Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Apr 2008
Endogenous melatonin increases in cerebrospinal fluid of patients after severe traumatic brain injury and correlates with oxidative stress and metabolic disarray.
Oxidative stress plays a significant role in secondary damage after severe traumatic brain injury (TBI); and melatonin exhibits both direct and indirect antioxidant effects. Melatonin deficiency is deleterious in TBI animal models, and its administration confers neuroprotection, reducing cerebral oedema, and improving neurobehavioural outcome. This study aimed to measure the endogenous cerebrospinal fluid (CSF) and serum melatonin levels post-TBI in humans and to identify relationships with markers of oxidative stress via 8-isoprostaglandin-F2alpha (isoprostane), brain metabolism and neurologic outcome. ⋯ Relationships between CSF melatonin and pyruvate (r=0.369, P=0.049) and glutamate (r=0.373, P=0.046) indicate that melatonin production increases with metabolic disarray. In conclusion, endogenous CSF melatonin levels increase after TBI, whereas serum levels do not. This elevation is likely to represent a response to oxidative stress and metabolic disarray, although further studies are required to elucidate these relationships.
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J. Cereb. Blood Flow Metab. · Apr 2008
Manganese-enhanced MRI of brain plasticity in relation to functional recovery after experimental stroke.
Restoration of function after stroke may be associated with structural remodeling of neuronal connections outside the infarcted area. However, the spatiotemporal profile of poststroke alterations in neuroanatomical connectivity in relation to functional recovery is still largely unknown. We performed in vivo magnetic resonance imaging (MRI)-based neuronal tract tracing with manganese in combination with immunohistochemical detection of the neuronal tracer wheat-germ agglutinin horseradish peroxidase (WGA-HRP), to assess changes in intra- and interhemispheric sensorimotor network connections from 2 to 10 weeks after unilateral stroke in rats. ⋯ Behaviorally, sensorimotor functions were initially disturbed but subsequently recovered and plateaued 17 days after stroke. This study shows that manganese-enhanced MRI can provide unique in vivo information on the spatiotemporal pattern of neuroanatomical plasticity after stroke. Our data suggest that the plateau stage of functional recovery is associated with restoration of ipsilateral sensorimotor pathways and enhanced interhemispheric connectivity.
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Autophagy is the chief machinery for bulk degradation of superfluous or aberrant cytoplasmic components. This study used the rat moderate fluid percussion injury model to investigate whether the autophagy pathway plays a key role after traumatic brain injury (TBI). Induction of autophagy is manifested by accumulation of autophagosomes (APs), observable under transmission electron microscopy (EM). ⋯ LC-3 immunostaining was mainly located in living neurons under confocal microscopy. These results clearly show that the autophagy pathway is persistently activated after TBI. Because the autophagy pathway is the chief machinery for bulk elimination of aberrant cell components, we propose that activation of this pathway serves as a protective mechanism for maintaining cellular homeostasis after TBI.
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J. Cereb. Blood Flow Metab. · Apr 2008
MRI of monocyte infiltration in an animal model of neuroinflammation using SPIO-labeled monocytes or free USPIO.
Magnetic resonance imaging (MRI) has been applied to visualize monocyte infiltration with the use of intravenously injected ultrasmall superparamagnetic iron oxide (USPIO). However, USPIO uptake in vivo remains elusive, and the heterogeneous enhancement patterns observed by MRI point to multiple pathophysiological events. This study focused on specific imaging of monocyte infiltration into the brain by transfusion of superparamagnetic iron oxide (SPIO)-labeled monocytes in a rat model of neuroinflammation, experimentally induced photothrombosis (PT). ⋯ Our study shows that MRI enables in vivo tracking of SPIO-labeled monocytes longitudinally. Moreover, our data suggest that contrast enhancement after injection of free USPIO does not primarily represent signals from peripherally labeled monocytes that migrated toward the inflammatory lesion. The use of SPIO-labeled monocytes provides a better tool to specifically assess the time window of monocyte infiltration.
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J. Cereb. Blood Flow Metab. · Feb 2008
Increases in cerebrospinal fluid caffeine concentration are associated with favorable outcome after severe traumatic brain injury in humans.
Caffeine, the most widely consumed psychoactive drug and a weak adenosine receptor antagonist, can be neuroprotective or neurotoxic depending on the experimental model or neurologic disorder. However, its contribution to pathophysiology and outcome in traumatic brain injury (TBI) in humans is undefined. We assessed serial cerebrospinal fluid (CSF) concentrations of caffeine and its metabolites (theobromine, paraxanthine, and theophylline) by high-pressure liquid chromatography/ultraviolet in 97 ventricular CSF samples from an established bank, from 30 adults with severe TBI. ⋯ Increases in CSF concentrations of the caffeine metabolites theobromine and paraxanthine were also associated with favorable outcome (P=0.018 and 0.056, respectively). Caffeine and its metabolites are commonly detected in CSF in patients with severe TBI and in an exploratory assessment are associated with favorable outcome. We speculate that caffeine may be neuroprotective by long-term upregulation of adenosine A1 receptors or acute inhibition of A2a receptors.