Experimental neurology
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Experimental neurology · Oct 2013
Endogenous descending facilitation and inhibition differ in control of formalin intramuscularly induced persistent muscle nociception.
In conscious rats, intramuscular injection of 2.5% formalin into the gastrocnemius muscle, at volumes between 25 and 200 μl, evoked dose-dependent biphasic persistent flinching activities: phase 1 (0-10 min) and phase 2 (10-60 min). During this intramuscular formalin-induced ipsilateral muscle nociception, bilateral secondary mechanical hyperalgesia and heat hypoalgesia assessed by measuring thresholds of paw withdrawal reflex to noxious mechanical and heat stimuli were observed (P<0.05). Lesion of either the ipsilateral dorsal funiculus (DF) or contralateral thalamic mediodorsal (MD) nucleus significantly alleviated the formalin-induced flinches in both phase 1 and phase 2 of the behavioral response, and blocked the occurrence of secondary mechanical hyperalgesia, but not heat hypoalgesia. ⋯ By contrast, microinjection of GABA into the thalamic VM nucleus significantly enhanced the formalin-induced nociceptive behavior in the late part (30-60 min) of phase 2, and the bilateral secondary heat hypoalgesia was temporarily prevented (P<0.05). The present study demonstrates that intramuscular formalin evokes biphasic muscle nociception, and that bilateral secondary mechanical hyperalgesia and heat hypoalgesia are differentially controlled by endogenous descending facilitation and inhibition respectively. It is further suggested that thalamic MD nucleus and VM nucleus constitute an endogenous discriminative, modulatory system that exerts, via pathways in the DF and DLF, descending facilitatory and inhibitory actions on responses to peripheral afferent activity evoked by noxious mechanical and heat stimulation.
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Experimental neurology · Oct 2013
Caffeine and modafinil promote adult neuronal cell proliferation during 48 h of total sleep deprivation in rat dentate gyrus.
It has been established that sleep deprivation (SD) reduces the proliferation of neuronal precursors in the adult hippocampus. It has also been reported that psychostimulant drugs modulate adult neurogenesis. We examined the modulatory role of two psychostimulant drugs modafinil and caffeine on adult neuronal cell proliferation (NCP) during 48 h of total SD. ⋯ Modafinil, but not caffeine, significantly decreased hippocampal adenosine level during SD in comparison to the SD+Vehicle group. It may be concluded that caffeine or modafinil treatment during 48 h of SD prevents the SD induced decline in neuronal proliferation and differentiation. Caffeine and modafinil induced alterations of NCP during SD may involve modulation of BDNF and adenosine levels.
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Experimental neurology · Oct 2013
Modeling clinically relevant blast parameters based on scaling principles produces functional & histological deficits in rats.
Blast-induced traumatic brain injury represents a leading cause of injury in modern warfare with injury pathogenesis poorly understood. Preclinical models of blast injury remain poorly standardized across laboratories and the clinical relevance unclear based upon pulmonary injury scaling laws. Models capable of high peak overpressures and of short duration may better replicate clinical exposure when scaling principles are considered. ⋯ Furthermore, hematoxylin and eosin staining showed the presence of red blood cells within the parenchyma and red, swollen neurons following blast injury. Exposure to blast with 90.10 PSI peak reflected overpressure resulted in immediate mortality associated with extensive intracranial bleeding. This work demonstrates one of the first examples of blast-induced brain injury in the rodent when exposed to a blast wave scaled from human exposure based on scaling principles derived from pulmonary injury lethality curves.
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Experimental neurology · Oct 2013
The trade-off between wiring cost and network topology in white matter structural networks in health and migraine.
The human brain organization of cortical networks has optimized trade-off architecture for the economical minimization of connection distance and maximizing valuable topological properties; however, whether this network configuration is disrupted in chronic migraine remains unknown. Here, employing the diffusion tensor imaging and graph theory approaches to construct white matter networks in 26 patients with migraine (PM) and 26 gender-matched healthy controls (HC), we investigated relationships between structural connectivity, cortical network architecture and anatomical distance in the two groups separately. Compared with the HC group, the patients showed longer global distance connection in PM, with proportionally less short-distance and more medium-distance; correspondingly, the patients showed abnormal global topology in their structural networks, mainly presented as a higher clustering coefficient. ⋯ Intriguingly, the network measure that combined the nodal anatomical distance and network topology could distinguish PM from HC with high accuracy of 90.4%. We also demonstrated a high reproducibility of our findings across different parcellation schemes. Our results demonstrated that long-term migraine may result in a abnormal optimization of a trade-off between wiring cost and network topology in white matter structural networks and highlights the potential for combining spatial and topological aspects as a network marker, which may provide valuable insights into the understanding of brain network reorganization that could be attributed to the underlying pathophysiology resulting from migraine.
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Experimental neurology · Oct 2013
A non-cholinergic neuronal loss in the pedunculopontine nucleus of toxin-evoked parkinsonian rats.
The pedunculopontine nucleus (PPN) controls various physiological functions, whilst being deemed a suitable target for low-frequency stimulation therapy for alleviating aspects of Parkinson's disease (PD). Previous studies showed that the PPN contains mainly cholinergic, γ-aminobutyric acid (GABA)ergic and glutamatergic neurons. Here we report on the total number of PPN neurons in laboratory rats, a species frequently used as an experimental model for simulating aspects of human PD. ⋯ Our data also show a significant loss which affected PPN non-cholinergic cells, but not cholinergic ones in rats lesioned unilaterally in the Substantia Nigra pars compacta (SNpc) with a single injection of 6-hydroxydopamine (6-OHDA) compared to control animals. This result differs from previous studies which reported a substantial cholinergic cell loss in the PPN of post-mortem PD brains and in 6-OHDA-lesioned monkeys. Since a noted demise of dopaminergic neurons residing in the SN was confirmed in the 6-OHDA-lesioned rats, the current study suggests that a "dying-back" mechanism may underlie the cell death affecting non-cholinergic PPN neurons.