A time course of contusion-induced oxidative stress and synaptic proteins in cortex in a rat model of TBI.
An imbalance between oxidants and antioxidants has been postulated to lead to oxidative damage in traumatic brain injury (TBI). Oxidative neurodegeneration is a key mediator of exacerbated morphological responses and deficits in behavioral recoveries. The present study was designed to delineate the early temporal sequence of this imbalance in order to enhance possible antioxidant therapy. Young adult male Sprague-Dawley rats were subjected to a unilateral moderate cortical contusion. At various times post-trauma (3, 6, 12, 24, 48, 72, and 96 h), animals were killed and the cortex analyzed for enzymatic and non-enzymatic oxidative stress markers. Fresh tissues were prepared for biochemical analysis of several antioxidants (glutathione [GSH], glutathione peroxidase [GPx], glutathione reductase [GR], glutathione-S-transferase [GST], and thiobarbituric acid reactive substances [TBARS]). Synaptic markers Synapsin-I, PSD-95, SAP-97 and GAP-43 were analyzed by Western blot with antibodies directed against them. All activity levels were compared to sham-operated animals. Activity of antioxidant enzymes and GSH clearly demonstrate a significant time-dependent increase in oxidative stress. Changes in pre- and post-synaptic proteins (Synapsin-I and PSD-95) occur early (24 h), whereas SAP-97 levels demonstrate a protracted reduction. These results indicate that depletion of antioxidant systems following trauma could adversely affect synaptic function and plasticity. Because of the observed differences in the time-course of various markers, it may be necessary to stagger selective types of anti-oxidant therapy to target specific oxidative components. The initial therapeutic window following TBI appears relatively short since oxidative damage occurs as early as 3 h.
Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536-0230, USA. mansa3@uky.edu
Mubeen A
MA
Ansari
Kelly N
KN
Roberts
Stephen W
SW
Scheff
D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology*; D000076122:Disks Large Homolog 4 Protein; D019922:GAP-43 Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D016704:Synapsins / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013995:Time
D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D019922:GAP-43 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016704:Synapsins; D017392:Thiobarbituric Acid Reactive Substances; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D051528:Guanylate Kinases; D005978:Glutathione