Astrocytes contrbute for the cellular and molecular mechansms assocated wth whte matter njury observed right after chronchypoxa,yet numerous of cell forms ncludng olgodendrocytes and ther progentors may also be nvolved.We’re currently analyznghypoxa nduced damage towards the olgodendrocyte lneage our anmal model of chronc pernatalhypoxa.Our prelmnary effects show that olgodendrocyte death occurs after the frst week ofhypoxa.Our studes also show that additional mature phases in the olgodendrocyte lneage are partcularly vulnerable tohypoxa nduced toxcty.other versions of pernatal branjury, ncludnghypoxa schema andhyperoxa nduced njury, thas beedemonstrated that late olgodendrocyte progentors are most vulnerable to njury.Therefore, t seems that dfferent forms of nsults to selleck chemical CGK 733 the developng whte matter impact dstnct phases on the olgodendrocyte lneage.Long term expermental analyss wl defne the dfferent cellular and molecular mechansms that underle whte matter njury chronchypoxa,hypoxa schema andhyperoxa nduced njury on the developng bran.
Our fndng that expressoof GLAST and GLT selelck kinase inhibitor 1 s reduced afterhypoxa s suggestve that modifications the concentratoof extracellular glutamate lkely come about the whte matter envronment.What are the physologcal consequences ofhypoxa nduced reductoastrocytc glutamate uptake the presence of excess glutamate, olgodendrocytes and ther progentors are damaged like a consequence of above actvatoof AMPA receptors and subsequent Ca2 nflux, whch ultmately leads to exctotoxcty.very well establshed that glutamate vescles are released from unmyelnated axons the whte matter and ths s a potental source of extra glutamate thehypoxc anmal.We demonstrate that vvo at P11 each GLAST and GLT one expressoare sgnfcantly decreased the whte matter, and that D aspartate uptake whte matter glosomes s sgnfcantly decreased afterhypoxa.These fndngs strongly recommend that astrocyte mpared abty to clear glutamate afterhypoxa would cause extra glutamate the extracellular area, whch turcauses exctotoxc harm to mmature olgodendrocytes and or prevents ther maturatoto myelnatng olgodendrocytes.
concluson, dysregulatoof glutamatehomeostass whte matter astrocytes afterhypoxa

s most lkely one of the contrbutng factors underlyng olgodendrocyte pathology afterhypoxc njury.the present study, we show that the cellular response of astrocytes tohypoxc njury vvo nvolves not only a reductoglutamate transporter expressothe developng whte matter whch turlkely affects glutamatehomeostass but also attenuatoof JAK STAT sgnalng resultng ammature phenotype, and these two responses are lkely to be causally related.Defnnghow the JAK STAT pathway regulates GLAST expressowl be mportant to develomolecular therapeutc targets to promote neuroprotectoor preventoof damage to the premature bran.