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<p>Cognitive impairment is a debilitating comorbidity in temporal lobe epilepsy (TLE), linked to suppressed hippocampal neurogenesis in the chronic phase. Building on evidence that links SDF-1 to epilepsy, emerging research, including our own preliminary data, suggests that its cleaved product, SDF-1(5–67), may play a critical role in this process. To investigate the therapeutic potential of SDF-1(5–67) neutralizing antibody (NAb) in a kainic acid (KA)-induced temporal lobe epilepsy (TLE) model. 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. Data were analyzed by one-way ANOVA with Tukey’s post hoc test, or repeated-measures ANOVA for water maze latency, presented as mean ± SEM. 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, <i>P</i> &lt; 0.05) was unaffected by NAb (195.84 ± 9.71, <i>P</i> &gt; 0.05). In the chronic phase, EP-C showed suppressed neurogenesis (51.63 ± 7.36 vs. SHAM-C 85.12 ± 5.51, <i>P</i> &lt; 0.01), which was rescued by NAb (77.56 ± 9.88, <i>P</i> &lt; 0.01). CA3 neuronal loss was attenuated by NAb in EP-C (174.33 ± 13.06 vs. EP-C 127.47 ± 10.22, <i>P</i> &lt; 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&#xa0;s vs. EP-C 35.80 ± 2.41&#xa0;s, <i>P</i> &lt; 0.05). NAb suppressed SDF-1(5–67) expression in both phases (<i>P</i> &lt; 0.05). 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.</p>

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SDF-1(5–67) neutralizing antibody enhances hippocampal neurogenesis and rescues cognitive deficits in chronic temporal lobe epilepsy

  • 期刊论文

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  • 发表日期：

    2025年12月17日

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  • Xiang-Yu Ma,
  • Li-Ping Zhao,
  • Qiu-Yu Teng,
  • Qi-Dong Tang,
  • Qu Li,
  • Xiao-Qian Zhang

摘要

Cognitive impairment is a debilitating comorbidity in temporal lobe epilepsy (TLE), linked to suppressed hippocampal neurogenesis in the chronic phase. Building on evidence that links SDF-1 to epilepsy, emerging research, including our own preliminary data, suggests that its cleaved product, SDF-1(5–67), may play a critical role in this process. To investigate the therapeutic potential of SDF-1(5–67) neutralizing antibody (NAb) in a kainic acid (KA)-induced temporal lobe epilepsy (TLE) model. 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. Data were analyzed by one-way ANOVA with Tukey’s post hoc test, or repeated-measures ANOVA for water maze latency, presented as mean ± SEM. 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). 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.