Insulin-like growth factor-1 improves postoperative cognitive dysfunction following splenectomy in aged rats

Postoperative cognitive dysfunction (POCD) is a serious complication following anesthesia and operations in aged patients undergoing surgical intervention. It is characterized by temporary or permanent cognitive decline, memory impairment and deterioration in language comprehension and social adaption ability. Therefore, the development of POCD prevention and treatment tools has become an area of interest. The current study assessed the therapeutic effects of insulin-like growth factor-1 (IGF-1) on POCD in aged rats and explored the underlying mechanisms. Model rats underwent splenectomy under 1.5-2% isoflurane and mechanical ventilation. IGF-1 (50 µg/kg) was diluted in normal saline and administered by abdominal hypodermic injection daily from the operation to day 7 post-operation. Following splenectomy, the animals showed marked cognitive impairment as determined by the Morris water maze test. Hippocampal protein levels of amyloid precursor protein (APP), β-site APP-cleaving enzyme-1 (BACE-1), amyloid-β (Aβ), capase3, Bax and Bcl-2 were assessed by immunoblotting. Neuronal apoptosis in the hippocampus was analyzed using a TUNEL assay. The results demonstrated that the levels of APP, BACE-1, Aβ, caspase3 and Bax were increased following splenectomy, while the levels of Bcl2 were reduced at days 1, 3 and 7 post-operation in aged rats. However, IGF-1 downregulated APP, BACE-1, Aβ, capase3 and Bax, and upregulated Bcl2 at these time points following splenectomy. TUNEL staining revealed that administration of IGF-1 significantly reduced neuronal apoptosis in the hippocampal CA1 region following splenectomy. These results indicated that IGF-1 decreased Aβ-protein production and inhibited neuronal apoptosis in the hippocampus following splenectomy, subsequently alleviating POCD.