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A Self-assembling Nanomaterial Reduces Acute Brain Injury and Enhances Functional Recovery in a Rat Model of Hypertensive Intracerebral Hemorrhage

Lynn Yan-Hua Sang, Yu-Xiang Liang, Kwok-Fai So, Gilberto Ka-Kit Leung, Rutledge G Ellis-Behnke and Raymond Tak-Fai Cheung

Intracerebral hemorrhage (ICH) carries a high morbidity and mortality rate. High systolic blood pressure promotes hematoma growth. A self-assembling peptide (SAP) can achieve immediate hemostasis via formation of a SAP nanofiber scaffold (SAPNS). A minimally invasive aspiration of hematoma plus local delivery of SAPNS may lead to decompression of brain tissue and prevent hematoma growth.
In a rat model of renovascular hypertension, experimental ICH was induced by a local injection of bacterial collagenase IV into the left basal ganglia. At 3.5 hours after induction of ICH, stereotactic clot aspiration or sham aspiration was performed manually. Following hematoma aspiration, an intrastriatal injection of 1% SAP, saline or sham injection was performed. Hematoma volume and brain swelling were quantified at 24 hours after ICH. Brain sections were immuno histochemically processed for myeloperoxidase and CD68 to detect the inflammatory infiltration in the perihematomal area. Perihematomal apoptotic cell death was determined using TUNEL staining. Functional recovery was assessed using neurological severity score and modified limb placement test at 1, 3, 7, 10 days after ICH.
The combined treatment with hematoma removal and locally delivered SAPNS decreased hematoma volume, hematoma growth, brain edema, perihematomal inflammatory cell infiltration and apoptosis, as well as improved sensorimotor functional recovery.
Locally delivered SAPNS after hematoma aspiration may prevent hematoma growth, facilitate the repair of ICHrelated brain injury and promote functional recovery. Such combined treatment may be effective in patients with hypertensive ICH.