Repetitive transcranial magnetic stimulation promotes functional recovery and differentiation of human neural stem cells in rats after ischemic stroke.

Stem cells hold great promise as a regenerative therapy for ischemic stroke by improving functional outcomes in animal models. However, there are some limitations regarding the cell transplantation, including low rate of survival and differentiation. Repetitive transcranial magnetic stimulation (rTMS) has been widely used in clinical trials as post-stroke rehabilitation in ischemic stroke and has shown to alleviate functional deficits following stroke. The present study was designed to evaluate the therapeutic effects and mechanisms of combined human neural stem cells (hNSCs) with rTMS in a middle cerebral artery occlusion (MCAO) rat model. The results showed that human embryonic stem cells (hESCs) were successfully differentiated into forebrain hNSCs for transplantation and hNSCs transplantation combined with rTMS could accelerate the functional recovery after ischemic stroke in rats. Furthermore, this combination not only significantly enhanced neurogenesis and the protein levels of brain-derived neurotrophic factor (BDNF), but also rTMS promoted the neural differentiation of hNSCs. Our findings are presented for the first time to evaluate therapeutic benefits of combined hNSCs and rTMS for functional recovery after ischemic stroke, and indicated that the combination of hNSCs with rTMS might be a potential novel therapeutic target for the treatment of stroke.

Gene order rearrangement of the M gene in the rabies virus leads to slower replication.

The matrix protein (M) is one of only five genes in the RV genome and is an important multifunctional protein. Besides to allow for the release of newly replicated virions pairing with G, the M protein also functions in virus replication, pathogenicity, and host cell apoptosis. The goal of present study is to generate recombinant viruses with M gene rearranged, thus laying the foundation for further exploring what will happen when the gene for M is relocated on the RV single-strand RNA. We used rHEP-Flury, an attenuated virus that remains virulent for less than 3 days in sucking mice, to reshuffle the M gene, using an approach that leaves the other viral nucleotide sequence intact. Two viruses with translocated M genes (N1M2 and N1M4) were recovered from each of the rearranged cDNAs, whose gene order is 3'-N-M-P-G-L-5' and 3'-N-P-G-M-L-5' respectively. The growth dynamics of these viruses showed slower replication than the wild-type virus in multiple-step growth curves, but they can grow to a comparable titer in tests of single-step growth curves. Further experimentation with these rearranged viruses will provide insights into the relationships between genome structure and virus phenotypes.