Hypoxic postconditioning reduces microglial activation, astrocyte and caspase activity, and inflammatory markers after hypoxia–ischemia in the neonatal rat brain

Abstract

Background: Postconditioning (PostC) with mild hypoxia shortly after a neonatal hypoxic-ischemic (HI) brain injury can reduce brain damage, however, the mechanisms underlying this protection are not known. We hypothesize that hypoxic PostC reduces brain markers of glial activity, inflammation, and apoptosis following HI injury. Methods: Sprague Dawley rat pups were exposed to right common carotid artery occlusion and hypoxia (7% oxygen, 3 h) on postnatal day 7 and 24 h later, pups were exposed to hypoxic PostC (8% O 2 for 1 h/day for 5 d) or kept at ambient conditions for the same duration. HI+N pups demonstrated ~10% loss in ipsilateral brain tissue which was rescued with HI+PostC. To investigate the cellular responses, markers of astrocytes, microglia, inflammation, and caspase 3 activity were examined using immunohistochemistry and enzyme-linked immunosorbent assay. results: PostC reduced the area of astrocyte staining compared to HI+N. There was also a shift in microglial morphology toward a primed state in both PostC groups. Protein levels of interleukin-1β and caspase 3 were elevated in HI+N brains and reduced by PostC. conclusion: This is the first demonstration that PostC can reduce glial activity, inflammatory mediators, and cell death after a neonatal HI brain injury.

Intranasal C3a treatment ameliorates cognitive impairment in a mouse model of neonatal hypoxic–ischemic brain injury

“…Consistent with previous reports (Chavez-Valdez et al, 2012;Qiu et al, 2007;Teo et al, 2015) we observed HI-induced astrocyte activation in the ipsilateral hippocampus. This astroglial response, which persists for at least 6 weeks after HI, was ameliorated by intranasal C3a treatment in a region specific manner.…”

Metformin treatment after the hypoxia-ischemia attenuates brain injury in newborn rats

“…In the CNS, Microglia are a major glial component and exhibit the function of immune-surveillance in a resting state. However, when the HI event occurs, microglia are strongly activated and release inflammatory factors contributing to inflammatory process in the brain gray matter [ 35 , 37 ]. In our study, we did find that the number of Iba-1 immunostaining cells was significantly increased in the cortex and hippocampus after HI, which indicated that microglia were activated by the HI insult.…”

Resveratrol post-treatment protects against neonatal brain injury after hypoxia-ischemia

“…Cytokines in the CNS are primarily derived from immune cells. Microglia are a major component of the immune cells in the CNS and strongly activated in the neonatal brain [3, 44, 46, 47]. When an ischemic event occurs, microglia are activated, and they release inflammatory factors leading to the deterioration of the injury.…”