Journal of neurotrauma
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Journal of neurotrauma · Jul 2011
Traumatic axonal injury in the optic nerve: evidence for axonal swelling, disconnection, dieback, and reorganization.
Traumatic axonal injury (TAI) is a major feature of traumatic brain injury (TBI) and is associated with much of its morbidity. To date, significant insight has been gained into the initiating pathogenesis of TAI. However, the nature of TAI within the injured brain precludes the consistent evaluation of its specific anterograde and retrograde sequelae. ⋯ Concomitant with this evolving axonal pathology, focal YFP fluorescence quenching occurred and mapped precisely to immunoreactive loci positive for Texas-Red-conjugated-IgG, indicating that blood-brain barrier disruption and its attendant edema contributed to this phenomenon. This was confirmed through the use of antibodies targeting endogenous YFP, which demonstrated the retention of intact immunoreactive axons despite YFP fluorescence quenching. Collectively, the results of this study within the injured optic nerve provide unprecedented insight into the evolving pathobiology associated with TAI.
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Journal of neurotrauma · Jul 2011
Contribution of Ih to neuronal damage in the hippocampus after traumatic brain injury in rats.
Traumatic brain injury (TBI) causes selective neuronal damage in the hippocampus; however, the underlying mechanisms are still unclear. Post-traumatic alterations of ion channel activity, which actively regulate neuronal excitability and thus impact on excitotoxicity, may be involved in TBI-induced neuronal injury. Here we report that hyperpolarization-activated cation current (I(h)) contributes to the distinct vulnerability of hippocampal neurons in TBI. ⋯ Moreover, blocking I(h) led to an increase of neuronal excitability, with greater effects seen in post-traumatic CA1 pyramidal cells than in CA3 neurons. In addition, the I(h) in mossy cells was dramatically inhibited early after TBI. Our findings indicate that differential changes of I(h) in hippocampal neurons may be one of the mechanisms of selective cell death, and that an enhancement of functional I(h) may protect hippocampal neurons against TBI.
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Journal of neurotrauma · Jul 2011
Cortical excitability changes in patients with sleep-wake disturbances after traumatic brain injury.
Although chronic sleepiness is common after head trauma, the cause remains unclear. Transcranial magnetic stimulation (TMS) represents a useful complementary approach in the study of sleep pathophysiology. We aimed to determine in this study whether post-traumatic sleep-wake disturbances (SWD) are associated with changes in excitability of the cerebral cortex. ⋯ Similarly to that reported in patients with narcolepsy, the cortical hypoexcitability may reflect the deficiency of the excitatory hypocretin/orexin-neurotransmitter system. These observations may provide new insights into the causes of chronic sleepiness in patients with TBI. A better understanding of the pathophysiology of post-traumatic SWD may also lead to better therapeutic strategies in these patients.
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Journal of neurotrauma · Jul 2011
The combination of either tempol or FK506 with delayed hypothermia: implications for traumatically induced microvascular and axonal protection.
Following traumatic brain injury (TBI), inhibition of reactive oxygen species and/or calcineurin can exert axonal and vascular protection. This protection proves optimal when these strategies are used early post-injury. Recent work has shown that the combination of delayed drug administration and delayed hypothermia extends this protection. ⋯ These studies illustrate the potential benefits of Tempol coupled to delayed hypothermia. However, these findings do not transfer to the use of FK506, which in previous studies proved beneficial when coupled with hypothermia. These divergent results may be a reflection of the different animal models used and/or their associated injury severity.
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Journal of neurotrauma · Jul 2011
Novel model to investigate blast injury in the central nervous system.
Blast-induced neurotrauma (BINT) is a common injury modality associated with the current war efforts and increasing levels of terrorist activity. Exposure to the primary blast wave generated by explosive devices causes significant neurological deficits and is responsible for many of the war-related pathologies. Despite research efforts, the mechanism of injury is still poorly understood. ⋯ Our findings demonstrate that direct exposure to the blast wave compressed nervous tissue at a rate of 60 m/sec and led to significant functional deficits. Damage to the isolated spinal cord was marked by increased axonal permeability, suggesting rapid compression from the shockwave-generated high strain rates that resulted in membrane disruption. The model provides new insight into the mechanism of BINT and permits direct observation that may contribute to the development of appropriate treatment regimens.