Effect of a neuroprotective exercise protocol on oxidative state and BDNF levels in the rat hippocampus.

Daily moderate intensity exercise (2 weeks of 20 min/day of treadmill training), which reduces damage to hippocampal slices from rats submitted to in vitro ischemia, did not modify oxidative stress parameters in the hippocampus nor the brain-derived neurotrophic factor (BDNF) levels in different brain regions. The aim was to investigate whether the modulation of hippocampal oxidative status and/or brain BDNF content is involved in exercise-induced neuroprotection. Wistar rats were submitted to daily exercise in the treadmill and were sacrificed approximately 16 h after the last treadmill running. Some several oxidative stress parameters were determined, specifically the free radical levels, the macromolecule damage, the total reactive antioxidant potential and reactivity levels, which represent the total antioxidant capacity, in the hippocampus. In addition, BDNF levels in different rat cerebral regions (hippocampus, cortex, striatum, and the cerebellum) were measured by ELISA. The used exercise protocol did not affect any oxidative stress parameters studied in the hippocampus, suggesting that it does not cause a significant oxidative stress nor induce adaptations of the cellular antioxidant system. Treadmill training also did not change the BDNF content in brain areas studied. Considering the fact that this exercise protocol have been shown to be neuroprotective, we might speculate that BDNF levels and oxidative status may not be directly involved with the mechanisms of exercise-induced neuroprotection after ischemia.

Exercise intensity influences cell injury in rat hippocampal slices exposed to oxygen and glucose deprivation.

We evaluated the effects of two levels of daily forced exercise intensity (moderate and high) in the treadmill over cell susceptibility to oxygen and glucose deprivation (OGD) in hippocampal slices from Wistar rats. Moderate exercise decreased lactate dehydrogenase (LDH) release after OGD, while a significant increase in LDH release was observed in the high intensity group submitted to OGD. Our data corroborate the hypothesis that higher training intensity exacerbates brain damage, while a moderate intensity reduces the injury caused by in vitro ischemia.

Total antioxidant capacity is impaired in different structures from aged rat brain.

Our data support a disproportion between free radicals levels and scavenging systems activity in different cerebral regions of the aging rat. We investigated the total reactive antioxidant potential and reactivity levels, which represent the total antioxidant capacity, in different cerebral regions of the aging rat (cortex, striatum, hippocampus and the cerebellum). In addition, we have determined several oxidative stress parameters, specifically the free radicals levels, the macromolecules damage (lipid peroxidation and carbonyl content), as well as the antioxidant enzymes activities in different cerebral areas from young (2 months-old), mature adult (6 months-old) and old (24 months-old) male Wistar rats. Free radicals levels, determined by 2',7'-dichlorofluorescein diacetate probe, were higher in striatum, cerebellum and hippocampus from aged rats. There was an age-related increase in lipoperoxidation in hippocampus and cerebral cortex. In the cerebellum, a high activity of superoxide dismutase and a decrease of catalase activity were observed. The striatum exhibited a significant catalase activity decrease; and glutathione peroxidase activity was diminished in the hippocampus of mature and aged rats. There was a marked decrease of total antioxidant capacity in hippocampus in both reactivity and potential levels, whereas striatum and cerebral cortex displayed a reduction on reactivity assay. We suggest that age-related variations of total antioxidant defenses in brain may predispose structures to oxidative stress-related neurodegenerative disorders.

Aging affects oxidative state in hippocampus, hypothalamus and adrenal glands of Wistar rats.

The aging process is associated with cognitive impairment and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as well as with oxidative stress. We determined some parameters of oxidative stress in homogenates of hippocampus, hypothalamus and adrenal glands from male 2-, 6- and 24-months-old Wistar rats. A significant age-dependent increase in the generation of free radicals was observed in hippocampus, hypothalamus and adrenal glands, as well as on lipid peroxidation in hippocampus and hypothalamus. The glutathione peroxidase (GPx) activity was significantly reduced in hypothalamus and hippocampus from 6-months-old rats; a decline on GPx and catalase activities in adrenal glands of 24-months-old animals was also present. Interestingly, a great decrease in total antioxidant capacity was found in all tissues tested. Reported findings support the idea that oxidative events participate on multiple neuroendocrine-metabolic impairments and suggest that the oxidative stress found in hippocampus, hypothalamus and adrenals might be associated with age-related physiological deficits.

Age-related susceptibility to oxygen and glucose deprivation damage in rat hippocampal slices.

Aging is an important risk factor for stroke. We evaluated the effects of aging on cell susceptibility to oxygen and glucose deprivation (OGD) in slices of the hippocampus from Wistar rats aged 2, 11 and 24 months. Lactate dehydrogenase (LDH) released to the incubation media and free radical content were markedly increased in the 24-month group submitted to OGD. These results confirm that hippocampal tissue from old animals is more susceptible to ischemia-reoxygenation injury.

