SDF-1(5-67) Neutralizing Antibody Enhances Hippocampal Neurogenesis and Rescues Cognitive Deficits in Chronic Temporal Lobe Epilepsy

Abstract Objective To investigate the therapeutic potential of SDF-1(5–67) neutralizing antibody (NAb) in a kainic acid (KA)-induced temporal lobe epilepsy (TLE) model. Methods TLE was induced in male Wistar rats by intraventricular KA injection. Animals were divided into acute (8 days) and chronic (72 days) phase groups, including acute phase control (SHAM-A), acute phase epilepsy model (EP-A), SDF-1(5–67) NAb-treated acute phase epilepsy (S + EP-A), chronic phase control (SHAM-C), chronic phase epilepsy model (EP-C), and SDF-1(5–67) NAb-treated chronic phase epilepsy groups (S + EP-C). NAb treatment was administered via osmotic pumps. Neurogenesis (DCX + cells), neuronal loss (Nissl staining), MFS (Timm staining), cognition (Morris water maze), and SDF-1(5–67) expression (western blot) were assessed. Results During the acute phase, increased dentate gyrus (DG) neurogenesis in EP-A vs. SHAM-A (210.43 ± 12.16 vs. 94.25 ± 7.76 cells/mm², P < 0.05) was unaffected by NAb (195.84 ± 9.71, P > 0.05). In the chronic phase, EP-C showed suppressed neurogenesis (51.63 ± 7.36 vs. SHAM-C 85.12 ± 5.51, P < 0.01), which was rescued by NAb (77.56 ± 9.88, P < 0.01). CA3 neuronal loss was attenuated by NAb in EP-C (174.33 ± 13.06 vs. EP-C 127.47 ± 10.22, P < 0.05). MFS was increased in both phases and was unaffected by NAb. NAb improved cognitive deficits in EP-C (escape latency: 28.14 ± 1.6 s vs. EP-C 35.80 ± 2.41 s, P < 0.05). NAb suppressed SDF-1(5–67) expression in both phases (P < 0.05). Conclusion SDF-1(5–67) NAb promoted neurogenesis and reduced neurodegeneration in chronic TLE, and improved cognitive function without affecting MFS or seizure duration. These findings highlight its potential for postepileptic cognitive rehabilitation.