Intravenous Administration of Achyranthes Bidentata Polypeptides Supports Recovery from Experimental Ischemic Stroke in Vivo

<div><p>Background</p><p><i>Achyranthes bidentata</i> Blume (<i>A. bidentata</i>) is a commonly prescribed Chinese medicinal herb. <i>A. bidentata</i> polypeptides (ABPP) is an active composite constituent, separated from the aqueous extract of <i>A. bidentata</i>. Our previous studies have found that ABPP have the neuroprotective function in vitro and in rat middle cerebral artery occlusion (MCAO) model in attenuating the brain infract area induced by focal ischemia-reperfusion. However, the ultimate goal of the stroke treatment is the restoration of behavioral function. Identifying behavioral deficits and therapeutic treatments in animal models of ischemic stroke is essential for potential translational applications.</p> <p>Methodology and Principal Findings</p><p>The effect of ABPP on motor, sensory, and cognitive function in an ischemic stroke model with MCAO was investigated up to day 30. The function recovery monitored by the neurological deficit score, grip test, body asymmetry, beam-balancing task, and the Morris Water Maze. In this study, systemic administration of ABPP by i.v after MCAO decreased the neurological deficit score, ameliorated the forepaw muscle strength, and diminished the motor and sensory asymmetry on 7^th and 30^th day after MCAO. MCAO has been observed to cause prolonged disturbance of spatial learning and memory in rats using the MWM, and ABPP treatment could improve the spatial learning and memory function, which is impaired by MCAO in rats, on 30^th day after MCAO. Then, the viable cells in CA1 region of hippocampus were counted by Nissl staining, and the neuronal cell death were significantly suppressed in the ABPP treated group.</p> <p>Conclusion</p><p>ABPP could improve the recovery of sensory, motor and coordination, and cognitive function in MCAO-induced ischemic rats. And this recovery had a good correlation to the less of neuronal injury in brain.</p> </div

Effect of ABPP on the neurological deficit score and the muscular strength.

<p>Treatment with ABPP reduced the neurological deficit score at 7^th day after MCAO (A), but did not reduce the score at 30^th day (B). However, treatment with ABPP reduced the score of muscular strength at 7^th (C) and 30^th day (D). Data are expressed as means ± SEM (n = 8); **<i>P</i><0.01, compared to the Sham group; #<i>P</i><0.05, compared to the NS group.</p

Effect of ABPP on the withdrawal latency time in front paw and in hind paw.

<p>Systemic administration of ABPP reduced the ratio of withdrawal latency time in the front paw at 7^th (A) and 30^th day (B) after MCAO. Treatment with ABPP reduced the ratio of withdrawal latency time in the hind paw at 7^th (C) and 30^th day (D). Data are expressed as means ± SEM (n = 8); **<i>P</i><0.01, compared to the Sham group; #<i>P</i><0.05, compared to the NS group.</p

Effect of ABPP on the neuronal density in the CA1 region of hippocampus.

<p>Systemic administration of ABPP inhibited the decrease of neuron density induced by MCAO at 30^th day after MCAO (A). Schematic depicting hippocampal subregions of interest (B). Neuronal density taken by a representative rat from each group at 30^th day after MCAO (C-I; bar, 50 µm). Data are expressed as means ± SEM (n = 8); **<i>P</i><0.01, compared to the Sham group; ##<i>P</i><0.01, compared to the NS group.</p

Effects of ABPP on the mortality and the brain infarct volume.

<p>Treatment with ABPP did not lower the mortality of ischemic rats (A, <i>P</i>>0.05, chi-square test), but did significantly decrease the brain infarct volumes at 7^th day after MCAO (B). Also shown is the representative TTC staining for the different groups (C). Data are expressed as means ± SEM; **<i>P</i><0.01, compared to the Sham group; #<i>P</i><0.05, ##<i>P</i><0.01, compared to the NS group.</p