Allosteric Modulation of NMDARs Reverses Patients' Autoantibody Effects in Mice

Background and ObjectivesTo demonstrate that an analog (SGE-301) of a brain-derived cholesterol metabolite, 24(S)-hydroxycholesterol, which is a selective positive allosteric modulator (PAM) of NMDA receptors (NMDARs), is able to reverse the memory and synaptic alterations caused by CSF from patients with anti-NMDAR encephalitis in an animal model of passive transfer of antibodies.MethodsFour groups of mice received (days 1–14) patients' or controls' CSF via osmotic pumps connected to the cerebroventricular system and from day 11 were treated with daily subcutaneous injections of SGE-301 or vehicle (no drug). Visuospatial memory, locomotor activity (LA), synaptic NMDAR cluster density, hippocampal long-term potentiation (LTP), and paired-pulse facilitation (PPF) were assessed on days 10, 13, 18, and 26 using reported techniques.ResultsOn day 10, mice infused with patients' CSF, but not controls' CSF, presented a significant visuospatial memory deficit, reduction of NMDAR clusters, and impairment of LTP, whereas LA and PPF were unaffected. These alterations persisted until day 18, the time of maximal deficits in this model. In contrast, mice that received patients' CSF but from day 11 were treated with SGE-301 showed memory recovery (day 13), and on day 18, all paradigms (memory, NMDAR clusters, and LTP) had reversed to values similar to those of controls. On day 26, no differences were observed among experimental groups.DiscussionAn oxysterol biology-based PAM of NMDARs is able to reverse the synaptic and memory deficits caused by CSF from patients with anti-NMDAR encephalitis. These findings suggest a novel adjuvant treatment approach that deserves future clinical evaluation.

Review of Magnetic Shape Memory Polymers and Magnetic Soft Materials

Magnetic soft materials (MSMs) and magnetic shape memory polymers (MSMPs) have been some of the most intensely investigated newly developed material types in the last decade, thanks to the great and versatile potential of their innovative characteristic behaviors such as remote and nearly heatless shape transformation in the case of MSMs. With regard to a number of properties such as shape recovery ratio, manufacturability, cost or programming potential, MSMs and MSMPs may exceed conventional shape memory materials such as shape memory alloys or shape memory polymers. Nevertheless, MSMs and MSMPs have not yet fully touched their scientific-industrial potential, basically due to the lack of detailed knowledge on various aspects of their constitutive response. Therefore, MSMs and MSMPs have been developed slowly but their importance will undoubtedly increase in the near future. This review emphasizes the development of MSMs and MSMPs with a specific focus on the role of the magnetic particles which affect the shape memory recovery and programming behavior of these materials. In addition, the synthesis and application of these materials are addressed.

Memory recovery in relation to default mode network impairment and neurite density during brain tumor treatment

OBJECTIVE The aim of this study was to test brain tumor interactions with brain networks, thereby identifying protective features and risk factors for memory recovery after resection. METHODS Seventeen patients with diffuse nonenhancing glioma (ages 22–56 years) underwent longitudinal MRI before and after surgery, and during a 12-month recovery period (47 MRI scans in total after exclusion). After each scanning session, a battery of memory tests was performed using a tablet-based screening tool, including free verbal memory, overall verbal memory, episodic memory, orientation, forward digit span, and backward digit span. Using structural MRI and neurite orientation dispersion and density imaging (NODDI) derived from diffusion-weighted images, the authors estimated lesion overlap and neurite density, respectively, with brain networks derived from normative data in healthy participants (somatomotor, dorsal attention, ventral attention, frontoparietal, and default mode network [DMN]). Linear mixed-effect models (LMMs) that regressed out the effect of age, gender, tumor grade, type of treatment, total lesion volume, and total neurite density were used to test the potential longitudinal associations between imaging markers and memory recovery. RESULTS Memory recovery was not significantly associated with either the tumor location based on traditional lobe classification or the type of treatment received by patients (i.e., surgery alone or surgery with adjuvant chemoradiotherapy). Nonlocal effects of tumors were evident on neurite density, which was reduced not only within the tumor but also beyond the tumor boundary. In contrast, high preoperative neurite density outside the tumor but within the DMN was associated with better memory recovery (LMM, p value after false discovery rate correction [Pfdr] < 10−3). Furthermore, postoperative and follow-up neurite density within the DMN and frontoparietal network were also associated with memory recovery (LMM, Pfdr = 0.014 and Pfdr = 0.001, respectively). Preoperative tumor and postoperative lesion overlap with the DMN showed a significant negative association with memory recovery (LMM, Pfdr = 0.002 and Pfdr < 10−4, respectively). CONCLUSIONS Imaging biomarkers of cognitive recovery and decline can be identified using NODDI and resting-state networks. Brain tumors and their corresponding treatment affecting brain networks that are fundamental for memory functioning such as the DMN can have a major impact on patients’ memory recovery.

