Abstract
The paper aims to optimize the therapeutic dose and time window of picroside II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models were established by bilateral common carotid artery occlusion (BCCAO) methods. The successful models were randomly divided into sixteen groups according to orthogonal experimental design and treated by injecting picroside II intraperitonenally at different ischemic time with different dose. The concentrations of neuron-specific enolase (NSE), neuroglial marker protein S100B and myelin basic protein (MBP) in serum were determined by enzyme linked immunosorbent assay to evaluate the therapeutic effect of picroside II in cerebral ischemic injury. The results indicated that best therapeutic time window and dose of picroside II in cerebral ischemic injury were ischemia 1.5 h with 20 mg/kg body weight according to the concentrations of NSE, S100B and MBP in serum. It is concluded that according to the principle of lowest therapeutic dose with longest time window, the optimized therapeutic dose and time window are injecting picroside II intraperitonenally with 20 mg/kg body weight at ischemia 1.5 h in cerebral ischemic injury in rats.
Highlights
S100B, a neuroglial marker protein, participates in cell multiplication, cytoskeleton regulation and other biological activities
A large number of activated S100B protein which is produced by glial cells is released into the extracellular after brain tissue injury [17], and leaks into cerebral spinal fluid (CSF) and blood through damaged blood brain barrier, and S100B level in serum is positively correlated with the severity of the injury of cerebral ischemia [18]
Brouns and his group have found that the concentration of S100B, which is in the cerebral spinal fluid (CSF) of the patients with acute ischemic stroke, is highly correlated to the severity of the injury and the prognosis of cerebral ischemia [19]
Summary
S100B, a neuroglial marker protein, participates in cell multiplication, cytoskeleton regulation and other biological activities. Clinical study [2] has found that S100B, a neuroglial marker protein, elevates significantly in the serum of patients with ischemic stroke, and S100B concentration is closely related to ischemic stroke type, severity, infarction volume and mortality [3]. Our previous studies have shown that in rats with cerebral ischemia for 1.5 h, intraperitoneal injection of picroside II (20 mg/kg) can suppress the expression of inflammatory cytokines and neuronal apoptosis [12,13,14,15]. This study attempts to detect the changes of NSE, S100B and MBP levels in serum to further explore the optimal therapeutic dose and the time window of picroside II for treatment of cerebral ischemic injury
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