A rat model for pituitary stalk electric lesion-induced central diabetes insipidus: application of 3D printing and further outcome assessments

Abstract

A stable and reproducible rat injury model is not currently available to study central diabetes insipidus (CDI) and the neurohypophyseal system. In addition, a system is needed to assess the severity of CDI and measure the accompanying neurobiological alterations. In the present study, a 3D-printed lesion knife with a curved head was designed to fit into the stereotaxic instrument. The neuro-anatomical features of the brain injury were determined by in vivo magnetic resonance imaging (MRI) and arginine vasopressin (AVP) immunostaining on brain sections. Rats that underwent pituitary stalk electrical lesion (PEL) exhibited a tri-phasic pattern of CDI. MRI revealed that the hyperintenseT1-weighted signal of the pituitary stalk was interrupted, and the brain sections showed an enlarged end proximal to the injury site after PEL. In addition, the number of AVP-positive cells in supraoptic nucleus (SON) and paraventricular nucleus (PVN) decreased after PEL, which confirmed the success of the CDI model. Unlike hand-made tools, the 3D-printed lesion knives were stable and reproducible. Next, we used an ordinal clustering method for staging and the k-means’ clustering method to construct a CDI index to evaluate the severity and recovery of CDI that could be used in other multiple animals, even in clinical research. In conclusion, we established a standard PEL model with a 3D-printed knife tool and proposed a CDI index that will greatly facilitate further research on CDI.

Microglial infiltration mediates cognitive dysfunction in rat models of hypothalamic obesity via a hypothalamic-hippocampal circuit involving the lateral hypothalamic area

“…For the lesion surgery, a stereotaxic apparatus was used. The coordinates of the ARC and VMH were determined based on previous research by our research group and the Paxinos and Watson rat brain atlas ( Roth et al, 2011 ; Feng et al, 2018a ; Zhou M. F. et al, 2019 ; Zhou et al, 2021 ). The Bregma point (AP: –2.6 mm, ML: ±0.6 mm, DV: –9.6 mm) was used as the target lesion point.…”

“…Our previous work elucidated the roles of microglial cells in the hypothalamus after injury to the pituitary stalk and evaluated metabolic function in patients with hypothalamic damage ( Feng et al, 2018a ; Zhou M. F. et al, 2019 ; Ou et al, 2020 ). Extending this line of research, in the present study, we investigated how lesion-induced HO may contribute to cognitive decline via the hypothalamic-hippocampal neural circuit and microglial infiltration.…”

Transcriptomic Analysis Reveals that Activating Transcription Factor 3/c-Jun/Lgals3 Axis Is Associated with Central Diabetes Insipidus after Hypothalamic Injury

“…After surgery, all mice were put back to the original metabolic cages and their daily water consumption (DWC), daily urine volume (DUV), and USG were monitored for 28 days. PEL surgery for rats was performed similarly according to our previous study [23].…”

“…All animals were allowed to acclimatize to their environment in independent metabolic cages for 3 days before surgery. Pituitary stalk electric lesion (PEL) surgery for mice was performed based on previous studies [23][24][25]. In brief, mouse was deeply anesthetized with 75 mg/kg sodium pentobarbital.…”

Applications of 3D printing in small animal magnetic resonance imaging

“…20 While the opportunities for 3D printing within clinical medicine are vast, this technology has had an equally positive impact on advancing preclinical research [21][22][23] and imaging. 22,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] Additive manufacturing permits the creation and customization of assemblies that facilitate the handling of an uncooperative animal, the control of anesthesia, the positioning of organs of interest within the imaging equipment, and the optimization of data acquisition. 25 Among the different imaging modalities employed in preclinical research, those challenges are often compounded in the context of small-animal magnetic resonance imaging (MRI).…”