Neuroprotective effects of carnosic acid on the hippocampus of 6-hydroxydopamine injured rats

The reduction of dopamine level caused by neurodegenerative diseases such as Parkinson''s disease (PD) may reduce the production of new neurons in dentate gyrus (DG) of the hippocampus. In addition، there is a direct link between the reduction of neurons in the hippocampus and memory impairment. In this study، the effect of carnosic acid (CA) on the hippocampal neurogenesis was evaluated after 6-OHDA injury. Male Wistar rats were randomly divided into six groups. First group was injected by bilateral intra-nigral of 6-OHDA at a dose of 6µg (injury). Groups 2-5 were injured rats which received orally Rosemary extract containing 40% CA at doses of 25، 50 and100 mg/kg (treated) and distilled water (control)، once daily in a period of 14 days before and after injury. The sixth group (sham) was injected with saline instead of neurotoxin. After treatment، the brains were removed and fixed with 4% paraformaldehyde، dehydrated، embedded in paraffin and cut into 10μm thick slices. Sections were stained with cresyl fast violet and cell counting of hippocampal regions was done. The loss of dopaminergic neurons in the 6-hydroxydopamine-lesioned rats، compared to sham-operated rats، was verified by tyrosine hydroxylase immunohistochemistry. Immunostaining analysis revealed a high density of TH+ cells in sham compared to injured group. The number of DG granular and CA1 pyramidal cells were decreased significantly in both control and injured groups compared to sham (P<0. 05). The number of granular and CA1pyramidal cells were increased significantly in CA (25، 50،100) and CA (50،100) treated groups respectively، compared to control and injured rats (P<0. 05). The number of CA3 pyramidal cells was not increased significantly in treated groups compared to control and injured rats. CA plays an important role in protecting hippocampal neurons from further damage in response to 6-OHDA. Then it is the effective herbal drug with treatment potential to improve memory impairment in PD which caused by neurons degeneration in the hippocampus