Partial neuroprotective effect of pretreatment with tanshinone IIA on neonatal hypoxia-ischemia brain damage.
Tanshinone IIA is a compound purified from the Chinese herb Danshen (Radix Salviae Miltiorrhiza Bge). The neuroprotective effect of tanshinone IIA was investigated in a neonatal rat model of hypoxia-ischemia brain damage. Hypoxia-ischemia encephalopathy was induced in rats at day 7 of postnatal age by ligation of the right common carotid artery, followed by 2 h of hypoxia. Tanshinone IIA (10 mg/kg, i.p.) was injected daily from day 2 before surgery for 9 or 16 d. Our results demonstrated significant and sustained brain damage in the hypoxia-ischemia- and vehicle-treated groups at 1 and 3 wk after surgery. Treatment with tanshinone IIA significantly reduced the severity of brain injury, as indicated by the increase in ipsilateral brain weight and neuron density, compared with those of sham-operated animals. The recovery of sensorimotor function and histology was observed in animals that received tanshinone IIA. The plasma of tanshinone IIA-treated rats exhibited higher antioxidant activities, as reflected by the oxygen radical absorbance capacity assay, compared with the vehicle-treated rats. In the neural progenitor cell line C17.2 that was subjected to 2,2'-azobis (2-amidino propane hydrochloride)-induced oxidative stress, tanshinone IIA increased cell viability and protected against mitochondrial damage (JC-1 assay). Our results suggest that tanshinone IIA has antioxidative activities and that treatment that is started before a hypoxic-ischemic insult is partially neuroprotective. Further studies are required to elucidate whether rescue treatment with tanshinone IIA is effective and to determine whether its protective effect is also associated with secondary cooling of the brain.
Xia
Wen Jie
WJ
The Institute of Chinese Medicine, The Chinese University of Hong Kong.
Yang
Mo
M
Fok
Tai Fai
TF
Li
Karen
K
Chan
Wood Yee
WY
Ng
Pak-Cheung
PC
Ng
Ho Keung
HK
Chik
Ki Wai
KW
Wang
Chi Chiu
CC
Gu
Goldie Jia Shi
GJ
Woo
Kam Sang
KS
Fung
Kwok Pui
KP
D045784:Abietanes; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D001831:Body Temperature; D001921:Brain / Q000473:pathology*; D001927:Brain Diseases / Q000517:prevention & control*; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D000860:Hypoxia; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology; D066298:In Vitro Techniques; D007511:Ischemia; D008928:Mitochondria / Q000378:metabolism; D008956:Models, Chemical; D009474:Neurons / Q000378:metabolism; D009929:Organ Size; D010100:Oxygen / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D045784:Abietanes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D005609:Free Radicals; D010616:Phenanthrenes; C021751:tanshinone; D010100:Oxygen