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Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response

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Abstract

The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood–brain barrier permeability.

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Acknowledgments

This research was supported by the Natural Scientific Research funds of China (No. 81371345) and Beijing Nova program (XX2013059). We thank EVER Neuro Pharma Consulting (Beijing) Ltd for helping the pharmacy usage and Dr. Yilin Sun from the department of ultrapathology of Beijing Neurosurgical Institute and Ms. Qinqin Wang for the technical assistance.

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    Authors and Affiliations

    1. Dalian Medical University, Dalian, 116044, Liaoning, China

      Yang Yang

    2. Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, 100700, China

      Yang Yang, Yan Zhang, Zhaotao Wang, Mou Gao, Ruxiang Xu, Chunyang Liang & Hongtian Zhang

    3. The Neurosurgical Research Center of Beijing Military Region, Beijing, 100700, China

      Yan Zhang, Shanshan Wang & Hongtian Zhang

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    1. Yang Yang
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    Yang Yang and Yan Zhang contributed equally to this work.

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    Yang, Y., Zhang, Y., Wang, Z. et al. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response. Neurochem Res 41, 748–757 (2016). https://doi.org/10.1007/s11064-015-1745-4

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