The effect of high dose albumin on permeability of blood-brain barrier in brain of rats after ischemic-reperfusion

Abstract

Objective To determine the effect of high dose albumin on permeability of blood brain barrier (BBB) in brain of rats after ischemic-reperfusion (IR) in order to explore its possible mechanism. Methods Establishment of brain ischemic reperfusion rat model by using middle cerebral artery occlusion (MCAO). Medicine treatment was given by caudal vein injection after 2 hours of MCAO. Thirty-six healthy male SD rats were then randomly (random number)divided into 6 groups (n=6 in each): 6 h and 24 h sham-operation groups (Group Sham: operation without ischemia), 6 h and 24 h normal saline groups (Group NS: NS injection 5 ml/kg) and 6 h and 24 h albumin group (Group Alb: 25 % Alb injection 1.25 g/kg). Six hours and 24 hours after the end of reperfusion, rats were measured by Zea-Longa score (neural function deficit) separately. Serum concentration of S100B was examined by the ELISA kit and Evans blue in brain tissue was detected by spectrophotometer. The level of AQP4 was examined by Western blot and immunohistochemistry. All data were analyzed by one-way analysis of variance (ANOVA), The intergroup comparisons were analyzed by the least-significant-difference (LSD) test by using SPSS version 17.0 software. Differences were considered statistically significant if P<0.05. Results Zea-Longa score significantly increased in both group NS and group Alb at 6 h and 24 h(P=0.000). However, there was no significant difference in ZEA-LONGA score of 6 h and 24 h between group Alb and group NS (P=1.000). The serum concentration of S100B in group NS 6 h was significantly lower than that in group Alb at 6 h(196.67±20.11 vs 160.04±14.00, P=0.000), and at 24 h(2.45±0.07 vs. 2.23±0.07, P=0.000). Furthermore, concentration of Evans blue in brain tissue in group Alb was significantly higher than that in group NS at both 6 h(0.97±0.08 vs. 0.74±0.06, P=0.000) and 24 h (2.45±0.07 vs. 2.23±0.07, P=0.000). The expression of AQP4 in brain tissue was higher in group Alb than that in group NS at both 6 h (0.72±0.11 vs. 0.57±0.06, P<0.01)and 24 h (0.80±0.03 vs 0.61±0.02, P<0.01). Conclusions High dose albumin contribute slightly in improvement of neural deficit in rats after IR. On the contrary, it can also aggravate the IR injury, which increases brain edema then increase the permeability of BBB. The mechanism may be associated with over-expression of AQP4 in brain tissue. Key words: Albumin; BBB; IR; Brain edema; Nuro-defect; S100B; AQP4