Journal of neurotrauma
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Journal of neurotrauma · Mar 2012
Cyclin D1 gene ablation confers neuroprotection in traumatic brain injury.
Cell cycle activation (CCA) is one of the principal secondary injury mechanisms following brain trauma, and it leads to neuronal cell death, microglial activation, and neurological dysfunction. Cyclin D1 (CD1) is a key modulator of CCA and is upregulated in neurons and microglia following traumatic brain injury (TBI). In this study we subjected CD1-wild-type (CD1(+/+)) and knockout (CD1(-/-)) mice to controlled cortical impact (CCI) injury to evaluate the role of CD1 in post-traumatic neurodegeneration and neuroinflammation. ⋯ In contrast, CD1(-/-) mice showed reduced CCA and neurodegeneration at 24 h, as well as improved cognitive function, attenuated hippocampal neuronal cell loss, decreased lesion volume, and cortical microglial activation at 21 days post-injury. These findings indicate that CD1-dependent CCA plays a significant role in the neuroinflammation, progressive neurodegeneration, and related neurological dysfunction resulting from TBI. Our results further substantiate the proposed role of CCA in post-traumatic secondary injury, and suggest that inhibition of CD1 may be a key therapeutic target for TBI.
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Journal of neurotrauma · Mar 2012
Amphetamine-enhanced motor training after cervical contusion injury.
Individually, motor training, pharmacological interventions, and housing animals in an enriched environment (EE) following spinal cord injury (SCI) result in limited functional improvement but, when combined, may enhance motor function. Here, we tested amphetamine (AMPH)-enhanced skilled motor training following a unilateral C3-C4 contusion injury on the qualitative components of reaching and on skilled forelimb function, as assessed using single-pellet and staircase reaching tasks. Kinematic analysis evaluated the quality of the reach, and unskilled locomotor function was also tested. ⋯ Kinematics provided no evidence that improved function was related to improved quality of reach. There was no evidence of neuroprotection in the cervical spinal cord. The absence of evidence for kinematic improvement or neuroprotection suggested that AMPH-enhanced motor training is due primarily to supraspinal effects, an enhancement of attention during skilled motor training, or plasticity in supraspinal circuitry involved with motor control.
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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
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
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.