Profound neuronal dysfunction in the entorhinal cortex contributes to early loss of short-term memory in Alzheimer’s disease1–3. Here we show broad neuroprotective effects of entorhinal brain-derived neurotrophic factor (BDNF) administration in several animal models of Alzheimer’s disease, with extension of therapeutic benefits into the degenerating hippocampus. In amyloid-transgenic mice, BDNF gene delivery, when administered after disease onset, reverses synapse loss, partially normalizes aberrant gene expression, improves cell signaling and restores learning and memory. These outcomes occur independently of effects on amyloid plaque load. In aged rats, BDNF infusion reverses cognitive decline, improves age-related perturbations in gene expression and restores cell signaling. In adult rats and primates, BDNF prevents lesion-induced death of entorhinal cortical neurons. In aged primates, BDNF reverses neuronal atrophy and ameliorates age-related cognitive impairment. Collectively, these findings indicate that BDNF exerts substantial protective effects on crucial neuronal circuitry involved in Alzheimer’s disease, acting through amyloid-independent mechanisms. BDNF therapeutic delivery merits exploration as a potential therapy for Alzheimer’s disease.

Summary Despite advances in promoting axonal regeneration after acute spinal cord injury (SCI), elicitation of bridging axon regeneration after chronic SCI remains a formidable challenge. We report that combinatorial therapies administered 6 weeks, and as long as 15 months, after SCI promote axonal regeneration into and beyond a mid-cervical lesion site. Provision of peripheral nerve conditioning lesions, grafts of marrow stromal cells and establishment of NT-3 gradients, supports bridging regeneration. Controls receiving partial components of the full combination fail to exhibit bridging. Notably, intraneuronal molecular mechanisms recruited by delayed therapies mirror those of acute injury, including activation of transcriptional activators and regeneration-associated genes. Collectively, these findings provide evidence that regeneration is achievable at unprecedented post-injury time points.

Electrode materials for recording biomedical signals, such as electrocardiography (ECG), electroencephalography (EEG) and evoked potentials data, are expected to be soft, hydrophilic and electroconductive to minimize the stress imposed on living tissue, especially during long-term monitoring. We have developed and characterized string-shaped electrodes made from conductive polymer with silk fiber bundles (thread), which offer a new biocompatible stress free interface with living tissue in both wet and dry conditions.An electroconductive polyelectrolyte, poly(3,4-ethylenedioxythiophene) -poly(styrenesulfonate) (PEDOT-PSS) was electrochemically combined with silk thread made from natural Bombyx mori. The polymer composite 280 µm thread exhibited a conductivity of 0.00117 S/cm (which corresponds to a DC resistance of 2.62 Mohm/cm). The addition of glycerol to the PEDOT-PSS silk thread improved the conductivity to 0.102 S/cm (20.6 kohm/cm). The wettability of PEDOT-PSS was controlled with glycerol, which improved its durability in water and washing cycles. The glycerol treated PEDOT-PSS silk thread showed a tensile strength of 1000 cN in both wet and dry states. Without using any electrolytes, pastes or solutions, the thread directly collects electrical signals from living tissue and transmits them through metal cables. ECG, EEG, and sensory evoked potential (SEP) signals were recorded from experimental animals by using this thread placed on the skin. PEDOT-PSS silk glycerol composite thread offers a new class of biocompatible electrodes in the field of biomedical and health promotion that does not induce stress in the subjects.

Amino acid transport system L has been proposed to be one of the major nutrient transport systems at the blood-brain barrier. Using immunohistochemical analyses, a system L transporter LAT1 was shown to be expressed in the brain capillary endothelial cells in rats. Because LAT1 was coexpressed with 4F2 heavy chain which brings LAT1 to the plasma membrane, LAT1 is proposed to be functional in the plasma membrane of brain capillary endothelial cells. Both LAT1 and 4F2hc immunoreactivities were detected in a double line appearance surrounding endothelial cell nuclei, suggesting both proteins are present in the luminal and abluminal membranes. LAT1 is, thus, a blood-brain barrier system L transporter responsible for the permeation of aromatic or branched-chain amino acids and amino acid-related drugs such as L-DOPA.

Previous studies indicate that peripheral nerve conditioning lesions significantly enhance central axonal regeneration via modulation of cAMP-mediated mechanisms. To gain insight into the nature and temporal dependence of neural mechanisms underlying conditioning lesion effects on central axonal regeneration, we compared the efficacy of peripheral sciatic nerve crush lesions to cAMP elevations (in lumbar dorsal root ganglia) on central sensory axonal regeneration when administered either before or after cervical spinal cord lesions. We found significantly greater effects of conditioning lesions compared to cAMP elevations on central axonal regeneration when combined with cellular grafts at the lesion site and viral neurotrophin delivery; further, these effects persisted whether conditioning lesions were applied prior to or shortly after spinal cord injury. Indeed, conditioning lesions recruited extensively greater sets of genetic mechanisms of possible relevance to axonal regeneration compared to cAMP administration, and sustained these changes for significantly greater time periods through the post-lesion period. We conclude that cAMP-mediated mechanisms account for only a portion of the potency of conditioning lesions on central axonal regeneration, and that recruitment of broader genetic mechanisms can extend the effect and duration of cellular events that support axonal growth.

A highly conductive textile was woven from nano-fibers coated with the PEDOT-PSS polymer. The aim of this study was to assess the usefulness of textile electrodes for ECG recording as a smart garment. Electrode textile pads and lead wires were sewn to the lining of sportswear and their tolerability to repeated washings were tested up to 150 times. The electrical conductivity of the textile electrode remained functional for up to 50 machine washes. To assess the level of motion artifacts or noise during the daily monitoring of ECG, a single lead ECG with conventional or textile electrodes was recorded during supine rest, seated rest, upright trunk rotation (i.e., twisting), and stepping movement in 66 healthy adults. A Holter system was used for data storage and analysis. ECG patterns of P, QRS, and T waves were comparable between the conventional and textile electrodes. However, the signal-to-artifact-and/or-noise ratio (SAR) during twisting was larger in the textile electrodes than in the conventional electrodes. No skin irritation was seen in the textile electrodes. The single lead textile electrodes embedded in an inner garment were usable for continuous and/or repeated ECG monitoring in daily life except during vigorous trunk movement.

No abstract

3 young Japanese sisters with congenital α₂-plasmin inhibitor (α₂-PI) deficiency are reported. They have mild umbilical bleeding and/or repeated prolonged bleeding after minor trauma, but rarely spontaneous bleedings. The most characteristic hemostatic findings were shortened whole blood clot lysis time and euglobulin lysis time. Activities of all hemostatic factors except α₂-PI were within normal range. Both functional and immunological absence of α₂-PI were found in the plasma, and this failure to detect α₂-PI was not corrected by the addition of the patient’s plasma of the first described case of α₂-PI deficiency. Clinical and laboratory data revealed that these patients were probably homozygous for α₂-PI deficiency and born of heterozygous parents, but not of consanguineous ones. Bleeding episodes due to deficiency of (α₂-PI in these patients were well controlled by an antifibrinolytic agent, tranexamic acid.