Neuroprotective Effects of Musk of Muskrat on Transient Focal Cerebral Ischemia in Rats

Abstract

Musk of musk deer has been one of the most precious traditional medicinal materials for treatment of stroke, but trading is prohibited. Musk of muskrat, Ondatra zibethicus, is an accessible substitute for musk of musk deer. However, neuroprotective effects of the musk of muskrat on stroke model are so far unclear. Aim of the study is to determine neuroprotective effects of the musk of muskrat on focal cerebral ischemia. The protective effects against focal cerebral ischemia were evaluated using a model of middle cerebral artery occlusion (90-minute occlusion followed by 24-hour reperfusion). Musk of muskrat was collected from scent bag of muskrat and orally administered at doses of 100 and 300 mg/kg twice at times of 0 and 90 min after occlusion. The effects on sensorimotor dysfunction were investigated by using balance beam test and rotarod test after brain ischemia. The expression of cyclooxygenase-2 (COX-2) was investigated by immunohistochemistry. Oral administration of musk at 300 mg/kg significantly reduced (p<0.001) the infarct volume by 32.4% compared with a vehicle-treated group. Oral administration of musk at 300 mg/kg also ameliorated ischemia-induced spontaneous and vestibule sensorimotor dysfunction in balance beam test and rotarod test compared with control group and COX-2 upregulation. Musk of muskrat may have neuroprotective effects against transient focal cerebral ischemia with recovery of sensorimotor dysfunction. Regarding the immunohistochemistry, the effects of muskrat may be due to anti-inflammatory properties through inhibition of COX-2 expressions.

Figure 1

Dose-dependent effect of musk of muskrat on infarct volume induced by MCAo. N=12 per group; ∗∗∗p<0.001 vs. Vehicle-treated control by one-way ANOVA with post hoc Dunnett's test.

Figure 2

The effect of musk of muskrat on balance beam test after MCAo. Musk; oral administration of musk of muskrat at dose of 300 mg/kg. N=5 per group; ### p < 0.001 vs. Sham group, ∗∗ p < 0.01 vs. vehicle-treated group.

Figure 3

The effect of musk of muskrat on rotarod test after MCAo. Musk; oral administration of musk of muskrat at dose of 300 mg/kg. N=5 per group; ### p < 0.001 vs. Sham group, ∗ p < 0.05 vs. vehicle-treated group.

Figure 4

Inhibitory effect of musk of muskrat on COX-2 expressions (A, B, C) in the peri-infarct cortex, 24 hours after 90 minutes of MCAo. Sham (A, a), vehicle administered group (B, b), musk of musk rat administered group (300 mg/kg, p.o.; C, c). Boxed regions in A, B, and C (x40) are shown in a, b, and c (x400), respectively.