Hypothalamic Neurogenesis Plays A Role In Central Diabetes Insipidus Induced By Pituitary Stalk Lesion

Hypothalamic or pituitary dysfunction often occurs in the hypothalamus and adjacent areas injury or after surgery on sellar region.One of the typical complications is central diabetes insipidus(CDI),which is characterized by water electrolytes,pituitary hormone hormonal disorders.Although there are many treatment options for maintaining a balanced internal environment,patients are still at risk of serious internal environmental disorders that can lead to death or chronic progression.In clinical practice,it has been found that some patients can recover after postoperative CDI.Similarly,recovery was also observed in animals with CDI due to pituitary injury.However,the mechanism and laws of recovery have not yet been clarified.For further study,a stable CDI rat model was established first,and a 3D metal-printed lesional knife was used to perform the pituitary stalk electric destruction model(PEL),and the urine volume,water intake,and urine specific gravity were measured for 28 days after PEL.The overall trend of diabetes insipidation was found to be three-phase type.Four clusters were used after cluster analysis.Acute urinary insurgery(postoperative day 1),temporary recovery period(day 2-4),and late urinary collapse(Days 5-17),and the recovery period of Dialysis(Days 18-28).At the same time,the CDI index was used to standardize the evaluation of the epidural collapse.By comparing the CDI index with serum AVP and plasma Na+ levels in each period,it was found that PEL could be restored after surgery.To explore the mechanism of recovery.PEL is labeled with bromodeoxyuridine(BrdU).Newborn cells(BrdU+)are found in both supraoptic nucleus(SON)and paraventricular nucleus(PVN),and many nascent cells differentiate into GABAergic and glutamatergic interneurons,which can also turn into glial cells and oligodendrocytes.Glial cells.The newborn interneurons are in contact with large cell neurons,and the new cells join the original neural circuit and function.Sequential staining of hypothalamic slices revealed that a large number of BrdU+ cells appeared in the short-term postoperatively in the medial hypoplasia(ME),and that these neonatal cells were mostly transformed from Nestin+Nkx 2.1+static neural stem cells(qNSCs)into BrdU+Nestin.+Nkx 2.1+ Activated neural stem cells(aNSCs)come from.The ME,SON,and PVN were regionally labeled with retroviruses.GFP+ cells were present in SON and PVN only when PEL was labeled in the ME group,confirming that ME was the origin of NSCs after PEL.In order to observe the migration path of newborn cells,markers of neural precursor cell migration(DCX)were used.Neoplastic cells in the ME area migrated from the ME to the supraoptic nucleus infuse and crossed the optic tract to the anterior supraoptic nucleus and PVN.The brain tissue was treated with transparency and the entire median bulge was observed under multiphoton scanning.Migration flow(MMS).In order to study the effect of neurogenesis regulating Nkx 2.1+NESTIN+ cells on CDI,LHX2 is an important regulator of Nkx 2.1+ cell differentiation into neurons.The inhibition of Nkx2.1+ cells with AAV-shLHX2 resulted in increased CDI symptoms,a high CDI index,and inability to recover from the symptoms of diabetes insipidus.At the same time,it was found that nascent cells express IGFI receptors,and by upregulation or downregulation of neurogenesis(IGF1 or Ara-C in the lateral ventricle),the postoperative CDI symptoms change.In this study,we confirmed that three-phase type of urinary collapse caused by the detachment of the pituitary stalk in rats,the symptoms of which were restored by activation of the qNSCs of ME into aNSCs,migration to SON and PVN,and differentiation into glutamatergic and GABA.Can interneurons,and join the neural circuit to produce functions to self-regulate.At the same time,it was confirmed that neurogenesis played an important role in the recovery of CDI caused by the detachment of the pituitary stalk.