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Background: Few studies have examined B cells among patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), including brain pathology., Objective: To describe cases of tumefactive MOGAD with B-cell dominant central nervous system (CNS) infiltration., Methods: In this study, we reviewed three cases with clinical and brain histopathological features with tumefactive MOGAD., Results: Forty-nine cases of tumefactive brain lesions (TBL) between January 2003 and December 2023 were included; of these, seven had MOGAD. Three underwent a brain biopsy. B-cell dominant CNS infiltration was observed in two cases. In two cases with B-cell dominant CNS infiltration, symptoms included fever, headache, nausea, somnolence, and focal neurological deficits. Cerebrospinal fluid examination revealed both mild pleocytosis and negative oligoclonal IgG bands. Magnetic resonance imaging of the brain revealed large abnormal lesions extending from the basal ganglia to the parietotemporal lobe in both cases. These cases showed a good response to steroids; however, one case relapsed. Brain pathology showed demyelination and perivascular lymphocytic infiltration. One showed small vessel vasculitis. Deposition of the activated complement component was absent or rarely observed. Loss of MOG was observed in two cases., Conclusion: MOGAD could exhibit B-cell dominant CNS infiltration and small vessel vasculitis. MOGAD should be considered in differential diagnosis of TBL., Competing Interests: RI received honoraria for talks from Alexion Pharmaceuticals, Biogen Idec Japan, Chugai Pharmaceutical Co., Ltd., and Novartis Pharma. TM received speaker honoraria from Tanabe Mitsubishi Pharma, Chugai Pharma, Novartis Pharma, Alexion Pharma, Teijin Pharma, Viela Bio, and Biogen Idec Japan, and received research support from Cosmic Corporation and Medical and Biological Laboratories Co.; and received Grant-in-Aid for scientific research from Ministry of Education, Culture, Sports, Science, and Technology. YS received honoraria for speakers from Alexion Pharmaceuticals, Novartis Pharma, Biogen Idec Japan, and Chugai Pharmaceutical Co., Ltd., (© The Author(s), 2024.)

Present study aimed to assess effect of pre-treatment with Mucuna pruriens seed extract and its bioactive molecule(s) on NMDAR and Tau protein gene expression in cerebral ischemic rodent model. Methanol extract of M. pruriens seeds was characterized by HPLC, and β-sitosterol was isolated by flash chromatography. In vivo studies to observe the effect of pre-treatment (28 days) with methanol extract of M. pruriens seed and β-sitosterol on the unilateral cerebral ischemic rat model. Cerebral ischemia induced by left common carotid artery occlusion (LCCAO) for 75 min (on day 29) followed by reperfusion for 12 h. Rats (n = 48) divided into four groups. GroupI (control,Untreated + LCCAO)-No pre-treatment + cerebral ischemia; GroupII(β-sitosterol + Sham)-pre-treatment with β-sitosterol, 10 mg/kg/day + sham-operated; GroupIII(β-sitosterol + LCCAO)-pre-treatment with β-sitosterol, 10 mg/kg/day + cerebral ischemia; GroupIV(methanol extract + LCCAO)-pre-treatment with methanol extract of M. pruriens seeds, 50 mg/kg/day + cerebral ischemia. Neurological deficit score was assessed just before sacrifice. Experimental animals were sacrificed after 12 h reperfusion. Brain histopathology was performed. Gene expression of NMDAR and Tau protein of left cerebral hemisphere (occluded side) was performed by RT-PCR. Results revealed that the neurological deficit score was lower in groups III and IV compared to group I. NMDAR and tau protein mRNA expression in left cerebral hemisphere were upregulated in Group I, downregulated in groups III and IV. Histopathology of left cerebral hemisphere (occluded side) in Group I showed features of ischemic brain damage. Groups III and IV, left cerebral hemisphere showed less ischemic damage compared GroupI. Right cerebral hemisphere showed no areas of ischemia-induced brain changes. Pre-treatment with β-sitosterol and methanol extract of M. pruriens seeds may reduce ischemic brain injury following unilateral common carotid artery occlusion in rats.

