Changes of blood-brain barrier permeability following intracerebral hemorrhage and the therapeutic effect of minocycline in rats

Abstract

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. Conclusion: 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. © Springer-Verlag/Wien 2011.