Group II Metabotropic Glutamate Receptors Reduce Apoptosis and Regulate BDNF and GDNF Levels in Hypoxic-Ischemic Injury in Neonatal Rats

Abstract

Birth asphyxia causes brain injury in neonates, but a fully successful treatment has yet to be developed. This study aimed to investigate the effect of group II mGlu receptors activation after experimental birth asphyxia (hypoxia-ischemia) on the expression of factors involved in apoptosis and neuroprotective neurotrophins. Hypoxia-ischemia (HI) on 7-day-old rats was used as an experimental model. The effects of intraperitoneal application of mGluR2 agonist LY379268 (5 mg/kg) and the specific mGluR3 agonist NAAG (5 mg/kg) (1 h or 6 h after HI) on apoptotic processes and initiation of the neuroprotective mechanism were investigated. LY379268 and NAAG applied shortly after HI prevented brain damage and significantly decreased pro-apoptotic Bax and HtrA2/Omi expression, increasing expression of anti-apoptotic Bcl-2. NAAG or LY379268 applied at both times also decreased HIF-1α formation. HI caused a significant decrease in BDNF concentration, which was restored after LY379268 or NAAG administration. HI-induced increase in GDNF concentration was decreased after administration of LY379268 or NAAG. Our results show that activation of mGluR2/3 receptors shortly after HI prevents brain damage by the inhibition of excessive glutamate release and apoptotic damage decrease. mGluR2 and mGluR3 agonists produced comparable results, indicating that both receptors may be a potential target for early treatment in neonatal HI.

Cognitive impairment is associated with BDNF‐TrkB signaling mediating synaptic damage and reduction of amino acid neurotransmitters in heart failure

“…Firstly, ischemia and hypoxia resulting from heart failure may lead to a decrease in BDNF levels. 68 Secondly, elevated miR-1 levels in the heart and blood of myocardial infarction may enter the brain through blood circulation, leading to a decrease in BDNF expression levels in the brain and ultimately leading to cognitive impairment. 69,70 Finally, both HF and CI share common pathological mechanisms, such as inflammation.…”

Dexmedetomidine alleviates cognitive impairment by promoting hippocampal neurogenesis via BDNF/TrkB/CREB signaling pathway in hypoxic–ischemic neonatal rats

“…1 Multiple studies 31,32 have demonstrated altered BDNF levels following HI insults, with reported increases and decreases in various brain regions. Specifically, several of these studies 33,34 have proposed that HI insults induce neurobehavioral deficits by decreasing BDNF levels in the developing brain.…”

“… 1 Multiple studies 31 , 32 have demonstrated altered BDNF levels following HI insults, with reported increases and decreases in various brain regions. Specifically, several of these studies 33 , 34 have proposed that HI insults induce neurobehavioral deficits by decreasing BDNF levels in the developing brain. Consistent with these observations, the present study confirmed a rapid decrease in BDNF levels in the ipsilateral hippocampus following neonatal HIBD.…”

Overexpression of Brain- and Glial Cell Line-Derived Neurotrophic Factors Is Neuroprotective in an Animal Model of Acute Hypobaric Hypoxia

“…Indeed, a number of studies have shown that recombinant neurotrophic factors are highly effective in models of various pathologies, including cerebral ischemia and neurodegenerative diseases, both in vitro and in vivo [ 25 , 26 , 34 , 35 , 36 ]. However, many methodological difficulties, including overcoming the blood–brain barrier and the short period of active molecules’ degradation, call into question the potential use of BDNF and GDNF in clinical practice.…”