myelin-basic-protein and Cognition-Disorders

Negative outcomes of mild traumatic brain injury (mTBI) can be exacerbated by repeated insult. Animal models of repeated closed-head mTBI provide the opportunity to define acute pathological mechanisms as the number of mTBI increases. Furthermore, little is known about the effects of mTBI impact site, and how this may affect brain function. We use a closed head, weight drop model of mTBI that allows head movement following impact, in adult female rats to determine the role of the number and location of mTBI on brain pathology and behaviour. Biomechanical assessment of two anatomically well-defined mTBI impact sites were used, anterior (bregma) and posterior (lambda). Location of the impact had no significant effect on impact forces (450 N), and the weight impact locations were on average 5.4 mm from the desired impact site. No between location vertical linear head kinematic differences were observed immediately following impact, however, in the 300 ms post-impact, significantly higher mean vertical head displacement and velocity were observed in the mTBI lambda trials. Breaches of the blood brain barrier were observed with three mTBI over bregma, associated with immunohistochemical indicators of damage. However, an increased incidence of hairline fractures of the skull and macroscopic haemorrhaging made bregma an unsuitable impact location to model repeated mTBI. Repeated mTBI over lambda did not cause skull fractures and were examined more comprehensively, with outcomes following one, two or three mTBI or sham, delivered at 1 day intervals, assessed on days 1-4. We observe a mild behavioural phenotype, with subtle deficits in cognitive function, associated with no identifiable neuroanatomical or inflammatory changes. However, an increase in lipid peroxidation in a subset of cortical neurons following two mTBI indicates increasing oxidative damage with repeated injury in female rats, supported by increased amyloid precursor protein immunoreactivity with three mTBI. This study of acute events following closed head mTBI identifies lipid peroxidation in neurons at the same time as cognitive deficits. Our study adds to existing literature, providing biomechanics data and demonstrating mild cognitive disturbances associated with diffuse injury, predominantly to grey matter, acutely following repeated mTBI.

Topics: Aldehydes; Animals; Antigens; Blood-Brain Barrier; Brain; Brain Injuries, Traumatic; Calcium-Binding Proteins; Cell Death; Cognition Disorders; Cohort Studies; Disease Models, Animal; Female; Glial Fibrillary Acidic Protein; Lipid Peroxidation; Microfilament Proteins; Myelin Basic Protein; Neurologic Examination; Neurons; Oligodendrocyte Transcription Factor 2; Oxidative Stress; Proteoglycans; Rats; Time Factors

Adverse early-life experience such as depriving the relationship between parents and children induces permanent phenotypic changes, and impairs the cognitive functions associated with the prefrontal cortex (PFC). However, the underlying mechanism remains unclear. In this work, we used rat neonatal maternal separation (NMS) model to illuminate whether and how NMS in early life affects cognitive functions, and what the underlying cellular and molecular mechanism is. We showed that rat pups separated from their dam 3 h daily during the first 3 postnatal weeks alters medial prefrontal cortex (mPFC) myelination and impairs mPFC-dependent behaviors. Myelination appears necessary for mPFC-dependent behaviors, as blockade of oligodendrocytes (OLs) differentiation or lysolecithin-induced demyelination, impairs mPFC functions. We further demonstrate that histone deacetylases 1/2 (HDAC1/2) are drastically reduced in NMS rats. Inhibition of HDAC1/2 promotes Wnt activation, which negatively regulates OLs development. Conversely, selective inhibition of Wnt signaling by XAV939 partly rescue myelination arrestment and behavior deficiency caused by NMS. These findings indicate that NMS impairs mPFC cognitive functions, at least in part, through modulation of oligodendrogenesis and myelination. Understanding the mechanism of NMS on mPFC-dependent behaviors is critical for developing pharmacological and psychological interventions for child neglect and abuse.

Topics: Animals; Animals, Newborn; Anxiety; Cognition Disorders; Demyelinating Diseases; Enzyme Inhibitors; Exploratory Behavior; Gene Expression Regulation, Developmental; Heterocyclic Compounds, 3-Ring; Histone Deacetylases; Lipopolysaccharides; Maternal Deprivation; Maze Learning; Myelin Basic Protein; Neurogenesis; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Valproic Acid; Wnt Proteins; Wnt Signaling Pathway

