Neuroscience
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Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. ⋯ The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization.
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The adult brain retains a considerable capacity to functionally reorganize its circuits, which mainly relies on the prevalence of three basic processes that confer plastic potential: synaptic plasticity, plastic changes in intrinsic excitability and, in certain central nervous system (CNS) regions, also neurogenesis. Experimental models of peripheral nerve injury have provided a useful paradigm for studying injury-induced mechanisms of central plasticity. In particular, axotomy of somatic motoneurons triggers a robust retrograde reaction in the CNS, characterized by the expression of plastic changes affecting motoneurons, their synaptic inputs and surrounding glia. ⋯ Our group has identified the highly reactive gas nitric oxide (NO) as one of these signals, by providing robust evidence for its key role to induce synapse elimination and increases in intrinsic excitability following motor axon damage. We have elucidated operational principles of the NO-triggered downstream transduction pathways mediating each of these changes. Our findings further demonstrate that de novo NO synthesis is not only "necessary" but also "sufficient" to promote the expression of at least some of the features that reflect reversion toward a dedifferentiated state in axotomized adult motoneurons.
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A primary goal of research on developmental critical periods (CPs) is the recapitulation of a juvenile-like state of malleability in the adult brain that might enable recovery from injury. These ambitions are often framed in terms of the simple reinstatement of enhanced plasticity in the growth-restricted milieu of an injured adult brain. Here, we provide an analysis of the similarities and differences between deprivation-induced and injury-induced cortical plasticity, to provide for a nuanced comparison of these remarkably similar processes. ⋯ This biphasic response profile emphasizes the transition from a period of cortical healing to one of reconnection and recovery of function. Yet while injury-induced plasticity in adult shares several salient characteristics with deprivation-induced plasticity during the CP, the degree to which the adult injured brain is able to functionally rewire, and the time required to do so, present major limitations for recovery. Attempts to recapitulate a measure of CP plasticity in an adult injury context will need to carefully dissect the circuit alterations and plasticity mechanisms involved while measuring functional behavioral output to assess their ultimate success.
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The gate control theory proposed that the nociceptive sensory information transmitted to the brain relies on an interplay between the inputs from nociceptive and non-nociceptive primary afferent fibers. Both inputs are normally under strong inhibitory control in the spinal cord. ⋯ However, under pathological conditions, this spinal inhibition may be altered and lead to chronic pain. This review summarizes our knowledge of presynaptic inhibition in pain control, with particular focus on how its alteration after nerve or tissue injury contributes to neuropathic or inflammatory pain syndromes, respectively.
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One of the most striking demonstrations of experience-dependent plasticity comes from studies of sensory-deprived individuals (e.g., blind or deaf), showing that brain regions deprived of their natural inputs change their sensory tuning to support the processing of inputs coming from the spared senses. These mechanisms of crossmodal plasticity have been traditionally conceptualized as having a double-edged sword effect on behavior. On one side, crossmodal plasticity is conceived as adaptive for the development of enhanced behavioral skills in the remaining senses of early-deaf or blind individuals. ⋯ In the present review we stress that this dichotomic vision is oversimplified and we emphasize that the notions of the unavoidable adaptive/maladaptive effects of crossmodal reorganization for sensory compensation/restoration may actually be misleading. For this purpose we critically review the findings from the blind and deaf literatures, highlighting the complementary nature of these two fields of research. The integrated framework we propose here has the potential to impact on the way rehabilitation programs for sensory recovery are carried out, with the promising prospect of eventually improving their final outcomes.