Exogenous Histamine In The Diencephalon Suppresses Recovery Of Spinal Cord Injury On Adult Zebrafish

The study of spinal cord injury(SCI)in the past,basically pay attention to the damaged spinal cord itself,whether in the basic research with animals model including rat,mouse and zebrafish,or clinical treatment research of new methods or new drugs.Brain tissue,which also belong to the central nervous system(CNS),in order to detect the new influencing factor and mechanisms on repair of injured spinal cord,brain tissue was contacted with SCI,while damaged spinal cord tissue was no longer the only concern.A monoamine neurotransmitter,histamine(HA),is derived from brain tissue and down to the spinal cord.However,the role of HA in SCI has been little reported.The past studies indicated that the brain monoamine neurotransmitter signaling such as dopamine and serotonin have important regulation of motor function,and have positive effect on repair of SCI zebrafish.In this study,adult zebrafish was used to establish the brain-derived HA high released SCI zebrafish model,whose diencephalon was first injected with HA solution,then the SCI surgery was performed on zebrafish after injection.The control group was injected with saline,following with SCI surgery.The results of behavioral analysis showed that the diencephalon injection with HA inhibited the motor function recovery of SCI zebrafish.Immunofluorescence staining showed that,at different time points after SCI,the diencephalon injection with HA leaded to different effects on different type glial cells at rostral injured spinal cord.At 3 days post injury(dpi),the intensity of microglia staining increased at rostral injured spinal cord,but returned to the same level of control group at 7 dpi.As to radial glial cells at rostral lesion site,whose proliferation was promoted by diencephalon injection with HA,while at 11 dpi this promotion on proliferation was gone,however,the radial glial cells showed multi-polar activation pattern which was not conducive to repair.Moreover,HA injection aggravated degeneration of projecting tyrosine hydroxylase-positive(TH+)and serotonergic-positive(5-HT+)fibers from brain down to the spinal cord after SCI.Furthermore,quantitative real-time polymerase chain reaction(qRT-PCR)results showed that the diencephalon injection with HA changed many factors expression at rostral lesion spinal cord after SCI,and reduced the expression of brain-derived neurotrophic factor(BDNF)at 1,3 dpi and insulin-like growth factor1(IGF-1)at 3 dpi.Hence,The data suggests that diencephalon injection with HA can suppress locomotor function recovery of adult zebrafish after SCI,which may be by regulating the neurotrophic and immunological microenvironment of lesion site,as well as promoting the disintegration of other monoamineergic fibers from the brain tissue.In this study,the brain-derived signal,HA,was object to explore its impact on repair of downstream injured spinal cord and a unique idea for discovering new mechanism of spinal cord injury repair was provided.