Brain tissue hypoxia and oxidative stress induced by obstructive apneas is different in young and aged rats

Abstract

Study objectives: To test the hypotheses that brain oxygen partial pressure (PtO2) in response to obstructive apneas changes with age and that it might lead to different levels of cerebral tissue oxidative stress.

Design: Prospective controlled animal study.

Setting: University laboratory.

Participants: Sixty-four male Wistar rats: 32 young (3 mo old) and 32 aged (18 mo).

Interventions: Protocol 1: Twenty-four animals were subjected to obstructive apneas (50 apneas/h, lasting 15 sec each) or to sham procedure for 50 min. Protocol 2: Forty rats were subjected to obstructive apneas or sham procedure for 4 h.

Measurements and results: Protocol 1: Real-time PtO2 measurements were performed using a fast-response oxygen microelectrode. During successive apneas cerebral cortex PtO2 presented a different pattern in the two age groups; there was a fast increase in young rats, whereas it remained without significant changes between the beginning and the end of the protocol in the aged group. Protocol 2: Brain oxidative stress assessed by lipid peroxidation increased after apneas in young rats (1.34 ± 0.17 nmol/mg of protein) compared to old ones (0.63 ± 0.03 nmol/mg), where a higher expression of antioxidant enzymes was observed.

Conclusions: The results suggest that brain oxidative stress in aged rats is lower than in young rats in response to recurrent apneas, mimicking obstructive sleep apnea. This could be due to the different PtO2 response observed between age groups and the increased antioxidant expression in aged rats.

Citation: Dalmases M, Torres M, Márquez-Kisinousky L, Almendros I, Planas AM, Embid C, Martínez-Garcia MA, Navajas D, Farré R, Montserrat JM. Brain tissue hypoxia and oxidative stress induced by obstructive apneas is different in young and aged rats.

Keywords: aging; animal model; obstructive apnea; oxidative stress; tissue oxygenation.

Figure 1

Study design. Protocol 1: Animals underwent obstructive apneas or sham during 50 min and oxygen partial pressure (PtO₂) in cerebral cortex was measured in real time. Protocol 2: Rats were subjected to obstructive apneas or sham for 4 h and brain oxidative stress markers were determined.

Figure 2

Time course of arterial oxygen saturation (SaO₂) and oxygen partial pressure in cerebral cortex (PtO₂) recorded in young (closed circles) and aged (open circles) sham rats. Results are shown as mean ± standard error.

Figure 3

Time course of maximum (closed circles) and minimum (open circles) values of oxygen partial pressure (PtO₂) in cerebral cortex and arterial oxygen saturation (SaO₂) recorded in both age groups during the application of obstructive apneas. Baseline value is represented by a triangle. Results are shown as mean ± standard error. * P < 0.05 with respect to the baseline in maximum and respect to the first apneic event in minimum.

Figure 4

Lipid peroxidation levels in cerebral cortex in young and aged rats subjected to sham or obstructive apneas for 4 h. Results are shown as mean ± standard error. ** is the difference between treatment P < 0.01 and ++ is for age differences P < 0.01.

Figure 5

Oxidized glutathione (GSSG) levels in cerebral cortex for all groups. Results are shown as mean ± standard error. * is difference between treatment P < 0.05. There were no differences between age groups.

Figure 6

Cu-Zn superoxide dismutase-1 (SOD), catalase (CAT), glutathione peroxidase-1 (GPx), and glutathione reductase (GPr) expression in brain tissue in young and aged rats subjected to apneas or sham. Results are expressed as percentage of increase over young sham rats. Results are shown as mean ± standard error. * and ** are differences between treatment P < 0.05 and P < 0.01, respectively. + and ++ are differences between age P < 0.05 and P < 0.01, respectively.