The Relationship Between Reversibility Of Neuronal Structure And Integrity Of Blood-Brain Barrier Following Cerebral Ischemia In Mice

Cerebral ischemia for a short period of time can cause serious damage to neuronal structure.Fortunately,the injured neural circuits can regain their initial structure if blood flow is restored in time.However,there are few reported studies elucidating the mechanisms of the morphological reversibility of neuronal structure following ischemia-reperfusion.We combined two-photon imaging in living animals and molecular techniques to explore the expression of the synaptic molecules and the integrity of blood-brain barrier(BBB)following different duration of ischemia,and further illuminate the relationship between the reversibility of neuronal structure and the integrity of BBB during the same process.Two-photon imaging results indicated that the neuronal structure became swollen after 30 min of ischemia.The injured neuronal structure recovered after 3 h of reperfusion.The BBB was intact and,the expression of inflammatory factors including CD 11b and IP 10 was norm after 30 min of ischemia.However,the swollen neuronal dendrites could not be repaired and obvious leakage of BBB occurred after ischemia for 3 h and reperfusion for 3 h.In addition,the expression of CD 11b and IP 10 were up-regulated significantly.The results of qRT-PCR showed that the expression of synaptic molecules including GluRl,GluR2,NMDARR1,PSD95 and synaptophysin also exhibited reversible changes when reversible ischemia damage was induced,but these molecules didnot gain their normal mRNA coding levels when reperfusion was carried out after 3 h of ischemia.These results suggest that the expression of synaptic molecules are associated with the changes of neuronal structure after ischemia and reperfusion.To identify whether the irreversible damage for neuronal structure after long time ischemia is triggered by the leakage of BBB,the BBB permeability was increased with mannitol.Animals treated with 30 min ischemia were induced BBB leakage,the extent of BBB leakage was comparable with that in animals treated with irreversible ischemia damage.In reversible damage models,our results indicated that increased BBB permeability increased the elimination rates of dendritic spines,down-regulated the expression of synaptic molecules in mRNA level,but didnot alter the reversibility of damaged dendritic shafts.This study demonstrated that the expression of synaptic molecules and the integrity of BBB were harder to maintain with longer ischemia time.The increased BBB permeability induced less mRNA translation of synaptic molecules and higher elimination rate of dendritic spines,but had no influence on the recovery of swollen dendrites.These new evidences illuminated the expression level of synaptic molecules and the permeability of BBB following ischemia-reperfusion.The results of this study will have important implications for the understanding of molecular events after ischemia and the further studies of the mechanisms underlying the reversibility of neuronal structure and the reorganization of neural circuits.