Experimental neurology
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Experimental neurology · Nov 2010
Reactive astrocytosis, microgliosis and inflammation in rats with neonatal hydrocephalus.
The deleterious effects of hydrocephalus, a disorder that primarily affects children, include reactive astrocytosis, microgliosis and inflammatory responses; however, the roles that these mechanisms play in the pathophysiology of hydrocephalus are still not clear in terms of cytopathology and gene expression. Therefore we have examined neuroinflammation at both the cellular and the molecular levels in an experimental model of neonatal obstructive hydrocephalus. On post-natal day 1, rats received an intracisternal injection of kaolin to induce hydrocephalus; control animals received saline injections. ⋯ Microarray analysis identified significant (1.5-fold) changes in 1729 of 33,951 genes, including 26 genes out of 185 genes (26/185) in the cytokine-cytokine receptor interaction pathway, antigen processing and presentation pathways (15/66), and the apoptosis pathway (10/69). Collectively, these results demonstrate alterations in normal physiology and an up-regulation of the inflammatory response. These findings lead to a better understanding of neonatal hydrocephalus and begin to form a baseline for future treatments that may reverse these effects.
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Experimental neurology · Nov 2010
Phenotypes and peripheral mechanisms underlying inflammatory pain-related behaviors induced by BmK I, a modulator of sodium channels.
The integrated mechanisms of dynamic signaling of sodium channels involved in clinical pain are still not yet clear. In this study, a new rat inflammatory pain model was developed by using the unilateral intraplantar injection of BmK I, a receptor site 3-specific modulator of sodium channels from the venom of scorpion Buthus martensi Karsch (BmK). It was found that BmK I could induce several kinds of inflammatory pain-related behaviors including spontaneous pain companied with unique episodic paroxysms, primary thermal hypersensitivity, and mirror-image mechanical hypersensitivity with different time course of development, which could be suppressed by morphine, indomethacin, or bupivacaine to a different extent. ⋯ Furthermore, the electrophysiological recordings showed that BmK I persistently increased whole-cell and tetrodotoxin-resistant (TTX-R) peak sodium currents and significantly delayed the inactivation phase of whole-cell sodium currents but could not enhance capsaicin-evoked inward currents, in acute isolated small dorsal root ganglion neurons of rat. The results strongly suggested that the dynamic modulation of BmK I on sodium channels located in peripheral primary afferent neurons, especially in capsaicin-sensitive neurons, mediated pain sensation. Thus, BmK I may be a valuable pharmacological tool to understand the sodium channel-involved pain mechanisms.
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Experimental neurology · Nov 2010
A pyrazole curcumin derivative restores membrane homeostasis disrupted after brain trauma.
We have assessed potential mechanisms associated with the deleterious effects of TBI on the integrity of plasma membranes in the hippocampus, together with consequences for behavioral function. In addition, we have investigated the efficacy of a dietary intervention based on a pyrazole curcumin derivative with demonstrated bioactivity and brain absorption, to re-establish membrane integrity. We report that moderate fluid percussion injury (FPI) increases levels of 4-Hydroxynonenal (HNE), an intermediary for the harmful effects of lipid peroxidation on neurons. ⋯ In addition, changes in iPLA2, 4-HNE, and STX-3 were proportional to reduced performance in a spatial learning task. In turn, the dietary supplementation with the curcumin derivative counteracted all the effects of FPI, effectively restoring parameters of membrane homeostasis. Results show the potential of the curcumin derivative to promote membrane homeostasis following TBI, which may foster a new line of non-invasive therapeutic treatments for TBI patients by endogenous up-regulation of molecules important for neural repair and plasticity.
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Experimental neurology · Nov 2010
Experience-dependent reactivation of ocular dominance plasticity in the adult visual cortex.
A crucial issue in neurobiology is to understand the main mechanisms restricting neural plasticity to brief windows of early postnatal life. The visual system is one of the paradigmatic models for studying experience-dependent plasticity. The closure of one eye (monocular deprivation, MD) causes a marked ocular dominance (OD) shift of neurons in the primary visual cortex only during the critical period. ⋯ We also found that EE leads to a reduced intracortical GABAergic inhibition and an increased BDNF expression and that the modulation of these molecular factors is neutralized by cortical infusion of the 5-HT synthesis inhibitor pCPA. Our results show that EE rejuvenates the adult visual cortex and that 5-HT is a crucial factor in this process, triggering a cascade of molecular events that allow the reinstatement of neural plasticity. The non-invasive nature of EE makes this paradigm particularly eligible for clinical application.
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Experimental neurology · Oct 2010
Validity of acute and chronic tactile sensory testing after spinal cord injury in rats.
Spinal cord injury (SCI) impairs sensory systems causing allodynia. Measuring the development of allodynia in rodent models of SCI is challenging due to spinal shock and marked motor impairments. Assessment of SCI-induced allodynia is not standardized across labs, making interpretation of results difficult. ⋯ Acute dorsal VFH thresholds collected before recovery of hindlimb weight support accurately predicted plantar VFH thresholds measured at late timepoints (chi(2)=8.479; p<0.05). Thus, standardized testing early after SCI using the dorsal VFH test or later using 10 stimuli in the Up-Down test produces valid measures of tactile sensation across many SCI severities. Early detection of allodynia in experimental SCI will allow identification of mechanisms responsible for pain development and determine targets for therapeutic interventions.