Experimental neurology
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Experimental neurology · Dec 2013
Juvenile traumatic brain injury evolves into a chronic brain disorder: behavioral and histological changes over 6months.
Traumatic brain injury (TBI) refers to physical trauma to the brain that can lead to motor and cognitive dysfunctions. TBI is particularly serious in infants and young children, often leading to long-term functional impairments. Although clinical research is useful for quantifying and observing the effects of these injuries, few studies have empirically assessed the long-term effects of juvenile TBI (jTBI) on behavior and histology. ⋯ Magnetic resonance imaging and histological data revealed that the effects of jTBI were evolving for up to 6months post-injury, with reduced cortical thickness, decreased corpus callosum area and CA1 neuronal cell death in jTBI animals distant to the impact site. These findings suggest that this model of jTBI produces long-term impairments comparable to those reported clinically. Although some deficits were stable over time, the variable nature of other deficits (e.g., memory) as well as changing properties of the lesion itself, suggest that the effects of a single jTBI produce a chronic brain disorder with long-term complications.
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Experimental neurology · Dec 2013
Brain inflammation induces post-synaptic changes during early synapse formation in adult-born hippocampal neurons.
An inflammatory reaction in the brain is primarily characterized by activation of parenchymal microglial cells. Microglia regulate several aspects of adult neurogenesis, i.e. the continuous production of new neurons in the adult brain. Hippocampal neurogenesis is thought to be important for memory formation, but its role in brain diseases is not clear. ⋯ The expression of interleukin-1-type 1 receptor (IL-1R1) on preferentially the somatic region of new neurons, often in close apposition to NL-2 clusters, may indicate a direct interaction between brain inflammation and synaptic proteins on newborn neurons. In summary, this study provides evidence that adult-born hippocampal neurons alter their inhibitory and excitatory synaptic integration when encountering an LPS-induced brain inflammation during the initial stages of synapse formation. Changes at this critical developmental period are likely to interfere with the physiological functions of new neurons within the hippocampus.
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Experimental neurology · Dec 2013
Dynamic genotype-selective "phenotypic switching" of CGRP expression contributes to differential neuropathic pain phenotype.
Using a genetic model we demonstrate the role played by "phenotypic switching" of calcitonin gene related peptide (CGRP) expression in axotomized large Aβ afferents in the development of neuropathic pain behavior in rats. After nerve injury both substance P and CGRP are upregulated in Aβ afferents in the corresponding DRGs. It has been proposed that intraspinal release of these neurotransmitters upon gentle stroking of skin drives ascending pain signaling pathways resulting in tactile allodynia. ⋯ Here we confirm this conclusion by showing: 1) that the time of emergence of CGRP-IR in DRG Aβ neurons and their central terminals in HA rats matches that of pain behavior, 2) that following spinal nerve lesion (SNL) selective activation of low threshold afferents indeed drives postsynaptic pain-signaling neurons and induces central sensitization in HA rats, as monitored using c-Fos as a marker. These changes are much less prominent in LA rats, 3) that intrathecal (i.t.) administration of CGRP induces tactile allodynia in naïve rats and 4) that i.t. administration of the CGRP-receptor antagonist BIBN4096BS (Olcegepant) attenuates SNL-evoked tactile allodynia, without blocking baseline nociception. Together, these observations support the hypothesis that genotype-selective phenotypic switching of CGRP expression in Aβ afferents following nerve injury is a fundamental mechanism of neuropathic tactile allodynia.
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Experimental neurology · Dec 2013
Increased autophagy in peripheral nerves may protect Wistar Ottawa Karlsburg W rats against neuropathy.
Wistar Ottawa Karlsburg W (RT1(u)) rats (WOKW) develop obesity, dyslipidemia, moderate hypertension, hyperinsulinemia and impaired glucose tolerance prone to induce peripheral neuropathy (PN). Autophagy has been shown to prevent neurodegeneration in the central and peripheral nervous system. We analyzed the potential protective role of autophagy in an established rat model in preventing PN. ⋯ Our results indicate that WOKW rats show an up-regulated autophagy and a mild inflammatory response but do not develop overt neuropathy. We suggest that autophagy and inflammatory cells may exert a protective role in preventing neuropathy in this rat model of the metabolic syndrome but the mechanism of action is still unclear.
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Experimental neurology · Nov 2013
Randomized Controlled TrialAntidepressant effects after short-term and chronic stimulation of the subgenual cingulate gyrus in treatment-resistant depression.
Deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) is an experimental approach in treatment-resistant depression (TRD). Apart from its potential long-term antidepressant effects acute stimulation effects have been described. We investigated putative neuroanatomical clusters in which such acute effects accumulate and followed patients over the long-term. ⋯ Our results confirm that stimulation of the SCG is capable of exerting moderate acute and chronic antidepressant effects. The predictive value of these findings needs to be addressed in future studies.