Roles of platelet-derived growth factor receptor-p on blood-brain barrier permeability in focal cerebral ischemia in mice

Objective: To investigate the roles of platelet-derived growth factor β-receptor (PDGFR-β) signal in blood-brain barrier repair and functional recovery after cerebral ischemia. Methods: A total of 204 mice with post-birth condition specific system PDGFR-β gene knockout were used to make an ischemic model of middle cerebral artery occlusion with the photochemical method, the PDGFR-β knockout mice (Esr-KO ischemic group) and non-gene knockout mice (Floxed ischemic group) (n =93 in each group). The other 18 sham-operation models (without laser irradiation) were divided into an Esr-KO sham-operation group and a Floxed sham-operation group (n =9 in each group). At day 6 and 14 after ischemia, the volume of cerebral infarction of both groups were calculated. The pericytes related α-smooth muscle actin (α-SMA) , basement membrane protein laminin (laminin) expression level, perivascular cell coverage level ( α-SMA/laminin) ,and peripheral cell proliferation level (Ki67/α-SMA) in both group were compared and the permeability differences of blood-brain barrier after cerebral ischemia were analyzed. Results: (1) At day 6 and 14 after ischemia, the cerebral infarction volume of the Esr-KO ischemic group was significantly larger than that of the Floxed ischemic group. The difference between the two groups was statistically significant (all P<0.01). (2) At day 6 after ischemia, the expression of PDGFR-β and α-SMA in the ischemic border region and center region in the Esr-KO ischemic group was decreased significantly compared with the Floxed ischemic group (all P < 0.01) , and there was no significant difference in the expression of laminin (all P > 0. 05 ). The double immunofluorescence staining showed that the α;-SMA/laminin and Ki67/ α-SMA in the ischemic border region of the Esr-KO ischemic group were significantly lower than those of the Floxed ischemia group (15 ±5% vs. 43 ±3% ; t =4. 221 ,P <0. 01; 14. 2 ± 1. 7% vs. 43. 7 ±3. 9% ; t =3. 964,P <0. 01]. (3) The analysis of the green fluorescence tracing technique showed that the vascular i permeability of ischemic border region was increased significantly in the Esr-KO ischemia group compared with the Floxed ischemic group (at day 3:40. 1 ±1.2% vs. 25.5 ± 1. 7% ;t =3. 882,P <0. 01 ;at day 6: 90. 1 ±8.7% vs. 36. 5 ± 4. 5% ; t = 4. 957,P < 0. 01). Conclusion: The PDGFR-β signaling system may be partially involved in the processes of blood-brain barrier repair and functional recovery after cerebral ischemia.