engleski

Changes of perineuronal nets morphology, hyperactive behavior and cognitive deficits in mild perinatal hypoxic brain lesion in rats

In the study, fifty-two Wistar Han® (RccHan®:WIST) rats, (26 females and 26 males) were randomly divided into hypoxic and control group on postnatal day 1 (P1) when hypoxia was induced in a warm (≈ 25°C) hypobaric chamber (Atm 350mmHg, pO2 73mmHg) during 2 hours, while controls were kept in normal housing conditions. Behavioral testing were performed at P30 and P70 using open field, hole board, social choice, and T-maze. Samples of brain tissue from adult animals (P105-120) were used for histochemical examination of cytoarchitectonics (Nissl staining), interneurons (parvalbumin immunohistochemistry) and perineuronal nets (Wisteria floribunda agglutinin, histochemistry). Twelve Wistar pups (P1), 6 females and 6 males, was sacrificed at 8, 12 and 24h after hypoxic treatment and samples of their brain tissue were used for examination of microglia (CD68, immunohistochemistry). After mild perinatal hypoxic brain lesion, structural cerebral cytoarchitectonics, as well as the laminar and structural organization of the telencephalon, were preserved. Although, distinct changes in morphology, number, and distribution of the parvalbumin-immunoreactive neurons and perineuronal nets in the midcingulate cortex and hippocampus were observed. Microglial reactivity in lateral ventricle was most prominent at 24h after hypoxia. Compared to controls, motor and socialization patterns were preserved, while treated rats had better performance in open field, especially treated females. Moreover, treated animals also shown impaired learning behavior. Thus, the mild perinatal hypoxic brain lesion in rats leads to consistent disturbances in brain connectivity related to cognitive processes that mimic perinatal mild post-hypoxia condition in humans. Further characterization and evaluation of this non-invasive brain lesion model, on molecular, cytological and connectivity levels, is needed to disclose developmental disturbances that are not compensated after the provoked hypoxia and therefore lead to cognitive deficits. Research was funded by the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience (project “Experimental and clinical research of hypoxic ischemic damage in perinatal and adult brain” GA KK 01 1 1 01 0007 funded by the European Union through the European Regional Development Fund) and Croatian Science Foundation.

hypoxia ; perineuronal nets ; learning ; microglia ; brain development

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