Mirtazapine modulates Glutamate and GABA levels in the animal model of maternal depression. MRI and 1H MRS study in female rats.

We aimed to determine, using in vivo magnetic resonance, whether maternal depression induced by chronic unpredictable stress (CUS) in the pre-gestational period in female rats would be evidenced by structural or neurometabolic changes in the hippocampal region of the brain. At the same time, appropriate behavioral tests were also administered after a relatively long two-month period of a stress paradigm. The objective of the study was not only to study an animal model of CUS using magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H MRS) focused on the hippocampus, but also to use this technique to verify the effectiveness of mirtazapine antidepressant treatment. In the group with CUS, we found a significant decrease in the relative concentration of γ-aminobutyric acid (GABA/tCr) and glutamate+glutamine (Glx/tCr) compared to the control group, while we did not observe any statistically significant change in hippocampal volumes. Moreover, the forced swim test revealed an increase in depression-like behavior. The most important finding was the return of GABA/tCr and Glx/tCr levels to control levels during mirtazapine treatment; however, behavioral tests did not demonstrate any effects from mirtazapine treatment. In vivo1H MRS confirmed mirtazapine modulation of CUS in an animal model more robustly than behavioral tests.

Emergency Uterine Artery Embolization Used for Managing Profuse Intra-Abdominal Bleeding and Uterine Rupture in a Patient with Advanced Cervical Cancer.

Advanced cervical cancer can lead to life-threatening vaginal bleeding. Emergency uterine artery embolization (UAE) has been successfully used in such cases to achieve hemostasis. Our case demonstrates the unusual emergency use of this procedure to cease heavy hemorrhage, which led to hematometra, uterine rupture and hemoperitoneum in a patient with a large tumor in the cervical region. Vaginal bleeding was minimal in this case. The emergency UAE controlled the bleeding, and the patient was scheduled for laparotomy soon after the procedure, where a supracervical hysterectomy with bilateral salpingo-oophorectomy and the removal of blood and blood clots was performed. Since the tumor primarily involved the parametria, a sample was taken for histopathology examination with the following result: squamocellular HPV-associated cervical carcinoma. The postoperative management of the patient consisted of combined chemotherapy and radiotherapy, with no complications related to the UAE. Four months after the procedure the patient is reasonably well. Urgent surgery was not the optimal decision because of the alteration of the pelvic anatomy by the tumor, and thus the UAE enabled us to manage this life-threatening condition quickly, allowing us to best prepare the patient for further therapeutic modalities.

Huperzine aggravated neurochemical and volumetric changes induced by D-galactose in the model of neurodegeneration in rats.

The multimodal MRI and 1H MRS study was designed to provide a structural and neurochemical view of D-galactose induced rat brain degeneration and its treatment with huperzine A. The volume changes were captured using MRI focused on the hippocampal region and a neurochemical profile was obtained from the same area using in vivo localized 1H MRS, which was compared with in vitro1H MRS hippocampal spectra at the high field after the animals were culled. At the four week point, we observed a small decrease in N-acetylaspartate/creatine (NAA/tCr), myo-inositol/creatine (mIns/tCr) and glutamine/creatine (Gln/tCr) in the group in which neurodegeneration was induced. At the eight week point, we found only slight but statistically significant decreases in NAA/tCr, mIns/tCr and glutamate/creatine (Glu/tCr) in this group in vivo. However, in the treated group, the decrease in NAA/tCr and Glu/tCr was much more pronounced compared to the D-gal group. In vitro1H MRS analysis from rat hippocampal samples showed very similar changes in metabolites, which were also much more pronounced in the treated group. Neurodegeneration was also confirmed by a significant decrease in γ-aminobutyrate/creatine (GABA/tCr) observed only in the treated group, but not in the D-gal group. MRI image data and subsequent volumetric quantification showed mild hippocampal degeneration at the four week point in D-gal group. At the eight week point, we observed a decrease in hippocampal volume in both experimental groups, with a more pronounced decrease in the huperzine-treated group. In conclusion, in our experimental design huperzine A treatment worsened the neurodegeneration of the rat brain, which was supported by all of the used MRI and 1H MRS methods.

D-galactose-induced aging in rats - The effect of metformin on bioenergetics of brain, skeletal muscle and liver.

Chronic D-galactose administration induces accelerated aging in rodents. The aim of the study was to find by in vivo31P MRS suitable markers of early stages of brain degeneration on this metabolic model in rats. Additionally, we studied the therapeutic effect of antidiabetic drug metformin. The study has been extended by in vitro determination of mitochondrial function in brain, skeletal muscle and liver mitochondria, oxidative stress parameter thiobarbituric acid reactive substances (TBARS), and lipophilic antioxidants levels. In vivo31P MRS revealed lower intracellular pH (pHi) and lower inorganic phosphate to ATP ratio (Pi/ATP), with higher index of oxidative phosphorylation - phosphocreatine (PCr) to Pi ratio - in brain of rats chronically administered with D-galactose. The function of brain mitochondria was not affected. Administration of metformin diminished changes in brain pHi and plasma TBARS. The function of skeletal muscle mitochondria and their coenzyme Q (CoQ) content were considerably reduced after D-galactose administration. Metformin administered simultaneously with D-galactose did not prevent these changes. The results of in vivo31P MRS revealed evidence of early stage of neurodegeneration that may indicate pre-inflammation. Our data show different susceptibility of brain, skeletal muscle, and liver to the chronic exposure to D-galactose and metformin. The D-galactose model presented in the literature as a model for "age-related dementia" had much more devastating effects on skeletal muscle than on the brain.

Diffusion Tensor Imaging: Tool for Tracking Injured Spinal Cord Fibres in Rat.

Spinal cord injury (SCI) is a severe disorder of the CNS leading to tissue damage and disability. Because it is critical to understand the pathological processes, it is important to find efficient ways to diagnose the severity of injured spinal cord tracts in situ from beginning up to a certain level of recovery following therapeutic interventions. In the current study, we set-up the criteria for diffusion tensor imaging (DTI) in order to capture changes of nerve fibre tracts in rat spinal cord compression injury. We tested four DTI parameters, such as fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity at the lesion site, in time course of 7 weeks. Afterwards, we compared DTI data with histological results and locomotor outcomes to examine their consistency and capability of reflecting the lesion development in time. Our data confirm that DTI is a valuable in vivo imaging tool capable to distinguish damaged white matter tracts after mild SCI in rat. Fractional anisotropy showed decreased values for injury site, while the mean diffusivity had higher values, with increased both axial and radial diffusivity in comparison to control subjects. Thus, the combination of DTI parameters can reflect the severity of lesion in time and may correlate with histological evaluation of spared tissue, but not with locomotor recovery following mild injury associated with spontaneous recovery.