Chronic stress significantly affects neuron morphometry and function in the prefrontal cortex, a brain region controlling cognition and emotion. However, whether and how chronic stress regulates the maturation of NG2-expressing oligodendrocyte precursor cell (NG2(+) cell) and the importance of these changes remained unknown. Here, we report that exposing adult mice to chronic stress results in NG2(+) cell atrophy and myelination arrested in the medial prefrontal cortex (mPFC), and impaired mPFC-dependent functions. These alterations, are phenocopied by overexpression of death receptor 6 (DR6) in NG2(+) cell. Conversely, selectively silencing of DR6 in the NG2(+) cell can partly rescue NG2(+) cell atrophy and cognitive deficiency caused by chronic stress. We further demonstrate that myelination appears necessary for mPFC-dependent cognitive processes, as lysolecithin (LPC)-induced demyelination specifically in the mPFC is sufficient to cause these behavioral and cognitive impairments. Our results indicate that chronic stress impairs cognitive functions, at least in part, through modulation of NG2(+) cell maturation and myelination, and suggest that myelination is require for normal cognitive functions.

Topics: Animals; Antigens; Autophagy-Related Proteins; Bromodeoxyuridine; Cognition Disorders; Disease Models, Animal; Gene Expression Regulation; Intracellular Signaling Peptides and Proteins; Memory Disorders; Mice; Mice, Inbred C57BL; Models, Molecular; Myelin Basic Protein; Neurofilament Proteins; Neurons; Prefrontal Cortex; Proteoglycans; Receptors, Tumor Necrosis Factor; RNA, Small Interfering; Stress, Psychological; Time Factors

Chemotherapy-induced cognitive impairment, also known as 'chemobrain', is now widely recognized as a frequent adverse side effect of cancer treatment that often persists into survivorship. There are no drugs available to prevent or treat chemotherapy-induced cognitive deficits. The aim of this study was to establish a mouse model of cisplatin-induced cognitive deficits and to determine the potential preventive effects of the anti-diabetic drug metformin.. Treatment of C57/BL6J mice with cisplatin (cumulative dose 34.5 mg/kg) impaired performance in the novel object and place recognition task as well as in the social discrimination task indicating cognitive deficits. Co-administration of metformin prevented these cisplatin-induced cognitive impairments. At the structural level, we demonstrate that cisplatin reduces coherency of white matter fibers in the cingulate cortex. Moreover, the number of dendritic spines and neuronal arborizations as quantified on Golgi-stained brains was reduced after cisplatin treatment. Co-administration of metformin prevented all of these structural abnormalities in cisplatin-treated mice. In contrast to what has been reported in other models of chemobrain, we do not have evidence for persistent microglial or astrocyte activation in the brains of cisplatin-treated mice. Finally, we show that co-administration of metformin also protects against cisplatin-induced peripheral neuropathy.. In summary, we show here for the first time that treatment of mice with cisplatin induces cognitive deficits that are associated with structural abnormalities in the brain. Moreover, we present the first evidence that the widely used and safe anti-diabetic drug metformin protects against these deleterious effects of cancer treatment. In view of the ongoing clinical trials to examine the potential efficacy of metformin as add-on therapy in patients treated for cancer, these findings should allow rapid clinical translation.

Topics: Animals; Behavior, Animal; Brain; Brain Injuries; Cisplatin; Cognition Disorders; Disease Models, Animal; Female; Hyperalgesia; Hypoglycemic Agents; Metformin; Mice; Mice, Inbred C57BL; Myelin Basic Protein; Pyramidal Cells

B lymphocytes cause post-stroke cognitive decline in mice. We therefore evaluated the association between autoantibodies and post-stroke cognitive decline in a prospectively collected human cohort. The mini-mental state exam (MMSE) was administered 30, 90, 180, and 365days after stroke. Antibody titers to myelin basic protein (MBP), proteolipid protein, and several non-specific proteins were determined. Among 58 subjects with initial MMSE≥20 and at least 2 MMSE examinations in the year after stroke, cognitive decline (MMSE decrease ≥2) occurred in 10 (17%) subjects. In multivariate analysis, MBP antibody titers were the only independent predictor of cognitive decline (OR=9.02 [1.18, 68.90]; P=0.03).

