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Introduction Diabetes is a well-known risk factor in pregnancy. Because maternal diabetes involves oxidative stress that is also induced by chronic hypoxia and can alter vascular function, we sought to determine the effects of chronic maternal hyperglycemia on the fetoplacental vasculature in rats and to compare it with the effects of chronic hypoxia. Methods Diabetes was induced in female rats by a streptozotocin injection at a neonatal age. When these animals reached adulthood, their hyperglycemia was confirmed and they were inseminated. Half of them were exposed to hypoxia (10% O2) for the last week before the delivery. One day before the expected date of delivery, one of their placentae was isolated and perfused. Results Fetoplacental vascular resistance was increased equally by experimental diabetes, chronic hypoxia, and their combination. Fetoplacental perfusion pressure-flow analysis suggested increased resistance in the small vessels in chronic hypoxia and in larger vessels in diabetes. Fetal plasma nitrotyrosine levels, measured as a marker of peroxynitrite (reaction product of superoxide and nitric oxide), mirrored the differences in fetoplacental resistance, suggesting a causative role. Fetoplacental vasoconstrictor reactivity to acute hypoxic stimuli was reduced similarly in all groups. Fasudil, a strong vasodilator agent, reduced fetoplacental vascular resistance similarly in all groups, suggesting that for the observed differences among the groups, the changes in vascular morphology were more important than variances in vascular tone. Discussion Maternal diabetes increases fetoplacental vascular resistance to a similar extent as chronic hypoxia. These stimuli are not additive. Changes in vascular tone are not responsible for these effects.

The vessels on the fetal side of the placenta differ from most other vascular beds except the lungs in that they respond to acute hypoxia by vasoconstriction. An essential role of calcium influx in the mechanism of this hypoxic fetoplacental vasoconstriction (HFPV) has been shown previously. That finding does not, however, exclude the possible involvement of other mechanisms of vascular tone regulation. In this study we tested the hypothesis that Rho-kinase-mediated calcium sensitization is involved in HFPV. We used a model of isolated rat placenta dually perfused (from both the maternal and fetal side) with Krebs salt solution saturated with normoxic and hypoxic gas mixture respectively at constant flow rate. Rho-kinase pathway was inhibited by fasudil (10 μM). We found that fasudil reduced basal normoxic fetoplacental vascular resistance and completely prevented HFPV. This suggests that the activity of Rho-kinase signaling pathway is essential for HFPV.

Objective : In this study, we present a simple closed head injury model as a two-stage experiment. The height of the weight drop enables gradation of head trauma severity. Methods : The head injury device consists of three parts and there are three adjustable parameters-weight (100-600 g), height of fall (5-100 cm) and elasticity of the springs. Thirty male Wistar rats underwent monitoring of intracranial pressure with and without induction of the head injury. Results : The weight drop from 45 to 100 cm led to immediate seizure activity and early death of the experimental animals. Severe head injury was induced from 40 cm weight drop. There was 50% mortality and all surviving rats had behavioral deterioration. Intracranial pressure was 9.3 ± 3.76 mmHg. Moderate head injury was induced from 35 cm, mortality decreased to 20-40%, only half of the animals showed behavioral pathology and intracranial pressure was 7.6 ± 3.54 mmHg. Weight drop from 30 cm caused mild head injury without mortality and neurological deterioration. Intracranial pressure was slightly higher compared to sham group- 5.5 ± 0.74 mmHg and 2.9 ± 0.81 mmHg respectively. Conclusion : This model is an eligible tool to create graded brain injury with stepwise intracranial pressure elevation. 10.3340/jkns.2010.47.1.7

Background: Chronic hypoxia induces lung vascular remodeling, which results in pulmonary hypertension. Vascular remodeling is associated with collagenolysis and activation of matrix metalloproteinases (MMPs). One of the possible sources of MMPs in hypoxic lung are mast cells. Objective: The role of lung mast cell collagenolytic activity in hypoxic pulmonary hypertension was tested by the inhibitor of mast cell degranulation disodium cromoglycate (DSCG). Methods: Rats were treated with DSCG in an early or later phase of isobaric hypoxia. Control groups were exposed to hypoxia only or to normoxia. Lung hemodynamics, muscularization and collagen metabolism in the walls of peripheral pulmonary vessels in the lungs were measured. Results: DSCG applied at an early phase of exposure to hypoxia reduced the development of pulmonary hypertension, inhibited muscularization in peripheral pulmonary arteries and decreased the amount of collagen cleavage fragments in prealveolar vessels. Conclusions: Mast cell degranulation plays a role in the initiation of hypoxic pulmonary vascular remodeling.

The role of the cerebellum in complex skilled movements was assessed by the use of functional ablation technique. Rats were trained to synchronize tongue and forepaw movements in a drinking box equipped with a retractable spout which was automatically withdrawn after every lick but could be returned by pressing and releasing a lever placed 4 cm below the spout. The animals learned to perform short presses synchronized with the lick cycle in such a way as to allow continuous drinking. The contribution of the neocerebellum to these lick-associated instrumental movements was estimated by intracranial injection of 2 ng of tetrodotoxin into the dentate and lateral part of interposed nuclei. Bilateral blockade of the mainly neocerebellar output interfered with learned synchronization of licking and bar pressing, but did not suppress licking from a stationary spout and only decreased the licking frequency by 10%. It is concluded that the tongue-forepaw synchronization is disrupted by elimination of the neocerebellar output but for a much shorter time (9 h) than the tetrodotoxin-induced inactivation of the lateral part of the caudate nucleus (72 h) reported earlier. The results confirm participation of cerebellar hemispheres in learned tongue-forepaw synchronization, but indicate at the same time that elimination of this link can be easily compensated.

Chronic hypoxia induces an increased production of nitric oxide (NO) in pulmonary prealveolar arterioles. Bioavailability of the NO in the pulmonary vessels correlates with concentration of L-arginine as well as activity of phosphodiesterase-5 enzyme (PDE-5). We tested a hypothesis whether a combination of L-arginine and PDE-5 inhibitor sildenafil has an additive effect in reduction of the hypoxic pulmonary hypertension (HPH) in rats. Animals were exposed to chronic normobaric hypoxia for 3 weeks. In the AH group, rats were administered L-arginine during chronic hypoxic exposure. In the SH group, rats were administered sildenafil during chronic hypoxic exposure. In the SAH group, rats were treated by the combination of L-arginine as well as sildenafil during exposure to chronic hypoxia. Mean PAP, structural remodeling of peripheral pulmonary arterioles (%DL) and RV/LV+S ratio was significantly decreased in the SAH group compared to hypoxic controls even decreased compared to the AH and the SH groups in first two measured parameters. Plasmatic concentration of cGMP and NOx were significantly lower in the SAH group compared to hypoxic controls. We demonstrate that NO synthase substrate L-arginine and phosphodiesterase-5 inhibitor sildenafil administered in combination are more potent in attenuation of the HPH compared to a treatment by substances given alone.