Neuroprotective effect of the traditional Chinese herbal formula Tongxinluo: a PET imaging study in rats

Abstract

Tongxinluo has been widely used in China for the treatment of acute stroke and for neuroprotection. However, there are few positron emission tomography (PET) studies on the neuroprotective effect of Tongxinluo on cerebral ischemia/reperfusion in small animals. In the present study, Tongxinluo superfine powder suspension or its vehicle was administered intragastrically to rats for 5 successive days before middle cerebral artery occlusion. 18F-fluorodeoxyglucose (FDG) small animal PET imaging showed that at 1 and 2 weeks after cerebral ischemia/reperfusion, glucose metabolism in the ischemic area was greater in rats that had received Tongxinluo than in those that had received the vehicle. Nissl staining showed that 2 weeks after cerebral ischemia/reperfusion, there was less neuronal loss in the prefrontal cortex in Tongxinluo-treated rats than in controls. In addition, Tongxinluo-treated animals showed better neurologic function and lower cerebral infarct volume than rats that received the vehicle. These findings suggest that Tongxinluo exhibits neuroprotective effects in cerebral ischemia/reperfusion injury and demonstrates that 18F-FDG small animal PET imaging is a useful tool with which to study the molecular pharmacology of traditional Chinese medicine.

Evaluation of Avulsion-Induced Neuropathology in Rat Spinal Cords with 18F-FDG Micro-PET/CT

“…Previous studies have demonstrated that the local bleeding in the dura sac, bleeding in the subarachnoid spaces and breakdown of the brain-blood barrier through rupture of the radical vessels are followed by vessel enlargement and proliferation of the spinal cord injury from the ventral root avulsion [ 27 – 29 ]. High glucose metabolism during this type of vascular response in cerebral vessel diseases and trauma of the nervous system have been found to contribute to higher uptake of 18 F-FDG [ 18 , 30 – 32 ]. This conclusion is supported by the data from this study, which showed persistently high uptake of the 18 F-FDG in the ipsilateral intervertebral foramen surrounding the corresponding spinal cord of the avulsion-injured rats.…”

“…The 18 F-FDG micro-PET/CT examination was performed on 45 of the rats in vivo followed by in vitro immunohistochemistry examination at time points of 3 d (n = 15, in each group), 1 w (n = 15, in each group), 2 w (n = 15, in each group), 4 w (n = 10, in each group), and 8 w (n = 5, in each group) following BPRA and GM1 treatment. The 18 F-FDG micro-PET/CT scan of the rats and the image analyses were carried out according to procedures from previous studies [ 14 , 18 ]. The rats, after fasting for 12 hours and having no access to water 6 hours before the experiments, were anesthetized with an intraperitoneal injection of 10% chloral hydrate (350 mg/kg).…”

“…In laboratory studies, 18 F-FDG micro-PET-CT (computed tomography) imaging, due to its inherent imaging characteristics, has allowed scientists to investigate whole body metabolic activity and acquire images reflecting quantitative metabolic information in regions of interests (ROIs) in small-animal models of different diseases [ 14 , 16 , 17 ]. Our recent study demonstrated that changes in 18 F-FDG micro-PET-CT images can reflect the size of ischemia and neuronal loss in the prefrontal cortex 2 weeks after cerebral ischemia/reperfusion of adult rats [ 18 ]. In the present study, we tested for changes in avulsion-induced ROIs in the spinal cord with 18 F-FDG micro-PET-CT imaging following BPRA of adult rats in vivo, and we determined the pathological changes in the corresponding spinal segments after sacrificing the animals.…”

Tongxinluo Enhances Neurogenesis and Angiogenesis in Peri‐Infarct Area and Subventricular Zone and Promotes Functional Recovery after Focal Cerebral Ischemic Infarction in Hypertensive Rats

“…In fact, the protective role of tongxinluo on cerebral ischemic injury was also reported by the other lab. However, in those studies, schemes with preapplication or pre-post administration of tongxinluo were applied, which was different from our postapplication of tongxinluo [ 10 , 17 ]. Although the infarcted area was decreased with tongxinluo preapplication, the preapplication of drug only showed preventive effect in the disease, but not therapeutic effect.…”