Experimental neurology
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Experimental neurology · Mar 2005
Comparative StudyElevation of hippocampal MMP-3 expression and activity during trauma-induced synaptogenesis.
The matrix metalloproteinase (MMP) enzyme family contributes to the regulation of a variety of brain extracellular matrix molecules. In order to assess their role in synaptic plasticity following traumatic brain injury (TBI), we compared expression of stromelysin-1 (MMP-3) protein and mRNA in two rodent models of TBI exhibiting different levels of recovery: adaptive synaptic plasticity following central fluid percussion injury and maladaptive synaptic plasticity generated by combined TBI and bilateral entorhinal cortical lesion (TBI + BEC). We sampled the hippocampus at 7 days postinjury, targeting a selectively vulnerable brain region and a survival interval exhibiting rapid synaptogenesis. ⋯ In the TBI + BEC model, MMP-3 up-regulation was spatio-temporally correlated with increased enzyme activity, an effect which was attenuated with the neuroprotective compound MK-801. These results show that distinct pathological conditions elicited by TBI can differentially affect MMP-3 expression during reactive synaptic plasticity. Notably, these effects are both transcriptional and translational and are correlated with functionally active enzyme.
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Experimental neurology · Mar 2005
A novel therapeutic derived from apolipoprotein E reduces brain inflammation and improves outcome after closed head injury.
Although apolipoprotein E4 (APOE4) was initially identified as a susceptibility gene for the development of Alzheimer's disease, the presence of the APOE4 allele is also associated with poor outcome after acute brain injury. One mechanism by which apoE may influence neurological outcome is by downregulating the neuroinflammatory response. ⋯ We demonstrate that a single intravenous injection of a small peptide derived from the apoE receptor binding region crosses the blood-brain barrier and significantly improves histological and functional outcomes after traumatic brain injury (TBI). The development of an apoE-based intervention represents a novel therapeutic strategy in the management of acute brain injury.
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Experimental neurology · Mar 2005
Effects of synchronous or asynchronous electroacupuncture stimulation with low versus high frequency on spinal opioid release and tail flick nociception.
Electroacupuncture stimulation (EAS) is known to change brain neurotransmitter release. In the present study, we investigated the effects of synchronous or asynchronous electroacupuncture stimulation with low versus high frequency on spinal opioid release and tail flick nociception. ⋯ Results were as follows: (1) 2/100 Hz EAS was 40% more potent than (2 + 100) Hz EAS (P < 0.01) in producing an anti-nociceptive effect. (2) Intrathecal (i.t.) injection of the mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP) blocked in a dose-dependent manner the anti-nociceptive effect produced by 2/100 Hz EAS but not by (2 + 100) Hz EAS, whereas i.t. injection of the kappa-opioid receptor antagonist norbinaltorphimide (Nor-BNI) blocked the anti-nociceptive effect induced by both modes of EAS. (3) I.t. injection of endomorphin-2 antiserum blocked in a dose-dependent manner the anti-nociceptive effect of 2/100 Hz EAS but not that of (2 + 100) Hz EAS, whereas i.t. injection of dynorphin antiserum blocked the anti-nociceptive effect induced by both modes of stimulation. (4) 2/100 Hz EAS increased the release of both endomorphin-2 and dynorphin, whereas (2 + 100) Hz EAS increased the release of dynorphin but not of endmorphin-2. We conclude that the more potent anti-nociceptive effect induced by 2/100 Hz EAS, as compared with that of (2 + 100) Hz EAS, was due, at least partly, to the synergistic interaction of endomorphin-2 and dynorphin in rat spinal cord.
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Experimental neurology · Mar 2005
Fibroblast growth factor 2 induces loss of adult oligodendrocytes and myelin in vivo.
Oligodendrocytes are the myelin-forming cells of the CNS and are lost in demyelinating diseases such as multiple sclerosis (MS). A role for fibroblast growth factor 2 (FGF2) has been proposed in the pathogenesis of demyelination and the failure of remyelination in experimental models of MS. However, the in vivo effects of FGF2 on oligodendrocytes and oligodendrocyte progenitors (OPCs) in the adult CNS had not previously been determined. ⋯ At the same time, FGF2 treatment resulted in the aberrant accumulation of immature oligodendrocytes with a premyelinating phenotype, together with NG2-expressing OPCs. Axons are patent within demyelinated lesions, and they are contacted but not ensheathed by surviving oligodendrocytes, newly formed premyelinating oligodendrocytes and OPCs. These results demonstrate that raised FGF2 induces demyelination in the adult CNS, and support a role for FGF2 in the pathogenesis of demyelination and regulation of remyelination in MS.
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Experimental neurology · Mar 2005
Changes in pituitary adenylate cyclase activating polypeptide expression in urinary bladder pathways after spinal cord injury.
These studies examined changes in the pituitary adenylate cyclase activating polypeptide (PACAP) expression in micturition reflex pathways after spinal cord injury (SCI) of various durations. In spinal-intact animals, PACAP immunoreactivity (IR) was expressed in fibers in the superficial dorsal horn in all segmental levels examined (L1, L2, L4-S1). Bladder-afferent cells (35-45%) in the dorsal root ganglia (DRG; L1, L2, L6, S1) from spinal-intact animals also exhibited PACAP-IR. ⋯ No changes were observed in the L4-L5 DRG. PACAP-IR was reduced throughout the urothelium and detrusor smooth muscle whole mounts after SCI. These studies demonstrate changes in PACAP expression in micturition reflex pathways after SCI that may contribute to urinary bladder dysfunction or reemergence of primitive voiding reflexes after SCI.