Decreased neural damage after spinal cord injury in tPA-deficient mice.
Tissue plasminogen activator (tPA) is a serine protease that converts plasminogen to plasmin. It plays an important role in the nervous system, including the processes of neuronal migration, neurite outgrowth, and neuronal plasticity. tPA has also been suggested to have a role in several neuropathological conditions, such as cerebral ischemia, seizures, and demyelinating diseases. To investigate the role of tPA in spinal cord injury, wild-type mice and mice with homozygous tPA deficiency (tPA(-/-) mice) were subjected to spinal cord contusion and the differences of hindlimb function, electrophysiological changes, and histopathological changes were assessed for 6 weeks. Functional recovery was greater in tPA(-/-) mice than in wild-type mice throughout the observation period. The time course of myoelectric motor-evoked potentials supported the hindlimb functional findings. Histological examination showed that injured areas were smaller in tPA(-/-) mice than wild-type mice on Luxol fast blue staining or myelin basic protein and neurofilament protein immunostaining at 6 weeks after contusion. Electron microscopy showed that the white matter was better preserved in tPA(-/-) mice than in wild-type mice. The expression of tPA protein was widespread on the first day after contusion and this expression was detected for at least a week. Activation of microglia/macrophages and apoptotic cell death were significantly reduced in tPA(-/-) mice after contusion. This study shows that neural damage is decreased in tPA(-/-) mice after spinal cord injury. Suppression of tPA production may help to decrease secondary injury after spinal cord contusion.
Abe
Yumiko
Y
Department of Orthopedic Surgery, Toyama Medical and Pharmaceutical University, Toyama, Japan. md991002@st.toyama-mpu.ac.jp
Nakamura
Hiroshi
H
Yoshino
Osamu
O
Oya
Takeshi
T
Kimura
Tomoatsu
T
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004195:Disease Models, Animal; D019054:Evoked Potentials, Motor / Q000235:genetics; D006614:Hindlimb / Q000502:physiology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology; D008854:Microscopy, Electron; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000737:chemistry / Q000473:pathology*; D020127:Recovery of Function / Q000235:genetics; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000172:deficiency* / Q000235:genetics
D010959:Tissue Plasminogen Activator