Early and delayed hypoxic postconditioning in the model of birth asphyxia in 7-day-old rats

• Autorzy: Makarewicz D. , Salinska E.
• Języki publikacji: EN

Abstrakty

EN

Lack of the clinically applicable effective pharmacological neuroprotection in different forms of brain ischemia triggers increasing interest in alternative methods of therapy, including induction of brain tolerance by pre- and postconditioning. It is known for a long time that hypoxic preconditioning reduces brain damage in the rat model of perinatal asphyxia (Vannucci et al., 1998, Cantagrel et al., 2003). Recent data demonstrate that also postconditioning with moderate hypoxia delayed for 24 h after the insult results in a modest brain neuroprotection in adult mice (Leconte et al., 2009), however similar studies using the immature rats were never done. It has been suggested that similar mechanisms are involved in the induction of tolerance to brain ischemia by pre- and postconditioning, but timing may differ in both cases. Two temporal profiles of brain tolerance induced by preconditioning have been recognized: an early tolerance induced within minutes and depending on fast posttranslational modifications of proteins and a delayed one, developing after several hours to days and dependent on de novo protein synthesis (Kirino, 2002). It is not clear whether brain tolerance to hypoxia/ischemia induced by hypoxic postconditioning is also a two-phase phenomenon. The aim of this study was to evaluate efficacy of normo- and hypobaric postconditionig initiated 1, 3, or 6 hours after the insult in 7-day-old rats submitted to hypoxia-ischemia (H-I). H-I was induced by ipsilateral carotid occlusion followed by 75 min. exposure to hypoxia (7.2 - 7.4% O2 in N2). Hypoxic postconditionig was conducted under normobaric conditions at 10% O2 in N2 for 75 min, or in the hypobaric chamber set at 360 torr corresponding to 10 % O2 at the sea level. The post-conditioning was repeated once a day for 3 consecutive days. The brain damage was evaluated two weeks after H-I and expressed as ipsilateral hemisphere weight deficit in percent of the contralateral hemisphere. The results of this study demonstrated that both, normobaric or hypobaric postconditioning resulted in a significant neuroprotection only if initiated 1 h or 6 h after H-I, but not after 3 h. These results demonstrate for the first time efficacy of hypoxic postconditioning in the rat model of H-I and suggest that depending on timing of the hypoxic postconditioning the early and delayed tolerance may be achieved. Experiments are in progress verifying the role of mild oxidative stress in the mechanism of hypoxic postconditioning. Supported by the Ministry of Science and Higher Education grant #0039/B/P01/2008/35.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: 1
• Opis fizyczny: p.154

Twórcy

autor

Makarewicz D.

• Mossakowski Medical Research Centre, Laboratory of Pharmaconeurochemistry, Department of Neurochemistry, Polish Academy of Sciences, Warsaw, Poland

autor

Salinska E.

• Mossakowski Medical Research Centre, Laboratory of Pharmaconeurochemistry, Department of Neurochemistry, Polish Academy of Sciences, Warsaw, Poland