Role of the bcl-2 gene after contusive spinal cord injury in mice.
OBJECTIVE
Apoptosis is indicated to have an important role in the secondary injury mechanisms of acute spinal cord injury (SCI). The proto-oncogene bcl-2 has been demonstrated to prevent apoptotic cell death in a wide variety of cell types. This study examined the recovery of behavioral function and histopathological variables after controlled-impact SCI in human bcl-2 transgenic (TG) mice and control mice.


METHODS
Six bcl-2 TG mice and five control mice were subjected to controlled-impact SCI of moderate severity at T10, with the use of a pneumatic impact device (0.25-mm-deep deformation; impact velocity, 2 m/s). Functional deficits were evaluated at times up to 28 days after SCI, with assessments of hindlimb reflexes and coordinated motor function. The extents of the lesions were histopathologically analyzed and quantified with morphometric measurements.


RESULTS
Both control and bcl-2 TG mice exhibited profound deficits immediately after injury, with subsequent gradual symptomatic recovery. The mean functional scores for the control mice were lower than those for the bcl-2 TG mice, although the Mann-Whitney U test revealed no significant differences. The mean lesion volume for the bcl-2 TG mice (mean +/- standard deviation, 2.9 +/- 1.1 x 10(-2) mm(3)) was significantly lower than that for the control mice (5.1 +/- 0.8 x 10(-2) mm(3); unpaired t test, P = 0.0101). Immunohistological analysis of the spinal cords from the bcl-2 TG mice revealed marked expression of Bcl-2 at the injury site and in adjacent regions.


CONCLUSIONS
Our results suggest that overexpression of the bcl-2 gene may play a protective role in neuropathological sequelae after SCI.
Seki
Toshitaka
T
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan. toseki@med.hokudai.ac.jp
Hida
Kazutoshi
K
Tada
Mitsuhiro
M
Koyanagi
Izumi
I
Iwasaki
Yoshinobu
Y
D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D019254:Genes, bcl-2 / Q000235:genetics*; D006801:Humans; D001523:Mental Disorders / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D000090063:Proto-Oncogene Mas; D020127:Recovery of Function / Q000235:genetics* / Q000502:physiology*; D012021:Reflex, Abnormal / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D013904:Thoracic Vertebrae / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors