Abstract:

Objective To discuss the effect of sodium cromoglycate （SCG） on the neural function and cognitive function in the rats with cerebral ischemic stroke （CIS）， and to clarify its mechanism. Methods A total of 80 male SD rats were selected and 18 were randomly selected as sham operation group. The remaining rats were constructed the cerebral ischemia/reperfusion（I/R） injury models by thread embolization method. The 45 successful modeling rats were randomly divided into I/R group， I/R + low dose of SCG group， and I/R +high dose of SCG group（n=15）.At 24 h after modeling， the rats in I/R+low dose of SCG group and I/R +high dose of SCG group were intraperitoneally injected with 20 and 60 mg·kg^－1 SCG for 2 weeks，respectively. The neurological scores of the rats in various groups were evaluated by modified neurological severity score（mNSS） criterion； the area of cerebral infarction was detected by using 2，3，5-triphenyltetrazolium chloride （TTC） staining；the Y-maze experiment was used to detect the memory abilities of the rats in various groups；electrophysiological measurement was used to analyze the accurate reaction rate， accurate reaction time， and field excitatory postsynaptic potential （fEPSP） slopes of the rats in various groups；Golgi staining was used to detect the morphology of dendritic spines in dentate gyrus of hippocampus in brain tissue of the rats in various groups；immunofluorescence method was used to detect the numbers of 5-bromodeoxyuridine （BrdU） positive cells and the expression levels of doublecortin （DCX） protein in dentate gyrus of hippocampus in brain tissue of the rats in various groups； Western blotting method was used to detect the expression levels of brain-derived neurotrophic factor （BDNF），tyrosine kinase B receptor （TrkB）， neurotrophin 3 （NT-3），and tyrosine kinase C receptor （TrkC） proteins in brain tissue of the rats in various groups. Results Compared with sham operation group， the neurological score and the cerebral infarction area of the rats in I/R group were increased（P<0.05），the accurate reaction rate was decreased （P<0.05），and the accurate reaction time was increased （P<0.05）， the fEPSP slope and the density of dendritic spine was decreased （P<0.05）， the number of BrdU positive cells in dentate gyrus of hippocampus in brain tissue and the expression level of DCX protein in hippocampus tissue had no significant differences（P>0.05），and the expression level of NT-3 protein in hippocampus tissue was increased（P<0.05），but the expression levels of BNDF，TrkB， and TrkC proteins had no significant differences（P>0.05）. Compared with I/R group， the neurological scores of the rats in I/R+high dose of SCG group was decreased （P<0.05）， the infarction area was decreased （P<0.05）， the accurate reaction rate was increased （P<0.05）， the accurate reaction time was decreased （P<0.05），the fEPSP slope and the dendritic spine density were increased （P<0.05），the number of BrdU positive cells and the expression level of DCX protein in dentate gyrus of hippocampus in the brain tissue were increased （P<0.05）， and the expression levels of BDNF，TrkB， NT-3， and TrkC proteins were significantly increased （P<0.05）. Conclusion SCG has the protective effect on the neurological and cognitive functions in the I/R model rats and its mechanism may be related to the increasing of the expressions of BDNF/TrkB and NT-3/TrkC signaling pathway related proteins and promoting the proliferation of the neurons.

Key words: Sodium cromoglycate, Stroke, Neurogenesis, Brain ischemia, Reperfusion injury, Cognitive function