Glial changes in the phrenic nucleus following superimposed cervical spinal cord hemisection and peripheral chronic phrenicotomy injuries in adult rats.
The objective of the present study was to characterize the microglial and astroglial reaction in the phrenic nucleus following either an ipsilateral C2 spinal cord hemisection, a peripheral phrenicotomy, or a combination of the two injuries in the same adult rat. The present study used three different fluorescent markers and a confocal laser image analysis system to study glial cells and phrenic motoneurons at the light microscopic level. Young adult female rats were divided into one combined injury group (left phrenicotomy and left C2 spinal hemisection with periods of 1 to 4 weeks between injuries, N = 12) and three other groups consisting of noninjured animals (N = 3), animals that received C2 hemisection only (N = 3), and animals with phrenicotomy only (survival periods of 2 (N = 3) and 4 (N = 3) weeks after phrenicotomy). Fluorogold was injected into the diaphragm to label phrenic motoneurons in all animals. Microglia and astrocytes were labeled with Texas red and fluorescein, respectively, and were visualized simultaneously along with phrenic motoneurons. The results suggest that the microglial and astrocytic response in the superimposed injury model are similar to the glial reactions characteristically seen in a peripheral axotomy alone model. These reactions include proliferation and migration of microglial cells along the perineuronal surface (peaking at 2 weeks) and the hypertrophy of astrocytes (peaking at 4 weeks). In addition, the increase in astrocytic tissue, which is characteristically seen in response to axotomy alone, is significantly enhanced in the superimposed injury model. Also, there is a large and rapid increase in GFAP-positive astrocytes within 24 hours after hemisection alone. The information gained from the present study will aid in determining, predicting, and eventually manipulating central nervous system responses to multiple injuries with the objective of reestablishing function in the damaged CNS.
Gould
D J
DJ
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Goshgarian
H G
HG
D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D002455:Cell Division; D002465:Cell Movement; D002818:Cordotomy; D003964:Diaphragm / Q000294:innervation; D005260:Female; D005456:Fluorescent Dyes; D006984:Hypertrophy; D007091:Image Processing, Computer-Assisted; D017628:Microglia / Q000473:pathology*; D018613:Microscopy, Confocal; D009046:Motor Neurons / Q000473:pathology*; D009121:Muscle Denervation; D010791:Phrenic Nerve / Q000293:injuries*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012183:Retrograde Degeneration; D013116:Spinal Cord / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000150:complications / Q000473:pathology*; D014945:Wound Healing
D005456:Fluorescent Dyes