| Objective: To investigate the impact of curcumin (Cur) regulating the brain-derived neurotrophic factor (BDNF)/tropomyosin related kinase B receptor (TrkB) signaling pathway on neuronal apoptosis in neonatal rat with bacterial meningitis (BM). Methods: 15 rats were randomly selected as non-infected group (NF group), other rats injected streptococcus pneumoniae ATCC49619 suspension into frontal subarachnoid space to construct BM rat model, the successful BM model was randomly divided into BM group, L-Cur group (1.25 mg/kg), M-Cur group (2.5 mg/kg), H-Cur group (5 mg/kg), H-Cur+K252a group (5 mg/kg Cur+2.5 μg/kg K252a), 15 rats in each group, once a day, the injections were given continuously for 3 weeks. The rats were weighed and clinical scored, HE staining and Nissl staining were used to observe the damage of nerve cells; TUNEL staining was used to evaluate neuronal apoptosis.The levels of glial fibrillary acid protein (GFAP) and spinal cord calcium ion adaptor protein-1 (IBA-1) were detected by immunofluorescence staining. The levels of inflammatory factors and chemokines in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Western blot was used to detect the expression of apoptosis protein and BDNF/TrkB pathway protein in brain tissue. Results: The brain tissue structure of the NF group was normal, large area of blue Nissl bodies appeared in the cytoplasm of neurons. In the BM group, a large amount of inflammatory exudate and inflammatory cell infiltration appeared in the subarachnoid space, the cell bodies were enlarged, the processes contracted, and the morphology was irregular; the number of Nissl bodies, weight, the levels of Bcl-2, BDNF, and p-TrkB/TrkB protein decreased obviously (P<0.05), the clinical score, the relative fluorescence intensity values of IBA-1 and GFAP, the relative expression of chemokine ligand-2 (CCL-2), chemokine ligand-3 (CCL-3), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), the rate of neuronal apoptosis, and the level of BCL2-Associated X protein (Bax) protein increased obviously (P<0.05). The inflammatory exudate and cell infiltration of brain tissue were reduced, the number of Nissl bodies, weight, the levels of B-lymphoblastoma-2 gene (Bcl-2), BDNF, and p-TrkB/TrkB protein increased obviously in each group after Cur treatment (P<0.05), the clinical score, the relative fluorescence intensity values of IBA-1 and GFAP, the relative expression of CCL-2, CCL-3, TNF-α, and IL-6, the rate of neuronal apoptosis, and the level of Bax protein decreased obviously (P<0.05), the higher the addition dose of Cur, the more obvious the change;the effect of H-Cur+K252a group was similar to that of BM group, K252a reversed the improvement effects of Cur on neuron apoptosis and damage in BM rat. Conclusion: Cur might reduced neuronal apoptosis in BM rat by activating BDNF/TrkB signaling pathway. |
