Role of brain metabolites during acute phase of mild traumatic brain injury in prognosis of post-concussion syndrome: A 1H-MRS study.

This study has investigated the potency and accuracy of early magnetic resonance spectroscopy (MRS) to predict post-concussion syndrome (PCS) in adult patients with a single mild traumatic brain injury (mTBI) without abnormality on a routine brain scan. A total of 48 eligible mTBI patients and 24 volunteers in the control group participated in this project. Brain MRS over regions of interest (ROI) and signal stop task (SST) were done within the first 72 hours of TBI onset. After six months, PCS appearance and severity were determined. In non-PCS patients, N-acetyl aspartate (NAA) levels significantly increased in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) relative to the control group, however, this increase of NAA levels were recorded in all ROI versus PCS subjects. There were dramatic declines in creatinine (Cr) levels of all ROI and a decrease in choline levels of corpus callosum (CC) in the PCS group versus control and non-PCS ones. NAA and NAA/Cho values in ACC were the main predictors of PCS appearance. The Cho/Cr level in ACC was the first predictor of PCS severity. Predicting accuracy was higher in ACC than in other regions. This study suggested the significance of neuro-markers in ACC for optimal prediction of PCS and rendered a new insight into the biological mechanism of mTBI that underpins PCS.

The role of lateral habenula NMDA receptors in tramadol-induced conditioning.

The role of the lateral habenula (LHb) as a hub for receiving and relaying signals from the limbic system to serotonergic, dopaminergic, and norepinephrinergic regions in the brainstem makes this area a critical region in the control of reward and addiction. Behavioral evidence reveals the vital role of the LHb in negative symptoms during withdrawal. In this investigation, we study the role of the LHb N-Methyl D-Aspartate receptor (NMDAR) in the modulation of tramadol reward. Male adult Wistar rats were used in this study. The effect of intra-LHb micro-injection of NMDAR agonist (NMDA, 0.1, 0.5, 2 µg/rat) and antagonist (D-AP5, 0.1, 0.5, 1 µg/rat) was evaluated in conditioned place preference (CPP) paradigm. The obtained results showed that intra-LHb administration of NMDA induced place aversion dose-dependently, while blockade of NMDAR in the LHb using D-AP5 micro-injection led to an increased preference score in the CPP task. Co-administration of NMDA (0.5 µg/rat) with tramadol (4 mg/kg) reduced preference score, while co-administration of D-AP5 (0.5 µg/rat) with a non-effective dose of tramadol (1 mg/kg) potentiate the rewarding effect of tramadol. LHb receives inputs from the limbic system and projects to the monoaminergic nuclei in the brainstem. It has been declared that NMDAR is expressed in LHb, and as obtained data revealed, these receptors could modulate the rewarding effect of tramadol. Therefore, NMDA receptors in the LHb might be a new target for modulating tramadol abuse.

Astaxanthin ameliorates spinal cord edema and astrocyte activation via suppression of HMGB1/TLR4/NF-κB signaling pathway in a rat model of spinal cord injury.

Spinal cord edema is a quick-onset phenomenon with long-term effects. This complication is associated with inflammatory responses, as well as poor motor function. No effective treatment has been developed against spinal edema, which urges the need to provide novel therapies. Astaxanthin (AST) is a fat-soluble carotenoid with anti-inflammatory effects and a promising candidate for treating neurological disorders. This study aimed to investigate the underlying mechanism of AST on the inhibition of spinal cord edema, astrocyte activation, and reduction of inflammatory responsesin a rat compression spinal cord injury (SCI) model. Male rats underwent laminectomy at thoracic 8-9, and the SCI model was induced using an aneurysm clip. After SCI, rats received dimethyl sulfoxide or AST via intrathecal injection. The effects of AST were examined on the motor function, spinal cord edema, integrity of blood-spinal cord barrier (BSCB), and expression of high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), glial fibrillary acidic protein (GFAP), and aquaporin-4 (AQP4), and matrix metallopeptidase- 9 (MMP-9) post-SCI. We showed that AST potentially improved the recovery of motor function and inhibited the spinal cord edema via maintaining the integrity of BSCB, reducing the expression of HMGB1, TLR4, and NF-κB, MMP-9 as well as downregulation of astrocyte activation (GFAP) and AQP4 expression. AST improves motor function and reduces edema and inflammatory responses in the spinal tissue. These effects are mediated by suppression of the HMGB1/TLR4/NF-κB signaling pathway, suppressing post-SCI astrocyte activation, and decreasing AQP4 and MMP-9 expression.

Perioperative seizure in patients undergoing brain mapping under awake craniotomy for language-related eloquent region gliomas: a prospective study.

