The mechanisms involving neuronal death after ischemic/hypoxic insult are complex, involving both rapid (excitotoxic) and delayed (apoptotic-like) processes. Recent evidence suggests that cell cycle regulators such as cyclin-dependent kinases are abnormally activated in neuropathological conditions, including stroke. However, the function of this activation is unclear. Here, we provide evidence...

Dynamic regulation of the expression of surface AMPA receptors (AMPARs) is a key mechanism to modulate synaptic strength and efficacy in the CNS and also to regulate auditory sensitivity. Here we address the role of surface AMPAR expression in excitotoxicity by blocking clathrin-mediated AMPAR endocytosis in auditory neurons. We used a membrane-permeable, dynamin-derived, myristoylated peptide ...

We present a new animal model of perinatal hypoxic/ischemic brain damage and compare this type of brain damage with the excitotoxic type of damage previously described in the brains of infant rats and monkeys treated systemically with glutamate (Glu). Ten-d-old rats with unilateral occlusion of the common carotid artery were subjected to hypobaric conditions for 75 min and sacrificed 0-4 hr lat...

The endogenous excitotoxin, glutamate (Glu), acting at the N-methyl-aspartate (NMA) subtype of Glu receptor, is thought to play a major role in hypoxic/ischemic neuronal degeneration. In the present study, the sensitivities of the developing rat CNS to hypoxic/ischemic neuronal degeneration and to the neurotoxic action of NMA were compared at various postnatal ages. In the hypoxic/ischemic expe...

NMDA receptors (NMDARs) mediate ischemic brain damage, for which interactions between the C termini of NR2 subunits and PDZ domain proteins within the NMDAR signaling complex (NSC) are emerging therapeutic targets. However, expression of NMDARs in a non-neuronal context, lacking many NSC components, can still induce cell death. Moreover, it is unclear whether targeting the NSC will impair NMDAR...

Overactivation of NMDA receptors is believed to induce neuronal death by increasing phospholipid hydrolysis and subsequent degradation. We showed previously that NMDA releases choline and inhibits incorporation of [3H]choline into phosphatidylcholine before excitotoxic neuronal death. On the basis of these results, we hypothesized that excitotoxicity results from inhibition of synthesis rather ...

Erythropoietin (Epo) has been gaining great interest for its potential neuroprotective effect in various neurological insults. However, the molecular mechanism underlying how Epo exerts the function is not clear. Recent studies have indicated that Zn(2+) may have a key role in selective cell death in excitotoxicity after injury. In the present study, we studied the effect of recombinant human E...

Endocannabinoids are released in response to pathogenic insults, and inhibitors of endocannabinoid inactivation enhance such on-demand responses that promote cellular protection. Here, AM374 (palmitylsulfonyl fluoride), an irreversible inhibitor of fatty acid amide hydrolase (FAAH), was injected i.p. into rats to test for endocannabinoid enhancement. AM374 caused a prolonged elevation of ananda...