RT Journal Article
SR Electronic
T1 New rat model of spinal cord infarction with long-lasting functional disabilities generated by intraspinal injection of endothelin-1
JF Stroke and Vascular Neurology
JO Stroke Vasc Neurol
FD BMJ Publishing Group Ltd
SP svn-2023-002962
DO 10.1136/svn-2023-002962
A1 Otani, Masayuki
A1 Kushida, Yoshihiro
A1 Kuroda, Yasumasa
A1 Wakao, Shohei
A1 Oguma, Yo
A1 Sasaki, Keisuke
A1 Katahira, Shintaro
A1 Terai, Ryohei
A1 Ryoke, Rie
A1 Nonaka, Hiroi
A1 Kawashima, Ryuta
A1 Saiki, Yoshikatsu
A1 Dezawa, Mari
YR 2024
UL http://svn.bmj.com/content/early/2024/06/20/svn-2023-002962.abstract
AB Background The current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days.Objective We aimed to establish a rat model characterised by long-term survival and enduring SC dysfunction by inducing selective ischaemic SC damage.Methods In 8-week-old male Wistar rats, a convection-enhanced delivery technique was applied to selectively deliver endothelin-1 (ET-1) to the anterior horn of the SC at the Th13 level, leading to SC infarction. The Basso, Beattie and Bresnahan (BBB) locomotor score was assessed for 56 days. The SC was examined by a laser tissue blood flowmeter, MRI, immunohistochemistry, triphenyl tetrazolium chloride (TTC) staining, Western blots and TUNEL staining.Results The puncture method was used to bilaterally inject 0.7 µL ET-1 (2.5 mg/mL) from the lateral SC into the anterior horns (40° angle, 1.5 mm depth) near the posterior root origin. Animals survived until day 56 and the BBB score was stably maintained (5.5±1.0 at day 14 and 6.2±1.0 at day 56). Rats with BBB scores ≤1 on day 1 showed stable scores of 5–6 after day 14 until day 56 while rats with BBB scores >1 on day 1 exhibited only minor dysfunction with BBB scores >12 after day 14. TTC staining, immunostaining and TUNEL staining revealed selective ischaemia and neuronal cell death in the anterior horn. T2-weighted MR images showed increasing signal intensity at the SC infarction site over time. Western blots revealed apoptosis and subsequent inflammation in SC tissue after ET-1 administration.Conclusions Selective delivery of ET-1 into the SC allows for more precise localisation of the infarcted area at the targeted site and generates a rat SC infarction model with stable neurological dysfunction lasting 56 days.All data relevant to the study are included in the article or uploaded as online supplemental information. Not applicable.