title: Suppressive effects of intrathecal granulocyte colony-stimulating factor on excessive release of excitatory amino acids in the spinal cerebrospinal fluid of rats with cord ischemia: role of glutamate transporters.
abstract: Recently, the hematopoietic factor, granulocyte colony-stimulating factor (G-CSF), has been shown to exhibit neuroprotective effects in CNS injuries. Our previous study demonstrated that intrathecal (i.t.) G-CSF significantly improved neurological defects in spinal cord ischemic rats. Considerable evidence indicates that the release of excessive amounts of excitatory amino acids (EAAs) plays a critical role in neuron injury induced by ischemic insult. In the present study, we used a spinal cord ischemia-microdialysis model to examine whether i.t. G-CSF exerted antiexcitotoxicity effects in a rat model of spinal cord ischemia. I.t. catheters and a microdialysis probe were implanted in male Wistar rats. The results revealed that spinal cord ischemia-induced neurological defects were accompanied by a significant increase in the concentration of EAAs (aspartate and glutamate) in the spinal dialysates from 30 min to 2 days after reperfusion. I.t administration of G-CSF immediately after the performance of surgery designed to induce ischemia led to a significant reduction in ischemia-induced increases in the levels of spinal EAAs. Moreover, i.t. G-CSF also brought about a significant reduction in the elevation of spinal EAA concentrations induced by exogenous i.t. administration of glutamate (10 microl of 500 mM). I.t. G-CSF attenuated spinal cord ischemia-induced downregulation of expression of three glutamate transporters (GTs), glial transporter Glu-Asp transporter (GLAST), Glu transporter-1 (GLT-1), and excitatory amino acid carrier 1 (EAAC1) protein 48 h after spinal cord ischemic surgery. Immunohistofluorescent staining showed that i.t. G-CSF significantly upregulated expression of the three GTs in the gray matter of the lumbar spinal cord from 3 to 24 h after injection. We propose that i.t. G-CSF possesses an ability to reduce the extent of spinal cord ischemia-induced excitotoxicity by inducing the expression of glutamate transporters.
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: W-F
authors.initials: WF
authors.lastname: Chen
authors.forename: C-S
authors.initials: CS
authors.lastname: Sung
authors.forename: Y-H
authors.initials: YH
authors.lastname: Jean
authors.forename: T-M
authors.initials: TM
authors.lastname: Su
authors.forename: H-C
authors.initials: HC
authors.lastname: Wang
authors.forename: J-T
authors.initials: JT
authors.lastname: Ho
authors.forename: S-Y
authors.initials: SY
authors.lastname: Huang
authors.forename: C-S
authors.initials: CS
authors.lastname: Lin
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Wen
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism; D004195:Disease Models, Animal; D020820:Dyskinesias / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000378:metabolism; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D018846:Excitatory Amino Acids / Q000134:cerebrospinal fluid* / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism*; D018698:Glutamic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D007278:Injections, Spinal; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D018846:Excitatory Amino Acids; D050491:Glutamate Plasma Membrane Transport Proteins; D018696:Neuroprotective Agents; C493398:Slc1a1 protein, rat; C493392:Slc1a3 protein, rat; D016179:Granulocyte Colony-Stimulating Factor; D001224:Aspartic Acid; D018698:Glutamic Acid