Abstract WMP38: Neurorestorative Therapy of Stroke in Type One Diabetes Rats with Human Umbilical Cord Blood Cell
Diabetes mellitus (DM) instigates a cascade of events leading to vascular damage and poor recovery after ischemic stroke. Our previous studies have found that treatment of stroke with bone-marrow-stromal cells initiated at 24h after stroke improves functional recovery in non-DM rats, but not in DM rats. Effective therapy for stroke in the non-DM population may not necessarily transfer to the DM population, prompting the need to develop therapeutic approaches specifically designed to reduce neurological deficits after stroke in the DM population. In this study, we hypothesize that treatment of stroke with human umbilical cord blood cells (HUCBCs) promotes neurorestorative effect in DM rats.
Methods: Type one DM (T1DM) was induced with a single injection of streptozotocin (60 mg/kg, ip) to adult male Wistar rats. These rats were subjected to 2h MCAo and were randomized to intravenous injection via tail-vein with: 1) phosphate-buffered saline control; 2) HUCBCs (5x106) at 24 hours after MCAo. A battery of functional tests were performed.
Results: HUCBC treatment did not decrease lesion volume and blood glucose level, but significantly improved functional outcome (p<0.05) after stroke in T1DM rats compared to T1DM-MCAo control. To test the mechanisms of HUCBC induced neurorestorative effects, vascular and white matter changes were measured. HUCBC treatment significantly increased percent areas of Bielschowsky silver (axon, control:30.96%±1.2; HUCBC:43.64%±5.7), Lucifer fast blue (myelin, control:37%±1.3; HUCBC:53.2%±3.3) and Synaptophysin (control: 34.6%±0.9; HUCBC: 45.5%±2.4) expression as well as increased vascular diameter (control:16.4um±0.65; HUCBC:20.9um±1.7) compared to T1DM-MCAo control. HUCBC treatment of stroke also significantly increased percent area of Angiopoietin-1 (Ang-1, control:6.1%±1.1; HUCBC:10.2±1.4) and decreased Angiogenin (control:10.8%±1.6; HUCBC: 4.8%±0.5) and MMP9 (control:4.7%±0.6; HUCBC:2.3%±0.4) expression in the ischemic border compared to T1DM-MCAo control.
Conclusion: HUCBC is an effective neurorestorative therapy for stroke in T1DM rats. Increasing Ang1 and decreasing Angiogenin and MMP9 may contribute to HUCBC induced brain plasticity and functional recovery after stroke in T1DM rats.
- © 2012 by American Heart Association, Inc.