Neuroprotective effects of self-assembling peptide nanofiber scaffold in a hypertension rat model of intracerebral haemorrhage

Abstract

INTRODUCTION: Intracerebral haemorrhage (ICH) has the highest mortality rate in all kinds of strokes. Haematoma growth is associated with high systolic blood pressure (SBP) and increased mortality. In this study, we hypothesised that treatment strategies by removing blood from the parenchyma and stopping haematoma growth might reduce brain injury and we tested the effects of a self-assembling peptide (SAP) in a renovascular hypertension (RVHT) rat model of ICH plus blood clot aspiration. METHOD: RVHT was achieved by applying a silver clip onto the left renal artery of male Sprague-Dawley rats. At 4 to 6 weeks after operation, rats with SBP greater than 150 mm Hg were selected to undergo ICH. At 3.5 hours after ICH onset, manual aspiration was performed to remove blood clot. Following the aspiration, 1% SAP solution or saline was injected into the lesion. Haematoma volume was quantified using Image J software at 24 hours after ICH. At 3 days after ICH, perihematomal cell death was determined with TUNEL staining. Inducible nitric oxide synthase (iNOS)-immunoreactive (IR) cells were detected immunohistochemically. RESULTS: Our results showed SAP treatment prevented hematoma enlargement compared with aspiration-only group and saline control group rats. The number of TUNEL positive cells in the perihematoma regions was reduced in SAP-treatment group (79.0±20.4 cells/mm2 ), as compared with the other groups (333.2±34 cells/mm2 for ICH-only group, 386.7±21.0 cells/mm2 for aspiration-only group, and 214.9±54.1cells/mm2 for saline control group). At 3 days after ICH, iNOS-IR–positive cells were present in the ipsilateral hemisphere. SAP treatment reduced iNOS expression (43.3±32.7 cells/mm2 ), as compared with saline control group (234.3±133.3 cells/mm2 ) and aspiration-only group (307.5±70.8 cells/mm2 ). CONCLUSION: Blood clot aspiration plus SAP administration after ICH protects the brain against both mechanical and chemical injury factors, resulting in a reduction in iNOS expression and cell apoptosis.