RESUMEN
We previously showed that TSC1 (a combination of transferrin and IGF-1) is a potent inductor of myelinogenesis in myelin deficient rats and in demyelinated adult mice. More recently, we demonstrated that regeneration of oligodendrocyte progenitors and myelin are possible with a single dose of TSC1 in a mouse model of Premature birth. Here, using the same mouse model of perinatal white matter damage due to glutamate excitotoxicity (GME), we tested the hypothesis that regeneration of endogenous nestin-expressing neural progenitors improves the outcome of prematurity. Treatments: N-methyl-D-aspartate (NMDA), saline, NMDA+TSC1 together or NMDA followed byTSC1 3 days later, were stereotaxically delivered into the corpus callosum of P4 mouse pups. Fluorescence analysis showed an intense enrichment of nestin-expressing cells in groups injected with NMDA+TSC1 from which many were generated by proliferation. Moreover, when TSC1 was injected three days after the primary insult it was still able to reduce ventricular enlargement and extensively rescue nestin-expressing progenitors. Cells co-expressing the proliferation marker Ki67, CNPase and faint nestin label were more abundant in groups injected with MNDA+TSC1 at 35 days after injection. Stereological analysis showed that the number of nestin-expressing cells in the sub-ventricular zone correlated inversely with the volume of the ventricle. A delayed administration of TSC1 after excitotoxicity reduced ventriculomegaly but not as much as, when NMDA and TSC1 were injected simultaneously. Thus, the earliest TSC1 was administered, the more tissue was rescued as shown by reduced ventriculomegaly. Astrocytes responded to GME by upregulating the expression of estrogen receptor and this expression was attenuated in the presence of TSC1 suggesting a decreased inflammation and a lesser need for estrogen-mediated central nervous system (CNS) neuroprotection.
RESUMEN
The efficacy of drug-eluting stents (DES) in reducing the rates of in-stent restenosis after percutaneous coronary intervention (PCI) compared to bare metal stents (BMS) in stable coronary artery disease has been well demonstrated. Thus, the Food and Drug Administration has approved the utilization of DES for stable coronary disease. However, there is still much debate surrounding the implantation of DES for patients with ST-segment elevation myocardial infarction (STEMI) given safety concerns about the possibility of increased rates of stent thrombosis with DES. The review of the current body of evidence comparing DES with BMS is consistent with results from previous trials in stable coronary disease and reveals lower rates of revascularization with DES in STEMI patients. The ultimate decision regarding the appropriate stent during PCI needs to be individualized as patients' compliance with dual antiplatelet therapy is critical. The data suggest that PCI with DES in STEMI patients who adhere to long-term dual antiplatelet therapy is safe and effective. Randomized trials with longer-term follow-up are necessary to better elucidate the safety and efficacy of DES versus BMS in patients with STEMI.
