Neuroprotective Effects Of Rheum Tanguficum Polysaccharides (RTP) On Rats With Traumatic Brain Injury (TBI)

Background Rhubarb, a traditional Chinese medicine, has pharmacological effects on digestive, cardiovascular, urinary, and immune system. It has been used to cure diseases for more than 2,000 years. It has also been treated diseases in nervous system(CNS), such as cerebral hemorrhage, psycosis, etc. It is now well recognized that there are two components of brain injury: primary and secondary injury. Primary injury consists of the initial biomechanical damage that occurs at the tune of injury. Secondary injury is progressive cellular damage that evolves as a result of degradative biochemical processes that are set in motion at the time of the injury. Nowaday, many kinds of drugs are used to block or inhibit the cascades. It was reported that rhubarb extracts was used to treat patients with severe cerebral injury complicated by hypothermia, renal failure, hemorrhage in the upper digestive tract, and increased intracranial pressure. Results showed that rhubarb had multiple therapeutic effects on severe brain injury. To identify the effective components of rhubarb, brain protectiveeffects of Rheum Tanguficum Polysaccharides(KTP) on traumatic brain injury(TBI) were investigated.Methods RTF were orally administrated at doses of 100mg·kg-1, 200 mg·kg-1 and 400 mg·kg-1 to rats once a day for five days before injured. A cortical injury in rats was made by the impact method described by Dennis. Animals were sacrificed at 6 hours, 24 hours and 48 hours, respectively after injured. Water content in brain was measured as an indicator of brain edema. Differences of pathology and ultrastructure were examined at different time points after injured, meanwhile, total superoxide dismutase(SOD) activity, Na+-K+ATPase activity and malondialdehyde (MDA) levels in the cortex of brains were determined. Express of heat shock protein(HSP)70 in cells of brain was detected by immunohistochemistry after injured and the changes of HSP70 were determined by Western-blotting. Neurons in the cortex of fetal rats were isolated, and laser scanning confocal microscope imaging of the calcium fluorescent indicator dye Fluo-3/AM were used to determine the kinetic changes of [Ca2+] in neurons.Results After RTF was administered at the doses of 200 mg·kg-1 and 400 mg·kg-1 respectively, the water content decreased at 6 hours and 24 hours compared with the control group(p<0.01). Total SOD activity and Na+-K+ATPase activity markedly increased, but MDA content significantly decreased. In 400 mg·kg-1 group, RTF exhibited significantly to lighten swelling of the mitochondria, dissolution of their cristae, and increasing in lysomomes. After injury 6 hours, numbers of HSP70 cells and expression of HSP70 markedly increased compared with model group(p<0.01), but after24 hours and 48 hours, positive cells of treatment group significantly decreased with respect to model groups, although increased than control groups. The similar result was obtained on HSP70 expression after injured at different time. RTF could decrease intracellular [Ca2+] of cultured neurons (p<0. 01).Conclusion Rheum Tanguficum Polysaccharides(RTP), one of rhubarb's important components, had a neuroprotective effect on cortical injury hi rats. The drug could inhibit edema of injured brain, increase the activity of SOD and Na+-K+ATPase, and decrease MDA level and calcium overload. These are related to the expression of HSP70 induced by RTF in cortex and switch on endogenous principle to protect injured neurons. Above all, polysaccharides might be one of the effective components of rhubarb which had neuroprotection.