Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response.
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.
Dalian Medical University, Dalian, 116044, Liaoning, China.|Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, 100700, China.
Yang
Y
Yang
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, 100700, China.|The Neurosurgical Research Center of Beijing Military Region, Beijing, 100700, China.
Yan
Y
Zhang
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, 100700, China.
Zhaotao
Z
Wang
The Neurosurgical Research Center of Beijing Military Region, Beijing, 100700, China.
Shanshan
S
Wang
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, 100700, China.
Mou
M
Gao
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, 100700, China.
Ruxiang
R
Xu
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, 100700, China. chunyangliang@126.com.
Chunyang
C
Liang
Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, 100700, China. zhanghongtian136@126.com.|The Neurosurgical Research Center of Beijing Military Region, Beijing, 100700, China. zhanghongtian136@126.com.
Hongtian
H
Zhang
D000210:Acute-Phase Reaction / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000596:Amino Acids / Q000627:therapeutic use*; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001929:Brain Edema / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D062507:Claudin-5 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020300:Intracranial Hemorrhages / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D062793:Occludin / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
D000596:Amino Acids; D051401:Aquaporin 4; D062507:Claudin-5; D053583:Interleukin-1beta; D015850:Interleukin-6; D018696:Neuroprotective Agents; D062793:Occludin; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; C006952:cerebrolysin
Aquaporin-4; Brain edema; Cerebrolysin; Inflammation response; Intracranial hemorrhage