The role of NMDA glutamate receptors in lung injury caused by chronic long-term intermittent hypobaric hypoxia.

Chronic intermittent hypoxia (CIH), a component of sleep apnea-hypopnea syndrome, is suggested to cause damage to lung tissue, and the role of glutamate is not well studied. We used a chronic long-term intermittent hypobaric hypoxia (CLTIHH) model of rats to find out if such procedure causes lung injury and the potential effect of N-methyl-D-aspartate receptors (NMDARs) by using receptor antagonist MK-801 (dizocilpine). Thirty-two rats were placed into four groups; a control and three CLTIHH groups where rats were placed into a low-pressure chamber set to 430 mmHg for 5 h/day, 5 days/week, for 5 weeks. Only one group received MK-801 (0.3 mg/kg, ip) daily. We evaluated tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nuclear factor (NF)-kB for the inflammatory process, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), total antioxidant status (TAS), and total oxidant status (TOS) for oxidative stress, and caspase-9 levels. Blood plasma, bronchoalveolar fluid (BALF), and lung tissue extracts were evaluated. Both oxidant and inflammatory parameters were significantly increased in all the mediums of the CLTIHH groups except the group that received MK-801. Significant evidence was collected on MK-801 alleviating the effect of CLTIHH. Histological evaluations revealed lung damage and fibrotic changes in the CLTIHH groups. It was first shown that the CLTIHH procedure caused chronic lung injury, and that inflammation and oxidant stress were influential in the formation of lung injury. Secondly, NMDAR antagonist MK-801 effectively inhibited the development of lung injury and fibrosis.

The role of NMDA glutamate receptors in lung injury caused by chronic long-term intermittent hypobaric hypoxia

Chronic intermittent hypoxia (CIH), a component of sleep apnea-hypopnea syndrome, is suggested to cause damage to lung tissue, and the role of glutamate is not well studied. We used a chronic long-term intermittent hypobaric hypoxia (CLTIHH) model of rats to find out if such procedure causes lung injury and the potential effect of N-methyl-D-aspartate receptors (NMDARs) by using receptor antagonist MK-801 (dizocilpine). Thirty-two rats were placed into four groups; a control and three CLTIHH groups where rats were placed into a low-pressure chamber set to 430 mmHg for 5 h/day, 5 days/week, for 5 weeks. Only one group received MK-801 (0.3 mg/kg, ip) daily. We evaluated tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nuclear factor (NF)-kB for the inflammatory process, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), total antioxidant status (TAS), and total oxidant status (TOS) for oxidative stress, and caspase-9 levels. Blood plasma, bronchoalveolar fluid (BALF), and lung tissue extracts were evaluated. Both oxidant and inflammatory parameters were significantly increased in all the mediums of the CLTIHH groups except the group that received MK-801. Significant evidence was collected on MK-801 alleviating the effect of CLTIHH. Histological evaluations revealed lung damage and fibrotic changes in the CLTIHH groups. It was first shown that the CLTIHH procedure caused chronic lung injury, and that inflammation and oxidant stress were influential in the formation of lung injury. Secondly, NMDAR antagonist MK-801 effectively inhibited the development of lung injury and fibrosis.

Long-term exposure to a continuous 900 MHz electromagnetic field disrupts cerebellar morphology in young adult male rats.

The pathological effects of exposure to an electromagnetic field (EMF) during childhood and adolescence may be greater than those from exposure during adulthood. We investigated possible pathological changes in the cerebellum of adolescent rats exposed to 900 MHz EMF daily for 25 days. We used three groups of six 21-day-old male rats as follows: unexposed control group (Non-EG), sham-exposed group (Sham-EG) and an EMF-exposed group (EMF-EG). EMF-EG rats were exposed to EMF in an EMF cage for 1 h daily from postnatal days 21 through 46. Sham-EG rats were placed in the EMF cage for 1 h daily, but were not subjected to EMF. No procedures were performed on the Non-EG rats. The cerebellums of all animals were removed on postnatal day 47, sectioned and stained with cresyl violet for histopathological and stereological analyses. We found significantly fewer Purkinje cells in the EMF-EG group than in the Non-EG and Sham-EG groups. Histopathological evaluation revealed alteration of normal Purkinje cell arrangement and pathological changes including intense staining of neuron cytoplasm in the EMF-EG group. We found that exposure to continuous 900 MHz EMF for 1 h/day during adolescence can disrupt cerebellar morphology and reduce the number of Purkinje cells in adolescent rats.