Background: Hyperthyroidism is associated with impairment in the neurotransmission and severe tissue damage in the brain. The present study explored the potential deleterious effects of experimentally-induced hyperthyroidism on the neurotransmitters, oxidative homeostasis, apoptosis and DNA fragmentation in cerebral cortex, thalamus & hypothalamus, and hippocampus in rats. Methods and Results: The ameliorative effects of N-acetylcysteine (NAC; 50 mg/kg, oral) and safranal (50 mg/kg, intraperitoneal) against hyperthyroidism (L-T4 500 µg/kg, subcutaneous) were investigated. All treatments continued daily over three weeks. Hyperthyroidism was manifested by significant elevations in serum fT3 and fT4 levels and a decline in serum TSH level and body weight. It was also characterized by significant elevations in the levels of dopamine, serotonin, and 5-hydroxyindole acetic acid, and monoamine oxidase activity to varying degrees in the brain regions examined and a significant reduction in norepinephrine in hippocampus only. Hyperthyroidism resulted in a significant oxidative stress in brain typified by elevations in malondialdehyde and nitric oxide content and reductions in glutathione level and SOD and catalase activities. This led to elevations in Caspases 9 and 3 and a reduction in Bcl2 resulting in DNA damage and confirmed by the histopathology of brain tissue. The administration of NAC or safranal with L-T4 prevented these deleterious effects by reducing the oxidative load and improving the brain antioxidant status. Conclusions: Hyperthyroidism disrupted the neurotransmitters in the brain which aggravated the oxidative stress and resulted in apoptosis. N-Acetylcysteine and safranal prevented these deleterious effects by enhancing the poor antioxidant milieu of the brain. [ABSTRACT FROM AUTHOR]

The water quality of rivers located in areas close to major cities is deteriorating significantly due to increased pollution. The Karasu River, which passes through Erzurum city Turkey, is getting polluted day by day due to domestic and industrial wastewater. In the study, various assessments were made in three different fish species to determine the impact of possible contamination here. Capoeta capoeta, Alburnus mossulensis and Squalius cephalus were caught from four stations of the river. Micronucleus test was applied to find out genotoxic alterations, and plasma total oxidant status (TOS) and total antioxidant status (TAS) were measured to determine oxidative effects. Histological changes in fish brain were also assessed by histopathological alterations index (HAI). The highest serum TOS levels and the lowest TAS levels were detected in fish species inhabiting polluted stations. A high erythrocytic nuclear abnormality frequency and HAI values were observed in all species from the Aşkale stations. The abnormalities observed in the peripheral blood cells were micronucleus, binucleus, kidney-shaped nucleus, notched nucleus, lobed nucleus and bud nucleus. Histological damages like dilatation, congestion, vacuolization in Purkinje layer, infiltration, hyperemia, degenerations, and axonopathy were noticed in all fish brains. It was determined that histopathological changes were more common in fish species inhabiting the polluted stations. S. cephalus showed to be more sensitive to the pollution. The most important result obtained from this study is that the pollution in the river adversely affects the fish species found in the natural fauna of the river. Histopathological abnormalities, genotoxicity and increased oxidative stress detected in fish are the most important indicators of this situation. [ABSTRACT FROM AUTHOR]

