The evidence base for the acellular dermal matrix AlloDerm: a systematic review.

BACKGROUND: Many decellularized dermal matrices are available with various applications, all with slight differences. AlloDerm appears to have the greatest presence in the literature. The purpose of this systematic review is to provide an overview of the experience with AlloDerm, stratified by clinical indication. METHODS: A literature search was performed across Medline, EMBASE, and the Cochrane Collaboration using the search terms "AlloDerm" and "acellular dermal matrix." Two independent authors applied a priori inclusion and exclusion criteria. Relevant articles were categorized by application, type of study, and evidence level. RESULTS: A total of 753 articles met the initial inclusion criteria, and 311 remained after discarding irrelevant articles: skin (25), head and neck (82), breast (34), trunk (66), pelvis (10), extremities (8), and basic science (86). Non-basic science study designs included 32 analytic articles (3 randomized controlled trials and 29 observational studies including 11 cohort studies, 1 cross-sectional study, and 17 case-controlled studies), 192 descriptive articles (106 case series, 51 case reports, 2 cross-sectional studies, and 33 qualitative studies), and 1 systematic review. More than 85% of articles had a level of evidence of 4 or 5. Articles showed outcomes that were 70% positive, 23% neutral, and 7% negative. CONCLUSIONS: AlloDerm has many clinical uses with promising results. Most evidence lies in descriptive and nonrandomized studies, but randomized trials are emerging. Cost and logistics of large trials with these products make large-scale trials challenging but necessary. Emphasis needs to shift to randomized controlled trials focusing on areas where most clinical benefit can be realized.

Ecologically relevant stressors modify long-term memory formation in a model system.

Stress can alter adaptive behaviours, and as well either enhance or diminish learning, memory formation and/or memory recall. We focus attention on how environmentally relevant stressors (e.g. predator detection, crowding, and low concentrations of environmental Ca(++)) alter memory formation in the pond snail, Lymnaea stagnalis. We specifically look at operant conditioning of aerial respiration and whether or not long-term memory forms following the acquisition of the learned event, not performing aerial respiration. We will also examine the strain differences in Lymnaea which allow or cause isolated populations to possess different heritable cognitive capabilities, as manifested by differing abilities to form long-term memory.

A clash of stressors and LTM formation.

Stress alters long-term memory formation sometimes enhancing its formation whilst at other times blocking it. It is unclear what the causal mechanisms are that allow stress to either enhance or suppress memory. We have made use of a relatively simple invertebrate model system to attempt to explore the causal mechanisms of how stress alters memory. Here we explore the consequences of presenting to the organism two different ecologically relevant stressors: detection of a predator and crowding. We find that the suppressive effect on memory formation elicited by crowding is more powerful than is the enhancing effect on predator-detection. That is, when the two stressors are experienced by the snail, long- term memory formation is suppressed.

Crowding, an environmental stressor, blocks long-term memory formation in Lymnaea.

Crowding is an environmental stressor. We found that this stressor altered (i.e. prevented) the ability of Lymnaea to form long-term memory (LTM) following operant conditioning of aerial respiratory behaviour. The ability to form LTM was compared between snails that had been crowded (20 snails per 100 ml of pond water) and those maintained in uncrowded conditions (two snails per 100 ml of pond water). Crowding either immediately before or after two different operant conditioning procedures - the traditional training procedure and the memory augmentation procedure - blocked LTM formation. However, if crowding is delayed by more than 1h following training or if crowding stops 1h before training, LTM results. If memory is already formed, crowding does not block memory recall. Pond water from a crowded aquarium or crowding with clean shells from dead snails, or a combination of both, is insufficient to block LTM formation. Finally, crowding does not block intermediate-term memory (ITM) formation. Since ITM is dependent on new protein synthesis whereas LTM is dependent on both new protein synthesis and altered gene activity, we hypothesize that crowding alters the genomic activity in neurons necessary for LTM formation.

The perception of stress alters adaptive behaviours in Lymnaea stagnalis.

Stress can alter adaptive behaviours, and as well either enhance or diminish learning, memory formation and/or memory recall. We show here that two different stressors have the ability to alter such behaviours in our model system, Lymnaea stagnalis. One, a naturally occurring stressor - the scent of a predator (crayfish) - and the other an artificially controlled one - 25 mmol l(-1) KCl - significantly alter adaptive behaviours. Both the KCl stressor and predator detection enhance long-term memory (LTM) formation; additionally predator detection alters vigilance behaviours. The predator-induced changes in behaviour are also accompanied by specific and significant alterations in the electrophysiological properties of RPeD1 - a key neuron in mediating both vigilance behaviours and memory formation. Naive lab-bred snails exposed to crayfish effluent (CE; i.e. the scent of the predator) prior to recording from RPeD1 demonstrated both a significantly reduced spontaneous firing rate and fewer bouts of bursting activity compared with non-exposed snails. Importantly, in the CE experiments we used laboratory-reared snails that have not been exposed to a naturally occurring predator for over 250 generations. These data open a new avenue of research, which may allow a direct investigation from the behavioral to the neuronal level as to how relevant stressful stimuli alter adaptive behaviours, including memory formation and recall.

One-trial conditioning of aerial respiratory behaviour in Lymnaea stagnalis.

Repeated spaced training sessions of contingent tactile stimulation to the pneumostome as it opens are required to cause long-term memory (LTM) formation of aerial respiratory behaviour making if difficult to determine exactly when memory forms. We have devised a single-trial aversive operant conditioning training procedure in Lymnaea to be better able to elucidate the causal mechanisms of LTM formation. Observations of baseline breathing behaviour in hypoxia were first made. Twenty-four hours later the snails were trained using the single trial procedure, by placing them in a small Petri dish containing 4 ml of 25 mM KCl for 30-35s as soon as the first pneumostome opening in hypoxia was attempted. LTM was present if (1) breathing behaviour following training was significantly less than before; and (2) breathing behaviour post-training was significantly less in experimental groups than in yoked control groups. LTM persisted for 24 h but not 48 h. Yoked controls that received an aversive stimulus not contingent with pneumostome opening had no evidence of memory. Cooling directly after, but not at any other time, blocks LTM formation. LTM formation was also prevented by removal of the cell body of the neuron RPeD1 before training.

Stressful stimuli modulate memory formation in Lymnaea stagnalis.

Stress has been shown to be a strong modulator of learning and memory in animals. We employ operant training of aerial respiratory behaviour in our model system, the pond snail Lymnaea stagnalis, to show that application of an acute consistent physical stressor enhances memory formation. A single 30 min operant conditioning training session, which normally results in intermediate-term memory (ITM) persisting 3h, results in long-term memory (LTM) persisting 24h if immediately preceded or followed by a stressor, for example a 30s exposure to 25 mM KCl. Other physical stressors (0.3% quinine-HCl or quick cooling and warming) similarly enhance memory formation. The memory is context specific and is not seen after the application of too much or too little stress. The memory can be extinguished by exposing snails to the hypoxic training environment and withholding reinforcing stimuli. The LTM that results from 30 min of training and stressor exposure is dependent on de novo protein synthesis and gene transcription in a single neuron, RPeD1. Because the soma of RPeD1 must be present for memory augmentation by the application of a stressor we are well placed for future investigations to directly determine the specific molecular alterations by which stress primes the formation of LTM.