Oxygen–Glucose Deprivation Differentially Affects Neocortical Pyramidal Neurons and Parvalbumin-Positive Interneurons

In vivo Neuroregeneration to Treat Ischemic Stroke Through NeuroD1 AAV-Based Gene Therapy in Adult Non-human Primates

“…As mentioned in Figure 4, we observed some PV neurons being protected in the NeuroD1-treated group (Figure 4G). It has been widely reported that ischemic injury tends to severely damage GABAergic neurons (Johansen et al, 1990;Tortosa and Ferrer, 1993;Wang, 2003;Povysheva et al, 2019). In accordance, we also found that compared to non-injured monkey cortex ( Figure 7A, left column), ischemic injury caused a significant loss of PV signal in the mCherry control group (Figure 7A, mCherry columns, green signal).…”

“…Quantitative analysis of the Iba1 intensity found that the NeuroD1-treated side showed consistent decrease of Iba1 signal compared to the control side at 2, 4, and 6 months after viral infection ( Figure 4H). Interestingly, when we investigated parvalbumin-positive (PV) GABAergic interneurons, which are often vulnerable after ischemic injury (Johansen et al, 1990;Tortosa and Ferrer, 1993;Wang, 2003;Povysheva et al, 2019), we found that many PV neurons were surprisingly protected in the vicinity of NeuroD1-mCherry infected areas ( Figure 4G, right panels, comparing to the left control side). Together, these results suggest that NeuroD1-mediated in vivo AtN conversion not only generates new neurons in the ischemic injured areas in the monkey cortex, but also reduces microglia and macrophage and protects GABAergic neurons after ischemic injury.…”

In Vivo Neuroregeneration to Treat Ischemic Stroke in Adult Non-Human Primate Brains through NeuroD1 AAV-based Gene Therapy

“…4F, right panels). Interestingly, when we investigated parvalbumin-positive (PV) GABAergic interneurons, which are often vulnerable after ischemic injury (Johansen et al, 1990; Povysheva et al, 2019; Tortosa and Ferrer, 1993; Wang, 2003), we found that many PV neurons were surprisingly protected in the vicinity of NeuroD1-mCherry infected areas (Fig. 4G, right panels, comparing to the left control side).…”

“…4G). It has been widely reported that ischemic injury tends to severely damage GABAergic neurons (Johansen et al, 1990; Povysheva et al, 2019; Tortosa and Ferrer, 1993; Wang, 2003). In accordance, we also found that compared to non-injured monkey cortex (Fig.…”

“…Interestingly, similar to our recent observations made in mouse stroke studies (Chen et al, 2019), we also observed significant protection of interneurons after NeuroD1 treatment in monkey stroke model. It is known that interneurons are vulnerable under ischemic injury (Johansen et al, 1990; Povysheva et al, 2019; Tortosa and Ferrer, 1993; Wang, 2003). The neuroprotective effect of in vivo cell conversion mediated by NeuroD1 may have important implications for therapeutic treatment.…”