Effects of ibuprofen and celecoxib as neuroprotective agents in chronic cerebral hypoperfusion-induced neurodegeneration in rats

Abstract

Neurodegeneration is a term that describes the progressive loss of structure or function of neurons. Common neurodegenerative diseases are Alzheimer`s disease, Parkinson`s disease and Huntington’s disease. Neurodegeneration is always related to aging process, cerebral hypoperfusion and inflammation. In this study, an animal model for chronic cerebral hypoperfusion-related neurodegenerative diseases was created by permanent, bilateral common carotid artery occlusion (2VO) in the rat. Ibuprofen, a non-selective cyclooxygenase (COX) inhibitor and Celecoxib, a selective COX-2 inhibitor, were tested as neuroprotective agents in this experiment. The rats were divided into 4 groups; SHAM group (negative control) undergone sham operation; 2VO-O group (positive control) undergone 2VO only; 2VO-I and 2VO-C groups were treated daily with Ibuprofen and Celecoxib respectively following 2VO. After 8 weeks, all the rats were euthanized and the hippocampi were isolated. Parameters tested were the neuronal cell count in the hippocampal CA1 region, hippocampal COX-2 mRNA expression and prostaglandin E2 (PGE2) level. For initial comparison, 2VO-O group was found to have significant difference compared to SHAM, in term of increase in neuronal cell death, increase in COX-2 mRNA expression and PGE-2 level. For Ibuprofen and Celecoxib treated groups, the viable neuronal cell counts of the hippocampal CA-1 region were significantly higher compared to the 2VO-O group. For the hippocampal COX-2 mRNA expression, the value in the 2VO-I group showed no significant difference when compared to the 2VO-O group. However, the value for 2VO-C group was significantly lower compared to the 2VO-O group. For the hippocampal PGE-2 level measurement, the value in 2VO-I and 2VO-C groups were found to be significantly lower in number compared to the 2VO-O group. In conclusion, chronic cerebral hypoperfusion-induced neurodegeneration by 2VO increases the neuronal cell death in the hippocampal CA-1 region and elevates both COX-2 mRNA expression and PGE-2 level in the hippocampus. In addition, Ibuprofen and Celecoxib are shown to have neuroprotective effect in chronic cerebral hypoperfusion-induced neurodegeneration.