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 e xpression of proteins associated with axonal elongation, such as microtubul e-associated protein 1B (MAP1B), its phosphorylated isoform (MAP1B-P), grow th-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 sev erity (2.4-2.6 atmospheres) in anesthetized rats. Uninjured (control) rats were subjected to anesthesia and surgery without injury or were subjected t o anesthesia alone. Within the site of maximal injury, only increases in MA P1B and MAP1B-P were observed. Increased immunoreactivity was observed bila terally for all growth-related proteins that were evaluated. By 24 hours po stinjury, 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 observ ed for all proteins examined. By 48 hours postinjury, GAP-43 was elevated b ilaterally within the inner molecular layers of the dentate gyrus (P < 0.00 5) and within the stratum lacunosum moleculare (P < 0.01), the stratum radi atum (P < 0.005), and the stratum oriens (P < 0.05) of the hippocampus. Inc reased numbers of PSA-NCAM-labeled neurons were observed in the granule cel l layers of the dentate gyrus from 48 hours through 2 weeks postinjury (P < 0.0005). The bilateral nature of increased expression of growth-related pr oteins differs from unilateral patterns of neuronal degeneration previously characterized for the lateral fluid-percussion model of brain injury. Take n together, these results suggest the existence of a temporary posttraumati c state in which the CNS may have increased regenerative potential. Enhance ment of such a response may be one therapeutic strategy in treating CNS inj ury. (C) 2000 Wiley-Liss, Inc.