Bilateral growth-related protein expression suggests a transient increase in regenerative potential following brain trauma.
The potential of mature central nervous system (CNS) neurons to regenerate after injury represents a fundamental issue in neurobiology. The regional expression of proteins associated with axonal elongation, such as microtubule-associated protein 1B (MAP1B), its phosphorylated isoform (MAP1B-P), growth-associated protein 43 (GAP-43), and polysialylated neural cell-adhesion molecule (PSA-NCAM), was examined using immunohistochemistry from 24 hours to 2 months following lateral fluid percussion brain injury of moderate severity (2.4-2.6 atmospheres) in anesthetized rats. Uninjured (control) rats were subjected to anesthesia and surgery without injury or were subjected to anesthesia alone. Within the site of maximal injury, only increases in MAP1B and MAP1B-P were observed. Increased immunoreactivity was observed bilaterally for all growth-related proteins that were evaluated. By 24 hours postinjury, MAP1B and MAP1B-P increased within the cortex (P < 0.01) and the hippocampus (P < 0.001), whereas MAP1B-P also was elevated in the thalamus (P < 0.05). Within the dentate gyrus, increased immunoreactivity was observed for all proteins examined. By 48 hours postinjury, GAP-43 was elevated bilaterally within the inner molecular layers of the dentate gyrus (P < 0.005) and within the stratum lacunosum moleculare (P < 0.01), the stratum radiatum (P < 0. 005), and the stratum oriens (P < 0.05) of the hippocampus. Increased numbers of PSA-NCAM-labeled neurons were observed in the granule cell layers of the dentate gyrus from 48 hours through 2 weeks postinjury (P < 0.0005). The bilateral nature of increased expression of growth-related proteins differs from unilateral patterns of neuronal degeneration previously characterized for the lateral fluid-percussion model of brain injury. Taken together, these results suggest the existence of a temporary posttraumatic state in which the CNS may have increased regenerative potential. Enhancement of such a response may be one therapeutic strategy in treating CNS injury.
Emery
D L
DL
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Raghupathi
R
R
Saatman
K E
KE
Fischer
I
I
Grady
M S
MS
McIntosh
T K
TK
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019922:GAP-43 Protein / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012794:Sialic Acids / Q000378:metabolism*; D013997:Time Factors
D019922:GAP-43 Protein; D008869:Microtubule-Associated Proteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C085284:microtubule-associated protein 1B; C103469:polysialyl neural cell adhesion molecule