Neuroprotection by both NMDA and non-NMDA receptor antagonists in in vitro ischemia

Pringle, Ashley K.; Iannotti, Fausto; Wilde, Geraint J. C.; Chad, John E.; Seeley, P.J.; Sundström, Lars

doi:10.1016/s0006-8993(97)00089-9

Cited by 146 publications

(134 citation statements)

References 62 publications

Supporting

Mentioning

115

Contrasting

Order By: Relevance

“…However, in in vitro models the situation is less clear. Our results are in line with those of Pringle et al (1997), who reported neuroprotective effects of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), another antagonist of the non-NMDA glutamate receptor, after 60 min hypoxia/hypoglycemia. In contrast, Tasker et al (1992) and Laake et al (1999) did not find any protective effect of CNQX.…”

Section: Discussion Energy Deficiency and Loss Of Intracellular Ion Hsupporting

confidence: 93%

“…Subsequently, many studies (e.g. Breder et al, 2000;Hatfield et al, 1992;Lobner and Lipton, 1993;Pringle et al, 1997) including the present one, showed that inhibition of the NMDA receptor by MK-801 rescues especially vulnerable neurons from ischemic damage in vivo and in vitro. In addition, a sudden and large ischemiainduced, mainly NMDA receptor-mediated, increase in [Ca 2ϩ ] i in the CA1 area of gerbil hippocampal slices (Liu et al, 1997), rat hippocampal slices (Zhang and Lipton, 1999) as well as in cortical cell cultures (Goldberg and Choi, 1993) has been reported, further supporting the view that Ca 2ϩ influx through NMDA receptors might determine neuronal vulnerability to ischemic damage.…”

Section: Discussion Energy Deficiency and Loss Of Intracellular Ion Hmentioning

confidence: 63%

“…Moreover, antagonists of this receptor type have been shown to protect neurons in vitro (Newell et al, 1995) and after transient global and focal ischemia (Foster et al, 1988;Hatfield et al, 1992). In contrast, the contribution of AMPA/ kainate receptors to both intracellular Ca 2ϩ and/or Na ϩ accumulation and neuronal cell loss is still controversial (Laake et al, 1999;Pringle et al, 1997;Tasker et al, 1992;Zhang and Lipton, 1999).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Na+ and Ca2+ homeostasis pathways, cell death and protection after oxygen–glucose-deprivation in organotypic hippocampal slice cultures

et al. 2004

View full text Add to dashboard Cite

elevation during OGD was due to Na ؉ influx through voltagedependent Na ؉ channels. In hippocampal slices, cellular degeneration occurring 24 h after OGD, selectively affected the pyramidal cell population through apoptotic and non-apoptotic cell death. OGD-induced cell loss was mediated by activation of ionotropic glutamate receptors, voltage-dependent Na ؉ channels, and both plasma membrane and mitochondrial Na ؉ /Ca 2؉ exchangers. Thus, we show that neuroprotection induced by blockade of NMDA receptors and plasma membrane Na ؉ /Ca 2؉ exchangers is mediated by reduction of Ca 2؉ entry into neuronal soma, whereas neuroprotection induced by blockade of AMPA/kainate receptors and mitochondrial Na ؉ /Ca 2؉ exchangers might result from reduced Na ؉ entry at dendrites level.

show abstract

Section: Discussion Energy Deficiency and Loss Of Intracellular Ion Hsupporting

confidence: 93%

Section: Discussion Energy Deficiency and Loss Of Intracellular Ion Hmentioning

confidence: 63%

mentioning

confidence: 99%

See 1 more Smart Citation

Na+ and Ca2+ homeostasis pathways, cell death and protection after oxygen–glucose-deprivation in organotypic hippocampal slice cultures

et al. 2004

View full text Add to dashboard Cite

show abstract

“…These studies suggested the possible role of glutamate receptors in the induction phase of IPC. This hypothesis was supported by studies in vivo in which inhibition of NMDA receptors with MK-801 during IPC resulted in blockade of ischemic tolerance by IPC in gerbils (Kato et al, 1992b) and in vitro (Pringle et al, 1997b). Gonzalez-Zulueta et al (2000) showed that, during OGD preconditioning in neuronal cell cultures, the signaling cascade was initiated by activation of the NMDA receptors, calcium influx, and production of nitric oxide in an RAS-extracellular signal-regulated protein kinase (ERK)-dependent manner, leading to the development of neuronal tolerance to ischemia.…”

