RESUMEN
AIMS: Central diabetes insipidus (CDI), a typical complication caused by pituitary stalk injury, often occurs after surgery, trauma, or tumor compression around hypothalamic structures such as the pituitary stalk and optic chiasma. CDI is linked to decreased arginine vasopressin (AVP) neurons in the hypothalamic supraoptic nucleus and paraventricular nucleus, along with a deficit in circulating AVP and oxytocin. However, little has been elucidated about the changes in AVP neurons in CDI. Hence, our study was designed to understand the role of several pathophysiologic changes such as endoplasmic reticulum (ER) stress and apoptosis of AVP neurons in CDI. METHODS: In a novel pituitary stalk electric lesion (PEL) model to mimic CDI, immunofluorescence and immunoblotting were used to understand the underlying regulatory mechanisms. RESULTS: We reported that in CDI condition, generated by PEL, ER stress induced apoptosis of AVP neurons via activation of the PI3K/Akt and ERK pathways. Furthermore, application of N-acetylcysteine protected hypothalamic AVP neurons from ER stress-induced apoptosis through blocking the PI3K/Akt and ERK pathways. CONCLUSION: Our findings showed that AVP neurons underwent apoptosis induced by ER stress, and ER stress might play a vital role in CDI condition through the PI3K/Akt and ERK pathways.
Asunto(s)
Apoptosis/fisiología , Arginina Vasopresina/metabolismo , Diabetes Insípida Neurogénica/fisiopatología , Estrés del Retículo Endoplásmico/fisiología , Neuronas/metabolismo , Acetilcisteína/farmacología , Animales , Apoptosis/efectos de los fármacos , Diabetes Insípida Neurogénica/tratamiento farmacológico , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico/efectos de los fármacos , Hipotálamo/efectos de los fármacos , Hipotálamo/fisiopatología , Sistema de Señalización de MAP Quinasas , Masculino , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Distribución Aleatoria , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To investigate the growth of craniopharyngioma involving the third ventricular floor with regard to the hypothalamus by detecting expressions of leukocyte common antigen (CD45) and intercellular adhesion molecule (ICAM-1) in the tumor tissue. METHODS: The expressions of CD45 and ICAM-1 proteins in 30 craniopharyngioma samples with third ventricular floor involvement were detected by SP immunohistochemistry. RESULTS: The inflammations labeled by CD45 were identified commonly in the craniopharyngioma tissues involving the third ventricular floor. The expression of ICAM-1 was mainly in the inner tumor cells and interstitial cells, but not detected in the basilar tumor cells growing toward the third ventricular floor. Adamantinomatous craniopharyngiomas showed markedly higher CD45 and ICAM-1 expressions than squamous papillary tumors (P<0.05). CONCLUSION: Inflammatory adhesion largely characterizes the growth of the craniopharyngioma tissues involving the third ventricular floor toward the hypothalamus without the tendency of invasion. The difference in the inflammation between the two types of craniopharyngioma may affect the prognosis of the patients.