Topics: Adult; Aged; Autoantibodies; Cognition Disorders; Cohort Studies; Female; Gene Expression Regulation; Humans; Male; Mental Status Schedule; Middle Aged; Myelin Basic Protein; Myelin Proteolipid Protein; Neuropsychological Tests; Stroke

Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals have HIV-associated neurocognitive disorders (HAND). Studies of antiretroviral-treated patients have revealed persistent white matter abnormalities including diffuse myelin pallor, diminished white matter tracts, and decreased myelin protein mRNAs. Loss of myelin can contribute to neurocognitive dysfunction because the myelin membrane generated by oligodendrocytes is essential for rapid signal transduction and axonal maintenance. We hypothesized that myelin changes in HAND are partly due to effects of antiretroviral drugs on oligodendrocyte survival and/or maturation. We showed that primary mouse oligodendrocyte precursor cell cultures treated with therapeutic concentrations of HIV protease inhibitors ritonavir or lopinavir displayed dose-dependent decreases in oligodendrocyte maturation; however, this effect was rapidly reversed after drug removal. Conversely, nucleoside reverse transcriptase inhibitor zidovudine had no effect. Furthermore, in vivo ritonavir administration to adult mice reduced frontal cortex myelin protein levels. Finally, prefrontal cortex tissue from HIV-positive individuals with HAND on cART showed a significant decrease in myelin basic protein compared with untreated HIV-positive individuals with HAND or HIV-negative controls. These findings demonstrate that antiretrovirals can impact myelin integrity and have implications for myelination in juvenile HIV patients and myelin maintenance in adults on lifelong therapy.

Topics: Adult; Animals; Animals, Newborn; Antirheumatic Agents; Cell Differentiation; Cells, Cultured; Cognition Disorders; Cohort Studies; Disease Models, Animal; Gangliosides; Gene Expression Regulation, Viral; HIV Infections; Humans; Male; Mice; Mice, Inbred C57BL; Middle Aged; Myelin Basic Protein; Myelin Proteolipid Protein; Myelin Sheath; Oligodendroglia; Reactive Oxygen Species

Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.

Topics: Animals; Animals, Newborn; Astrocytes; Behavior, Animal; Brain; Brain Injuries; Cognition Disorders; Disease Models, Animal; Female; Hypoxia-Ischemia, Brain; Male; Membrane Potential, Mitochondrial; Mitochondria; Myelin Basic Protein; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Resveratrol; Stilbenes

Myelination failure is associated with perinatal cerebral hypoxia-ischemia (PHI) induced brain injury in premature infants. How to efficiently promote remyelination is crucial for improving cognitive deficits caused by brain injury. Here, we demonstrated that quercetin (Que), a kind of flavonoids, significantly improved cognitive deficits and the behavior of PHI-rat in Morris water maze and open field tasks. After administration of Que to PHI-rat, the number of neogenetic Olig2⁺ oligodendrocyte progenitor cells (OPCs) was evidently increased in the subventricular zone. Additionally, in corpus callosum (CC), the expression of MBP (myelin basic protein) was increased, and the myelin sheaths reached normal level at 30 days with more compact while less damaged myelin sheaths and more mature oligodendrocytes (OLs) repopulating the CC compared with PHI groups. In a word, our findings indicated that Que could remarkably improve both cognition performance and myelination in the context of PHI-induced brain injury by promoting the proliferation of OPCs and strengthening survival of OLs in vivo.

Topics: Animals; Animals, Newborn; Basic Helix-Loop-Helix Transcription Factors; Cell Proliferation; Cognition Disorders; Corpus Callosum; Exploratory Behavior; Gene Expression; Hippocampus; Hypoxia-Ischemia, Brain; Locomotion; Maze Learning; Myelin Basic Protein; Myelin Sheath; Nerve Tissue Proteins; Neural Stem Cells; Neuroprotective Agents; Oligodendrocyte Transcription Factor 2; Oligodendroglia; Quercetin; Rats

Type I diabetes mellitus (DM1) is a widespread metabolic disease ofsocial significance due to early disability in youngpatients and reduced life expectancy. One of the DMI complications is CNS lesions resulting in cognitive dysfunction mediated through metabolic disorders. This condition can be partly or completely reversed if diagnosed and treated'at an early stage. The aim of this study was to determine the level ofneurospecific proteins in 58 patients aged 16-30years with type I diabetes mellitus and cognitive disorders in comparison with 29 healthy controls of simnilar age. All the participants underwent neuropsychological testing based on the Montreal scale for rapid screening of cognitive disorders (MoCA-test). Protein S100, glial fibrillary acidic protein, and myelin basic protein served as early markers of cognitive dysfunction. The study revealed an enhanced level of neurospecific proteins that correlated with hyperglycemia and cognitive deficit (MoCA score 26).

