Effects of Manganese (Mn) on the Developing Rat Brain: Oxidative-Stress Related Endpoints

Dysregulated glutamate signaling, leading to neuronal excitotoxicity and death, has been associated with neurodegenerative pathologies. 17β-estradiol (E2) is a human steroid hormone having a role in reproduction, sexual maturation, brain health and biological activities. The study aimed to explain the neuroprotective role of E2 against glutamate-induced ROS production, MAP kinase-dependent neuroinflammation, synaptic dysfunction and neurodegeneration in the cortex and hippocampus of postnatal day 7 rat brain. Biochemical and immunofluorescence analyses were applied. Our results showed that a single subcutaneous injection of glutamate (10 mg/kg) induced brain oxidative stress after 4 h by disturbing the homeostasis of glutathione (GSH) and revealed an upsurge in ROS and LPO levels and downregulated the expression of Nrf2 and HO-1 antioxidant protein. The glutamate-exposed P7 pups illustrated increased phosphorylation of stress-activated c-Jun N-terminal kinase (JNK) and p38 kinase (p38) and downregulated expression of P-Erk1/2. This was accompanied by pathological neuroinflammation as revealed by enhanced gliosis with upregulated expression of GFAP and Iba-1, and the activation of proinflammatory cytokines (TNF-α) in glutamate-injected P7 pups. Moreover, exogenous glutamate also reduced the expression of synaptic markers (PSD-95, SYP) and induced apoptotic neurodegeneration in the cortical and hippocampal regions by dysregulating the expression of Bax, Bcl-2 and caspase-3 in the developing rat brain. On the contrary, co-treatment of E2 (10 mg/kg) with glutamate significantly abrogated brain neuroinflammation, neurodegeneration and synapse loss by alleviating brain oxidative stress by upregulating the Nrf2/HO-1 antioxidant pathway and by deactivating pro-apoptotic P-JNK/P-p38 and activation of pro-survival P-Erk1/2 MAP kinase pathways. In brief, the data demonstrate the neuroprotective role of E2 against glutamate excitotoxicity-induced neurodegeneration. The study also encourages future studies investigating if E2 may be a potent neuroprotective and neurotherapeutic agent in different neurodegenerative diseases.

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Protective effects of Celosia argentea Linn. Vitamin E and dexamethasone on radiation-induced damage on the developing rat cerebellum

Anatomy Journal of Africa ◽

10.4314/aja.v8i2.190407 ◽

2019 ◽

Vol 8 (2) ◽

pp. 1647-1661 ◽

Cited By ~ 1

Author(s):

Love Chioma Kanu ◽

Olatunde Owoeye ◽

Innocent Ohiorenuan Imosemi ◽

Adelofolarin Obanishola Malomo

Keyword(s):

Oxidative Stress ◽

Vitamin E ◽

Gamma Radiation ◽

Rat Brain ◽

Control Group ◽

Rat Cerebellum ◽

Group I ◽

Celosia Argentea ◽

Radiation Induced ◽

Developing Rat

The potential neuroprotective effect of aqueous extract of Celosia argentea Linn (AECA), Vitamin E (Vit E) and Dexamethasone (Dexa) on radiation-induced damage on the developing rat cerebellum was studied. Forty-two female rats weighing between 147 g and 222 g were randomized into six groups (N=7). Control group – Group I, Irrad group – Group II, AECA group – Group III, AECA + Irrad group – Group IV, Vit E + Irrad group – Group V and Dexa+ Irrad group – Group VI. Rats were mated and pregnant rats were exposed to 2.5 Gy gamma radiation on gestation day 7. The administration of 400 mg/kg of AECA, 500 mg/kg of Vit E and 0.005 ml/rat of Dexa started from gestation day 1 till postnatal day 28. Postpartum, 5 pups from each group were exposed to behavioural and biochemical tests and then sacrificed. Brain tissue fixed in 10% formalin, processed by paraffin wax method was stained with H&E and Cresyl violet stains for histology. Radiation significantly (p<0.05) reduced gross, behavioural, histological and histomorphometric parameters, while eliciting oxidative stress relative to control group on post-natal days 7, 14, 21 and 28. Treatment with AECA, Vit E and Dexa with radiation significantly (p<0.05) reduced most of the alterations induced by radiation in the various parameters. This study confirmed development of oxidative stress in rat pups using single dose 2.5 Gy gamma-irradiation. The antioxidant properties of AECA and Vit E and the anti-inflammatory property of Dexa were able to mitigate the alterations in the developing rat brain parameters.Key words: Gamma-radiation, neuroprotective, plant products, rat brain.

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Oxidative Stress in the Developing Rat Brain due to Production of Reactive Oxygen and Nitrogen Species

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/5057610 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 26

Author(s):

Jiří Wilhelm ◽

Richard Vytášek ◽

Jiří Uhlík ◽

Luděk Vajner

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Lipid Peroxidation ◽

Rat Brain ◽

Strong Correlation ◽

Reactive Oxygen ◽

Nitrogen Species ◽

Elastic Laminae ◽

Further Development ◽

Developing Rat

Oxidative stress after birth led us to localize reactive oxygen and nitrogen species (RONS) production in the developing rat brain. Brains were assessed a day prenatally and on postnatal days 1, 2, 4, 8, 14, 30, and 60. Oxidation of dihydroethidium detected superoxide; 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate revealed hydrogen peroxide; immunohistochemical proof of nitrotyrosine and carboxyethyllysine detected peroxynitrite formation and lipid peroxidation, respectively. Blue autofluorescence detected protein oxidation. The foetuses showed moderate RONS production, which changed cyclically during further development. The periods and sites of peak production of individual RONS differed, suggesting independent generation. On day 1, neuronal/glial RONS production decreased indicating that increased oxygen concentration after birth did not cause oxidative stress. Dramatic changes in the amount and the sites of RONS production occurred on day 4. Nitrotyrosine detection reached its maximum. Day 14 represented other vast alterations in RONS generation. Superoxide production in arachnoidal membrane reached its peak. From this day on, the internal elastic laminae of blood vessels revealed the blue autofluorescence. The adult animals produced moderate levels of superoxide; all other markers reached their minimum. There was a strong correlation between detection of nitrotyrosine and carboxyethyllysine probably caused by lipid peroxidation initiated with RONS.

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