Matrix metalloproteinases (MMPs) influence synaptic recovery following traumatic brain injury (TBI). Membrane type 5-matrix metalloproteinase (MT5-MMP) and a distintegrin and metalloproteinase-10 (ADAM-10) are membrane-bound MMPs that cleave N-cadherin, a protein critical to synapse stabilization. This study examined protein and mRNA expression of MT5-MMP, ADAM-10, and N-cadherin after TBI, contrasting adaptive and maladaptive synaptogenesis. The effect of MMP inhibition on MT5-MMP, ADAM-10, and N-cadherin was assessed during maladaptive plasticity and correlated with synaptic function. Rats were subjected to adaptive unilateral entorhinal cortical lesion (UEC) or maladaptive fluid percussion TBI + bilateral entorhinal cortical lesion (TBI + BEC). Hippocampal MT5-MMP and ADAM-10 protein was significantly elevated 2 and 7 days postinjury. At 15 days after UEC, each MMP returned to control level, while TBI + BEC ADAM-10 remained elevated. At 2 and 7 days, N-cadherin protein was below control. By the 15-day synapse stabilization phase, UEC Ncadherin rose above control, a shift not seen for TBI + BEC. At 7 days, increased TBI + BEC ADAM-10 transcript correlated with protein elevation. UEC ADAM-10 mRNA did not change, and no differences in MT5-MMP or Ncadherin mRNA were detected. Confocal imaging showed MT5-MMP, ADAM-10, and N-cadherin localization within reactive astrocytes. MMP inhibition attenuated ADAM-10 protein 15 days after TBI + BEC and increased N-cadherin. This inhibition partially restored long-term potentiation induction, but did not affect pairedpulse facilitation. Our results confirm time-and injury-dependent expression of MT5-MMP, ADAM-10, and N-cadherin during reactive synaptogenesis. Persistent ADAM-10 expression was correlated with attenuated N-cadherin level and reduced functional recovery. MMP inhibition shifted ADAM-10 and N-cadherin toward adaptive expression and improved synaptic function.

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Neuroglia play an important role in synaptogenesis after traumatic brain injury (TBI). The magnitude of glial response appears to be injury specific, potentially facilitating or attenuating synaptic recovery. Our prior studies also show that matrix metalloproteinases (MMPs) are differentially upregulated within reactive glia as a function of injury. Here, we contrasted glial response in models of adaptive (unilateral entorhinal cortex lesion; UEC) or maladaptive (combined fluid percussion injury and bilateral entorhinal cortex lesion; TBI+BEC) synaptic plasticity. Rats received UEC or TBI+BEC and were sacrificed 7d postinjury. Excised brains were processed for immunohistochemistry (IHC) with antibodies specific to astrocytes (GFAP), microglia (Iba‐1) and membrane‐bound MMPs, ADAM‐10 and MT5‐MMP. Confocal images revealed an increase in GFAP and Iba‐1 over deafferented neuropil in both models compared to uninjured controls. Microglial response was similar in the two models, however, TBI+BEC showed a greater GFAP increase across both dentate molecular and granule cell layers. Only GFAP+ cells were co‐labeled ADAM‐10 and MT5‐MMP. Results suggest that extent and distribution of TBI glial response is injury specific. Moreover, astrocytic ADAM‐10 and MT5‐MMP expression during reactive plasticity is a potential therapeutic target to facilitate synaptogenesis after TBI. Supported by: NIH grants NS44372, NS57758.

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Interactive teaching methods, such as in‐class written exercises, can be added to traditional lectures to assess and enhance student learning. The goal of this study was to determine if student performance on in‐class written exercises could be used to predict exam performance. A set of identical written exercises, consisting of 5–6 questions, was administered to 45 allied health graduate students immediately before (PRE) and after (POST) three review lectures in a gross anatomy course. Students were given the correct answers to the questions after completing the POST exercise. For all three blocks, student performance increased significantly between PRE and POST exercises, suggesting short term knowledge acquisition. PRE scores were positively correlated with block exam scores (1:r2=0.29, 2:r2=0.16, 3:r2=0.11; p<0.05), while POST scores only showed a significant positive correlation with the first and second block exam scores (1:r2=0.14, 2:r2=0.23; p<0.05). Student feedback indicated that exercises enhanced the learning experience and subject matter understanding. Our findings suggest that a moderate positive correlation exists between PRE/POST exercise and exam performance, although not uniform in nature. While in‐class exercise performance may not be a strong predictor for exam performance, exercises can be used to enhance student learning and self‐assessment in traditional lecture formats.Grant Funding Source: n/a