Topics: Adolescent; Adult; Biomarkers; Cognition Disorders; Diabetes Mellitus, Type 1; Female; Glial Fibrillary Acidic Protein; Humans; Male; Myelin Basic Protein; S100 Calcium Binding Protein beta Subunit; Young Adult

Neurologic sequelae, including cognitive deficits, after childhood tick-borne encephalitis (TBE) and neuroborreliosis (NB) are not well-characterized. These infections are among the most common affecting the central nervous system in children and can be difficult to diagnose due to vague symptomatology. The aim of this study was to investigate long-term (>1 year) consequences of pediatric TBE and NB as well as the value of markers for brain damage and genetic susceptibility.. From a previous prospective study, children diagnosed with TBE (n = 8) and NB (n = 12) as well as pediatric controls (n = 15) were followed up by clinical examination, semistructured interview and screening for cognitive dysfunction by the Five-to-Fifteen Questionnaire. The follow-up also included detection of serum autoantibodies against the neural proteins; glial fibrillary acidic protein and myelin basic protein, as well as genotyping of a 32 basepair deletion in the chemokine receptor type 5 gene.. Children diagnosed with TBE displayed significantly more long-term subjective complaints (ie, fatigue, headache and irritability) compared with the NB and control groups. Significantly higher frequency of disabilities was also detected by the Five-to-Fifteen Questionnaire in the TBE group. Both TBE and NB cause consequences (eg, prolonged convalescence, worries and financial loss) for the families. Markers for genetic susceptibility and brain damage had no prognostic values in this cohort.. Pediatric TBE results in long-lasting residual symptoms and neurologic deficits affecting daily life. Vigilance for TBE-related morbidity among pediatricians and long-term clinical follow-up with assessment of cognitive dysfunctions and appropriate interventions seems reasonable for these children.

Topics: Adolescent; Animals; Autoantibodies; Autoimmune Diseases; Child; Child, Preschool; Cognition Disorders; Encephalitis, Tick-Borne; Female; Follow-Up Studies; Glial Fibrillary Acidic Protein; Humans; Lyme Neuroborreliosis; Male; Myelin Basic Protein; Nerve Growth Factors; Receptors, CCR5; Surveys and Questionnaires

Although the white matter lesions, so called leuko-araiosis, often seen in elderly people have been gaining attention due to their association with cognitive dysfunction (CD) and high risk of incident stroke, the pathological significance of these lesions still remains controversial. Therefore, in the present study, we investigated the alterations in oligodendrocytes (OLG), including oligodendrocytes progenitor cells (OPCs), myelin, and CD following chronic cerebral ischemia in rats. SD rats were subjected to bilateral common carotid artery occlusion. Immunohistochemical staining was performed at 2, 4, 6, 8, and 12weeks after the induction of ischemia with anti-NG2 (OPCs), anti-GST-π (OLG), and anti-MBP antibodies in paramedian corpus callosum (CC). CD was assessed by the Morris water maze test. There was a significant decrease in the number of GST-π positive cells at 2weeks after the start of ischemia compared with that seen in the sham group. There was a significant increase of the number of NG2 positive cells at 4weeks in the ischemia group compared with the sham group. In the ischemic group, the amount of MBP was observed to have decreased significantly at each time point compared with the sham group. CD was observed in the ischemic group than that in the sham group at all time points. Our results indicate that remyelination is strongly correlated with the recovery of cognitive dysfunction following chronic cerebral ischemia.

Topics: Analysis of Variance; Animals; Antigens; Brain Ischemia; Bromodeoxyuridine; Cell Count; Chronic Disease; Cognition Disorders; Corpus Callosum; Disease Models, Animal; Gene Expression Regulation; Maze Learning; Myelin Basic Protein; Myelin Sheath; Oligodendroglia; Proteoglycans; Rats; Rats, Sprague-Dawley; Receptor, Platelet-Derived Growth Factor alpha; Time Factors

