Experimental neurology
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Experimental neurology · Jan 2009
Immediate short-duration hypothermia provides long-term protection in an in vivo model of traumatic axonal injury.
A prospective, multicenter, randomized trial did not demonstrate improved outcomes in severe traumatic brain injured patients treated with mild hypothermia [Clifton, G. L., Miller, E. R., Choi, S. ⋯ Immediate post-injury hypothermia (32 degrees C) for 3 h reduced axonal degeneration in the core (p=0.027). There was no differential protection based on axon size. These results support further clinical investigation of temporally optimized therapeutic hypothermia after traumatic brain injury.
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Experimental neurology · Jan 2009
Cilostazol preserves CA1 hippocampus and enhances generation of immature neuroblasts in dentate gyrus after transient forebrain ischemia in rats.
In the present study, cerebral ischemia was induced by a 10 min transient bilateral common carotid artery occlusion in rats combined with arterial blood pressure lowering to 37-42 mm Hg during occlusion. When histologically evaluated at 7 and 28 days after the forebrain ischemia (DAI) by staining with cresyl violet and Fluoro-Jade, the hippocampal CA1 region was most prominently damaged. At 7 DAI, treatment with cilostazol (60 mg/kg/day, orally) significantly reduced the neuronal damage in the CA1 region. ⋯ To elucidate whether cilostazol enhances hippocampal neurogenesis after ischemia, we planned a co-labeling study using 5-bromo-2'-deoxyuridine (BrdU), NeuN (a marker for mature neurons) and doublecortin (DCX) (a marker for immature migratory neuroblasts). Double immunofluorescence staining at 7 DAI showed that cilostazol significantly increased the immunoreactivities of both DCX and phosphorylated cAMP-response element-binding protein (CREB) in the dentate gyrus that was co-expressed with BrdU. These results suggest that cilostazol has dual beneficial effects preserving the CA1 hippocampal region and promoting the generation of immature migratory neuroblasts in the dentate gyrus by upregulation of CREB phosphorylation after transient forebrain ischemia.
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Experimental neurology · Jan 2009
Clinical TrialThe STN beta-band profile in Parkinson's disease is stationary and shows prolonged attenuation after deep brain stimulation.
Producing accurate movements may rely on the functional independence of sensorimotor circuits within basal ganglia nuclei. In parkinsonism there is abnormal synchrony of electrical activity within these circuits that results in a loss of independence across motor channels. Local field potential (LFP) recordings reflect the summation of local electrical fields and an increase in LFP power reflects increased synchrony in local neuronal networks. ⋯ Beta-band power was attenuated after intra-operative STN DBS (p<0.05). The attenuation lasted for 10 s after short periods (30 s) and for up to 50 s after longer periods (5 min) of DBS. The finding that longer periods of DBS attenuated beta power for a longer time suggests that there may be long-acting functional changes to networks in the STN in PD after chronic DBS.
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Experimental neurology · Jan 2009
Distinct MRI pattern in lesional and perilesional area after traumatic brain injury in rat--11 months follow-up.
To understand the dynamics of progressive brain damage after lateral fluid-percussion induced traumatic brain injury (TBI) in rat, which is the most widely used animal model of closed head TBI in humans, MRI follow-up of 11 months was performed. The evolution of tissue damage was quantified using MRI contrast parameters T(2), T(1rho), diffusion (D(av)), and tissue atrophy in the focal cortical lesion and adjacent areas: the perifocal and contralateral cortex, and the ipsilateral and contralateral hippocampus. In the primary cortical lesion area, which undergoes remarkable irreversible pathologic changes, MRI alterations start at 3 h post-injury and continue to progress for up to 6 months. ⋯ Our data show that TBI induced by lateral fluid-percussion injury triggers long-lasting alterations with region-dependent temporal profiles. Importantly, the temporal pattern in MRI parameters during the first 23 d post-injury can indicate the regions that will develop secondary damage. This information is valuable for targeting and timing interventions in studies aiming at alleviating or reversing the molecular and/or cellular cascades causing the delayed injury.
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Experimental neurology · Jan 2009
Impaired dendritic development and synaptic formation of postnatal-born dentate gyrus granular neurons in the absence of brain-derived neurotrophic factor signaling.
Neurons are continuously added to the hippocampal dentate gyrus throughout life. These neurons must develop dendritic arbors and spines by which they form synapses for making functional connections with existing neurons. The molecular mechanisms that regulate dendritic development and synaptic formation of postnatal-born granular neurons in the dentate gyrus are largely unknown. ⋯ Even though, these BDNF-deficient granular neurons develop immature dendritic spines to initiate synaptic contacts with afferent axons, they fail to develop or maintain mature spine structures. Thus, these postnatal-born neurons have fewer numbers of synapses, particularly mature synaptic spines. These results suggest that BDNF plays an important role during dendritic development, synaptic formation and synaptic maturation in postnatal-born granular neurons of the HDG in vivo.