Introduction: Hypertension is associated with an increased mortality and poor neurological outcome compared with non-hypertensive patients after intracerebral hemorrhage (ICH). To bring thymosin ß4 (Tß4) closer to clinical application, we investigated the Tß4 effects of ICH in hypertensive and normotensive rats.
Methods: ICH was induced by stereotactic injection of 100 ml of autologous blood into the striatum in normotensive (nSHR) and spontaneously hypertensive rats (SHR). Histological and functional measurements were used for comparison. Intraperitoneal Tß4 (12 mg/kg) or saline was administered starting at 24 hours post-ICH and then every 3 days for 4 additional doses. Neurological function (mNSS and corner turn) was determined and immunostaining performed for BrdU. Statistical analysis was obtained using ANOVA.
Results: Systolic artery blood pressure (SBP) and mean artery blood pressure (MBP) was significantly higher in the SHR when compared with nSHR rats after ICH. Both strains had neurological recovery per the mNSS and corner testing at days 4, 7, and 14 after ICH, but SHR rats had more severe deficits for mNSS. In SHR-ICH rats, treatment with Tß4 improved performance significantly (P<0.05) on NSS compared with the saline-treated rats; however, no significant difference in corner test scores was detected. In the nSHR-ICH rats treatment with Tß4 improved performance significantly (P<0.05) on NSS and corner test compared with controls. Additionally, the saline-treated SHR-ICH rats exhibited significantly less cell proliferation within the ipsilateral SVZ and peri-hematoma compared with saline-treated nSHR-ICH rats. Treatment with Tß4 increased cell proliferation significantly (P<0.05) in both nSHR and SHR rats.
Conclusions: Hypertension is associated with reduction of cell proliferation and poor neurological functional recovery after ICH. Treatment of hypertensive ICH rats with Tß4 improves functional recovery that is likely fostered by enhancement of cell proliferation.
Patient Care: Learning the differences in histology and recovery in SHR and nSHR after ICH will assist in the future treatment of patients suffering from ICH.
Learning Objectives: 1) To understand the potential mechanisms of thymosin in treating experimental ICH
2) To understand the implication of cell proliferation on neural recovery after ICH
3) To learn the differences in histology and recovery in SHR and nSHR after experimental ICH