Hippocampal antioxidant system in neonates from methylmercury-intoxicated rats.

Methylmercury (MeHg) is a well-known environmental pollutant toxic to the nervous tissue, particularly during development. We recently described transitory hippocampal changes in neonate rats prenatally exposed to MeHg. In this study, we evaluate oxidative stress in the hippocampus on the 1st and 30th postnatal days. Motor behavior (open-field, foot-fault and strength tests) of these animals also was studied after the 30th postnatal day. Female Wistar rats were injected with MeHg (5 mg/Hg/day) on the 12th, 13th and 14th gestational days. Biochemical parameters measured for oxidative stress were levels of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). Total antioxidant reactivity (TAR) and protein oxidation (contents of tryptophan and tyrosine) were also recorded. Our results showed low activities of antioxidant enzymes in the MeHg group at birth. SOD activity remained reduced on the 30th postnatal day. Moreover, a decrease of TAR and protein oxidation was observed only at 30 days of age. No changes were observed in the motor behavior of these animals. Although mercury content in hippocampus is present at undetectable levels at 30 days of age, we observed more persistent changes in oxidative balance. Our data confirm that mercury induces oxidative stress in hippocampus and that this alteration, particularly SOD activity, remained altered even when mercury was no longer present.

Neuroprotective effects of Ptychopetalum olacoides Bentham (Olacaceae) on oxygen and glucose deprivation induced damage in rat hippocampal slices.

Alcoholic infusions of Ptychopetalum olacoides Bentham (PO, Olacaceae) are used in traditional medicine by patients presenting age associated symptoms and those recovering from stroke. The aim of this study is to evaluate the neuroprotective properties of PO ethanol extract (POEE) using hippocampal slices from Wistar rats exposed to oxygen and glucose deprivation (OGD, followed by reoxygenation). Mitochondrial activity, an index of cell viability, was assessed by the MTT assay; in addition, the free radicals content was estimated by the use of dichlorofluorescein diacetate as probe. The OGD ischemic condition significantly impaired cellular viability, and increased free radicals generation. In non-OGD slices, incubation with POEE (0.6 microg/ml) increased (approximately 40%) mitochondrial activity, without affecting free radicals levels. In comparison to OGD controls, slices incubated with POEE (0.6 microg/ml) during and after OGD exposure had significantly increased cellular viability. In addition, at this same concentration, POEE prevented the increase of free radicals content induced by OGD. In view of the fact that respiratory chain inhibition and increased generation of free radicals are major consequences of the ischemic injury, this study suggests that Ptychopetalum olacoides contains useful neuroprotective compounds and, therefore, deserves further scrutiny.

S100B content and SOD activity in amniotic fluid of pregnancies with Down syndrome.

OBJECTIVES: We measured S100B levels and superoxide dismutase (SOD) activity retrospectively in amniotic fluid samples from pregnancies with normal and Down syndrome (DS) fetuses. DESIGN AND METHODS: Samples from 26 normal and 71 Down syndrome fetuses were studied. S100B protein levels were determined using LIA-mat Sangtec kit, and SOD activity was measured with the RANSOD kit. RESULTS: We observed significantly higher levels of S100B in the Down group (median of 1.24 microg/l) than in the control group (median 0.69 microg/l). S100B concentration in DS samples increased from the 13th to the 18th week of gestation and was positively correlated with gestational age. The amniotic fluid SOD activity in the DS group (16.60 U/mg/prot) was significantly higher than in the normal one (10.78 U/mg/prot). CONCLUSIONS: This study indicates that S100B and SOD in amniotic fluid could be used as additional parameters for prenatal screening of trissomy 21 and that S100B values are associated with the gestational age.

Ptychopetalum olacoides, a traditional Amazonian "nerve tonic", possesses anticholinesterase activity.

The cholinergic hypothesis of Alzheimer disease (AD) has provided the rationale for the current pharmacotherapy of this disease, in an attempt to downgrade the cognitive decline caused by cholinergic deficits. Nevertheless, the search for potent and long-acting acetylcholinesterase (AChE) inhibitors that exert minimal side effects to AD patients is still an ongoing effort. Amazonian communities use traditional remedies prepared with Ptychopetalum olacoides (PO, Olacaceae) roots for treating various central nervous system conditions, including those associated with aging. The fact that PO ethanol extract (POEE) has been found to facilitate memory retrieval in the step down procedure in young and aged mice prompt us to evaluate its effects on AChE activity in memory relevant brain areas. POEE significantly inhibited AChE activity in vitro in a dose- and time-dependent manner in rat frontal cortex, hippocampus and striatum; a significant inhibition was also found in these same brain areas of aged (14 months) mice after acute administration of POEE (100 mg/kg ip). We propose that such AChE inhibitory activity is a neurochemical correlate of a number of therapeutic properties traditionally claimed for P. olacoides, particularly those associated with cognition.