Section: Discussionmentioning

confidence: 82%

“…A previous study by Pringle et al (1997b) in organotypic slice culture demonstrated that administration with 1 M NMDA for 3 hr significantly reduced the neuronal damage produced by either 45 or 60 min of ischemia. In contrast to that study, our data show robust neuroprotection when slices were exposed to NMDA for only 1 hr.…”

Section: Discussionmentioning

confidence: 87%

εPKC Is Required for the Induction of Tolerance by Ischemic and NMDA-Mediated Preconditioning in the Organotypic Hippocampal Slice

et al. 2003

View full text Add to dashboard Cite

Glutamate receptors and calcium have been implicated as triggering factors in the induction of tolerance by ischemic preconditioning (IPC) in the brain. However, little is known about the signal transduction pathway that ensues after the IPC induction pathway. The main goals of the present study were to determine whether NMDA induces preconditioning via a calcium pathway and promotes translocation of the protein kinase C ⑀ (⑀PKC) isozyme and whether this PKC isozyme is key in the IPC signal transduction pathway. We corroborate here that IPC and a sublethal dose of NMDA were neuroprotective, whereas blockade of NMDA receptors during IPC diminished IPC-induced neuroprotection. Calcium chelation blocked the protection afforded by both NMDA and ischemic preconditioning significantly, suggesting a significant role of calcium. Pharmacological preconditioning with the nonselective PKC isozyme activator phorbol myristate acetate could not emulate IPC, but blockade of PKC activation with chelerythrine during IPC blocked its neuroprotection. These results suggested that there might be a dual involvement of PKC isozymes during IPC. This was corroborated when neuroprotection was blocked when we inhibited ⑀PKC during IPC and NMDA preconditioning, and IPC neuroprotection was emulated with the activator of ⑀PKC. The possible correlation between NMDA, Ca 2ϩ , and ⑀PKC was found when we emulated IPC with the diacylglycerol analog oleoylacetyl glycerol, suggesting an indirect pathway by which Ca 2ϩ could activate the calcium-insensitive ⑀PKC isozyme. These results demonstrated that the ⑀PKC isozyme played a key role in both IPC-and NMDA-induced tolerance.

show abstract

Mexiletine and magnesium independently, but not combined, protect against permanent focal cerebral ischemia in Wistar rats

et al. 1999

View full text Add to dashboard Cite

The neuroprotective effect of mexiletine (Mex), a potent Na(+) channel blocker which decreases neuronal energy demands and prevents energy depletion during ischemia, was evaluated in Wistar rats subjected to permanent middle cerebral artery (MCA) occlusion. Postmortem infarct volumes were determined by quantitative image analysis of triphenyltetrazolium (TTC)-stained brain sections. Pretreatment with Mex resulted in a significant infarct volume reduction when administered intraperitoneally, either at the dosage of 50 or 60 mg/kg, 1 hr before MCA occlusion (P < 0.05). Delayed treatment with Mex (50 mg/kg) also had neuroprotective effects when given at 0.5 hr (< 0.05), but not 2-4 hr, after MCA occlusion. Intraarterial administration of MgSO(4) (90 mg/kg), in combination with Mex at 60 mg/kg, showed no additive neuroprotective effect, although each agent independently reduced the MCA occlusion-induced infarction volume (P < 0.05). Our results indicate that a single, acute administration of Mex is neuroprotective against permanent focal cerebral ischemia, but perhaps chronic administration is needed to establish a more effective therapeutic window beyond 0.5 hr. Moreover, the present in vivo data do not favor a combined use of Mg(2+) with Mex for limiting ischemic injury in the brain, since these agents caused cardiopulmonary suppression, which may have led to the loss of the neuroprotective effect of each agent independently.

show abstract

Neuroprotection by both NMDA and non-NMDA receptor antagonists in in vitro ischemia

Cited by 146 publications

References 62 publications

Na+ and Ca2+ homeostasis pathways, cell death and protection after oxygen–glucose-deprivation in organotypic hippocampal slice cultures

Na+ and Ca2+ homeostasis pathways, cell death and protection after oxygen–glucose-deprivation in organotypic hippocampal slice cultures

εPKC Is Required for the Induction of Tolerance by Ischemic and NMDA-Mediated Preconditioning in the Organotypic Hippocampal Slice

Mexiletine and magnesium independently, but not combined, protect against permanent focal cerebral ischemia in Wistar rats

Contact Info

Product

Resources

About