The Kynurenic Acid Analog SZR72 Enhances Neuronal Activity after Asphyxia but Is Not Neuroprotective in a Translational Model of Neonatal Hypoxic Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) remains to be a major cause of long-term neurodevelopmental deficits in term neonates. Hypothermia offers partial neuroprotection warranting research for additional therapies. Kynurenic acid (KYNA), an endogenous product of tryptophan metabolism, was previously shown to be beneficial in rat HIE models. We sought to determine if the KYNA analog SZR72 would afford neuroprotection in piglets. After severe asphyxia (pHa = 6.83 ± 0.02, ΔBE = −17.6 ± 1.2 mmol/L, mean ± SEM), anesthetized piglets were assigned to vehicle-treated (VEH), SZR72-treated (SZR72), or hypothermia-treated (HT) groups (n = 6, 6, 6; Tcore = 38.5, 38.5, 33.5 °C, respectively). Compared to VEH, serum KYNA levels were elevated, recovery of EEG was faster, and EEG power spectral density values were higher at 24 h in the SZR72 group. However, instantaneous entropy indicating EEG signal complexity, depression of the visual evoked potential (VEP), and the significant neuronal damage observed in the neocortex, the putamen, and the CA1 hippocampal field were similar in these groups. In the caudate nucleus and the CA3 hippocampal field, neuronal damage was even more severe in the SZR72 group. The HT group showed the best preservation of EEG complexity, VEP, and neuronal integrity in all examined brain regions. In summary, SZR72 appears to enhance neuronal activity after asphyxia but does not ameliorate early neuronal damage in this HIE model.

Иммуногистохимическая характеристика пролиферативного потенциала в головном мозге крыс в неонатальном и молочном периоде

The authors studied the percentage of Ki-67-positive cells in subventricular zone of the lateral ventricles, the dentate gyrus and hippocampal field 1 in the brain of 5- and 14-day-old rats. It was found out that in 5-day and 14-day-old animals the maximum percentage of proliferating cells was revealed in subventricular area, the minimum in the hippocampal field 1. In the dentate gyrus, the proportion of Ki-67-positive cells in 5-day-old was 70,8 % of that in subventricular area, in 14-day-old rats it was significantly lower (11,9 %). It was suggested that rats in this age interval demonstrated changes of the significance of the different neurogenic niches showing the increase in the number of generated neurons and gliocytes.

Spatiotemporal patterns of rodent hippocampal field potentials uncover spatial representations

Spatiotemporal patterns of large-scale spiking and field potentials of the rodent hippocampus encode spatial representations during maze run, immobility and sleep. Here, we showed that multi-site hippocampal field potential amplitude at ultra-high frequency band (FPAuhf) provides not only a fast and reliable reconstruction of the rodent’s position in wake, but also a readout of replay content during sharp wave ripples. This FPAuhf feature may serve as robust real-time decoding strategy from large-scale (up to 100,000 electrodes) recordings in closed-loop experiments. Furthermore, we developed unsupervised learning approaches to extract low-dimensional spatiotemporal FPAuhf features during run and ripple periods, and to infer latent dynamical structures from lower-rank FPAuhf features. We also developed a novel optical flow-based method to identify propagating spatiotemporal LFP patterns from multi-site array recordings, which can be used for decoding application. Finally, we developed a prospective decoding strategy to predict animal’s future decision in goal-directed navigation.