Abstract:

BACKGROUND: Numerous studies have shown that, transient ischemic preconditioning (IP) induces cerebral ischemic tolerance. However, the underlying mechanisms of endogenous protection following IP remain unclear.
OBJECTIVE: To investigate the changes of blood-brain barrier permeability and matrix metalloproteinase-9 expression in a rat model of IP-induced cerebral ischemic tolerance at varying time points following focal ischemia/reperfusion.
METHODS: Wistar rats were randomly assigned to three groups: sham-surgery (n = 14), model (n = 70), and IP (n = 70). For IP group, the rats were given middle cerebral artery occlusion for 10 minutes to establish focal IP models. At 1, 3, 7, 14, and 21 days after IP, rat models were again subjected to ischemia for 2 hours. IP was not given to the model group. Sham-surgery group did not received middle cerebral artery occlusion. Neurological functions were determined at 22 hours following reperfusion. Cerebral infarct volume was measured with TTC staining. Change of blood-brain barrier permeability was evaluated by measuring the content of Evans blue. Matrix metalloproteinase-9 protein and mRNA expressions were determined by immunohistochemical staining and in situ hybridization, respectively.
RESULTS AND CONCLUSION: Compared with the model group, the neurological deficit scores, infarct volume, blood-brain barrier permeability, ischemic brain edema, matrix metalloproteinase-9 protein and mRNA expression were significantly decreased or attenuated at 1, 3, 7 days of IP group (P < 0.05 or P< 0.01), these changes were apparent at 3 days. IP induced cerebral ischemic tolerance, the altered blood-brain barrier permeability and the decreased matrix metalloproteinase-9 expression induced by IP might contribute to brain ischemic tolerance.