Experimental neurology
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Experimental neurology · Sep 2013
Mindin is a critical mediator of ischemic brain injury in an experimental stroke model.
Stroke is the second leading cause of death among adults worldwide. Mindin is an ECM protein that plays important roles in regulating inflammation, angiogenesis and neuronal outgrowth. The role of mindin in the context of brain ischemia has not been examined. ⋯ Mindin KO mice exhibited minor infarctions, an attenuated inflammatory response and low levels of neuronal apoptosis following an ischemic insult. These data demonstrate that mindin is a critical mediator of ischemic brain injury in an experimental stroke model. Akt signaling most likely mediates the biological function of mindin in this model of cerebral ischemia.
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Experimental neurology · Sep 2013
Mobilisation of the splenic monocyte reservoir and peripheral CX₃CR1 deficiency adversely affects recovery from spinal cord injury.
Macrophages in the injured spinal cord originate from resident microglia and blood monocytes. Whether this diversity in origins contributes to their seemingly dual role in immunopathology and repair processes has remained poorly understood. Here we took advantage of Cx₃cr1(gfp) mice to visualise monocyte-derived macrophages in the injured spinal cord via adoptive cell transfer and bone marrow (BM) chimera approaches. ⋯ Adoptive transfer experiments further suggested high turnover of inflammatory monocytes in the spinal cord at 7 days post-injury. Consistent with this, only a small proportion of infiltrating cells unequivocally expressed polarisation markers for pro-inflammatory (M1) or alternatively activated (M2) macrophages at this time point. Our findings offer new insights into the origins of monocyte-derived macrophages after SCI and their contribution to functional recovery, providing a basis for further scrutiny and selective targeting of Ly6C(high) monocytes to improve outcomes from neurotraumatic events.
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Experimental neurology · Sep 2013
Effects of hypothermia on oligodendrocyte precursor cell proliferation, differentiation and maturation following hypoxia ischemia in vivo and in vitro.
Hypoxic-ischemia (HI) not only causes gray matter injury but also white matter injury, leading to severe neurological deficits and mortality, and only limited therapies exist. The white matter of animal models and human patients with HI-induced brain injury contains increased oligodendrocyte precursor cells (OPCs). However, little OPC can survive and mature to repair the injured white matter. ⋯ The myelinated axons and animal behavior both markedly increased in hypothermic- compared to normothermic-animals after HI. In summary, these data suggest that hypothermia has the effects to protect OPC and to promote OL maturation and myelin repair in hypoxic-ischemic events in the neonatal rat brain. This study proposed new aspects that may contribute to elucidate the mechanism of hypothermic neuroprotection for white matter injury in neonatal rat brain injury.
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Experimental neurology · Sep 2013
Diaphragm activation via high frequency spinal cord stimulation in a rodent model of spinal cord injury.
As demonstrated in a canine model, high frequency spinal cord stimulation (HF-SCS) is a novel and more physiologic method of electrical activation of the inspiratory muscles compared to current techniques. The dog model, however, has significant limitations due to cost and societal concerns. Since the rodent respiratory system is also a relevant model for the study of neuronal circuitry function, the aims of the present study were to a) assess the effects of HF-SCS and b) determine the methodology of application of this technique in rats. ⋯ Moreover, HF-SCS was successful in pacing these animals over a 60-min period without evidence of system fatigue. Our results suggest that, similar to the dog model, HF-SCS in the rat results in the activation of spinal cord tracts which synapse with the phrenic motoneuron pool, allowing the processing of the stimulus and consequent physiologic activation of the inspiratory muscles. The rat may be a useful model for further studies evaluating phrenic motoneuron physiology.
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Experimental neurology · Sep 2013
Anatomical correlates of recovery in single pellet reaching in spinal cord injured rats.
Modeling spinal cord injury (SCI) in animals is challenging because an appropriate combination of lesion location, lesion severity and behavioral testing is essential to analyze recovery of motor function. For particular tests such as single pellet reaching, the contribution of individual descending tracts to recovery has been investigated using specific tract ablation or graded lesions. However, it has not been established whether single pellet reaching is sufficiently sensitive for assessing the efficacy of treatments for cervical SCI (e.g., one of the currently most successful treatment approaches: rehabilitative training). ⋯ The DLQ lesion likely strikes a balance between tissue sparing and functional impairment and is, therefore, best suited to maximize the potential to observe treatment effects of plasticity-promoting treatments using single pellet reaching. Because of the specific lesion size that is necessary to observe treatment effects, the single pellet skilled reaching task can be considered a stringent behavioral test and therefore may be useful for predicting translational success of potential treatments. However, due to the variability in the success rate, the labor-intensive nature, and the limited usefulness to test functional outcome of a wide range of lesion severities, we are hesitant to continue to use single pellet reaching to assess the effectiveness of currently available treatments for cervical SCI.