Experimental neurology
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Experimental neurology · May 2012
ReviewCortical and subcortical compensatory mechanisms after spinal cord injury in monkeys.
This is a review of our investigations into the neuronal mechanisms of functional recovery after spinal cord injury (SCI) in a non-human primate model. In primates, the lateral corticospinal tract (l-CST) makes monosynaptic connections with spinal motoneurons. The existence of direct cortico-motoneuronal (CM) connections has been thought to be the basis of dexterous digit movements, such as precision gripping. ⋯ Such changes in cortical activity in M1 and PMv have been shown to accompany changes in the expressions of plasticity-related genes, such as GAP-43. Changes in the dynamic properties of neural circuits, both at the cortical and subcortical levels, are time-dependent. Multidisciplinary studies to clarify how the changes in the dynamic properties of individual components of the large-scaled networks are coordinated during recovery will help to develop effective therapeutic strategies to recovery from SCI.
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Experimental neurology · May 2012
ReviewTraining and anti-CSPG combination therapy for spinal cord injury.
Combining different therapies is a promising strategy to promote spinal cord repair, by targeting axon plasticity and functional circuit reconnectivity. In particular, digestion of chondroitin sulphate proteoglycans at the site of the injury by the activity of the bacterial enzyme chondrotinase ABC, together with the development of intensive task specific motor rehabilitation has shown synergistic effects to promote behavioural recovery. This review describes the mechanisms by which chondroitinase ABC and motor rehabilitation promote neural plasticity and we discuss their additive and independent effects on promoting behavioural recovery.
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Experimental neurology · Apr 2012
ReviewImmune responses of microglia in the spinal cord: contribution to pain states.
The role of microglia and their contribution to the development and maintenance of pain states has emerged as an attractive field of study. Sensitization of central nociceptors and interneurons is thought to be responsible for the symptoms of chronic neuropathic pain states. Microglia interact with these neurons at the site of injury or disease as well as remotely. ⋯ Activated microglia also exhibit a modulated cell surface receptor and ion channel profile. The activation of several intracellular pathways in microglia has also been implicated in pain states. Attenuation of microglia activity is being presented as a viable therapeutic approach with regard to not only the reduction of pain symptoms but also in preventing the development of chronic pain states.
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Experimental neurology · Apr 2012
Peri-sciatic administration of recombinant rat IL-1β induces mechanical allodynia by activation of src-family kinases in spinal microglia in rats.
Previous studies have shown that Interleukin-1 beta (IL-1β) is implicated in the modulation of pain sensitivity. In the present study, we found that a single peri-sciatic administration of rat recombinant IL-1β (rrIL-1β) at doses of 20 and 200 pg (100, 1000 ng/l, in 200 μl volume) induced mechanical allodynia in bilateral hindpaws in rats, lasting for about 50 days. No axonal or Schwann cell damage at the drug administration site was found following 1000 ng/l rrIL-1β administration. ⋯ Intrathecal delivery of minocycline (100 μg in 10 μl volume), a selective inhibitor of microglia, started 30 min before rrIL-1β administration and once daily thereafter for 7 days, blocked mechanical allodynia induced by rrIL-1β completely and inhibited the upregulation of p-SFKs. Intrathecal delivery of SFKs inhibitor PP2 (12 μg in 10 μl volume) also blocked mechanical allodynia induced by rrIL-1β completely. These data suggest that activation of SFKs in spinal microglia mediates mechanical allodynia induced by peri-sciatic administration of rrIL-1β.
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Experimental neurology · Apr 2012
ReviewSpatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats.
In the spinal cord, neuron and glial cells actively interact and contribute to neurofunction. Surprisingly, both cell types have similar receptors, transporters and ion channels and also produce similar neurotransmitters and cytokines. The neuroanatomical and neurochemical similarities work synergistically to maintain physiological homeostasis in the normal spinal cord. ⋯ In this review, we describe time and regional dependence of glial activation and describe activation mechanisms in various SCI models in rats. These data are placed in the broader context of glial activation mechanisms and chronic pain states. Our work in the context of work by others in SCI models demonstrates that dysfunctional glia, a condition called "gliopathy", is a key contributor in the underlying cellular mechanisms contributing to neuropathic pain.