Effects of Rotigotine Extended‐release Microspheres Therapy on Stroke‐induced Brain Injury
Authors: Fu Fenghua , Wang Wenqian , Meng Xiaoyu , Lv Huaiyou , Zhang Leiming , Wang Tian 
Published: June 2021

Objective

Rotigotine, a non‐ergot dopamine agonist, is a novel compound for the treatment of Parkinson's disease (PD). Rotigotine extended‐release microspheres (RoMS) was developed by Shandong Luye Pharmaceutical Co., Ltd. Previous studies demonstrate that a single RoMS administration continuously release rotigotine for 2 weeks. The purpose of this study is to investigate the effect of RoMS therapy on stroke‐induced brain injury in mice.

Methods

CD‐1 mice were intramuscularly administered with a single RoMS (10 or 40 mg/kg). At 7th or 14th day after RoMS treatment, intracerebral hemorrhage model was established by an intrastriatal injection of bacterial collagenase. After 24 h, Garcia test and brain water content were evaluated. Sprague‐Dawley rats were treated with RoMS (5 or 20 mg/kg) and then they were subjected to 90‐minute cerebral ischemia followed by reperfusion. After 24 h, functional recovery was assessed by cylinder test, beam walking test, and adhesive test. Brain water content assay was also conducted.

Results

On the 7th and 14th day, the Garcia test score in the control group was 18.00 ± 0.11, 18.00 ± 0.24. The Garcia test score in the model group was decreased (7.00 ± 1.12, 7.75 ± 1.75, respectively, P<0.01). The Garcia test score in RoMS groups were increased (P<0.01). On the 7th and 14th day, the perihematomal brain water content in the ipsilateral basal ganglia of the model group (83.08 ± 1.46%, 82.91 ± 1.28%) was augmented compared with that of the control group (77.22 ± 1.60%, 77.72 ± 0.88%, P<0.01), while the perihematomal brain water content did not show a difference among RoMS groups and the model group. On the 7th and 14th day, the rats in the model group (67.7 ± 0.06%, 68.4 ± 0.06%) displayed a significant preference for the use of the unimpaired forepaw compared with control group (51.9 ± 0.04%,48.2 ± 0.03%, P<0.01). The rats in the model group (10.0 ± 3.4 s, 8.1 ± 1.0 s) spent a markedly longer time crossing the beam compared with control group (3.6 ± 0.5 s, 3.6 ± 0.7 s, P<0.01). The contact time in the model group (59.1 ± 50.5 s, 82.2 ± 43.1 s) were significantly prolonged compared with the sham group (16.4 ± 3.5 s, 12.9 ± 3.3 s, P<0.01). RoMS therapy neither attenuated nor deteriorated the neurological function of ischemic stroke rats. The brain water content of ischemic hemisphere in the model group (79.8 ± 1.38%, 80.6 ± 1.35%) was increased significantly (78.0 ± 0.56%, 78.4 ± 0.22%, P<0.01). RoMS therapy had no effect on the brain water content in ischemic hemisphere.

Conclusion

If the animals treated with RoMS are on an attack of stroke, the brain injury will be neither attenuated nor deteriorated. RoMS therapy in PD patients with high risk factor for stroke does not aggravate stroke‐induced brain injury, which provides supports for clinical application of RoMS.

Support or Funding Information

National Natural Science Foundation of China (Grant No. 81573639).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.