Hypothermic circulatory arrest (HCA) is associated with neurologic morbidity, in part mediated by activation of the N-methyl-D-aspartate glutamate receptor causing excitotoxicity and neuronal apoptosis. Using a canine model, we hypothesized that the N-methyl-D-aspartate receptor antagonist MK801 would provide neuroprotection and that MK801 conjugation to dendrimer nanoparticles would improve efficacy. Male hound dogs were placed on cardiopulmonary bypass, cooled to 18°C, and underwent 90 min of HCA. Dendrimer conjugates (d-MK801) were prepared by covalently linking dendrimer surface OH groups to MK801. Six experimental groups received either saline (control), medium- (0.15 mg/kg) or high-dose (1.56 mg/kg) MK801, or low- (0.05 mg/kg), medium-, or high-dose d-MK801. At 24, 48, and 72 h after HCA, animals were scored by a standardized neurobehavioral paradigm (higher scores indicate increasing deficits). Cerebrospinal fluid was obtained at baseline, eight, 24, 48, and 72 h after HCA. At 72 h, brains were examined for histopathologic injury in a blinded manner (higher scores indicate more injury). Neurobehavioral deficit scores were reduced by low-dose d-MK801 on postoperative day two (P < 0.05) and by medium-dose d-MK801 on postoperative day 3 (P = 0.05) compared with saline controls, but free drug had no effect. In contrast, high-dose free MK801 significantly improved histopathology scores compared with saline (P < 0.05) and altered biomarkers of injury in cerebrospinal fluid, with a significant reduction in phosphorylated neurofilament-H for high-dose MK801 versus saline (P < 0.05). Treatment with MK-801 demonstrated significant improvement in neurobehavioral and histopathology scores after HCA, although not consistently across doses and conjugates. • Hypothermic circulatory arrest (HCA) is a technique used for thoracic aorta work. • We tested MK801, an NMDA receptor antagonist, as a neuroprotectant during HCA. • To reduce side effects, we tested MK801 conjugated to dendrimer, a nanoparticle. • Treatment inconsistently improved postoperative behavior and brain histopathology. [ABSTRACT FROM AUTHOR]

To study the molecular mechanism of WTKYR in the treatment of depression. SD rats were divided into a control group, model group, WTKYR group, and fluoxetine group. Each group consisted of 21 rats. The chronic unpredictable mild stress model was used. Body weighing and SPT were performed regularly. After treatment, histopathology of the brain tissue was performed, and concentrations of 5-HT (5-hydroxytryptamine), NE (norepinephrine), and DA (dopamine) in the hippocampus were determined. The WTKYR group showed higher body weight and sucrose consumption than the control groups. Moreover, the concentrations of 5-HT, NE, and DA in the hippocampus were significantly different in the WTKYR group in comparison to those in the other groups. The hippocampus histomorphology of the WTKYR group exhibited less dematous pyramidal cells and mild inflammatory cell infiltration. The treatment effect of WTKYR in depression may be based on improvement in the content of 5-HT, NE, and DA in the hippocampus, extenuating edema of the cortical surface and pyramidal cells and decreasing the infiltration of inflammatory cells into hippocampus tissue. [ABSTRACT FROM AUTHOR]

Cerebral autoregulation is impaired after traumatic brain injury (TBI), contributing to poor outcome. In the context of the neurovascular unit, cerebral autoregulation contributes to neuronal cell integrity and clinically Glasgow Coma Scale is correlated to intactness of autoregulation after TBI. Cerebral Perfusion Pressure (CPP) is often normalized by use of vasoactive agents to increase mean arterial pressure (MAP) and thereby limit impairment of cerebral autoregulation and neurological deficits. However, current vasoactive agent choice used to elevate MAP to increase CPP after TBI is variable. Vasoactive agents, such as phenylephrine, dopamine, norepinephrine, and epinephrine, clinically have not sufficiently been compared regarding effect on CPP, autoregulation, and survival after TBI. The cerebral effects of these clinically commonly used vasoactive agents are incompletely understood. This review will describe translational studies using a more human like animal model (the pig) of TBI to identify better therapeutic strategies to improve outcome post injury. These studies also investigated the role of age and sex in outcome and mechanism(s) involved in improvement of outcome in the setting of TBI. Additionally, this review considers use of inhaled nitric oxide as a novel neuroprotective strategy in treatment of TBI. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study was aimed to assess the effect of unilateral common carotid artery occlusion on brain pathophysiology in rats pretreated with subchronic hypoxia. MATERIALS AND METHODS: Rats (200 ± 20 g) were randomized into three groups: Group 1 served as sham, Group 2 were normoxic (21% O2 and 79% N2), and Group 3 were hypoxia preconditioned (10% O2 and 90% N2) for 21 days before left common carotid artery occlusion (LCCAO). The LCCAO was done for 75 min followed by reperfusion for 12 h. Neurological scores were recorded. Serum malondialdehyde (MDA) and nitric oxide (NO) levels at pre- and 12 h post-LCCAO were measured. Brain histopathological assessments were also done. RESULTS: Higher neurological deficits scores in Group 2 as compared to Group 3 rats were noticed. Serum MDA and NO levels at 12 h post-LCCAO in Group 2 rats showed significant elevation as compared to preocclusion levels. Group 3 rats did not show such elevations. On histopathology of left and right cerebral hemispheres of Group 1 (sham) did not show any specific changes. In Group 2 rats, the right cerebral hemisphere (nonoccluded) showed no areas of ischemia-induced brain changes, but in the left side (occlusive), there were features of ischemic brain damage including cerebral edema. In the case of Group 3 rats, there were less ischemic damages in the left occluded side as compared to the left side of the Group 2 rats. CONCLUSION: This study clearly demonstrates that subchronic hypoxia pretreatment can reduce ischemic brain injury by unilateral common carotid artery occlusion in rats. [ABSTRACT FROM AUTHOR]

