p-Hydroxybenzyl Alcohol Prevents Brain Injury and Behavioral Impairment by Activating Nrf2, PDI, and Neurotrophic Factor Genes in a Rat Model of Brain Ischemia

• Published in: Molecules and cells Vol. 31; no. 3; pp. 209 - 215
• Main Authors: Kam, K.Y., Inje University, Gimhae, Republic of Korea, Yu, S.J., Inje University, Gimhae, Republic of Korea, Jeong, N.H., Inje University, Gimhae, Republic of Korea, Hong, J.H., Inje University, Gimhae, Republic of Korea, Anthony Jalin, Angela M.A., Inje University, Gimhae, Republic of Korea, Lee, S.J., Inje University, Gimhae, Republic of Korea, Choi, Y.W., Inje University, Gimhae, Republic of Korea, Lee, C.K., Busan Paik Hospital, Inje University, Busan, Republic of Korea, Kang, S.G., Inje University, Gimhae, Republic of Korea
• Format: Journal Article
• Language: English
• Published: Springer Korean Society for Molecular and Cellular Biology 01.03.2011; Korea Society for Molecular and Cellular Biology; 한국분자세포생물학회
• Subjects: Animals; Bacitracin - pharmacology; Behavior, Animal - drug effects; Benzyl Alcohols - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Brain Injuries - enzymology; Brain Injuries - prevention & control; Brain Injuries - psychology; Brain Ischemia - drug therapy; Brain Ischemia - genetics; Brain Ischemia - pathology; Cell Biology; Cell Death - drug effects; Cerebral Cortex - pathology; Corpus Striatum - pathology; Disease Models, Animal; Enzyme Activation; Female; Hippocampus - drug effects; Hippocampus - metabolism; Hydrogen Peroxide - adverse effects; Infarction, Middle Cerebral Artery - pathology; ISCHAEMIA; ISCHEMIE; ISQUEMIA; Life Sciences; Nerve Growth Factors - genetics; Neurologic Examination; neuroprotection; neurotrophic factor; NF-E2-Related Factor 2 - metabolism; Nrf2; Ovariectomy; p-hydroxybenzyl alcohol; PC12 Cells; Protein Disulfide-Isomerases - antagonists & inhibitors; Protein Disulfide-Isomerases - metabolism; protein disulphide isomerase; Protein Transport - drug effects; Rats; Rats, Sprague-Dawley; Up-Regulation - drug effects; 생물학; hydroxybenzyl alcohol (HBA); neurotrophic factor; Nrf2; neuroprotection; ischemia; protein disulphide isomerase
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-011-0028-4

The therapeutic goal in treating cerebral ischemia is to reduce the extent of brain injury and thus minimize neurological impairment. We examined the effects of p-hydroxybenzyl alcohol (HBA), an active component of Gastrodia elata Blume, on transient focal cerebral ischemia-induced brain injury with respect to the involvement of protein disulphide isomerase (PDI), nuclear factor-E2-related factor 2 (Nrf2), and neurotrophic factors. All animals were ovariectomized 14 days before ischemic injury. Ischemic injury was induced for 1 h by middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion. Three days before MCAO, the vehicle-treated and the HBA-treated groups received intramuscular sesame oil and HBA (25 mg/kg BW), respectively. 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed decreased infarct volume in the ischemic lesion of HBA-treated animals. HBA pretreatment also promoted functional recovery, as measured by the modified neurological severity score (mNSS; p less than 0.05). Moreover, expression of PDI, Nrf2, BDNF, GDNF, and MBP genes increased by HBA treatment. In vitro, H₂O₂-induced PC12 cell death was prevented by 24 h HBA treatment, but bacitracin, a PDI inhibitor, attenuated this cytoprotective effect in a dose-dependent manner. HBA treatment for 2 h also induced nuclear translocation of Nrf2, possibly activating the intracellular antioxidative system. These results suggest that HBA protects against brain damage by modulating cytoprotective genes, such as Nrf2 and PDI, and neurotrophic factors.