BACKGROUND: Awake craniotomy (AC) is standard of care for lesions of eloquent brain areas. One important complication during AC is occurrence of intraoperative seizure (IOS), reported to occur among 3.4-20% of the patients. In this study, we report our experience with IOS during AC for resection of gliomas of the language eloquent regions and evaluate the predisposing factors and consequences. METHODS: Patients who underwent AC for language related regions of the dominant hemisphere from August 2018 to June 2021 were enrolled. The rate of IOS during AC and relationship between predisposing factors and IOS were evaluated. RESULTS: Sixty-five patients were enrolled (mean age: 44.4±12.5 years). Among 6 patients with IOS (9.2%), only one needed conversion to general anesthesia (GA) due to repeated seizures; while in the remaining 5, AC accomplished successfully despite one seizure attack in the awake phase. Tumor location (especially premotor cortex lesions, P=0.02, uOR:12.0, CI: 1.20-119.91), higher tumor volume (P=0.008, uOR: 1.9, CI: 1.06-1.12) and a functional tumor margin during surgery (P=0.000, uOR: 3.4, CI: 1.47-12.35) were significantly linked with IOS. CONCLUSIONS: Occurrence of IOS was associated with a longer ICU stay after surgery and worse immediate neurological outcome, but had no impact on the late neurological status. IOS can usually be managed during AC without need to converting to GA. Those with larger tumors, frontal premotor lesions and positive brain mapping are susceptible to IOS. Early neurological deterioration observed after IOS, seems to be transient with no major long-term consequence on the neurological outcome.

Disparity of Primary and Secondary Language Outcomes in Bilingual Patients Undergoing Resection of Glioma of the Speech-Related Regions.

BACKGROUND: The existing data about language recovery in bilingual patients come from few studies on acute lesional deficits like stroke or traumatic injury. Still, little is known about the neuroplasticity potential of bilingual patients who undergo resection of gliomas affecting language-eloquent brain regions. In this study, we prospectively evaluated the pre- and postoperative language functions among bilinguals with eloquent region gliomas. METHODS: We have prospectively collected the preoperative, 3-month and 6-month postoperative data from patients with tumors infiltrating the dominant hemisphere language areas during a 15-month period. Validated Persian/Turkish version of Western Aphasia Battery test and Addenbrooke Cognitive Examination were assessed for main language (L1) and second acquired languages (L2) in each visit. RESULTS: Twenty-two right-handed bilingual patients were enrolled, and language proficiencies were assessed using mixed model analysis. On baseline and postoperative points, L1 had higher scores in all Addenbrooke Cognitive Examination and Western Aphasia Battery subdomains than L2. Both languages had deterioration at 3-month visit; however, L2 was significantly more deteriorated in all domains. At 6-month visit, both L1 and L2 showed recovery; however, L2 recovered to a less extent than L1. The single most parameter affecting the ultimate language outcome in this study was the preoperative functional level of L1. CONCLUSIONS: This study shows L1 is less vulnerable to operative insults and L2 may be damaged even when L1 is preserved. We would suggest the more sensitive L2 be used as the screening tool and L1 be used for confirmation of positive responses during language mapping.

Prediction of lymphovascular space invasion in cervical carcinoma using diffusion kurtosis imaging.

BACKGROUND: This study aimed to investigate the potential relationship between diffusion kurtosis imaging (DKI)- derived parameters and lymphovascular space invasion (LVSI) in patients with cervical carcinoma. PATIENTS AND METHODS: This prospective study included 30 patients with cervical carcinoma. The patients underwent MRI, diffusion-weighted imaging (DWI), and DKI prior to surgery. The surgical pathology results were accepted as the reference standard for determining the LVSI status. The DKI-derived parameters, including mean diffusivity (MD) and mean kurtosis (MK), were measured. The apparent diffusion coefficient (ADC) value was also assessed. RESULTS: The MD value of LVSI positive cervical carcinomas was significantly lower than LVSI negative carcinomas (p-value = 0.01). MK value was significantly higher in LVSI positive tumors (p-value = 0.01). However, the ADC value did not show a significant difference between LVSI positive and LVSI negative tumors (p-value = 0.2). MD and MK parameters showed similar diagnostic accuracy in identifying the LVSI status, with the area under the curve of 0.77 and 0.78, respectively. CONCLUSION: In this study, DKI-derived parameters were associated with the LVSI status in cervical carcinomas. Further studies with larger sample size are required to confirm these results.

Changes in Cognitive Functioning After Surgical Resection of Language-related, Eloquent-area, High-grade Gliomas Under Awake Craniotomy.