There is limited research on the effect of electromagnetic field on aquatic organisms, especially freshwater fish species. This study was conducted to evaluate the effect of extremely low frequency electromagnetic field (ELF-EMF) (50 Hz) exposure on brain histopathology ofCyprinus carpio, one of the important species of Caspian Sea with significant economic value. A total of 200 healthy fish were used in this study. They were classified randomly in two groups: sham-exposed group and experimental group, which were exposed to five different magnetic field intensities (0.1, 1, 3, 5, and 7 mT) at two different exposure times (0.5 and 1 h). Histologic results indicate that exposure ofC. carpioto artificial ELF-EMF caused severe histopathological changes in the brain at field intensities ≥3 mT leading to brain necrosis. Field intensity and duration of exposure were key parameters in induction of lesion in the brain. Further studies are needed to elucidate exact mechanism of EMF exposure on the brain. [ABSTRACT FROM AUTHOR]

Bioenergetics dysfunction has been postulated as an important pathomechanism of brain damage in glutaric aciduria type I, but this is still under debate. We investigated activities of citric acid cycle (CAC) enzymes, lactate release, respiration and membrane potential (Δ Ψm ) in mitochondrial preparations from cerebral cortex and striatum of 30-day-old glutaryl-CoA dehydrogenase deficient ( Gcdh−/− ) and wild type mice fed a baseline or a high lysine (Lys, 4.7%) chow for 60 or 96 h. Brain histological analyses were performed in these animals, as well as in 90-day-old animals fed a baseline or a high Lys chow during 30 days starting at 60-day-old. A moderate reduction of citrate synthase and isocitrate dehydrogenase activities was observed only in the striatum from 30-day-old Gcdh−/− animals submitted to a high Lys chow. In contrast, the other CAC enzyme activities, lactate release, the respiratory parameters state 3, state 4, the respiratory control ratio and CCCP-stimulated (uncoupled) state, as well as Δ Ψm were not altered in the striatum. Similarly, none of the evaluated parameters were changed in the cerebral cortex from these animals under baseline or Lys overload. On the other hand, histological analyses revealed the presence of intense vacuolation in the cerebral cortex of 60 and 90-day-old Gcdh−/− mice fed a baseline chow and in the striatum of 90-day-old Gcdh−/− mice submitted to Lys overload for 30 days. Taken together, the present data demonstrate mild impairment of bioenergetics homeostasis and marked histological alterations in striatum from Gcdh−/− mice under a high Lys chow, suggesting that disruption of energy metabolism is not mainly involved in the brain injury of these animals. [ABSTRACT FROM AUTHOR]

