Adamantinomatous Craniopharyngioma Cyst Fluid can Trigger Inflammatory Activation of Microglia to Damage the Hypothalamic Neurons by Inducing the Production of β-Amyloid

Introduction: The mechanism by which adamantinomatous craniopharyngioma (ACP) damages the hypothalamus is still unclear. Cyst fluid rich in lipids and inflammatory factors is a characteristic pathological manifestation of ACP and may play a very important role in hypothalamic injury caused by tumors. Objective: To construct a reliable animal model of ACP cyst fluid-induced hypothalamic injury and explore the specific mechanism of hypothalamic injury caused by cyst fluid. Methods: An animal model was establish by injecting human ACP cyst fluid into the bilateral hypothalamus of mice . ScRNA-seq was performed on the mice hypothalamus and on an ACP sample to obtain a complete gene expression profile for analysis. Data verification was performed through pathological means. Results: ACP cystic fluid caused growth retardation and an increased obesity index in mice, affected the expression of the Npy, Fgfr2, Rnpc3, Sst, and Pcsk1n genes that regulate growth and energy metabolism in hypothalamic neurons, and enhanced the cellular interaction of Agrp-Mc3r. ACP cystic fluid significantly caused inflammatory activation of hypothalamic microglia. The cellular interaction of CD74-APP is significantly strengthened between inflammatory-activated microglia and hypothalamic neurons. Beta-amyloid, a marker of neurodegenerative diseases, was deposited in the ACP tumor tissues and in the hypothalamus of mice injected with ACP cyst fluid. Conclusion: In this study, a novel animal model of ACP cystic fluid-hypothalamic injury was established. For the first time, it was found that ACP cystic fluid can trigger inflammatory activation of microglia to damage the hypothalamus, which may be related to the upregulation of the CD74-APP interaction and deposition of β-amyloid, implying that there may be a similar mechanism between ACP cystic fluid damage to the hypothalamus and neurodegenerative diseases.

Transcriptomic Analysis Reveals that Atf3/c-Jun/Lgals3 axis is associated with Central Diabetes Insipidus after Hypothalamic Injury

Background: Hypothalamic injury causes several complicated neuroendocrine-associated disorders, such as water-electrolyte imbalance, obesity, and hypopituitarism. Among these, central diabetes insipidus (CDI), characterized by polyuria, polydipsia, low urine specific gravity, and deficiency of arginine vasopressin contents, is a typical complication after hypothalamic injury. Methods: CDI was induced by hypothalamic pituitary stalk injury in male animals. Behavioral parameters and blood sample were collected to evaluate the characteristics of body fluid metabolism imbalance. The brains were harvested for high-throughput RNA sequencing and immunostaining to identify pathophysiological changes in corresponding hypothalamic nuclei. Results: Based on transcriptomic analysis, we demonstrated the upregulation of the Atf3/c-Jun axis and identified Lgals3, a microglial activation related gene, as the most significant target gene in response to the body fluid imbalance in CDI. Furthermore, we found that the microglia possessed elevated phagocytic ability, which could promote the elimination of arginine vasopressin neurons after hypothalamic injury. Conclusion: Our findings suggested that the Atf3/c-Jun/Lgals3 axis was associated with the microglial activation, and might participate in the loss of functional arginine vasopressin neurons in CDI after hypothalamic injury.

Cognitive interference processing in adults with childhood craniopharyngioma using functional magnetic resonance imaging

Purpose To assess cognitive interference processing in adults with childhood craniopharyngioma (CP), with and without hypothalamic injury, respectively, in terms of behavioral performance and functional magnetic resonance imaging (fMRI) activity, using the multi-source interference task (MSIT). Methods Twenty-eight CP patients (median age 34.5 [29.0–39.5] years) were investigated at median 20.5 (16.3–28.8) years after treatment with surgical resection and in some cases additional radiotherapy (n = 10) and compared to 29 matched controls (median age 37.0 [32.5–42.0] years). The subjects performed the MSIT during fMRI acquisition and behavioral performance in terms of response times (ms) and accuracy performance (%) were recorded. Results The MSIT activated the cingulo-fronto-parietal (CFP) attention network in both CP patients and controls. No differences were found in behavioral performance nor fMRI activity between CP patients (interference effect 333.9 [287.3–367.1] ms and 3.1 [1.6–5.6]%, respectively) and controls (309.1 [276.4–361.0] ms and 2.6 [1.6–4.9]%). No differences were found in behavioral performance nor fMRI activity between the two subgroups with (332.0 [283.6–353.4] ms and 4.2 [2.3–5.7]%, respectively) and without hypothalamic injury (355.7 [293.7–388.7] ms and 2.1 [1.0–5.2]%, respectively), respectively, and controls. Conclusion Adults with childhood CP performed cognitive interference processing equally well as controls and demonstrated no compensatory fMRI activity in the CFP attention network compared to controls. This was also true for the two subgroups with and without hypothalamic injury. The results can be useful to better characterize this condition, and to optimize treatment and support for these individuals.

Relationship Between Hyperhidrosis and Hypothalamic Injury in Patients With Mild Traumatic Brain Injury

Hyperhidrosis is clinical symptom of various diseases and is an important clinical feature of paroxysmal sympathetic hyperactivity(PSH). Traumatic brain injury(TBI) is the most common condition associated with PSH, and PSH has been mainly reported in moderate and severe TBI. However, very little has been reported on PSH or hyperhidrosis in mild TBI patients. In this study, we used diffusion tensor imaging(DTI) to investigate the relationship between hyperhidrosis and hypothalamic injury in patients with mild TBI. Seven patients with hyperhidrosis after mild TBI and 21 healthy controls were recruited for this study. The Hyperhidrosis Disease Severity Scale was used for evaluation of sweating at the time of DTI scanning. The fractional anisotropy(FA) and apparent diffusion coefficient(ADC) DTI parameters were measured in the hypothalamus. In the patient group, the FA values for both sides of the hypothalamus were significantly lower than those of the control group (p<0.05). By contrast, the ADC values for both sides of the hypothalamus were significantly higher in the patient group than in the control group(p<0.05). In conclusion, we detected hypothalamic injuries in patients who showed hyperhidrosis after mild TBI. Based on the results, it appears that hyperhidrosis in patients with mild TBI is related to hypothalamic injury.

Charles H. Frazier’s craniopharyngioma treatment: the pivotal role of the transfrontal approach

Charles H. Frazier (1870–1936), one of the pioneers of neurosurgery in the US, is known worldwide for devising surgical procedures to relieve trigeminal neuralgia and intractable pain. Less well-known are his substantial contributions to understanding and treating pituitary and parahypophyseal lesions. Along with Bernard Alpers, he defined Rathke’s cleft tumors as a different pathological entity from adenomas and hypophyseal stalk tumors (craniopharyngiomas [CPs]). The surgical challenge posed by CPs piqued Frazier’s interest in these lesions, although he never published a complete account of his CP series. An examination of the Charles Frazier papers at the College of Physicians of Philadelphia allowed the authors to identify 54 CPs that he had treated during his career. In the early 1910s, Frazier developed the subfrontal approach, which would become the primary surgical route to access these lesions, providing better control of the adjacent vital neurovascular structures than the transsphenoidal route hitherto used. Nevertheless, strong adhesions between CPs and the third ventricle floor, the major reason underlying Frazier’s disappointing results, moved him to advocate incomplete tumor removal followed by radiotherapy to reduce both the risk of hypothalamic injury and CP recurrence. This conservative strategy remains a judicious treatment for CPs to this day.