Journal of neurotrauma
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Journal of neurotrauma · Mar 2012
Endogenous GFAP-positive neural stem/progenitor cells in the postnatal mouse cortex are activated following traumatic brain injury.
Interest in promoting regeneration of the injured nervous system has recently turned toward the use of endogenous stem cells. Elucidating cues involved in driving these precursor cells out of quiescence following injury, and the signals that drive them toward neuronal and glial lineages, will help to harness these cells for repair. Using a biomechanically validated in vitro organotypic stretch injury model, cortico-hippocampal slices from postnatal mice were cultured and a stretch injury equivalent to a severe traumatic brain injury (TBI) applied. ⋯ Our results indicate that a source of quiescent endogenous stem cells residing in the cortex and subcortical tissue proliferate in vitro following TBI. Moreover, these proliferating cells are multipotent and are derived mostly from GFAP-expressing cells. This raises the possibility of using this endogenous source of stem cells for repair following TBI.
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Journal of neurotrauma · Mar 2012
Multicenter Study Clinical TrialThe Graded Redefined Assessment of Strength Sensibility and Prehension: reliability and validity.
With the advent of new interventions targeted at both acute and chronic spinal cord injury (SCI), it is critical that techniques and protocols are developed that reliably evaluate changes in upper limb impairment/function. The Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) protocol, which includes five subtests, is a quantitative clinical upper limb impairment measure designed for use in acute and chronic cervical SCI. The objectives of this study were to: (1) establish the inter-rater and test-retest reliability, and (2) establish the construct and concurrent validity with the International Standards of Neurological Classification of Spinal Cord Injury (ISNCSCI), Spinal Cord Independence Measure II (SCIM), and the Capabilities of Upper Extremity Questionnaire (CUE). ⋯ The GRASSP is about 50% more sensitive (construct validity) than the ISNCSCI when defining sensory and motor integrity of the upper limb; the subtests showed concurrence with the SCIM, SCIM self-care subscale, and CUE. The strongest concurrence to impairment was with self-perception of function (CUE) (0.57-0.83, p<0.0001). The GRASSP was found to demonstrate reliability, construct validity, and concurrent validity for use as a standardized upper limb impairment measure for individuals with tetraplegia.
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Journal of neurotrauma · Mar 2012
Mitochondrial injury after mechanical stretch of cortical neurons in vitro: biomarkers of apoptosis and selective peroxidation of anionic phospholipids.
Mechanical injury of neurites accompanied by rupture of mitochondrial membranes may lead to immediate nonspecific release and spreading of pro-apoptotic factors and activation of proteases, that is, execution of apoptotic program. In the current work, we studied the time course of the major biomarkers of apoptosis as they are induced by exposure of rat cortical neurons to mechanical stretch. By using transmission electron microscopy, we found that mitochondria in the neurites were damaged early (1 h) after mechanical stretch injury whereas somal mitochondria were significantly more resistant and demonstrated structural damage and degenerative mitochondrial changes at a later time point after stretch (12 h). ⋯ Notably, caspase activation and phosphatidylserine externalization - two irreversible apoptotic events designating a point of no return - are substantially delayed and do not occur until 6-12 h after the initial impact. The early onset of reactive oxygen species production and cytochrome c release may be relevant to direct stretch-induced damage to mitochondria. The delayed emergence of apoptotic neuronal death after the immediate mechanical damage to mitochondria suggests a possible window of opportunity for targeted therapies.
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Journal of neurotrauma · Mar 2012
Development and characterization of a novel rat model of cervical spondylotic myelopathy: the impact of chronic cord compression on clinical, neuroanatomical, and neurophysiological outcomes.
Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord impairment worldwide and is a risk factor for traumatic central cord syndrome. Despite advances in surgery, there are no effective neuroprotective treatments for CSM, which reflects a limited understanding of its pathophysiology. In order to develop therapeutic strategies, we have developed a novel rat model of chronic progressive cervical spinal cord compression that mimics CSM. ⋯ The CCD model results in chronic and precise cervical cord compression. The compression is associated with mechanical allodynia and measurable neurobehavioral, neurophysiological, and neuropathological deficits. We anticipate that the CCD model will enable the investigation of translationally-relevant therapeutic strategies for CSM.
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Journal of neurotrauma · Mar 2012
The neuroprotective effect of pyrroloquinoline quinone on traumatic brain injury.
Pyrroloquinoline quinone (PQQ) is a water-soluble, anionic, quinonoid substance that has been established as an essential nutrient in animals. Owing to the inherent properties of PQQ as an antioxidant and redox modulator in various systems, PQQ is expected to be used in pharmacological applications in the near future. Although many recent studies have investigated its neuroprotective effects, the effect of PQQ on traumatic brain injury (TBI) has not been examined. ⋯ We found apparent expression upregulation of β-1,4-GalT-I and -V after PQQ was systemically administered. Lectin-fluorescent staining with RCA-I also revealed that PQQ contributed to expression upregulation of the galactosidase β-1 (Gal β-1), 4-galactosyltransferase N-acylsphingosine (4-GlcNAc) group in microglia and neurons of the cortex and hippocampal CA2 region. In summary, our experiment established that PQQ may play an important role in recovery post-TBI.