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

Abstract

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.

Postnatal Antioxidant and Anti-inflammatory Treatments Prevent Early Ketamine-Induced Cortical Dysfunctions in Adult Mice

“…Supporting these findings, previous observations, obtained on the same animal model, showed both early and persistent increased levels of 8-hydroxydeoxyguanosine (8OHdG), an indirect marker of oxidative stress, and NOX2, a ROS-producing enzyme, in the same brain region ( Schiavone et al, 2020 ). Accordingly, it has been reported that, although oxidative stress contributes to the physiological postnatal brain development in rodents, the effects of increased ROS levels on the CNS, following an external insult, might be revealed later in life ( Wilhelm et al, 2016 ). Moreover, antioxidant treatment with N-acetyl cysteine in mice could prevent cognitive and behavioral dysfunctions at adulthood, resulting from ketamine administration at PNDs 7, 9, and 11 ( Phensy et al, 2017 ).…”

Inhibition of HDAC3 Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice In Vivo and In Vitro

“…The remarkable increase of reactive oxygen species (ROS) is one of the pathophysiological characteristics of diabetes [40]. ROS can not only directly cause oxidative damage of tissues and organs but also indirectly inhibit the activity of the endothelial nitric oxide synthase (eNOS) via the decoupling and activation of PKC- β , which induces the production of peroxynitrite anion (ONOO − ) with stronger protein nitration ability and cytotoxicity, thereby aggravating the injury [41, 42]. It suggests that the enhancements of oxidative stress and the secondary damage caused by enhanced oxidative stress in diabetic state are probably the main reasons why the organs of diabetic patients are vulnerable to I/R injury.…”

Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin

“…In particular, the possibility that local oxidative stress and inflammation events are indeed the key focal determinants of lesion development and may act in concert to drive CCM pathogenesis can explain the clear discrepancy between the pan-endothelial loss of CCM proteins and the focal nature of CCM lesions in neonatal mouse models (Boulday et al, 2011, Chan et al, 2011). Intriguingly, there is evidence that oxidative stress occurs after normal birth (Wilhelm et al, 2016), as well as that the immature brain is particularly susceptible to free radical injury because of its poorly developed scavenging systems and high availability of iron for the catalytic formation of free radicals (Blomgren and Hagberg, 2006). Besides providing further support to the role of oxidative stress in CCM pathogenesis, these observations could also explain why the formation of CCM-like lesions in neonatal mouse models of CCM disease occur only if the endothelial-specific deletion of CCM genes is induced immediately after birth (P1) but not in the adult phase (Boulday et al, 2011).…”