Effect Of VPA Treatment On Astrocyte-activated Glial Scar Formation After Traumatic Brain Injury

ObjectiveThe activation of astrocytes can generate neurotrophic factors in the early traumatic brain injury and suppress the diffusion of inflammatory reaction.However,the hypertrophic and hyperplastic astrocytes can form glial scar in the later period of traumatic brain injury and hinder the regeneration of the brain axon.VPA is a kind of histone deacetylase inhibitor,which is widely used to treat epilepsy and bipolar disorder in the clinic treatment.In recent years,some article reported VPA has neuroprotection effect in the traumatic brain injury.Now more and more people begin to put focus on VPA research.Our research used brain stereotaxic apparatus and weight drop device to create traumatic brain injury in mice model.We observed and analyzed the effect of the activation of astrocyte and the formation of glial scar and the angiogenesis restoration after traumatic brain injury by VPA intraperitoneal injection.MethodsIn the experiment,under the condition of the daylight and night light time cycle,healthy adult C57BL/6 mice with the weight between 23 and 27 was chosen as experiment subject.the mice was randomly divided two group:TBI+VPA group and TBI+Vehicle group.The TBI model was induced by weight drop device.At 1d,3d,7d after TBI,TBI+VPA group adopted VPA injection intraperitoneally with each dose of 10ul/g.Equal vehicle was administrated in TBI+vehicle.Immunohistochemical/immunofluorescence staining was applied to observe the effect of the activation of astrocytes and the formation of glial scar and the angiogenesis restoration after 1d,3d,7d traumatic brain injury with VPA intraperitoneal injection.ResultsImmunohistochemical DAB staining revealed a large number of astrocytes activation after 3d traumatic brain injury.DAB-Brdu staining showed proliferation of Brdu+ cells were mainly astrocyte.After 1d traumatic brain injury with 3d VPA intraperitoneal injection continuously,immunofluorescence staining indicated the number of reactive astrogliosis between the VPA treatment group and vehicle group has no significant statistical difference.After Id traumatic brain injury with 1 week VPA intraperitoneal injection continuously,immunofluorescence staining indicated the number of GFAP fluorescence intensity(mm2)between the VPA treatment group and vehicle group has no significant statistical difference.After 3d traumatic brain injury with 2 week VPA intraperitoneal injection continuously,immunofluorescence staining showed the number of GFAP fluorescence intensity(mm2)in the VPA treatment group is significantly lower than vehicle group.After 7d traumatic brain injury with 1 week VPA intraperitoneal injection continuously,immunofluorescence staining revealed compared to vehicle group,the number of collagen IV fluorescence intensity(mm2)with the VAP treated has significant increased.ConclusionIn the early traumatic brain injury,VPA injection can not enhance the activation of astrocyte.After traumatic brain injury,short period of VPA injection can not inhibit the formation of glial scar,while long term of VPA injection can suppress the formation of glial scar and facilitate the angiogenesis restoration after traumatic brain injury.