Microglial turnover in the injured CNS: activated microglia undergo delayed DNA fragmentation following peripheral nerve injury.
Microglial proliferation and activation are common events in the injured CNS. The mechanisms, however, by which activated microglia are eliminated following a pathological stimulus are still poorly understood. The present study has therefore examined microglial proliferation by 3H-thymidine autoradiography and programmed cell death by terminal transferase-mediated nick end labeling (TUNEL) and in situ end labeling (ISEL) of nuclear DNA fragments in two models of peripheral nerve injury, i.e. sciatic and hypoglossal nerve transection in the rat. In these models, microglial activation and proliferation occur in CNS projection areas, i.e. in the ventral and dorsal gray matter of lumbar spinal cord and in the nucleus gracilis after sciatic nerve transection as well as in the axotomized hypoglossal nucleus. At these sites, microglial proliferation had a relatively sharp peak between days 2 and 3 post-lesion and then rapidly declined. DNA fragmentation was detected in lectin (GSI-B4)-positive microglia from day 6 after axotomy onward, reached an apparent peak at day 21 and was downregulated by day 60, i.e. the latest time point investigated. However, the expression of bcl-2 and c-myc, i.e. genes potentially controlling programmed cell death, was found to be unchanged during this period. Programmed cell death thus appears to be one mechanism by which activated microglia are gradually eliminated following CNS injury and steady state of microglial cell numbers is achieved in vivo. Expression of microglial growth factors may be instrumental in controlling these processes.
Gehrmann
J
J
Department of Pathology, University Hospital Zürich, Switzerland.
Banati
R B
RB
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000166:cytology / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000032:analysis / Q000378:metabolism*; D007002:Hypoglossal Nerve / Q000473:pathology* / Q000502:physiology; D061228:Hypoglossal Nerve Injuries; D008297:Male; D017628:Microglia / Q000166:cytology / Q000473:pathology*; D009416:Nerve Regeneration; D010487:Periaqueductal Gray / Q000166:cytology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012584:Sciatic Nerve / Q000293:injuries* / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000473:pathology*; D013997:Time Factors
D004247:DNA