Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells

Science

Volumn 277, Issue 5334, 1997, Pages 2000-2002

  Li, Ying ^a   Field, Pauline M ^a   Raisman, Geoffrey ^a  

^a NATIONAL INSTITUTE FOR MEDICAL RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN INJURY; CELL TRANSPLANTATION; NERVE CELL GROWTH; NERVE FIBER GROWTH; NERVE TRANSECTION; NONHUMAN; OLFACTORY BULB; PRIORITY JOURNAL; PYRAMIDAL TRACT; RAT;

ANIMALS; AXONS; BRAIN TISSUE TRANSPLANTATION; CELL TRANSPLANTATION; CELLS, CULTURED; DENERVATION; FEMALE; MICROSCOPY, ELECTRON; MYELIN SHEATH; NERVE REGENERATION; NEUROGLIA; OLFACTORY BULB; OLFACTORY NERVE; RATS; SPINAL CORD; SPINAL CORD INJURIES;

EID: 0030769193     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.277.5334.2000     Document Type: Article

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18. Unilateral lesions of the CST were produced (on the side that offered access with minimal damage to pial vessels) by a current of 10 μA for 8 to 10 min passed through a stainless steel electrode inserted to a vertical depth of 1 mm, at 1 mm caudal to the obex, and 0.3 mm from the midline in 71 young adult female AS rats (6 to 8 months old, body weights 200 to 220 g). Immediately after withdrawing the lesioning electrode, 50 rats received 5 μl of a suspension containing about 125,000 cultured OECs injected into the lesion site over a period of 1 to 2 min through a glass micropipette (3). In 30 rats 10% BD was injected stereotaxically into the contralateral medullary pyramid (4) 6 days before they were killed to allow time for anterograde labeling of the CST axons. At survival times of 6 days (n = 6), 10 days (n = 9), 3 weeks (n = 4), 4 weeks (n = 7), and 9 weeks (n = 4) after the lesioning and transplantation, the rats were killed and perfusion fixed (4). Longitudinal Vibratome sections 100 μm thick were used to identify the OECs by immunofluorescence for p75 low-affinity neurotrophin receptor and the CST axons by immunofluorescence for BD, and the results were recorded by confocal microscopy of serial longitudinal sections through the operated area. The remaining 20 rats [after survivals of 10 days (n = 3), 20 days (n = 3), 4 weeks (n = 7), and 2 to 3 months (n = 7)] were killed and perfusion fixed for electron microscopy (4).
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20. Perfusion-fixed spinal cords of all 28 tested rats were divided coronally, from the obex caudally, into 20 consecutive 0.7-mm-thick blocks; three blocks corresponded to one cervical segment (as ascertained from surface observation of the spinal nerve roots). The lesions damaged an area of tissue about 0.5 mm in cross section and 1 to 2 mm in a rostrocaudal direction. In semithin sections, the descending CST axons were distinguished from the larger ascending sensory fibers of the dorsal columns by their position as a well-delineated, compact bundle in the medioventral edge of the dorsal columns, by their smaller fiber diameter (about 1 μm), and by the denser packing of the interfascicular glial cells. The extent of the lesions, the position of the transplants, and the presence of transplanted OECs and OEC-myelinated axons were recorded in camera lucida drawings of 1-μm-thick coronal sections. The area of any remaining part of the CST was measured.
21. We thank D. Li for consultation and collaboration. Y. Ajayi adapted the method for culturing the OECs. Supported by the Medical Research Council, the British Neurological Research Trust, the International Spinal Research Trust, the Barnwood House Trust, and Smith's Charities.