BACKGROUND: Dominant-hemisphere tumors, especially gliomas, as infiltrative tumors, frequently affect cognitive functioning. Establishing a balance between extensive resection, which is proven to result in longer survival, and less extensive resection, in order to maintain more cognitive abilities, is challenging. OBJECTIVE: To evaluate changes in cognitive functioning before and after surgical resection of language-related, eloquent-area, high-grade gliomas under awake craniotomy. METHOD: We provided individuals with newly diagnosed high-grade gliomas of the language-related eloquent areas with the same standard of care, including surgical resection of the glioma using intraoperative sensory-motor and cognitive mapping under awake craniotomy, and the same protocol for chemoradiotherapy. Cognitive functioning was assessed using Addenbrooke's Cognitive Examination-Revised (ACE-R) at four time points (preoperatively, early after surgery, and 3 and 6 months postoperatively). RESULTS: The preoperative evaluation revealed a range of cognitive impairments in 70.7% of the individuals, affecting all of the cognitive subdomains (mostly attention and visuospatial abilities). Overall cognitive functioning (ie, ACE-R score) dropped by 13.5% (P = 0.169) early postoperatively. At the 3-month evaluation, an average of 15.3% (P = 0.182) recovery in cognitive functioning was observed (mostly in verbal fluency: 39.1%). This recovery improved further, reaching 29% (P < 0.001) at the 6-month evaluation. The greatest improvement occurred in verbal fluency: 68.8%, P = 0.001. CONCLUSION: Extensive resection of eloquent-area gliomas with the aid of modern neuroimaging and neuromonitoring techniques under awake craniotomy is possible without significant long-term cognitive sequela.

A Probabilistic Atlas of the Pineal Gland in the Standard Space.

Pineal gland (PG) is a structure located in the midline of the brain, and is considered as a main part of the epithalamus. There are numerous reports on the facilitatory role of this area for brain function; hormone secretion and its role in sleep cycle are the major reports. However, reports are rarely available on the direct role of this structure in brain cognition and in information processing. A suggestion for the limited number of such studies is the lack of a standard atlas for the PG; none of the available MRI templates and atlases has provided parcellations for this structure. In this study, we used the three-dimensional (3D) T1-weighted MRI data of 152 healthy young volunteers, and provided a probabilistic map of the PG in the standard Montreal Neurologic Institute (MNI) space. The methods included collecting the data using a 64-channel head coil on a 3-Tesla Prisma MRI Scanner, manual delineation of the PG by two experts, and robust template and atlas construction algorithms. This atlas is freely accessible, and we hope importing this atlas in the well-known neuroimaging software packages would help to identify other probable roles of the PG in brain function. It could also be used to study pineal cysts, for volumetric analyses, and to test any associations between the cognitive abilities of the human and the structure of the PG.

The Changes in 1H-MRS Metabolites in Cuprizone-Induced Model of Multiple Sclerosis: Effects of Prior Psychological Stress.

Stress is considered as an important risk factor in the progression and the onset of many disorders such as multiple sclerosis. However, metabolite changes as a result of demyelination under the detrimental effects of stress are not well understood. Thus, 36 female Wistar rats (i.e., groups (1) no-cuprizone (Cont), (2) no-stress + cuprizone-treated (Cup), (3) physical stress + cuprizone-treated (P-Cup), (4) psychological stress + cuprizone-treated (Psy-Cup), (5) physical stress + no-cuprizone-treated (P), (6) psychological stress + no-cuprizone-treated (Psy)) were used in this study. Following induction of repetitive stress, cuprizone treatment was carried out for 6 weeks to instigate demyelination in all groups except the control animal. Relative metabolite concentrations of the brain were investigated by single-voxel proton magnetic resonance spectroscopy (reporting N-acetyl-aspartate (NAA), glycerophosphocholine with phosphocholine (tCho) relative to total creatine (tCr)). According to 1H-MRS, rats in the Cup group indicated a reduction in NAA/ tCr (p < 0.001) as well as tCho/ tCr (p < 0.05) compared with that in the Cont group. In contrast, in both stress + cuprizone-treated groups, NAA/tCr and tCho/tCr ratios remarkably increased versus the Cup group (p < 0.001) and the Cont group (p < 0.001 for the Psy-Cup group and p < 0.05 for the P-Cup group). Both P and Psy groups revealed normal metabolite concentrations similar to the Cont group 6 weeks post stress. Seemingly, in the case of cuprizone alone, decreased level of metabolites is mainly relevant to neuronal cell impairments. Meanwhile, as a result of oxidative stress enhancement due to stress exposure, oligodendrocyte becomes the main victim indicating the increased level of metabolite ratios.

Neurochemicals of limbic system and thalamofrontal cortical network: Are they different between patients with idiopathic generalized epilepsy and psychogenic nonepileptic seizure?

