Magnetic resonance imaging (MRI) is increasingly used in the assessment of the severity and progression of neurotrauma. We evaluated temporal and regional changes after mild fluid percussion (FPI) and controlled cortical impact (CCI) injury using T2-weighted-imaging (T2WI) and diffusion-weighted imaging (DWI) MRI over 7 days. Region of interest analysis of brain areas distant to the injury site (such as the hippocampus, retrosplenial and piriform cortices, and the thalamus) was undertaken. In the hippocampus of CCI animals, we found a slow increase (51%) in apparent diffusion coefficients (ADC) over 72 h, which returned to control values. The hippocampal T2 values in the CCI animals were elevated by 18% over the 7-day time course compared to control, indicative of edema formation. Histological analysis supported the lack of overt cellular loss in most brain regions after mild CCI injury. FPI animals showed a generalized decrease in hippocampal ADC values over the first 72 h, which then returned to sham levels, with decreased T2 values over the same period, which remained depressed at 7 days. Histological assessment of FPI animals revealed numerous shrunken cells in the hippocampus and thalamus, but other regions showed little damage. Increased immunohistochemical staining for microglia and astroglia at 7 days post-injury was greater in FPI animals within the affected brain regions. In summary, traumatic brain injury is less severe in mild CCI than FPI, based on the temporal events assessed with MRI.

There were varying amounts of inflammation in the basal turn of the cochleae in all four implanted temporal bones. Trauma to the facial nerve at the facial recess was noticed in one case. Surviving dendrites varied from 5% to 30% among four cases, with no relationship to clinical performance. The speech recognition scores, measured with Central Institute of the Deaf (CID) sentence score, varied among patients from 4% to 89%, while the patient with the highest SGCs had the best clinical outcome.

Magnocellular neuroendocrine cells of the supraoptic nucleus (SON) release vasopressin (VP) systemically and locally during osmotic challenge. Although both central VP and nitric oxide (NO) release appear to reduce osmotically stimulated systemic VP release, it is unknown whether they interact locally in the SON to enhance somatodendritic release of VP, a phenomenon believed to regulate systemic VP release. In this study, we examined the contribution of VP receptor subtypes and NO to local VP release from the rat SON elicited by systemic injection of 3.5 m saline. Treatment of SON punches with VP receptor antagonists decreased osmotically stimulated intranuclear VP release. Similarly, blockade of NO production, or addition of NO scavengers, reduced stimulated VP, glutamate, and aspartate release, suggesting that local NO production and activity are critical for osmotically induced intranuclear VP and excitatory amino acid release. An increase in endogenous NO release from SON punches in response to hyperosmolality was confirmed by enzymatic NO assay. Consistent with enhanced glutamate and VP release from stimulated rat SON punches, the ionotropic glutamate receptor blocker kynurenate decreased stimulated local VP release without affecting NO release. These data suggest that NO enhances local VP release in part by facilitating local release of glutamate/aspartate and that glutamate receptor activity is required for the stimulation of local VP release by osmotic challenge. Collectively, these results suggest that local VP receptors, NO, and glutamatergic signaling mediate the amplification of intranuclear VP release during hyperosmolality and may contribute to efficient, but not exhaustive, systemic release of VP during osmoregulatory challenge.

We found statistically improved operative times, hospital stay, and blood loss the first 2 years with a low rate of temporary complications. It appears that minimally invasive video-assisted thyroidectomy is a safe and feasible option to standard thyroidectomy in selected patients.

Iron is a trace metal essential for normal brain development but toxic in excess as it is capable of generating highly reactive radicals that damage cells and tissue. Iron is stringently regulated by the iron regulatory proteins, IRP1 and IRP2, which regulate proteins involved in iron homeostasis at the posttranscriptional level. In this study, 12 distinct regions were microdissected from the mouse brain and regional changes in the levels of loosely bound and non-heme iron that occur with development were measured. We examined 6, 12, and 24 week old wildtype C57BL/6 mice and mice with a targeted deletion of iron regulatory protein 2 (IRP2-/-) that have been reported to develop neurodegenerative symptoms in adulthood. In wildtype mice, levels of loosely bound iron decreased while non-heme iron increased with development. In contrast, an increase in loosely bound and a more pronounced increase in non-heme iron was seen in IRP2-/-mice between 6 and 12 weeks of age, stemming from lower levels at 6 weeks (the youngest age examined) compared to wildtype. These results have implications for understanding the increase in regional brain iron that is associated with normal aging and is postulated to be exacerbated in neurodegenerative disorders.

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IntroductionAltered brain iron metabolism in the face of aging is cited as a significant risk factor for development of Alzheimer's Disease. In order to correlate brain iron pools (total, loosely bound, non-heme) with novel magnetic resonance imaging (MRI) an experimental mouse model with an engineered deletion of iron regulatory protein-2 (IRP-2) was used. The novel MR sequences are termed susceptibility weighted imaging (SWI). These mice display signs of neurodegeneration after six months of age, manifested by ataxia, vestibular dysfunction, tremors, and postural abnormalities. The purpose of this study was to develop a dissection technique that enabled a standardized and reproducible method to secure regions of interest (ROI) for iron assay measurements.Methods35 C57/B1 mice were euthanized with the Muromachi Microwave Fixator. Controlled microwave brain fixation provides immediate fixation of brain metabolites and conservation of iron in its various pools. Craniotomies are performed to expose the underlying fixed brain. We are able to dissect 12 distinct ROI from each hemisphere (5-10 mg in quantities, ww).ResultsOur dissection technique allowed isolation of the following ROI: olfactory bulbs, frontal cortex, parietal cortex, cerebellum, hippocampus, nucleus accumbens, striatum, ventral midline basal nucleus, quadrigeminal plate, lower midbrain, entorhinal cortex, and brainstem. The validity of the dissection was verified by the reconstruction of the ROI followed by histological sectioning, and T2 MRI imaging.ConclusionsControlled brain microwave fixation gives the brain tissue the unique consistency necessary for the successful isolation of distinct ROI. The newly created dissection protocol allows for the: a) identification and removal of 12 such structures, b) sufficient tissues for analyzing amounts of iron or other metabolites, and c) the unique ability to correlate iron content in its various pools with image SWI MRI. The mouse model will form the basis of the interpretation of human brain iron MR determinations.