Journal of neurotrauma
-
Journal of neurotrauma · May 2013
Consequences of common data analysis inaccuracies in CNS trauma injury basic research.
The development of successful treatments for humans after traumatic brain or spinal cord injuries (TBI and SCI, respectively) requires animal research. This effort can be hampered when promising experimental results cannot be replicated because of incorrect data analysis procedures. To identify and hopefully avoid these errors in future studies, the articles in seven journals with the highest number of basic science central nervous system TBI and SCI animal research studies published in 2010 (N=125 articles) were reviewed for their data analysis procedures. ⋯ Reanalysis of our published data using the most common inappropriate statistical procedures resulted in a 14.1% average increase in significant effects compared to the original results. Specifically, an increase of 15.5% occurred with Independent t-tests and 11.1% after incorrect post hoc t-tests. Utilizing proper statistical procedures can allow more-definitive conclusions, facilitate replicability of research results, and enable more accurate translation of those results to the clinic.
-
Journal of neurotrauma · May 2013
Axonal and glial responses to a mid-thoracic spinal cord hemisection in the Macaca fascicularis monkey.
A comprehensive understanding of the pathology of spinal cord injury (SCI) in non-human primates may facilitate greatly the development of new strategies to promote recovery in humans with SCI. Relatively few studies, however, have been conducted to systemically examine pathological changes in the monkey, a non-human primate, after SCI. We report axonal, glial, and fibrotic responses in the spinal cord of monkey Macaca fascicularis after a thoracic (T) 8-9 lateral hemisection. ⋯ In contrast to rodents, substantial reactive astrocytic responses at the lesion border were not observed in the monkey. Conversely, a deposit of robust fibrotic scar was observed at the injury epicenter, which filled the space originally created by the hemisection. Thus, understanding the pathology of monkey SCI may provide clinically relevant information in designing repair strategies targeting specific problems associated with human SCIs.
-
Journal of neurotrauma · May 2013
The Ryk receptor is expressed in glial and fibronectin-expressing cells after spinal cord injury.
Wnt proteins play a critical role in central nervous system development and have been implicated in several neuropathologies, including spinal cord injury (SCI). Ryk, an unconventional Wnt receptor, regulates axonal regeneration after SCI, although its expression pattern in this neuropathology remains unclear. Therefore, we sought to define the spatiotemporal and cellular pattern of Ryk expression after a contusive SCI in adult rats using quantitative reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemical analysis. ⋯ Following SCI, we observed an increase in Ryk mRNA expression from 24 h post-injury until 7 days post-injury, whereas its protein levels were significantly augmented at 7 and 14 days post-injury. Moreover, the spatial and cellular Ryk expression pattern was altered in the damaged tissue, where this receptor was observed in reactive astrocytes and microglia/macrophages, NG2+ glial precursors, fibronectin+ cells, oligodendrocytes, and axons. In conclusion, we demonstrate that Ryk is expressed in the unlesioned spinal cord and that, after SCI, its spatiotemporal and cellular expression pattern changed dramatically, being expressed in cells involved in the spinal cord response to damage.
-
Journal of neurotrauma · May 2013
Intravenous infusion of magnesium chloride improves epicenter blood flow during the acute stage of contusive spinal cord injury in rats.
Vasospasm, hemorrhage, and loss of microvessels at the site of contusive or compressive spinal cord injury lead to infarction and initiate secondary degeneration. Here, we used intravenous injection of endothelial-binding lectin followed by histology to show that the number of perfused microvessels at the injury site is decreased by 80-90% as early as 20 min following a moderate T9 contusion in adult female rats. Hemorrhage within the spinal cord also was maximal at 20 min, consistent with its vasoconstrictive actions in the central nervous system (CNS). ⋯ The magnesium treatment seemed safe as it did not increase hemorrhage, despite the improved parenchymal blood flow. However, the treatment did not reduce acute microvessel, motor neuron or oligodendrocyte loss, and when infused for 7 days did not affect functional recovery or spared epicenter white matter over a 4 week period. These data suggest that microvascular blood flow can be restored with a clinically relevant treatment following spinal cord injury.
-
Journal of neurotrauma · May 2013
Characterization of a cervical spinal cord hemicontusion injury in mice using the infinite horizon impactor.
The majority of clinical spinal cord injuries (SCIs) are contusive and occur at the cervical level of the spinal cord. Most scientists and clinicians agree that the preclinical evaluation of novel candidate treatments should include testing in a cervical SCI contusion model. Because mice are increasingly used because of the availability of genetically engineered lines, we characterized a novel cervical hemicontusion injury in mice using the Infinite Horizon Spinal Cord Impactor (Precisions Systems & Instrumentation, Lexington, KY). ⋯ Added dwell time of 15 or 30 sec significantly worsened behavioral outcome, and mice demonstrated minimal ability of grasping, paw usage, and overground locomotion. Besides worsening of behavioral deficits, added dwell time also reduced residual white and gray matter at the epicenter and rostral-caudal to the injury, including on the contralateral side of the spinal cord. Taken together, we developed and characterized a new hemicontusion SCI model in mice that produces sufficient and sustained impairments in gross and skilled forelimb function and produced primarily unilateral functional deficits.