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

Abstract

Neonatal hypoxic-ischemic (HI) brain injury is a devastating disease that often leads to death and detrimental neurological deficits. The present study was designed to evaluate the ability of metformin to provide neuroprotection in a model of neonatal hypoxic-ischemic brain injury and to study the associated molecular mechanisms behind these protective effects. Here, we found that metformin treatment remarkably attenuated brain infarct volumes and brain edema at 24 h after HI injury, and the neuroprotection of metformin was associated with inhibition of neuronal apoptosis, suppression of the neuroinflammation and amelioration of the blood brain barrier breakdown. Additionally, metformin treatment conferred long-term protective against brain damage at 7 d after HI injury. Our study indicates that metformin treatment protects against neonatal hypoxic-ischemic brain injury and thus has potential as a therapy for this disease.

Neuroprotective exendin-4 enhances hypothermia therapy in a model of hypoxic-ischaemic encephalopathy

“…Additionally, high dose exendin-4 administration resulted in significantly higher levels of brain cAMP, suggesting involvement of the cAMP signalling pathway, also proposed in other studies ( Teramoto et al , 2011 ; Kim et al , 2017 ). Interestingly, metformin, another type 2 diabetes mellitus medication with diverse pharmacological activities, also ameliorates brain infarction in neonatal hypoxic-ischaemic rats ( Fang et al , 2017 ).…”

Behavioral, cognitive and histological changes following neonatal anoxia: Male and female rats' differences at adolescent age

“…On the other hand, age impacts on brain functioning, once it was observed in a previous study that the same neonatal anoxia model, at PND 90, decreased the %OAT and the percentage of time spent on the closed arm was significantly higher in adult male subjected to neonatal anoxia than in control animals Which altered cellular mechanisms would be responsible for these damages? Accumulated evidence has acknowledged the following events: neuronal apoptosis, reactive gliosis, oxidative stress, excitotoxicity, inflammation and disruption of blood-brain barrier as linked to the neonatal brain damage induced by neonatal anoxia (Beilharz et al, 1995;Buwalda et al, 1995;Wei et al, 2004;Borutaite et al, 2013;Fang et al, 2017;Li et al, 2017;Li et al, 2018). Notably, sex-specificity in many of these processes occurs in normal brain development and may be a reason to male and female differentially respond to neonatal oxygen deprivation, which in turn alters their developmental program and cognitive functions, as also shown in the onset of ontogenetic reflexes and somatic development (Kumar et al, 2017).…”

Metformin Promotes Axon Regeneration after Spinal Cord Injury through Inhibiting Oxidative Stress and Stabilizing Microtubule

“…Recently, studies have shown that metformin treatment has improved locomotor recovery after SCI [31,32], but the underlying mechanism of its action is still unclear, especially its role in reducing oxidative stress or promoting axonal regeneration after SCI. Moreover, the other studies have indicated that metformin can protect against hypoxic-ischemic brain injury-induced neuronal cell apoptosis [33]. However, it is unknown whether metformin protects against neuronal damage after SCI by promoting axonal regeneration.…”