Journal of neurotrauma
-
Journal of neurotrauma · Jun 2011
Activation of PI3 kinase/Akt signaling in chronic subdural hematoma outer membranes.
Chronic subdural hematoma (CSDH) is an angiogenic disease that is recognized as a cause of treatable dementia with unknown pathogenesis. Vascular endothelial growth factor (VEGF), a potent growth factor regulating angiogenesis through the phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway, has been implicated in its etiology. The status of this signaling pathway in CSDH outer membranes was examined in the present study, using outer membranes obtained during trepanation surgery. ⋯ PI3-kinase, Akt, eNOS, and VE-cadherin were detected in all cases. The magnitude of the expression of p-Akt varied among cases; however, the localization was revealed to be present in endothelial cells of vessels in CSDH outer membranes, together with VEGF and VE-cadherin detected in endothelial cells of vessels. These findings suggest that the PI3-kinase/Akt signaling is activated in CSDH outer membranes, and indicate the possibility that the PI3 kinase/Akt pathway might be activated by VEGF and play a critical role in the angiogenesis of CSDH.
-
Journal of neurotrauma · Jun 2011
Imipramine treatment improves cognitive outcome associated with enhanced hippocampal neurogenesis after traumatic brain injury in mice.
Previous animal and human studies have demonstrated that chronic treatment with several different antidepressants can stimulate neurogenesis, neural remodeling, and synaptic plasticity in the normal hippocampus. Imipramine is a commonly used tricyclic antidepressant (TCA). We employed a controlled cortical impact (CCI) mouse model of traumatic brain injury (TBI) to assess the effect of imipramine on neurogenesis and cognitive and motor function recovery after TBI. ⋯ Immunofluorescence double-labeling with BrdU and neuron-specific markers at 4 weeks after injury showed that most progenitors became neurons in the DG and astrocytes in the hilus. Notably, treatment with imipramine increased preservation of the total number of newly-generated neurons. Our findings provide direct evidence that imipramine treatment contributes to cognitive improvement after TBI, perhaps by enhanced hippocampal neurogenesis.
-
Journal of neurotrauma · Jun 2011
Time-dependent changes in serum biomarker levels after blast traumatic brain injury.
Neuronal and glial proteins detected in the peripheral circulating blood after injury can reflect the extent of the damage caused by blast traumatic brain injury (bTBI). The temporal pattern of their serum levels can further predict the severity and outcome of the injury. As part of characterizing a large-animal model of bTBI, we determined the changes in the serum levels of S100B, neuron-specific enolase (NSE), myelin basic protein (MBP), and neurofilament heavy chain (NF-H). ⋯ However, serum NF-H levels increased in a unique, rapid manner, peaking at 6 h post-injury only in animals exposed to severe blast with poor clinical and pathological outcomes. We conclude that the sudden increase in serum NF-H levels following bTBI may be a useful indicator of injury severity. If additional studies verify our findings, the observed early peak of serum NF-H levels can be developed into a useful diagnostic tool for predicting the extent of damage following bTBI.
-
Journal of neurotrauma · Jun 2011
Intermittent fasting in mice does not improve hindlimb motor performance after spinal cord injury.
Previously, we reported that every-other-day-fasting (EODF) in Sprague-Dawley rats initiated after cervical spinal cord injury (SCI) effectively promoted functional recovery, reduced lesion size, and enhanced sprouting of the corticospinal tract. More recently, we also showed improved behavioral recovery with EODF after a moderate thoracic contusion injury in rats. In order to make use of transgenic mouse models to study molecular mechanisms of EODF, we tested here whether this intermittent fasting regimen was also beneficial in mice after SCI. ⋯ EODF had no beneficial effect on tissue sparing and failed to improve behavioral recovery of hindlimb function. Hence this observation stands in stark contrast to our earlier observations in Sprague-Dawley rats. This is likely due to the difference in the metabolic response to intermittent fasting as evidenced by different ketone levels during the first week of the EODF regimen.
-
Journal of neurotrauma · Jun 2011
Long-term complications of decompressive craniectomy for head injury.
There is currently much interest in the use of decompressive craniectomy for intracranial hypertension. Though technically straightforward, the procedure is not without significant complications. A retrospective analysis was undertaken of 164 patients who had had a decompressive craniectomy for severe head injury in the years 2004 to 2009 at the two major hospitals in Western Australia. ⋯ Complications attributable to the subsequent cranioplasty included: sudden death due to massive cerebral swelling in 3 patients (2.2%), infection requiring removal of the bone flap in 16 patients (11.6%), and bone flap resorption requiring augmentation in 10 patients (7.2%). After excluding simple complications such as subdural effusion and brain herniation through the skull defect and some patients who died as a direct consequence of traumatic brain or extracranial injury, 81 patients (55.5%) had at least one complication after decompressive craniectomy. The occurrence of at least one complication after decompressive craniectomy was significantly associated with an increased risk of prolonged stay in the hospital or rehabilitation facility (odds ratio 2.54, 95%confidence interval 1.22,5.24, p=0.013), after adjusting for predicted risk of unfavorable outcome.