Abstract: Titanium dioxide nanoparticles (TiO2 NPs) are now in daily use including popular sunscreens, toothpastes, and cosmetics. However, the effects of TiO2 NPs on human body, especially on the central nervous system, are still unclear. The aim of this study was to determine whether TiO2 NPs exposure results in persistent alternations in nervous system function. ICR mice were exposed to TiO2 NPs through intragastric administration at 0, 5, 10 and 50 mg/kg body weight every day for 60 days. The Y-maze test showed that TiO2 NPs exposure could significantly impair the behaviors of spatial recognition memory. To fully investigate the neurotoxicological consequence of TiO2 NPs exposure, brain elements and neurochemicals were also investigated. The contents of Ca, Mg, Na, K, Fe and Zn in brain were significantly altered after TiO2 NPs exposure. Moreover, TiO2 NPs significantly inhibited the activities of Na+/K+-ATPase, Ca2+-ATPase, Ca2+/Mg2+-ATPase, acetylcholine esterase, and nitric oxide synthase; the function of the central cholinergic system was also noticeably disturbed and the contents of some monoamines neurotransmitters such as norepinephrine, dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid, 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid were significantly decreased, while the contents of acetylcholine, glutamate, and nitric oxide were significantly increased. These first findings indicated that exposure to TiO2 NPs could possibly impair the spatial recognition memory ability, and this deficit may be possibly attributed to the disturbance of the homeostasis of trace elements, enzymes and neurotransmitter systems in the mouse brain. Therefore, the application of TiO2 NPs and exposure effects especially on human brain for long-term and low-dose treatment should be cautious. [Copyright &y& Elsevier]

Abstract: Purpose: In the present study, diffusion-weighted magnetic resonance imaging (DW-MRI) and histology were used to assess cerebral edema and lesions in mice intoxicated by a convulsive dose of soman, an organophosphate compound acting as an irreversible cholinesterase inhibitor. Methods: Three hours and 24 h after the intoxication with soman (172 μg/kg), the mice were anesthetized with an isoflurane/N2O mixture and their brain examined with DW-MRI. After the imaging sessions, the mice were sacrificed for histological analysis of their brain. Results: A decrease in the apparent diffusion coefficient (ADC) was detected as soon as 3 h after the intoxication and was found strongly enhanced at 24 h. A correlation was obtained between the ADC change and the severity of the overall brain damage (edema and cellular degeneration): the more severe the damage, the stronger the ADC drop. Anesthesia was shown to interrupt soman-induced seizures and to attenuate edema and cell change in certain sensitive brain areas. Finally, brain water content was assessed using the traditional dry/wet weight method. A significant increase of brain water was observed following the intoxication. Conclusions: The ADC decrease observed in the present study suggests that brain edema in soman poisoning is mainly intracellular and cytotoxic. Since entry of water into the brain was also evidenced, this type of edema is certainly mixed with others (vasogenic, hydrostatic, osmotic). The present study confirms the potential of DW-MRI as a non-invasive tool for monitoring the acute neuropathological consequences (edema and neurodegeneration) of soman-induced seizures. [Copyright &y& Elsevier]

Hypoxia appears to be a prominent component of brain damage among patients with hyponatremic encephalopathy. Effects of hypoxia on brain in the presence of hyponatremia are not known. In order to evaluate the contributions of hypoxia to brain damage, three separate experiments were conducted in three groups of rodents. Experiment I evaluated the effects of hypoxia and acute (<4 h) hyponatremia (plasma Na <120 mmol/l) on brain adaptation in rabbits. Experiment II evaluated the effects of hypoxia and chronic (4 days) hyponatremia on cerebral perfusion in rats. Experiment III evaluated the effects of hypoxia and chronic hyponatremia on brain histology in rats. In experiment I, rabbits with acute hyponatremia demonstrated brain adaptation with significant falls in brain Na content (by 14.2%, P<0.01) and osmolality (by 8.3%, P<0.01), and a rise in brain water (by 10.6%, P<0.05). Rabbits with combined hypoxia and hyponatremia failed to demonstrate brain adaptation. In experiment II, rats with chronic hyponatremia plus hypoxia had a decrease in cerebral perfusion index by more than 50% (P<0.01). In experiment III, 23% of hypoxic rats had brain lesions, which were in the cerebellum, thalamus, reticular formation, and basal ganglia. Hyponatremia without hypoxia resulted in no brain lesions. Hypoxia in normonatremic animals results in cerebral edema and histopathologic lesions similar to those found in rats whose plasma Na was overcorrected. Hypoxia in hyponatremic animals aggravates cerebral edema, impairs brain adaptation, and decreases cerebral perfusion.Kidney International (2006) 69, 1319–1325. doi:10.1038/sj.ki.5000187; published online 22 February 2006 [ABSTRACT FROM AUTHOR]

