Endothelial cell loss is not a major cause of neuronal and glial cell death following contusion injury of the spinal cord.
Contusion of the spinal cord causes an immediate local loss of neurons and disruption of vasculature; additional loss continues thereafter. To explore the possibility of a causal link between delayed endothelial cell (EC) death and secondary neural cell loss, we evaluated neural and endothelial cell survival, and measured inflammatory cell infiltration, at times up to 48 h after contusion injury to the adult rat thoracic spinal cord. Female Fischer rats (200 g), subjected to moderate (10 g x 12.5 mm) weight drop injuries by the MASCIS (NYU) impactor, were analyzed at 15 min and at 1, 8, 24 and 48 h. ECs, neurons, astrocytes, oligodendrocytes, neutrophils and activated macrophages/microglia were counted in transverse sections. At the injury site, 90% of all neurons died within 48 h of injury; no medium-large diameter neurons survived beyond 48 h. EC death occurred with kinetics similar to glial cell death. Because, in the injury site, most cell death occurred before 8 h, it preceded inflammatory cell infiltration. Three millimeters rostral and caudal to the injury epicenter neuronal numbers were stable for 8 h, and a sharp decrease in neuronal numbers beginning at 8 h strongly correlated with the onset of inflammatory cell infiltration. Glial and blood vessel numbers remained relatively stable in these areas up to 48 h. These results suggest that the loss of ECs during the first 48 h after a contusion injury is not a major cause of neuronal and glial cell death and, in tissue adjacent to the epicenter, inflammatory cell infiltration leads to neuronal loss.
Casella
Gizelda T B
GT
The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, FL 33136, USA.
Bunge
Mary Bartlett
MB
Wood
Patrick M
PM
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D053331:Ectodysplasins / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007797:Laminin / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D009418:S100 Proteins / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors; D014048:Tolonium Chloride; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
D053331:Ectodysplasins; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D009418:S100 Proteins; D014048:Tolonium Chloride; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D010751:Phosphopyruvate Hydratase