These results suggest that daily LEV treatment has beneficial effects on histological, molecular, and behavioral elements of neurological recovery after TBI, in part, via modulation of neuroinflammatory and excitatory pathways.

Explicit and implicit learning and memory networks exist where each network can facilitate or inhibit memory. Clinical evidence suggests that implicit networks are relatively preserved after traumatic brain injury (TBI). Non-spatial pre-training (NSPT) in the Morris water maze (MWM) provides the necessary behavioral components to complete the task, while limiting the formation of spatial maps. Our study utilized NSPT in the MWM to assess implicit and explicit learning and memory system deficits in the controlled cortical impact (CCI) model of TBI. 76 adult male Sprague-Dawley rats were divided: CCI vs. sham surgery, NSPT vs. No-NSPT, and cued vs. non-cued groups. NSPT occurred for 4d prior to surgery (dynamic hidden platform location, extra-maze cues covered, static pool entry point). Acquisition (d14–18), Probe/Visible Platform (d19), and Reversal (d20–21) trials were conducted with or without extra-maze cues. Novel time allocation and search strategy selection metrics were utilized. Results indicated implicit and explicit learning/memory networks are distinguishable in the MWM. In the cued condition, NSPT reduced thigmotaxis, improved place learning, and largely eliminated the apparent injury-induced deficits typically observed between untrained CCI and sham rats. However, among NSPT groups, incorporation of cues into search strategy selection for CCI rats was relatively impaired compared to shams. Non-cued condition performance showed sham/NSPT and CCI/NSPT rats perform similarly, suggesting implicit memory networks are largely intact 2 weeks after CCI. Place learning differences between CCI/NSPT and sham/NSPT rats more accurately reflect spatial deficits in our CCI model compared to untrained controls. These data suggest NSPT as a clinically relevant construct for evaluating potential neurorestorative and neuroprotective therapies. These findings also support development of non-spatial cognitive training paradigms for evaluating rehabilitation relevant combination therapies.

Background Following traumatic brain injury (TBI), clinical cognitive training paradigms harness implicit and explicit learning and memory systems to improve function; however, these systems are differentially affected by TBI, highlighting the need for an experimental TBI model that can test efficacy of cognitive training approaches. Objectives To develop a clinically relevant experimental cognitive training model using the Morris water maze (MWM) wherein training on implicitly learned task components was provided to improve behavioral performance post-TBI. Methods: 81 adult male rats were divided by injury status [controlled cortical impact (CCI)/Sham], non-spatial cognitive training (CogTrained/No-CogTrained), and extra-maze cues (Cued/Non-Cued) during MWM testing. Platform latencies, thigmotaxis, and search strategies were assessed during MWM trials. Results Cognitive training was associated with improved platform latencies, reduced thigmotaxis, and more effective search strategy use for Sham and CCI rats. In the Cued and Non-Cued MWM paradigm, there were no differences between CCI/CogTrained and Sham/No-CogTrained groups. During novel testing conditions, CogTrained groups applied implicitly learned knowledge/skills; however, sham-cued CogTrained/rats better incorporated extramaze cues into their search strategy than the CCI-Cued group. Cognitive training had no effects on contusion size or hippocampal cell survival. Conclusions The results provide evidence that CCI-CogTrained rats that learned the non-spatial components of the MWM task applied these skills during multiple conditions of the place-learning task, thereby mitigating cognitive deficits typically associated with this injury model. The results show that a systematic application of clinically relevant constructs associated with cognitive training paradigms can be used with experimental TBI to affect place learning.

Enterococcus hirae is a gram-positive coccus that is rarely implicated in human disease and has not been reported in pediatric patients. We report a case of catheter-associated bloodstream infection and prolonged bacteremia in a 7-month-old infant dependent on total parenteral nutrition. The species was identified by the VITEK2 system and confirmed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The organisms was susceptible to ampicillin, vancomycin, and high-level gentamicin. The patient was treated with vancomycin and gentamicin with adjunctive vancomycin lock therapy but had persistent bacteremia. Therapy was changed to dual β-lactam therapy of ampicillin and ceftriaxone with synergistic gentamicin, which led to clearance of the enterococcal bacteremia. E hirae is an unusual species that may be difficult for the microbiology laboratory to identify. This is the first pediatric case and the second case of invasive E hirae in the United States.

Previous work demonstrates that spatial (explicit) and non-spatial (implicit) elements of place learning in the Morris water maze (MWM) task can be dissociated and examined in the context of experimental traumatic brain injury (TBI). Providing non-spatial cognitive training (CT) after injury can improve place learning compared to untrained controls. In the present study, we hypothesized that brief exposure to extra-maze cues, in conjunction with CT, may further improve MWM performance and extra-maze cue utilization compared to CT alone. Adult male Sprague-Dawley rats (n=66) received controlled cortical impact (CCI) injury or sham surgery. Beginning D8 post-surgery, CCI and Sham rats received 6 days to no training (NT) or cognitive training with/without brief, non-contextualized exposure to extra-maze cues (BE and CT, respectively). Acquisition (D14-D18), Visible Platform (VP; D19), Carryover (CO; D20-D26), and periodic probe trials were performed. Platform latencies, peripheral and target zone time allocation, and search strategies were assessed. CCI/BE rats had shorter acquisition trial latencies than CCI/NT (p<0.001) and tended to have shorter latencies than CCI/CT rats (p<0.10). Both BE and CT reduced peripheral zone swimming for CCI rats vs. CCI/NT. CCI/BE animals increased spatial swim strategies from D14 to D18 relative to CCI/CT and showed similar swim strategy selection to the Sham/NT group. These data suggest that visual priming improves initial place learning in the MWM. These results support the visual priming response as another clinically relevant experimental rehabilitation construct, to use when assessing injury and treatment effects of behavioral and pharmacological therapies on cognition after TBI.