Journal of neurotrauma
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Journal of neurotrauma · Sep 2011
Mild stretch-induced injury increases susceptibility to interleukin-1β-induced release of matrix metalloproteinase-9 from astrocytes.
Traumatic brain injury (TBI) results in the activation of glia and the release of proinflammatory cytokines, including interleukin (IL)-1β. The response of astrocytes to mild TBI has not been well studied. We used an in vitro model of cell stretch to investigate the effects of mild mechanical insult on astrocyte injury (lactate dehydrogenase and propidium iodide), and on mediators of inflammation including IL-1β, the chemokine CX3CL1, and nitrite. ⋯ In contrast, the combination of mild stretch followed by IL-1β resulted in greater activation of the ERK pathway compared to either stimulus alone, and also resulted in an increase in the production of MMP-9 by astrocytes. Inhibition of the ERK pathway suppressed the increase in MMP-9 induced by the combination of stretch and IL-1β treatment. These results suggest that a primary mild mechanical injury renders astrocytes more susceptible to a secondary exposure to a proinflammatory cytokine such as IL-1β via the activation of the ERK pathway, and suggest a mechanism by which a mild head injury may confer increased susceptibility to neurologic injury caused by a subsequent insult.
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Journal of neurotrauma · Sep 2011
The effect of progesterone dose on gene expression after traumatic brain injury.
Microarray-based transcriptional profiling was used to determine the effect of progesterone in the cortical contusion (CCI) model. Gene ontology (GO) analysis then evaluated the effect of dose on relevant biological pathways. Treatment (vehicle, progesterone 10 mg/kg or 20 mg/kg given i.p.) was started 4 h post-injury and administered every 12 h post-injury for up to 72 h, with the last injection 12 hr prior to death for the 24 h and 72 h groups. ⋯ At 7 days, there was only a modest difference in high-dose progesterone compared to vehicle, with only 14 differentially expressed genes. In contrast, low-dose progesterone resulted in 551 differentially expressed genes compared to vehicle. GO analysis identified genes for the low-dose treatment involved in positive regulation of cell proliferation, innate immune response, positive regulation of anti-apoptosis, and blood vessel remodeling.
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Journal of neurotrauma · Sep 2011
Human dental pulp cells: a new source of cell therapy in a mouse model of compressive spinal cord injury.
Strategies aimed at improving spinal cord regeneration after trauma are still challenging neurologists and neuroscientists throughout the world. Many cell-based therapies have been tested, with limited success in terms of functional outcome. In this study, we investigated the effects of human dental pulp cells (HDPCs) in a mouse model of compressive spinal cord injury (SCI). ⋯ We also demonstrated that HDPCs were able to express some glial markers such as GFAP and S-100. The functional analysis also showed locomotor improvement in these animals. Based on these findings, we propose that HDPCs may be feasible candidates for therapeutic intervention after SCI and central nervous system disorders in humans.
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Journal of neurotrauma · Sep 2011
Kinematic study of locomotor recovery after spinal cord clip compression injury in rats.
After spinal cord injury (SCI), precise assessment of motor recovery is essential to evaluate the outcome of new therapeutic approaches. Very little is known on the recovery of kinematic parameters after clinically-relevant severe compressive/contusive incomplete spinal cord lesions in experimental animal models. In the present study we evaluated the time-course of kinematic parameters during a 6-week period in rats walking on a treadmill after a severe thoracic clip compression SCI. ⋯ We also showed that treadmill training increased the swing duration variability during locomotion suggesting an activity-dependent compensatory mechanism of the motor control system. However, no effect of training was observed on the main locomotor parameters probably due to a ceiling effect of self-training in the cage. These findings constitute a kinematic baseline of locomotor recovery after clinically relevant SCI in rats and should be taken into account when evaluating various therapeutic strategies aimed at improving locomotor function.
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Journal of neurotrauma · Sep 2011
Quantitative relationship between axonal injury and mechanical response in a rodent head impact acceleration model.
A modified Marmarou impact acceleration model was developed to study the mechanical responses induced by this model and their correlation to traumatic axonal injury (TAI). Traumatic brain injury (TBI) was induced in 31 anesthetized male Sprague-Dawley rats (392±13 g) by a custom-made 450-g impactor from heights of 1.25 m or 2.25 m. An accelerometer and angular rate sensor measured the linear and angular responses of the head, while the impact event was captured by a high-speed video camera. ⋯ Average linear acceleration, peak angular velocity, average angular acceleration, and surface righting time were also significantly different between the two groups. A positive correlation was observed between normalized total TAI counts and average linear acceleration (R(2)=0.612, p<0.05), and time to surface right (R(2)=0.545, p<0.05). Our study suggested that a 2.25-m drop in the Marmarou model may not always result in a severe injury, and TAI level is related to the linear and angular acceleration response of the rat head during impact, not necessarily the drop height.