Changes of blood-brain barrier permeability following intracerebral hemorrhage and the therapeutic effect of minocycline in rats.
OBJECTIVE
to investigate the changes of blood-brain barrier (BBB) permeability and expressions of VEGF, NGF and HPS70 in brain at different time points following intracerebral hemorrhage (ICH) in rats, and observe therapeutic effect of minocycline (MC).


METHODS
rat ICH model was induced with Type IV collagenase. Early MC treatment was administrated via intraperitoneal injection. BBB permeability was evaluated by Evans blue (EB) amount exuded out of cerebral vessels. VEGF, NGF, and HPS70 expressions were determined with immunohistochemical staining.


RESULTS
EB exudation amount in MC treatment group was less than the ICH group (P < 0.05). The former showed a transient EB exudation peak only 1 h after modeling and then gradually decreased, while the latter showed two EB exudation peaks 1 and 4 days after modeling, respectively. The number of VEGF-positive cells in MC treatment group was less than the ICH group (P < 0.05), whereas the number of NGF- and HSP70-positive cells were more than the ICH group (P < 0.05). All three were mainly expressed in neurons and gitter cells, but there were only few expressions in the control group.


CONCLUSIONS
after ICH, the BBB permeability was destroyed, with neuron function affected. In the early stage, VEGF increased BBB permeability, while NGF and HSP70 showed protective effects on nerve cells. Early intraperitoneal injection with MC could reduce the damage of BBB and increase the protective effect on nerve cells, the mechanism of which may be achieved by reducing VEGF expression and enhancing NGF and HSP70 expressions.
Department of Neurosurgery, Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xiwu Road, Xi'an 710004, P.R, China. sweins@21cn.com
Wei
W
Shi
Zizhang
Z
Wang
Jingnan
J
Pu
Ruizhi
R
Wang
Zhengyu
Z
Guo
Chongxiao
C
Liu
Jianjun
J
Sun
Ligui
L
Gao
Ren
R
Zhou
D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D002452:Cell Count / Q000379:methods; D002543:Cerebral Hemorrhage / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005070:Evans Blue; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use; D020932:Nerve Growth Factor / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D042461:Vascular Endothelial Growth Factor A; D005070:Evans Blue; D020932:Nerve Growth Factor; D008911:Minocycline