex representation after for stimulations at 2 mm caudal to bregma and 1.5-2.5 mm traumatic spinal-cord injury. By intracortical lateral to the midline. Stimulation at these coordinates microstimulation, we defined a cortical area that usually activated hind-limb flexor muscles and, more consistently and exclusively yielded hind-limb rarely, extensor muscles. In two animals, muscles of the muscle responses in normal adult rats. Four weeks tail base were activated. We determined the stimulus after a bilateral transsection of the corticospinal threshold by increasing stimulus intensities and recording tract (CST) in the lower thoracic spinal cord, we again the lowest intensity at which a consistent movement was stimulated this cortical field and found forelimb, observed [7]. The average threshold was 49.6 A (Ϯ 18.1 whisker, and trunk responses, thus demonstrating standard deviation [SD], n ϭ 32), and animals with threshreorganization of the cortical motor olds above 100 A were not used for physiological evaluarepresentation. Anterograde tracing of corticospinal tion. After the stimulation, the animals received an addifibers originating from this former hind-limb area tional dose of anaesthetic (xylazine), and the scalp wasrevealed that sprouting greatly increased the sutured. Subsequently, the spinal cord was exposed at a normally small number of collaterals that lead into mid-thoracic level (T8), and the dorsal columns, including the cervical spinal cord rostral to the lesion. We the main component of the corticospinal tract (CST), were conclude that the corticospinal motor system has transsected bilaterally as described [10]. Care was taken greater potential to adapt structurally to lesions than not to compromise the dorsolaterally running rubrospinal was previously believed and hypothesize that this tract (Figure 1). In a control group, the spinal cord was spontaneous growth response is the basis for the exposed but not transsected (sham operation). The tissue observed motor representation rearrangements overlying the spinal cord was sutured, and the animals and contributes to functional recov...
Background: Plain radiography (XR) series are standard of care for detection of fall-related fractures in older patients with low-energy falls (LEF) in the emergency department (ED). We have investigated the prevalence of fractures and diagnostic accuracy of XR imaging in the ED. Methods: 2839 patients with LEF, who were presented to two urban level I trauma centers in 2016 and received XR and computed tomography (CT), were consecutively included in this retrospective cohort study. The primary endpoint was the prevalence of fractures of the vertebral column, rib cage, pelvic ring, and proximal long bones. Secondary endpoints were diagnostic accuracy of XR for fracture detection with CT as reference standard and cumulative radiation doses applied. Results: Median age was 82 years (range 65–105) with 64.1% female patients. Results revealed that 585/2839 (20.6%) patients sustained fractures and 452/2839 (15.9%) patients received subsequent XR and CT examinations of single body regions. Cross-tabulation analysis revealed sensitivity of XR of 49.7%, a positive likelihood ratio of 27.6, and negative likelihood ratio of 0.5. Conclusions: XR is of moderate diagnostic accuracy for ruling-out fractures of the spine, pelvic ring, and rib cage in older patients with LEF. Prospective validations are required to investigate the overall risk–benefit of direct CT imaging strategies, considering the trade-off between diagnostic safety, health care costs, and radiation exposure.
Since PPI is considered as a measure of sensorimotor gating, our data indicate that sensorimotor gating deficits induced by MK-801 are subject to a sensitization process. These findings may be relevant for current hypotheses relating schizophrenic symptoms to sensitization.
BACKGROUND/OBJECTIVES: To determine the prevalence and severity of traumatic intracranial hemorrhage (tICH) in a large cohort of older adults presenting with lowenergy falls and the association with anticoagulation or antiplatelet medication. DESIGN: Bicentric retrospective cohort analysis. SETTING: Two level 1 trauma centers in Switzerland and Germany. PARTICIPANTS: Consecutive sample of older adults (aged ≥65 y) presenting to the emergency department (ED) over a 1-year period with low-energy falls who received cranial computed tomography (cCT) within 48 hours of ED presentation. MEASUREMENTS: The prevalence and severity of tICHs was assessed and the outcomes (in-hospital mortality, admission to intensive care unit [ICU], or neurosurgical intervention) were specified. We used multivariate regression models to measure the association between anticoagulation/antiplatelet therapy and the risk for tICH after adjustment for known predictors. RESULTS: The overall prevalence for tICH detected by cCT was 176 of 2567 (6.9%). Neurosurgical intervention was performed in 15 of 176 (8.5%) patients with tICH, 28 of 176 (15.9%) patients were admitted to the ICU, and 14 of 176 (8.0%) died in the hospital. CT-detected skull fracture and signs of injury above the clavicles were the strongest predictors for the presence of tICH (odds ratio [OR] = 4.28; 95% confidence interval [CI] = 2.79-6.51; OR = 1.88; 95% CI = 1.3-2.73, respectively). Among 2567 included patients, 1424 (55%) were on anticoagulation/antiplatelet therapy. Multivariate regression models showed no differences for the risk of tICH (OR = 1.05; 95% CI = .76-1.47; P = .76) or association with the head-specific Injury Severity Scale (incident rate ratio = 1.08; 95% CI = .97-1.19; P = .15) with or without anticoagulation/antiplatelet therapy. CONCLUSION: Medication with anticoagulants or antiplatelet agents was not associated with higher prevalence and severity of tICH in older patients with low-energy falls undergoing cCT examination. In addition to cCT-detected skull fractures, visible injuries above the clavicles were the strongest clinical predictors for tICH. Our findings merit prospective validation. J Am Geriatr Soc 68:977-982, 2020.
The regional distribution of nitric oxide synthase (NOS) was investigated in alcoholic post-mortem brains compared with brains of non-alcoholic control individuals. Total enzyme activity in 28 brain regions was determined using the [(3)H]l-citrulline formation assay, whereas Western blot analyses were used for semi-quantitative measurement of the neuronal isoform of NOS (nNOS). In the alcoholic brain, nNOS protein expression was increased in the following regions: frontal cortex (85%), the cingulate gyrus (294%), the nucleus accumbens (54%), the entorhinal cortex (85%) and the thalamus (51%). These increases were, however, not associated with higher total NOS activity. Interestingly, nNOS protein content was increased in the frontal cortex and the nucleus accumbens, brain regions which are suggested to be involved in the dopaminergic mesolimbic reward system. It is concluded that upregulation of signal transduction pathways, such as the adenosine 3',5'-monophosphate and the protein kinase C-dependent pathway, due to stimulation of G-protein-coupled neurotransmitter receptor regulation, as a form of functional tolerance, could be responsible for increased nNOS protein expression, and downregulation of NOS enzyme activity in these brain regions.
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