title: Calcium influx and activation of calpain I mediate acute reactive gliosis in injured spinal cord.
abstract: Buffering extracellular pH at the site of a spinal cord crush-injury may stimulate axonal regeneration in rats (1; Guth et al., Exp. Neurol. 88: 44-55, 1985). We demonstrated in cultured astrocytes that acidic pH initiates a rapid increase in immunoreactivity for GFAP (GFAP-IR), a hallmark of reactive gliosis (2; Oh et al., Glia 13: 319-322, 1995). We extended these studies by investigating the effects of certain treatments on reactive gliosis developing in situ in a rat spinal cord injury model. A significant reactive gliosis was observed within 2 days of cord lesion in untreated crush or vehicle-treated, crush control animals as evidenced by increased GFAP-IR and hypertrophy of astrocytes. By contrast, infusion of Pipes buffer (pH 7.4) into the lesion site significantly reduced this increase. The increased GFAP-IR appeared to be linked to Ca2+ influx since infusion of a blocker of L-type calcium channels, nifedipine, reduced the ensuing reactive gliosis significantly. While Ca2+ modulates many signaling pathways within cells, its effect on reactive gliosis appeared to result from an activation of calpain I. Calpain inhibitor I, a selective inhibitor of mu-calpain, also significantly reduced reactive gliosis. However, calpain inhibitor II, a close structural analog which blocks m-calpain, had no salutary effect. We suggest, therefore, that the initial reactive gliosis seen in vivo may result from the activation of a neutral, Ca2+-dependent protease, calpain I, through calcium influx.
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: S
authors.initials: S
authors.lastname: Du
authors.forename: A
authors.initials: A
authors.lastname: Rubin
authors.forename: S
authors.initials: S
authors.lastname: Klepper
authors.forename: C
authors.initials: C
authors.lastname: Barrett
authors.forename: Y C
authors.initials: YC
authors.lastname: Kim
authors.forename: H W
authors.initials: HW
authors.lastname: Rhim
authors.forename: E B
authors.initials: EB
authors.lastname: Lee
authors.forename: C W
authors.initials: CW
authors.lastname: Park
authors.forename: G J
authors.initials: GJ
authors.lastname: Markelonis
authors.forename: T H
authors.initials: TH
authors.lastname: Oh
mesh_terms: D000208:Acute Disease; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002154:Calpain / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000209:etiology* / Q000473:pathology; D006984:Hypertrophy; D007150:Immunohistochemistry; D008297:Male; D009409:Nerve Crush; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D014949:Wounds, Nonpenetrating / Q000150:complications* / Q000378:metabolism / Q000473:pathology
chemical_list: D002121:Calcium Channel Blockers; D005904:Glial Fibrillary Acidic Protein; D002154:Calpain; D009543:Nifedipine; D002118:Calcium