Key result
Intracerebral hemoglobin injection significantly increased Evans blue permeation and perihematoma water content at all time points compared to sham and normal controls (P<0.05).
RCT (n=70)
randomized
Hemoglobin induces RhoA/ROCK signal pathway activation after intracerebral hemorrhage, which may contribute to increased blood-brain barrier permeability and cerebral edema.
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Hemoglobin may mediate BBB leakage and edema via RhoA/ROCK in rodent ICH; hypothesis-generating, requires human validation before any clinical consideration.
Objective To reveal whether increased blood brain barrier (BBB) permeability induced by hemoglobin is attributed to RhoA/Rho associated coiled coil forming protein kinase (ROCK) signal pathway activation.Methods Seventy male SD rats were randomized into normal control group (n=10),sham-operated group (n=30) and intracerebral hemoglobin injection group (Hb group,n=30).Rats in sham-operated group and Hb group were each divided into three subgroups (6,12 and 24 h after hemoglobin injection,n=10).Rat models of cerebral hemorrhage in the Hb group were induced by intracerebral hemoglobin injection; BBB permeability was measured by Evans blue dye; dry-wet method was used to measure the brain tissue water content for all groups; the distributions of RhoA and ROCK2 were detected by immunohistochemistry (DAB stainning); the mRNA expressions of RhoA and ROCK2 were evaluated by real time fluorescent quantitative PCR.Results As compared with those in the sham-operated group and normal control group,Evans blue permeation and water content of perihematoma significantly increased in the Hb group at all time points (P＜0.05).Immunohistochemistry indicated no obvious expressions of RhoA and ROCK2 in the normal control group,while RhoA and ROCK2 showed claybank in the brain tissue of Hb group,which mainly expressed in the cytoplasm.As compared with those in the normal control group and sham-operated group,the mRNA level of RhoA significantly elevated in the Hb group at all time points (P＜0.05) and that of ROCK2 significantly elevated in the Hb group at 6 and 12 h time points (P＜0.05).Conclusion Hemoglobin induces RhoA/ROCK signal pathway activation after intracerebral hemorrhage,which may attribute to BBB permeability increase and subsequent cerebral edema formation.
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Fu et al. (2013) conducted an RCT in Cerebral hemorrhage (n=70). Intracerebral hemoglobin injection vs. Normal control and sham-operated groups was evaluated on Evans blue permeation and water content of perihematoma (p=<0.05). Intracerebral hemoglobin injection significantly increased Evans blue permeation and perihematoma water content at all time points compared to sham and normal controls (P<0.05).
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