Background and Purpose: We have recently shown that hypoxaemic reperfusion, after an ischaemic brain insult, improves neurological outcome and decreases lipid peroxidation. In the present study, we investigated the effect of hypoxaemic reperfusion on brain histopathological changes.Methods: Sixteen pigs subjected to a 10-min global cerebral ischaemia were either hypoxaemically (PaO2 = 35 mmHg, hypoxaemic reperfusion (HR) group, n = 8) or hyperoxaemically (PaO2 > 300 mmHg, control (C) group, n = 8) reperfused. The brains were removed 24 h after reperfusion and six neuropathological abnormalities were evaluated blindly and scored semi-quantitatively (0: normal to 3: severe injury) on eight representative regions of the brain. The overall cumulative score of the abnormalities and their regional prevalence, as well as the neurological outcome, were compared between the two groups.Results: The neuronal degeneration, assessed in terms of cumulative score (P = 0.002) and regional prevalence (P = 0.025 to P = 0.041), was lower in the HR group than in the C group. Spongy degeneration attained statistically significant difference only in cerebellum (P = 0.002) and inflammation only in hippocampus (P = 0.046) but the difference in the cumulative score of these abnormalities was not statistically significant. The difference of the three neurological assessments over time was statistically significant between the two groups, i.e. after resuscitation (P = 0.001), at 8 h (P = 0.006) and at 24 h (P = 0.001) after reperfusion.Conclusions: Hypoxaemic reperfusion during resuscitation from a severe global ischaemic cerebral insult is associated with statistically significantly fewer histopathological changes of the brain than in controls. This is associated with a superior neurological outcome. [ABSTRACT FROM AUTHOR]

Glutaric acidemia type I (GA I) is a neurometabolic disorder of lysine (Lys) catabolism caused by glutaryl-CoA dehydrogenase (GCDH) deficiency. Patients are susceptible to develop acute striatum degeneration during catabolic stress situations whose underlying mechanisms are not fully established. Thus, in the present work we investigated the effects of a single intrastriatal Lys administration (1.5–4 μmol) to 30-day-old wild type (WT) and GCDH deficient (Gcdh−/−) mice on brain morphology, neuronal injury, astrocyte reactivity and myelin structure, as well as signaling pathways of redox homeostasis. We observed a marked vacuolation/edema in striatum and at higher doses also in cerebral cortex of Gcdh−/− , but not of WT mice. Lys also provoked a reduction of NeuN and synaptophysin, as well as an increase of astrocytic GFAP, in the striatum of Gcdh−/− mice, indicating neuronal loss and astrocyte reactivity. Furthermore, we verified an increase of Nrf2 and NF-κB expression in the nuclear fraction, and a decrease of heme oxygenase-1 (HO-1) content in the striatum of Lys-injected Gcdh−/− mice, implying disruption of redox homeostasis. Finally, it was found that Lys provoked alterations of myelin structure reflected by decreased myelin basic protein (MBP) in the cerebral cortex of Gcdh−/− mice. Taken together, the present data demonstrate neuronal loss, gliosis, altered redox homeostasis and demyelination caused by acute Lys overload in brain of Gcdh−/− mice, supporting the hypothesis that increased brain concentrations of glutaric and 3-hydroxyglutaric acids formed from Lys may be responsible for the acute brain degeneration observed in GA I patients during episodes of metabolic decompensation. • Acute Lys overload provoked vacuolation in striatum and cerebral cortex of Gcdh−/− mice. • Acute Lys overload caused neuronal and astrocytic damage in striatum of Gcdh−/− mice. • Oxidative stress signaling pathways were involved in the Gcdh−/− mice striatum injury. • Acute Lys overload altered myelin structure in cerebral cortex of Gcdh−/− mice. [ABSTRACT FROM AUTHOR]