NMDA receptors hypoxia

Sebastiao AM, de Mendonca A, Moreira T, Ribeiro JA (2001) Activation of synaptic NMDA receptors by action potential-dependent release of transmitter during hypoxia impairs recovery of synaptic transmission on reoxygenation. J Neurosci 21(21) 8564-8571 Shen H, Chen GJ, Harvey BK, Bickford PC, Wang Y (2005) Inosine reduces ischemic brain injury in rats. Stroke 36(3) 654-659... 

Environmental factors that contribute to the development of schizophrenia also converge on NMDA receptors. For example, it has been hypothesized that perinatal hypoxia, an important risk factor for schizophrenia, leads to the neurotoxic degeneration of NMDA-bearing cells, an effect that may only produce behavioral symptoms later in development (Olney et al., 1999). 

A third excitatory amino acid (EAA) receptor that is now receiving attention is the N-methyl-D-aspartate (NMDA) receptor. This receptor may be involved in epileptic discharges and hypoxia damage. There are also selective agonists (NMDA and cyclopentane glutamate) and a selective antagonist (D-APV5) available for sophisticated studies to demonstrate the extent brain processes are affected by NMDA activation of its receptors. 

Excitotoxicity also plays a role in epileptic seizures and cerebral ischemia. During ischemic injury, a rapid accumulation of glutamate takes place. This induces a noxious Ca + influx into the cytoplasm. The Ca + conductance of NMDA receptors explains the efficacy of NMDA antagonists against hypoxic damage. In addition, AMPA antagonists have also a protective function in hypoxia (Siesjo et al., 1991)... 

Gurd, J. W., Bissoon, N., Beesley, P. W., Nakazawa, T., Yamamoto, T., and Vannucci, S. J. (2002). Differential effects of hypoxia-ischemia on subunit expression and tyrosine phosphorylation of the NMDA receptor in 7- and 21-day-old rats. J. Neurochem. 82, 848-856. 

Fetal guinea pig and newborn piglet model stndies have demonstrated that brain tissue hypoxia results in brain cell membrane damage as evidenced by increased membrane lipid peroxidation and decreased Na+, K+-ATPase activity. Brain hypoxia was found to increase the NMDA receptor agonist-dependent Ca + in synaptosomes of hypoxic as compared to normoxic fetuses (Mishra and Delivoria-Papadopoulos, 1999). 

Memantine has been known since 1963 and was used in several human diseases such as Parkinson s disease and stroke. This compound affects several transmitters [203] and has an anti-hypoxia and anti-ischaemia effect. It is a non-competitive antagonist of NMDA receptors and blocks Ca entry through serotonin operated channels and binds to the phencyclidine recognition site in the NMDA-operated Ca channel [204,205]. 

A. Both dextromethorphan and its o-demethylated metabolite appear to antagonize /V-methyl-D-aspartate (NMDA) glutamate receptors, which may explain anticonvulsant properties and protection against hypoxia-ischemia observed in animal models. 

Gozal D, Xue YD, Simakajomboon N. Hypoxia induces c-Fos protein expression in NMDA but not AMPA glutamate receptor labeled neiuons within the nucleus tractus sohtarii of the conscious rat. Neurosci Lett 1999 262 93-96. 

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