Non Edible Oil-Based Epoxy Resins from Jatropha Oil and Their Shape Memory Behaviors

The use of bio-based polymers in place of conventional polymers gives positives effects in the sense of reduction of environmental impacts and the offsetting of petroleum consumption. As such, in this study, jatropha oil was used to prepare epoxidized jatropha oil (EJO) by the epoxidation method. The EJO was used to prepare a shape memory polymer (SMP) by mixing it with the curing agent 4-methylhexahydrophthalic anhydride (MHPA) and a tetraethylammonium bromide (TEAB) catalyst. The resulting bio-based polymer is slightly transparent and brown in color. It has soft and flexible properties resulting from the aliphatic chain in jatropha oil. The functionality of SMP was analyzed by Fourier transform infrared (FTIR) spectroscopy analysis. The thermal behavior of the SMP was measured by thermogravimetric analysis (TGA), and it showed that the samples were thermally stable up to 150 °C. Moreover, the glass transition temperature characteristic was obtained using differential scanning calorimetry (DSC) analysis. The shape memory recovery behavior was investigated. Overall, EJO/MHPA was prepared by a relatively simple method and showed good shape recovery properties.

Neural correlates of memory recovery: Preliminary findings in children and adolescents with acquired brain injury

Background: After acquired brain injury (ABI), patients show various neurological impairments and outcome is difficult to predict. Identifying biomarkers of recovery could provide prognostic information about a patient’s neural potential for recovery and improve our understanding of neural reorganization. In healthy subjects, sleep slow wave activity (SWA, EEG spectral power 1–4.5 Hz) has been linked to neuroplastic processes such as learning and brain maturation. Therefore, we suggest that SWA might be a suitable measure to investigate neural reorganization underlying memory recovery. Objectives: In the present study, we used SWA to investigate neural correlates of recovery of function in ten paediatric patients with ABI (age range 7–15 years). Methods: We recorded high-density EEG (128 electrodes) during sleep at the beginning and end of rehabilitation. We used sleep EEG data of 52 typically developing children to calculate age-normalized values for individual patients. In patients, we also assessed every-day life memory impairment at the beginning and end of rehabilitation. Results: In the course of rehabilitation, memory recovery was paralleled by longitudinal changes in SWA over posterior parietal brain areas. SWA over left prefrontal and occipital brain areas at the beginning of rehabilitation predicted memory recovery. Conclusions: We show that longitudinal sleep-EEG measurements are feasible in the clinical setting. While posterior parietal and prefrontal brain areas are known to belong to the memory “core network”, occipital brain areas have never been related to memory. While we have to remain cautious in interpreting preliminary findings, we suggest that SWA is a promising measure to investigate neural reorganization.

GluN2B and GluN2A-containing NMDAR are differentially involved in extinction memory destabilization and restabilization during reconsolidation

Extinction memory destabilized by recall is restabilized through mTOR-dependent reconsolidation in the hippocampus, but the upstream pathways controlling these processes remain unknown. Hippocampal NMDARs drive local protein synthesis via mTOR signaling and may control active memory maintenance. We found that in adult male Wistar rats, intra dorsal-CA1 administration of the non-subunit selective NMDAR antagonist AP5 or of the GluN2A subunit-containing NMDAR antagonist TCN201 after step down inhibitory avoidance (SDIA) extinction memory recall impaired extinction memory retention and caused SDIA memory recovery. On the contrary, pre-recall administration of AP5 or of the GluN2B subunit-containing NMDAR antagonist RO25-6981 had no effect on extinction memory recall or retention per se but hindered the recovery of the avoidance response induced by post-recall intra-CA1 infusion of the mTOR inhibitor rapamycin. Our results indicate that GluN2B-containing NMDARs are necessary for extinction memory destabilization whereas GluN2A-containing NMDARs are involved in its restabilization, and suggest that pharmacological modulation of the relative activation state of these receptor subtypes around the moment of extinction memory recall may regulate the dominance of extinction memory over the original memory trace.