ABSTRACT
Photodynamic treatment (PDT) causes a significant increase in the permeability of the blood-brain barrier (BBB) in healthy mice. Using different doses of laser radiation (635 nm, 10-40 J/cm2) and photosensitizer (5-aminolevulinic acid - 5-ALA, 20 and 80 mg/kg, i.v.), we found that the optimal PDT for the reversible opening of the BBB is 15 J/cm2 and 5-ALA, 20 mg/kg, exhibiting brain tissues recovery 3 days after PDT. Further increases in the laser radiation or 5-ALA doses have no amplifying effect on the BBB permeability, but are associated with severe damage of brain tissues. These results can be an informative platform for further studies of new strategies in brain drug delivery and for better understanding of mechanisms underlying cerebrovascular effects of PDT-related fluorescence guided resection of brain tumor.
ABSTRACT
Sex differences in stress-related diseases such as stroke and stomach cancer are well established, but the mechanisms underlying this phenomenon remain unknown. Despite the fact that sexual hormones play an important role in the high resistance of females to harmful effects of stress compared with males, the regulation of oxygenation status can be a potential factor, which might explain sex differences in stress-induced cerebrovascular catastrophes in newborn rats and in mutagens activation in adult rats with stomach cancer.
Subject(s)
Cerebral Cortex/metabolism , Gastric Mucosa/metabolism , Oxygen/metabolism , Stomach Neoplasms/etiology , Stress, Psychological/complications , Stroke/etiology , Animals , Animals, Newborn , Cell Hypoxia , Cerebral Cortex/pathology , Disease Models, Animal , Female , Gastric Mucosa/pathology , Housing, Animal , Male , Nitrosamines , Noise/adverse effects , Oxygen/blood , Rats , Sex Factors , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Stress, Psychological/metabolism , Stroke/metabolism , Stroke/pathology , Tumor HypoxiaABSTRACT
We studied the level of blood oxygen saturation (SpO2) in the brain in newborn rats in the pre- and post-stroke periods, as well as the changes in cerebral blood flow and beta-arrestin-1 as a marker of hypoxic stress. Our results show that mild hypoxia precedes the stroke development and is associated with venous relaxation and decrease blood outflow from the brain resulting in the elevation of synthesis of beta-arrestin-1 in the brain. The incidence of stroke is characterized by severe hypoxia, which is accompanied by the progression of pathological changes in cerebral veins and the high level of beta-arrestin-1.
Subject(s)
Brain/blood supply , Brain/metabolism , Cerebrovascular Circulation , Hypoxia/blood , Intracranial Hemorrhages/blood , Oxygen Consumption , Oxygen/blood , Stroke/blood , Animals , Animals, Newborn , Biomarkers/blood , Cell Hypoxia , Cerebral Veins/metabolism , Cerebral Veins/physiopathology , Disease Models, Animal , Hypoxia/physiopathology , Intracranial Hemorrhages/physiopathology , Rats , Stroke/physiopathology , Time Factors , Up-Regulation , Vasodilation , beta-Arrestin 1/metabolismABSTRACT
Stress is a major factor for a risk of cerebrovascular catastrophes. Studying of mechanisms underlying stress-related brain-injures in neonates is crucial for development of strategy to prevent of neonatal stroke. Here, using a model of sound-stress-induced intracranial hemorrhages in newborn rats and optical methods, we found that cerebral veins are more sensitive to the deleterious effect of stress than arteries and microvessels. The development of venous insufficiency with decreased blood outflow from the brain accompanied by hypoxia, reduction of complexity of venous blood flow and high production of beta-arrestin-1 are possible mechanisms responsible for a risk of neonatal hemorrhagic stroke.
