Non-invasive High Frequency Repetitive Transcranial Magnetic Stimulation (hfrTMS) Robustly Activates Molecular Pathways Implicated in Neuronal Growth and Synaptic Plasticity in Select Populations of Neurons.

Patterns of neuronal activity that induce synaptic plasticity and memory storage activate kinase cascades in neurons that are thought to be part of the mechanism for synaptic modification. One such cascade involves induction of phosphorylation of ribosomal protein S6 in neurons due to synaptic activation of AKT/mTOR and via a different pathway, activation of MAP kinase/ERK1/2. Here, we show that phosphorylation of ribosomal protein S6 can also be strongly activated by high frequency repetitive transcranial magnetic stimulation (hfrTMS).

Delayed Degradation and Impaired Dendritic Delivery of Intron-Lacking -/ mRNA in Transgenic Mice.

is a unique immediate early gene (IEG) whose expression is induced as synapses are modified during learning. Newly-synthesized mRNA is rapidly transported throughout dendrites and localizes near recently activated synapses. mRNA levels are regulated by rapid degradation, which is accelerated by synaptic activity in a translation-dependent process.

Characterization of ectopic colonies that form in widespread areas of the nervous system with neural stem cell transplants into the site of a severe spinal cord injury.

We reported previously the formation of ectopic colonies in widespread areas of the nervous system after transplantation of fetal neural stem cells (NSCs) into spinal cord transection sites. Here, we characterize the incidence, distribution, and cellular composition of the colonies. NSCs harvested from E14 spinal cords from rats that express GFP were treated with a growth factor cocktail and grafted into the site of a complete spinal cord transection.

A re-assessment of long distance growth and connectivity of neural stem cells after severe spinal cord injury.

As part of the NIH "Facilities of Research Excellence-Spinal Cord Injury" project to support independent replication, we repeated key parts of a study reporting robust engraftment of neural stem cells (NSCs) treated with growth factors after complete spinal cord transection in rats. Rats (n=20) received complete transections at thoracic level 3 (T3) and 2weeks later received NSC transplants in a fibrin matrix with a growth factor cocktail using 2 different transplantation methods (with and without removal of scar tissue). Control rats (n=9) received transections only.

A re-assessment of treatment with a tyrosine kinase inhibitor (imatinib) on tissue sparing and functional recovery after spinal cord injury.

This study was undertaken as part of the NIH "Facilities of Research Excellence-Spinal Cord Injury" project to support independent replication of published studies. Here, we repeat key parts of a study reporting that rats treated with imatinib (Gleevec®, Novartis) after spinal cord contusion injury exhibited enhanced bladder function, greater recovery of motor function, and increased tissue sparing. Young adult female SCA Sprague-Dawley rats received moderate contusion injuries at T9-T10 using the MASCIS weight drop device.

A re-assessment of the effects of treatment with a non-steroidal anti-inflammatory (ibuprofen) on promoting axon regeneration via RhoA inhibition after spinal cord injury.

This study was undertaken as part of the NIH "Facilities of Research Excellence-Spinal Cord Injury" project to support independent replication of published studies. Here, we repeat key parts of a study reporting that rats treated with ibuprofen via subcutaneous minipump exhibited greater recovery of motor function and enhanced axonal growth after spinal cord injury. We carried out 3 separate experiments in which young adult female Sprague-Dawley rats received dorsal over-hemisections at T6-T7, and then were implanted with osmotic minipumps for subcutaneous delivery of ibuprofen or saline.

A re-assessment of the effects of treatment with an epidermal growth factor receptor (EGFR) inhibitor on recovery of bladder and locomotor function following thoracic spinal cord injury in rats.

This study was undertaken as part of the NIH "Facilities of Research Excellence-Spinal Cord Injury" project to support independent replication of published studies. Here, we repeat an experiment in which rats that received an inhibitor of the epidermal growth factor receptor (EGFR) exhibited greater sparing/recovery of bladder and motor function and enhanced sparing at the lesion site after contusion injuries at the thoracic level. Young adult female Sprague-Dawley rats received moderate contusions with the NYU impactor (10 g from 12.

A re-assessment of the effects of intracortical delivery of inosine on transmidline growth of corticospinal tract axons after unilateral lesions of the medullary pyramid.

This study was undertaken as part of the NIH "Facilities of Research Excellence-Spinal Cord Injury", which supports independent replication of published studies. Here, we repeat an experiment reporting that intracortical delivery of inosine promoted trans-midline growth of corticospinal tract (CST) axons in the spinal cord after unilateral injury to the medullary pyramid. Rats received unilateral transections of the medullary pyramid and 1 day later, a cannula assembly was implanted into the sensorimotor cortex contralateral to the pyramidotomy to deliver either inosine or vehicle.

A re-assessment of a combinatorial treatment involving Schwann cell transplants and elevation of cyclic AMP on recovery of motor function following thoracic spinal cord injury in rats.

This study was undertaken as part of the NIH "Facilities of Research-Spinal Cord Injury" project to support independent replication of published studies. Here, we repeated a study reporting that a combinatorial treatment with transplants of Schwann cells, systemic delivery of Rolipram to enhance cyclic AMP levels, and intra-spinal injections of dibutyryl cyclic AMP enhanced locomotor recovery in rats after contusion injuries at the thoracic level. We compared the following experimental groups: 1) rats that received Schwann cell transplants, systemic Rolipram, and injections of db-cyclic AMP (the combined treatment group that showed the greatest improvement in function); 2) rats that received Schwann cell transplants only and implantation of empty pumps as control; 3) rats that received Rolipram only and implantation of empty pumps as control, and 4) control rats that received no treatment other than the injection of DMEM into the spinal cord and implantation of empty pumps.

Regenerative growth of corticospinal tract axons via the ventral column after spinal cord injury in mice.

Studies that have assessed regeneration of corticospinal tract (CST) axons in mice after genetic modifications or other treatments have tacitly assumed that there is little if any regeneration of CST axons in normal mice in the absence of some intervention. Here, we document a previously unrecognized capability for regenerative growth of CST axons in normal mice that involves growth past the lesion via the ventral column. Mice received dorsal hemisection injuries at thoracic level 6-7, which completely transect descending CST axons in the dorsal and dorsolateral column.

A re-assessment of the effects of a Nogo-66 receptor antagonist on regenerative growth of axons and locomotor recovery after spinal cord injury in mice.

This study was undertaken as part of the NIH "Facilities of Research-Spinal Cord Injury" project to support independent replication of published studies. Here, we repeated a study reporting that treatment with the NgR antagonist peptide NEP1-40 results in enhanced growth of corticospinal and serotonergic axons and enhanced locomotor recovery after thoracic spinal cord injury. Mice received dorsal hemisection injuries at T8 and then received either NEP1-40, Vehicle, or a Control Peptide beginning 4-5 h (early treatment) or 7 days (delayed treatment) post-injury.

TANMEI/EMB2757 encodes a WD repeat protein required for embryo development in Arabidopsis.

We identified the Arabidopsis (Arabidopsis thaliana) tanmei/emb2757 (tan) mutation that causes defects in both embryo and seedling development. tan mutant embryos share many characteristics with the leafy cotyledon (lec) class of mutants in that they accumulate anthocyanin, are intolerant of desiccation, form trichomes on cotyledons, and have reduced accumulation of storage proteins and lipids. Thus, TAN functions both in the early and late phases of embryo development.