engleski

A non-invasive rat model of perinatal hypoxic brain lesion

The Rice-Vannuci hypoxic-ischemic-brain lesion in the rat, and its various modifications, used as a standard model for hypoxic brain lesions, are invasive surgical treatments classified as severe procedure (EU Directive 63/10, Article 15). We aim to introduce a non-invasive hypoxic brain lesion rat model of mild to moderate severity, to serve for the research targeting the fetal hypoxic brain lesions occurring during midgestation (23-32 weeks post- conception) in humans. In the present study, Wistar rats (9 females and 10 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, pO273mmHg) during 2 hours, while controls were kept in normal housing conditions. Possible behavioral deficits were examined in a battery of tests: open field, hole board, the T-maze and social choice at P30 and P70. 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). Compared to controls, hypoxic animals had intact exploratory, anxiety-like and social behavior, but displayed significantly impaired learning. There were no disturbances in the brain macro-morphology or any other pathoanatomical consequence of the treatment, and the cytoarchitecture, as well as the laminar and structural organization of the telencephalon, were preserved. However, changes in morphology, number, and distribution of the parvalbumin-immunoreactive neurons and perineuronal nets, distinct in different regions of the telencephalon were observed. In conclusion, the proposed rat model of non- invasive hypoxic brain injury has indicated consistent disturbances in brain connectivity related to cognitive processes, that mimic perinatal mild post-hypoxia condition in humans. Further characterization and evaluation of the 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. (Fund: KK.01.1.1.01.0007, CoRE – Neuro).

Rice-Vannuci model ; hypoxia ; parvalbumin ; brain development ; perineuronal nets ; learning

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