Frontiers in physiology
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Frontiers in physiology · Jan 2012
Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury.
Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI). Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. A mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. ⋯ Prior work from our group has shown that stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after SCI. We review these basic phenomena, how these findings relate to the broader spinal plasticity literature, discuss the cellular and molecular mechanisms, and finally discuss implications of these and other findings for improved rehabilitative therapies after SCI.
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Frontiers in physiology · Jan 2012
Altered patterns of reflex excitability, balance, and locomotion following spinal cord injury and locomotor training.
Spasticity is an important problem that complicates daily living in many individuals with spinal cord injury (SCI). While previous studies in human and animals revealed significant improvements in locomotor ability with treadmill locomotor training, it is not known to what extent locomotor training influences spasticity. In addition, it would be of considerable practical interest to know how the more ergonomically feasible cycle training compares with treadmill training as therapy to manage SCI-induced spasticity and to improve locomotor function. ⋯ Both locomotor trained groups revealed decreased lesion volume (rostro-caudal extension) and more spared tissue at the lesion site. These improvements were accompanied by marked upregulation of BDNF, GABA/GABA(b), and monoamines (e.g., norepinephrine and serotonin) which might account for these improved functions. These data are the first to indicate that the therapeutic efficacy of ergonomically practical cycle training is equal to that of the more labor-intensive treadmill training in reducing spasticity and improving locomotion following SCI in an animal model.
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Frontiers in physiology · Jan 2012
Sympathetic responses to central hypovolemia: new insights from microneurographic recordings.
Hemorrhage remains a major cause of mortality following traumatic injury in both military and civilian settings. Lower body negative pressure (LBNP) has been used as an experimental model to study the compensatory phase of hemorrhage in conscious humans, as it elicits central hypovolemia like that induced by hemorrhage. ⋯ The purpose of this review is to describe recent results obtained using microneurography in our laboratory as well as those of others that have revealed new insights into mechanisms underlying compensatory increases in MSNA during progressive reductions in central blood volume and how MSNA is altered at the point of hemodynamic decompensation. We will also review recent work that has compared direct MSNA recordings with non-invasive surrogates of MSNA to determine the appropriateness of using such surrogates in assessing the clinical status of hemorrhaging patients.
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Remote ischemic conditioning (RIC) is a therapeutic strategy for protecting organs or tissue against the detrimental effects of acute ischemia-reperfusion injury (IRI). It describes an endogenous phenomenon in which the application of one or more brief cycles of non-lethal ischemia and reperfusion to an organ or tissue protects a remote organ or tissue from a sustained episode of lethal IRI. ⋯ The recent discovery that RIC can be induced non-invasively by simply inflating and deflating a standard blood pressure cuff placed on the upper arm or leg, has facilitated its translation into the clinical setting, where it has been reported to be beneficial in a variety of cardiac scenarios. In this review article we provide an overview of RIC, the potential underlying mechanisms, and its potential as a novel therapeutic strategy for protecting the heart and other organs from acute IRI.
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Frontiers in physiology · Jan 2012
Hepatoprotectant ursodeoxycholyl lysophosphatidylethanolamide increasing phosphatidylcholine levels as a potential therapy of acute liver injury.
It has been long known that hepatic synthesis of phosphatidylcholine (PC) is depressed during acute such as carbon tetrachloride-induced liver injury. Anti-hepatotoxic properties of PC as liposomes have been recognized for treatment of acute liver damage. Ursodeoxycholate (UDCA) is a known hepatoprotectant in stabilizing cellular membrane. ⋯ Among PC synthesis genes tested, UDCA-LPE treatment of mouse hepatocytes increased transcription of CDP-diacylglycerol synthase 1 which is an enzyme catalyzing phosphatidic acid to generate intermediates for PC synthesis. Thus, UDCA-LPE as a hepatoprotectant was able to induce synthesis of protective PC which would supplement for the loss of PC occurring during acute liver injury. This property has placed UDCA-LPE as a candidate agent for therapy of acute hepatotoxicity such as acetaminophen poisoning.