EMAIL THIS PAGE TO A FRIEND

Oncotarget

The indirect NMDAR inhibitor flupirtine induces sustained post-ischemic recovery, neuroprotection and angioneurogenesis.


PMID 26050199

Abstract

N-methyl-D-aspartate receptor (NMDAR) activation induces excitotoxicity, contributing to post-stroke brain injury. Hitherto, NMDAR deactivation failed in clinical trials due to insufficient pre-clinical study designs and drug toxicity. Flupirtine is an indirect NMDAR antagonist being used as analgesic in patients. Taking into account its tolerability profile, we evaluated effects of flupirtine on post-stroke tissue survival, neurological recovery and brain remodeling.Mice were exposed to stroke and intraperitoneally treated with saline (control) or flupirtine at various doses (1-10 mg/kg) and time-points (0-12 hours). Tissue survival and cell signaling were studied on day 2, whereas neurological recovery and tissue remodeling were analyzed until day 84.Flupirtine induced sustained neuroprotection, when delivered up to 9 hours. The latter yielded enhanced neurological recovery that persisted over three months and which was accompanied by enhanced angioneurogenesis. On the molecular level, inhibition of calpain activation was noted, which was associated with increased signal-transducer-and-activator-of-transcription-6 (STAT6) abundance, reduced N-terminal-Jun-kinase and NF-κB activation, as well as reduced proteasomal activity. Consequently, blood-brain-barrier integrity was stabilized, oxidative stress was reduced and brain leukocyte infiltration was diminished.In view of its excellent tolerability, considering its sustained effects on neurological recovery, brain tissue survival and remodeling, flupirtine is an attractive candidate for stroke therapy.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB1405701
Anti-DCX antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
D9818
Anti-Doublecortin (C-terminal) antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
SAB4500629
Anti-Doublecortin, C-Terminal antibody produced in rabbit, affinity isolated antibody
SAB4504451
Anti-phospho-c-Jun (pSer243) antibody produced in rabbit, affinity isolated antibody
J2128 Anti-phospho-c-Jun (pSer63) antibody produced in rabbit, affinity isolated antibody, buffered aqueous glycerol solution
SAB4504368
Anti-phospho-c-Jun (pSer63) antibody produced in rabbit, affinity isolated antibody
J2253 Anti-phospho-c-Jun (pSer73) antibody produced in rabbit, affinity isolated antibody, buffered aqueous glycerol solution
SAB4504369
Anti-phospho-c-Jun (pSer73) antibody produced in rabbit, affinity isolated antibody
SAB4504452
Anti-phospho-c-Jun (pThr239) antibody produced in rabbit, affinity isolated antibody
SAB4504453
Anti-phospho-c-Jun (pThr91) antibody produced in rabbit, affinity isolated antibody
SAB4504454
Anti-phospho-c-Jun (pThr93) antibody produced in rabbit, affinity isolated antibody
SAB4504455
Anti-phospho-c-Jun (pTyr170) antibody produced in rabbit, affinity isolated antibody
SAB4300015
Anti-phospho-JUN (pSer243) antibody produced in rabbit, affinity isolated antibody
SAB4300002
Anti-phospho-JUN (pSer73) antibody produced in rabbit, affinity isolated antibody
SAB4300014
Anti-phospho-JUN (pThr239) antibody produced in rabbit, affinity isolated antibody
SAB4300011
Anti-phospho-JUN (pThr91) antibody produced in rabbit, affinity isolated antibody
SAB4300012
Anti-phospho-JUN (pThr93) antibody produced in rabbit, affinity isolated antibody
SAB4300013
Anti-phospho-JUN (pTyr170) antibody produced in rabbit, affinity isolated antibody
SAB4300039
Anti-phospho-STAT6 (pThr645) antibody produced in rabbit, affinity isolated antibody
SAB4504545
Anti-phospho-STAT6 (pThr645) antibody produced in rabbit, affinity isolated antibody
SAB4300038
Anti-phospho-STAT6 (pTyr641) antibody produced in rabbit, affinity isolated antibody
S5061 Anti-phospho-STAT6 (pTyr641) antibody produced in rabbit, affinity isolated antibody, buffered aqueous glycerol solution
SAB4504546
Anti-phospho-STAT6 (pTyr641) antibody produced in rabbit, affinity isolated antibody
WH0001641M1
Monoclonal Anti-DCX antibody produced in mouse, clone 1G12, purified immunoglobulin, buffered aqueous solution
SAB1403727 Monoclonal Anti-DCX antibody produced in mouse, clone 3B7, purified immunoglobulin, buffered aqueous solution
J4399 Monoclonal Anti-phospho-c-Jun (pThr91,93) antibody produced in mouse, ~2 mg/mL, clone C-J 4C4/1, purified immunoglobulin, buffered aqueous solution