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Page 22 of 24 Neuroimmunol Neuroinflammation 2019;6:15 I http://dx.doi.org/10.20517/2347-8659.2019.019

30. Thrombolysis with rhTNK-tPA at different therapeutic time windows in animal model of
embolic stroke

2
1
1
2
1
Wei-Ting Wang , Chun-Hua Hao , Zhuan-You Zhao , Li-Da Tang , Jia-Hua Hu , Guo-Hui Mu , Sen
1
Wang , Qin Yang 2
2
1 Tianjin Institute of Pharmaceutical Research, Tianjin, China
2 Guangzhou Recomgen Biotech Co., Ltd., Guangzhou, China
It is essential for us to investigate the effects and characteristics of thrombolytics on different therapeutic
time windows (TTW) in an animal model of embolic stroke. In our research, we investigated the
thrombolysis with recombinant human TNK-tPA (rhTNK-tPA) on thromboembolic stroke in an animal
model at different TTW. Rats were subjected to embolic middle cerebral artery occlusion. RhTNK-tPA and
positive control drugs rt-PA were administered 1, 2, 3, 4.5, and 6 h after inducing thromboembolic stroke.
Neurological deficit scoring (NDS) was evaluated at 6 and 24 h after the treatment. The lesion volume
in cerebral hemispheres was measured by MRI using MRI scanning machine after 6 h of thrombolysis,
and the infarct volume was measured by TTC stain, together with hemorrhagic volume quantified by
a spectrophotometric assay after 24 h of thrombolysis. The results show that rhTNK-tPA 1.6 mg/kg
significantly improved the NDS after cerebral thromboembolism in rats at different TTW. RhTNK-tPA
improved the NDS by 36.4% (P < 0.05), 41.7% (P < 0.01), 37.5% (P < 0.01), 36.0% (P < 0.05), and 26.1% (P >
0.05) at 1, 2, 3, 4.5, and 6 h TTW with 6 h treatment, respectively, and by 45.8% (P < 0.01), 50.0% (P < 0.01),
48.0% (P < 0.05), 37.5% (P > 0.05), and 28.0% (P > 0.05)at 1, 2, 3, 4.5, and 6 h TTW with 24 h treatment,
respectively. Rt-PA improved the NDS by 40.9% (P < 0.05), 37.5% (P < 0.05), 33.3% (P < 0.05), 28.0% (P
> 0.05), and 8.7% (P > 0.05) at 1, 2, 3, and 4.5 h TTW with 6 h treatment, respectively, and by 50.0% (P <
0.01), 50.0% (P < 0.01), 48.0% (P < 0.05), 33.3% (P > 0.05), and 12.0% (P > 0.05) at 1, 2, 3, 4.5, and 6 h TTW
with 24 h treatment, respectively. RhTNK-tPA significantly reduced the extent of brain lesions examined
by MRI at different TTW. At 1, 2, 3, 4.5, and 6 h TTW, lesion volume was reduced by 73.3% (P < 0.001),
64.2% (P < 0.01), 62.1% (P < 0.01), 46.1% (P < 0.05), and 39.6% (P > 0.05) at rhTNK-tPA dose of 1.6 mg/kg,
respectively, and by 61.7% (P < 0.01), 59.4% (P < 0.05), 48.1% (P < 0.05), 49.1% (P < 0.05), and 17.8% (P > 0.05)
at rt-PA dose of 9 mg/kg, respectively. RhTNK-tPA significantly reduced the extent of cerebral infarction
examined by TTC at different TTW. At 1, 2, 3, 4.5, and 6 h TTW, infarction volume was reduced by 63.8% (P
< 0.01), 71.0% (P < 0.05), 63.2% (P < 0.05), 58.0% (P < 0.01), and 35.7% (P > 0.05) at rhTNK-tPA dose of 1.6
mg/kg, respectively, and by 53.4% (P < 0.01), 60.9% (P < 0.05), 51.7% (P < 0.05), 54.6% (P < 0.05), and 20.4%
(P > 0.05) at rt-PA dose of 9 mg/kg, respectively. The amount of hemorrhage in rhTNK-tPA rats increased
slightly with the prolongation of the TTW (P > 0.05), and the amount of bleeding at 6 h TTW increased
approximately 1.6 folds compared with the model group (P = 0.0748). The amount of hemorrhage in rt-PA
rats increased with the prolongation of the TTW, and the amount of bleeding at 6 h TTW increased more
than two folds compared with the model group (P < 0.01). Thus, rhTNK-tPA had an obvious therapeutic
effect on ischemic stroke caused by thrombosis, and could be started within 4.5 h TTW.

31. Role of glutamate in the pathogenesis of acquired epilepsy in alzheimer’s disease

Hattapark Dejakaisaya, Patrick Kwan, Nigel Jones

Monash University, Australia

Alzheimer’s disease (AD) can increase the risk of epileptogenesis up to 10-fold in the patient, compared
to healthy age-matched controls. However, the relationship between acquired epilepsy and AD is yet to