The Kynurenic Acid Analog SZR72 Enhances Neuronal Activity after Asphyxia but Is Not Neuroprotective in a Translational Model of Neonatal Hypoxic Ischemic Encephalopathy
| Autor: | Róbert Berkecz, Andrea Pénzes, László Vécsei, Valéria Tóth-Szűki, Tímea Körmöczi, Ferenc Domoki, Viktória Kovács, Gábor Remzső |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Caudate nucleus
therapeutic hypothermia Hippocampal formation Kynurenic Acid birth asphyxia Brain Ischemia Translational Research Biomedical chemistry.chemical_compound Kynurenic acid Premovement neuronal activity Biology (General) Spectroscopy Neurons Asphyxia Neonatorum Neocortex neonatal encephalopathy Electroencephalography General Medicine CA3 Region Hippocampal Computer Science Applications Chemistry medicine.anatomical_structure medicine.symptom medicine.medical_specialty QH301-705.5 Neuroprotection Article Catalysis Inorganic Chemistry Internal medicine medicine Animals Humans Physical and Theoretical Chemistry CA1 Region Hippocampal Molecular Biology QD1-999 newborn pig Asphyxia business.industry Neonatal encephalopathy Organic Chemistry medicine.disease Rats kynurenine Disease Models Animal Endocrinology chemistry nervous system Evoked Potentials Visual business |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 4822, p 4822 (2021) International Journal of Molecular Sciences Volume 22 Issue 9 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|