OBJECTIVE: Thalamofrontal cortical network and limbic system are proposed to be involved in psychogenic nonepileptic seizure (PNES) and idiopathic generalized epilepsy (IGE). This study aimed to investigate neurochemical changes in prefrontal cortex, thalamus, and limbic circuits in patients with PNES and IGE. We also analyzed the interaction between cognitive functions and neurochemical changes in both groups. METHODS: Hydrogen proton magnetic resonance spectroscopy (1H-MRS) was used to measure N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), glutamate-glutamine (Glx), and myo-inositol (MI). The voxels were placed on the bilateral dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), anterior cingulate cortex (ACC), and thalamus. Attention and inhibitory control, as well as general intelligence status, were investigated using the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT) and the Wechsler Adult Intelligence Scale (WAIS), respectively, in patients with PNES and IGE, as well as healthy volunteers. RESULTS: The 1H-MRS showed a decreased ratio of NAA/Cr in the right and left thalamus, right DMPFC, and right ACC in patients with IGE and PNES. Furthermore, a decrease of the NAA/Cr ratio in the left DMPFC and an increase of NAA/Cr ratio in the right DLPFC were observed in patients with PNES compared with the controls. The patient groups had a decreased ratio of Cho/Cr in right ACC compared with the healthy subjects. Moreover, the NAA/Cr ratio in the left thalamus and left DMPFC was correlated with seizure frequency in patient groups. Reduced NAA/Cr ratio in the right ACC and left DLPFC were also correlated with poor IVA-CPT scores. CONCLUSION: This study highlighted the dysfunction in prefrontal-thalamic-limbic circuits and impairment in neurocognition in patients with PNES and IGE.

Changes in Effective Connectivity Network Patterns in Drug Abusers, Treated With Different Methods.

INTRODUCTION: Various treatment methods for drug abusers will result in different success rates. This is partly due to different neural assumptions and partly due to various rate of relapse in abusers because of different circumstances. Investigating the brain activation networks of treated subjects can reveal the hidden mechanisms of the therapeutic methods. METHODS: We studied three groups of subjects: heroin abusers treated with abstinent based therapy (ABT) method, heroin abusers treated with Methadone Maintenance Therapy (MMT) method, and a control group. They were all scanned with functional magnetic resonance imaging (fMRI), using a 6-block task, where each block consisted of the rest-craving-rest-neutral sequence. Using the dynamic causal modeling (DCM) algorithm, brain effective connectivity network (caused by the drug craving stimulation) was quantified for all groups. In this regard, 4 brain areas were selected for this analysis based on previous findings: ventromedial prefrontal cortex (VMPFC), dorsolateral prefrontal cortex (DLPFC), amygdala, and ventral striatum. RESULTS: Our results indicated that the control subjects did not show significant brain activations after craving stimulations, but the two other groups showed significant brain activations in all 4 regions. In addition, VMPFC showed higher activations in the ABT group compared to the MMT group. The effective connectivity network suggested that the control subjects did not have any direct input from drug-related cue indices, while the other two groups showed reactions to these cues. Also, VMPFC displayed an important role in ABT group. In encountering the craving pictures, MMT subjects manifest a very simple mechanism compared to other groups. CONCLUSION: This study revealed an activation network similar to the emotional and inhibitory control networks observed in drug abusers in previous works. The results of DCM analysis also support the regulatory role of frontal regions on bottom regions. Furthermore, this study demonstrates the different effective connectivity patterns after drug abuse treatment and in this way helps the experts in the field.

Effects of high-fat diet on the numerical density and number of neuronal cells and the volume of the mouse hypothalamus: a stereological study.

It has been demonstrated that the type of diet affects the brain structure and function. Consumption of fat-rich food is one of the most important factors that lead to increase in the prevalence of cardiovascular and neurological diseases. High-fat diet may change the volume and neuronal number or density in the hypothalamus, which is the center of energy control. Therefore, this study was designed to study the effect of high-fat diet on the density and number of neurons, and also the volume of hypothalamus in adult male mice. Forty male mice were divided into the control and experimental groups. The control group were fed with standard and the experimental groups, with high-fat diet for 4 (short-term) or 8 (long-term) weeks. The animals were perfused and brains were immediately removed, post-fixed and cut coronally and serially using cryostat at 30-µm thickness. Every 6th sections were stained by cresyl violet. The numerical density and number of neuron and the volume of hypothalamus were estimated by using unbiased stereological methods. Data analysis showed that both short and long time consumption of high-fat diet decreased the neuronal cell density of the hypothalamus. Interestingly, despite a decrease in the neuronal cell density, long time consumption of high-fat diet could significantly increase the volume of hypothalamus (P<0.05). High fat diet decreased the neuronal cell density and increased the volume of the hypothalamus, but it did not significantly change its total neurons. These changes might be due to an increase in the extracellular space through inflammation or gliosis in the hypothalamus.