Journal of neurotrauma
-
Journal of neurotrauma · Mar 2012
Activation of the nuclear factor E2-related factor 2/antioxidant response element pathway is neuroprotective after spinal cord injury.
The activation of oxidative damage, neuroinflammation, and mitochondrial dysfunction has been implicated in secondary pathomechanisms following spinal cord injury (SCI). These pathophysiological processes lead to cell death and are tightly regulated by nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling. Here, we investigated whether activation of Nrf2/ARE is neuroprotective following SCI. ⋯ As early as 30 min after SCI, levels of Nrf2 transcription factor were increased in both nuclear and cytoplasmic fractions of neurons and astrocytes at the lesion site and remained elevated for 3 days. Treatment of injured rats with sulforaphane, an activator of Nrf2/ARE signaling, significantly increased levels of Nrf2 and glutamate-cysteine ligase (GCL), a rate-limiting enzyme for synthesis of glutathione, and decreased levels of inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) thus leading to a reduction in contusion volume and improvement in coordination. These results show that activation of the Nrf2/ARE pathway following SCI is neuroprotective and that sulforaphane is a viable compound for neurotherapeutic intervention in blocking pathomechanisms following SCI.
-
Journal of neurotrauma · Mar 2012
Review Meta AnalysisDiagnostic accuracy of clinical characteristics for identifying CT abnormality after minor brain injury: a systematic review and meta-analysis.
Clinical features can be used to identify which patients with minor brain injury need CT scanning. A systematic review and meta-analysis was undertaken to estimate the value of these characteristics for diagnosing intracranial injury (including the need for neurosurgery) in adults, children, and infants. Potentially relevant studies were identified through electronic searches of several key databases, including MEDLINE, from inception to March 2010. ⋯ Limited studies were undertaken in children and only a few studies reported data for neurosurgical injuries. In conclusion, this review identifies clinical characteristics that indicate increased risk of intracranial injury and the need for CT scanning. Other characteristics, such as headache in adults and scalp laceration of hematoma in children, do not reliably indicate increased risk.
-
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.
-
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.
-
Journal of neurotrauma · Mar 2012
Characteristics of lower extremity clonus after human cervical spinal cord injury.
Clonus can interfere with self-care and rehabilitation of people with spinal cord injury. Our aim was to characterize clonus and to evaluate factors that influence clonus duration in muscles paralyzed chronically by spinal cord injury. Electromyographic activity was recorded from soleus and 7 other limb muscles (5 ipsilateral, 2 contralateral) during clonus. ⋯ Clonus was intermediate (median: 21 sec) with activation of three or four ipsilateral muscles and these contractions were associated with greater activation of ipsilateral flexors. Clonus was short (<5 sec) when ipsilateral and contralateral muscles were activated (five or six muscles). Activation of extraneous afferent input, particularly contralateral muscles, may provide a way to shorten clonus after spinal cord injury.