Comparison of four methods for the estimation of intracranial volume: a gold standard study.

Investigators can infer how much reduction in volume has occurred since brain volume was at its peak, by combining measures of brain volume with measures of intracranial volume (ICV). Several methodologies have been proposed to asses the ICV. However, we have not seen a gold-standard study evaluating the results of the methodologies for the assessment of ICV. In the present study, the actual intracranial volume of 20 dry skulls was measured using the water-filling method, using this as a gold standard. Anthropometry, cephalometry, point-counting, and planimetry techniques were applied to the same skulls to estimate the ICV. Anthropometric and cephalometric measurements were carried out directly on skulls and roentgenograms, respectively. Consecutive computed tomography sections at a thickness of 10 mm were used to estimate the ICV of the skulls by means of the point-counting and planimetry methods. The mean (+/-SD) of the actual ICV measured by the water-filling method was 1,262.0 +/- 160.4 cm(3) (1,389.5 +/- 96.5 cm(3) for males and 1,134.5 +/- 94.3 cm(3) for females, respectively). Our results showed that the estimated values obtained by all four methods differed from the actual volumes of the skulls (P < 0.05). The data obtained by anthropometry resulted in overestimation. However, cephalometry, point-counting, and planimetry methods produced underestimation. After calibration, there were no significant differences between the actual volumes and the results of the four methods (P > 0.05). While the anthropometric method is easy and quick to apply, its result may deviate from the actual values. The optimized stereological techniques of point-counting and planimetry methods may provide unbiased ICV results since they take the third dimension of the structures into account.

Therapeutic effects of intracarotid infusion of spermine/nitric oxide complex on cerebral vasospasm.

BACKGROUND: Vasospasm is one of the underlying causes of morbidity and mortality in subarachnoid haemorrhage (SAH). The therapeutic effects of intracarotid infusion of spermine/nitric oxide complex (SPER/NO) on cerebral vasospasm in an experimental model of SAH were investigated. METHOD: Twenty-four adult male New Zealand white rabbits (2.6-3.4 kg in weight) were randomly divided into four groups (n=6), as follows: (I) control group (without SAH and drug), (II) SAH alone group (with SAH, without drug), (III) SAH placebo group (with SAH and saline), and (IV) SAH-SPER/NO group (with SAH and SPER/NO). The fresh autologous non-heparinized blood was injected into the cisterna magna to induce a SAH, after 24 hour SAH, the substance (saline or SPER/NO) was delivered to animals. All rabbits were scarified at 48-hours of induced SAH. The basilar artery with surrounding tissue was removed from the cranium and processed for paraffin embedding. Histopathological and stereological examinations of the basilar artery were done. FINDINGS: In the SPER/NO treated group of rabbits, the histopathological changes were less severe than in the SAH-alone and SAH-placebo groups. Regarding the intracarotid pressure, there was a statistically significant difference between SAH-alone and SAH-SPER/NO groups and also between SAH-SPER/NO and control groups (p<0.05). The mean cross sectional area of basilar arteries was 0.26 mm(2) in the control, whereas in SAH alone, placebo and SAH-SPER/NO groups were 0.13, 0.15 and 0.20 mm(2), respectively. INTERPRETATION: It is well known that NO is a critical substance involved in cerebral vascular dynamics. Present results indicate that treatment of vasospasm with SPER/NO in SAH may be promising. However, further studies should be done on this substance to clarify its effect on vasospasm before using the drug in clinical situations.