Focal cerebral ischemia induces increased myelin basic protein and growth-associated protein-43 gene transcription in peri-infarct areas in the rat brain

Although oligodendrocytes are vulnerable to focal cerebral ischemia, remyel ination of denuded or regenerating axons in the peri-infarct area has been observed in the central nervous system. We studied the expression of myelin basic protein (MBP), a major component of central nervous system myelin, i n peri-infarct areas in adult rat brain after transient middle cerebral art ery occlusion (MCAO) and correlated it to the expression of the growth-asso ciated protein-43 (GAP-43), a marker for axonal regeneration and sprouting, using nonradioactive in situ hybridization techniques. Within the infarct, MBP messenger RNA (mRNA) had disappeared by 24 h, whereas myelin protein, identified by MBP and myelin oligodendrocyte glycoprotein (MOG) immunohisto chemistry, appeared structurally intact until day 3. Peri-infarct oligodend rocytes increased their expression of MBP mRNA from 24 h to maximal levels at day 7, corresponding to the appearance of process-bearing MBP and occasi onal MOG-immunoreactive oligodendrocytes in parallel sections. Quantitative analysis revealed significant increases in the density of oligodendrocytes (up to 7.6-fold) and in the level of MBP mRNA expressed by individual cell s. Parallel sections showed that increased expression of GAP-43 mRNA in neu rons was concomitant to MBP mRNA upregulation in oligodendrocytes. While th e mechanisms regulating oligodendrocyte survival and myelination signals ar e not clear at this point, axonal sprouting could putatively serve as a sti mulus for the upregulation of oligodendrocyte cell numbers, differentiation state, and/or active myelination in the peri-infarct areas.