Journal of neurotrauma
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Journal of neurotrauma · Mar 2012
Rapamycin promotes autophagy and reduces neural tissue damage and locomotor impairment after spinal cord injury in mice.
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that negatively regulates autophagy. Rapamycin, an inhibitor of mTOR signaling, can promote autophagy and exert neuroprotective effects in several diseases of the central nervous system (CNS). In the present study, we examined whether rapamycin treatment promotes autophagy and reduces neural tissue damage and locomotor impairment after spinal cord injury (SCI) in mice. ⋯ These results indicate that rapamycin promoted autophagy by inhibiting the mTOR signaling pathway, and reduced neural tissue damage and locomotor impairment after SCI. The administration of rapamycin produced a neuroprotective function at the lesion site following SCI. Rapamycin treatment may represent a novel therapeutic strategy after SCI.
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Journal of neurotrauma · Mar 2012
Microglial contribution to secondary injury evaluated in a large animal model of human spinal cord trauma.
Spinal cord injury (SCI) in dogs is a well recognized animal model to study pathogenesis and treatment modalities of the debilitating human disease. To define the contributing role of microglial cell activation to the secondary wave following SCI, microglia from 15 dogs with SCI confirmed by imaging, gross, and histopathological examination were isolated and characterized in terms of morphology, immunophenotype, and function ex vivo by flow cytometry, allowing single cell analysis. The results were compared to region-specific findings obtained from healthy control dogs. ⋯ In addition, phagocytosis and reactive oxygen species (ROS) generation were significantly increased in dogs with spinal cord trauma. Regional differences within the spinal cord were observed by demonstrating disparities in microglial immunophenotypes in the traumatized cervical compared to the thoracolumbar spinal cord. In contrast to histopathology, microglia activation analyzed on a single cell basis did not depend upon the time span following SCI.
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Journal of neurotrauma · Mar 2012
Development of post-traumatic epilepsy after controlled cortical impact and lateral fluid-percussion-induced brain injury in the mouse.
The present study investigated the development of hyperexcitability and epilepsy in mice with traumatic brain injury (TBI) induced by controlled cortical impact (CCI) or lateral fluid-percussion injury (FPI), which are the two most commonly used experimental models of human TBI in rodents. TBI was induced with CCI to 50 (14 controls) and with lateral FPI to 45 (15 controls) C57BL/6S adult male mice. The animals were followed-up for 9 months, including three 2-week periods of continuous video-electroencephalographic (EEG) monitoring, and a seizure susceptibility test with pentylenetetrazol (PTZ). ⋯ Finally, two independent series of experiments in both injury models provided comparable data demonstrating reproducibility of the modeling. These data show that different types of impact can trigger epileptogenesis in mice. Even though the frequency of spontaneous seizures in C57BL/6S mice is low, a large majority of animals develop hyperexcitability.
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Journal of neurotrauma · Mar 2012
Severity of locomotor and cardiovascular derangements after experimental high-thoracic spinal cord injury is anesthesia dependent in rats.
Anesthetics affect outcomes from central nervous system (CNS) injuries differently. This is the first study to show how two commonly used anesthetics affect continuously recorded hemodynamic parameters and locomotor recovery during a 2-week period after two levels of contusion spinal cord injury (SCI) in rats. We hypothesized that the level of cardiovascular depression and recovery of locomotor function would be dependent upon the anesthetic used during SCI. ⋯ This study shows that anesthetics affect hemodynamic parameters differently, which in turn can affect functional outcome measures. This supports the need for a careful evaluation of cardiovascular and other physiological measures in experimental models of SCI. Choice of anesthetic should be an important consideration in experimental designs and data analyses.