Lateral fluid-percussion injury leads to pituitary atrophy in rats

Abstract

Traumatic brain injury (TBI) causes neuroendocrine dysregulation in up to 40% of humans, which is related to impaired function of the hypothalamo-hypophyseal axis and contributes to TBI-related co-morbidities. Our objective was to investigate whether hypophyseal atrophy can be recapitulated in rat lateral fluid-percussion injury model of human TBI. High-resolution structural magnetic resonance images (MRI) were acquired from rats at 2 days and 5 months post-TBI. To measure the lobe-specific volumetric changes, manganese-enhanced MRI (MEMRI) scans were acquired from rats at 8 months post-TBI, which also underwent the pentylenetetrazol (PTZ) seizure susceptibility and Morris water-maze spatial memory tests. MRI revealed no differences in the total hypophyseal volume between TBI and controls at 2 days, 5 months or 8 months post-TBI. Surprisingly, MEMRI at 8 months post-TBI indicated a 17% reduction in neurohypophyseal volume in the TBI group as compared to controls (1.04 ± 0.05 mm 3 vs 1.25 ± 0.05 mm 3 , p < 0.05). Moreover, neurohypophyseal volume inversely correlated with the number of PTZ-induced epileptiform discharges and the mean latency to platform in the Morris water-maze test. Our data demonstrate that TBI leads to neurohypophyseal lobe-specific atrophy and may serve as a prognostic biomarker for post-TBI outcome.

White and gray matter integrity evaluated by MRI-DTI can serve as noninvasive and reliable indicators of structural and functional alterations in chronic neurotrauma

“…It is well known that there is a notable difference in the anatomy and physiology of nonhuman mammals (in particular rodents) and human brains. Manganese-enhanced MRI scans revealed that LFP injury caused a 17% reduction in neurohypophyseal volume in the TBI group as compared to controls 64 , suggesting that TBI leads to pituitary atrophy and may serve as a prognostic biomarker for the post-TBI outcome. No single animal model will ever be able to replicate the complete spectrum of changes in human TBI.…”

Pathophysiology of Pediatric Traumatic Brain Injury

“…Basic science and understanding of molecular mechanisms in this area are also lacking in pediatrics. While there are several studies that address pituitary dysfunction following TBI (151)(152)(153)(154)(155)(156)(157), these studies have only been done in adult rats. Greco et al, utilized an adolescent mild rTBI model to examine hypopituitarism following TBI.…”

The ketone ester, 3-hydroxybutyl-3-hydroxybutyrate, attenuates neurobehavioral deficits and improves neuropathology following controlled cortical impact in male rats

“…Whole brain slices were imaged using a Zeiss AxioScan microscope (Zeiss, Jena, Germany) under a 10X objective. Lesion volume was quantified by a researcher blind to the experimental conditions using ImageJ software (National Institute of Health, USA, version 1.52k) as previously published [25]. The region of interest (ROI) outlining the CCI lesion was manually drawn in the coronal plane using ImageJ software.…”