Effect of hypothermia on motor function of adult rats after neonatal hyperthermic hypoxic–ischemic brain insult
Regarding therapeutic hypothermia for human neonatal hyperthermic hypoxic–ischemic encephalopathy (HIE), we investigated the motor function of a neonatal hyperthermic HIE rat model, and also performed systemic hypothermia using the model. Forty-two neonatal Wistar rats at 7-days-old were used in this study. The left common carotid artery of 34 neonatal rats was ligated under isoflurane anesthesia. We also established a sham group (S group, n = 8). After 1-h recovery, all rats were exposed to 8% oxygen at an ambient temperature (T a) of 40°C for 15 min. Following insult, 16 rats were placed in a chamber at a T a of 30°C (H group) and the other 18 rats at a T a of 37°C after arterial ligation (N group), and all rats in the S group were placed in a chamber at a T a of 37°C for 12 h. A Rota-Rod test was performed involving all rats at 8 weeks old. The rod was rotated at 5, 5, and 7 rpm on three consecutive days, respectively. Rats in the N group stayed on the rotating rod for a significantly shorter period than those in S and H groups only on the second day of measurement. The width of the insulted hemisphere in N group rats was significantly smaller than those in S and H groups. There was no significant correlation between S and H groups regarding the motor function and anatomy. These results suggest that neonatal hyperthermic hypoxic–ischemic insult impairs the motor function, which may be rescued by systemic hypothermia after insult.
KeywordsRat Neonate Hypoxic–ischemic encephalopathy Rota-Rod test Hypothermia
We thank Dr. Hirotsugu Fukuda, who instructed us in the procedures to produce hyperthermic HIE model rats. This work was supported by a Grant-in-Aid for Scientific Research, No. 20590239, from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and also by Kyoudoukennkyuuhi-B from Osaka Electro-Communication University.
Conflicts of interest statement
- Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH (2005) Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 353:1574–1584CrossRefPubMedGoogle Scholar