Journal of neurotrauma
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Journal of neurotrauma · Apr 2012
Neuroprotection with an erythropoietin mimetic peptide (pHBSP) in a model of mild traumatic brain injury complicated by hemorrhagic shock.
Pyroglutamate helix B surface peptide (pHBSP) is an 11 amino acid peptide, designed to interact with a novel cell surface receptor, composed of the classical erythropoietin (EPO) receptor disulfide linked to the beta common receptor. pHBSP has the cytoprotective effects of EPO without stimulating erythropoiesis. Effects on early cerebral hemodynamics and neurological outcome at 2 weeks post-injury were compared in a rat model of mild cortical impact injury (3m/sec, 2.5 mm deformation) followed by 50 min of hemorrhagic hypotension (MAP 40 mm Hg for 50 min). ⋯ Both agents improved recovery of cerebral blood flow in the injured brain following resuscitation, and resulted in more rapid recovery of performance on beam balancing and beam walking tests. These studies suggest that pHBSP has neuroprotective effects similar to EPO in this model of combined brain injury and hypotension. pHBSP may be more useful in the clinical situation because there is less risk of thrombotic adverse effects.
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The epidemiology of traumatic brain injury (TBI) is changing in several Western countries, with an increasing proportion of elderly TBI patients admitted to the intensive care unit (ICU). We describe a series of 1366 adult patients admitted to three neuro-ICUs in which 44% of cases were 50 years of age or older. The health status before trauma (rated using the APACHE score) was worse in older patients. ⋯ Additionally, the odds ratios were very high for age and health status before TBI. Patients admitted to the ICU are increasingly older, have co-morbidities, and have specific types of intracranial lesions. Early rescue, surgical treatment, and intensive care of these patients may produce excellent results up to the age of 59 years, with favorable outcomes still possible for 39% of cases aged 60-69 years, without an excessive burden of severely disabled patients.
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In general, cranioplasty is viewed as a straightforward surgical procedure, and for many years the complications associated with the procedure have been underestimated. We reviewed our 5-year experience consisting of 218 cranioplasties. Study outcomes focused specifically on the occurrence of complications after cranioplasty. ⋯ In particular, patients with a bifrontal cranioplasty had a 2-fold increased risk of complication (CI 95 1.1-3.6, p=0.017) and a 2.5-fold increased risk of developing infection (CI 95 1.3-4.9, p=0.009) compared with hemispheric/bihemispheric cranioplasty. Our analysis confirms that cranioplasty is burdened by a significant complication rate. In this context, bifrontal cranioplasty is related to a higher risk of complication and, in particular, infection.
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Calcium influx into cells is responsible for initiating the cell death in neuronal tissue after hypoxic injury. Changes in intracellular calcium with subsequent increased expression of ryanodine receptor 2 (RyR2) are hypothesized to cause cell death after hypoxic injury. In the present study we have examined the time-dependent changes of RyR2 expression in hypoxic/reperfusion injury of spinal cord dorsal column. ⋯ In summary, we provide evidence that RyR2 gene and protein expression in astrocyte and axons is markedly increased after hypoxic injury. Further CaMKII/JNK pathway upregulates RyR2 expression after hypoxic injury. Therefore we propose that inhibitors of CaMKII/JNK pathway would reduce the cellular oxidative load and thereby have a neuroprotective role.
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Journal of neurotrauma · Apr 2012
Modulation of transcription factor Nrf2 in an in vitro model of traumatic brain injury.
Traumatic brain injury (TBI) afflicts approximately 1.4 million people in the United States and TBIs have been labeled a major cause of death and disability on a global scale. Regulatory responses in a variety of neuronal loss conditions have supported the protective involvement of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription factor. Nrf2 regulates antioxidant enzyme genes, and an increase in Nrf2 expression may counteract oxidative damage that results from TBI. ⋯ We confirmed that Trx and HSP70 were upregulated by treatment with tBHQ. We observed that tBHQ protected neurons from either insult, and that this was evident by different measures of cell viability and a decrease in annexin V binding. Neuronal health after insult was improved approximately 50% by tBHQ, indicating that neurons exposed to TBI in vitro can be protected.