Behind armor blunt trauma (BABT) describes a nonpenetrating injury to the organs of an individual wearing body armor. The aim of this study was to investigate the neurologic and functional changes that occur in the central nervous system after high-velocity BABT of the spine as well as its biomechanical characteristics.. This study evaluated 28 healthy adult white pigs. Animals were randomly divided into three experimental groups: (1) 15 animals (9 in the exposed group and 6 in the control group) were tested for neurologic changes; (2) 10 animals (5 in the exposed group and 5 in the control group) were used for studies of cognitive function; (3) and 3 animals were used for examination of biomechanics. In the group tested for neurologic changes, 9 anesthetized pigs wearing body armor (including a ceramic plate and polyethylene body armor) on the back were shot on the eighth thoracic vertebrae (T8) with a 5.56-mm rifle bullet (velocity appropriately 910 m/s). As a control, six pigs were shot with blank ammunition. Ultrastructural changes of the spinal cord and brain tissue were observed with light and electron microscopy. Expression levels of myelin basic protein, neuron-specific enolase (NSE), and glial cytoplasmic protein (S-100B) were investigated in the serum and cerebrospinal fluid using enzyme-linked immunosorbent assays. Electroencephalograms (EEGs) were monitored before and 10 minutes after the shot. Pressures in the spine, common carotid artery, and brain were detected. Acceleration of the 10th vertebrae (T10) was tested. Finally, cognitive outcomes between exposed and control groups were compared.. Neuronal degeneration and nerve fiber demyelination were seen in the spinal cord. The concentrations of neuron-specific enolase, myelin basic protein, and S-100B were significantly increased in the serum and cerebrospinal fluid 3 hours after trauma (p < 0.05). The electroencephalogram was suppressed within 3 to 6 minutes after trauma. The pressure detected in the brain was higher than that detected in the common carotid artery (p < 0.01). The trauma resulted in paralysis of two hind limbs and in cognitive dysfunction.. The results from our animal model indicate that high-velocity BABT of the spine generates high pressure and acceleration in the spine, induces varying degrees of paralysis of hind limbs, and disturbs cerebral function. The neuronal degeneration caused by the pressure wave may be one of the important pathologic events involved in the development of trauma-related complications.

Topics: Analysis of Variance; Animals; Biomarkers; Biomechanical Phenomena; Cognition Disorders; Disease Models, Animal; Electroencephalography; Forensic Ballistics; Immunohistochemistry; Injury Severity Score; Linear Models; Microscopy, Electron; Motor Skills; Myelin Basic Protein; Neurologic Examination; Phosphopyruvate Hydratase; Protective Clothing; Random Allocation; Reference Values; Spinal Injuries; Sus scrofa; Swine; Wounds, Gunshot; Wounds, Nonpenetrating

Central nervous system prophylaxis of childhood acute lymphoblastic leukemia has dropped rates of relapses but has been associated with neurotoxicity and imaging abnormalities. Predictors of neurotoxicity are lacking, because of inconsistency between clinical symptoms and imaging. Some have suggested that cerebrospinal fluid myelin basic protein (MBP) levels to be of potential interest. A retrospective analysis of MBP levels in correlation with clinical and radiologic data is presented.. MBP levels obtained at the time of intrathecals, charts, and neuroradiology reports were retrospectively analyzed. Academic achievement data were obtained from phone contacts with patients and families.. We retrieved 1248 dosages of MBP in 83 patients, 381 neurologic examinations in 34 patients and 69 neuroradiologic investigations in 27 patients. Fifty-two patients had abnormal MBP levels. Radiologic anomalies were present in 47% of those investigated, 14% of them having school difficulties. Proportions of patients with school difficulties in the groups with abnormal MBP levels but no radiologic anomalies or with no radiologic investigations were 0% and 3%, respectively, which was lower than in the group of patients with normal MBP levels (100%, 22%, and 5%, respectively).. Notwithstanding the retrospective character of our study, we conclude that there is limited usefulness of systematic dosage of MBP as indicator of treatment-induced neurotoxicity in acute lymphoblastic leukemia patients.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Brain; Central Nervous System Neoplasms; Child; Child, Preschool; Cognition Disorders; Combined Modality Therapy; Cranial Irradiation; Female; Humans; Infant; Infant, Newborn; Injections, Spinal; Male; Myelin Basic Protein; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Although periventricular white matter injury is a leading cause of major neurologic disability in premature infants, the relationship between myelination deficiency and long-term cognitive dysfunction is not well understood. The purpose of this study was to investigate oligodendrocytes myelination and long-term spatial cognitive function in rats with perinatal hypoxia-ischemia (HI). Postnatal day 3 (P3) rats were subjected to right carotid artery ligation followed by 2.5 h of hypoxia (6% oxygen). Brain injury during the early and late phases was evaluated by immunostaining at P6 (72 h after the injury) and P47. Spatial cognitive function was evaluated at P42 using the Morris Water Maze test followed by histologic evaluation. HI caused an increase in pre-oligodendrocytes, astrocytes, and microglia in the ipsilateral white matter 72 h after the insult compared to contralateral regions and sham-operated controls (both p<0.05). There were significant decreases in myelin basic protein (MBP)and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-labeled oligodendrocytes with glial fibrillary acidic protein (GFAP)-labeled glial scarring in the ipsilateral periventricular white matter at P47 compared to contralateral regions and sham-operated controls (all p<0.05). The rats with HI had spatial learning deficits in navigation trials (longer escape latency and swimming distance) and memory dysfunction in probe trials (fewer number of platform crossings and percentage of time in the target quadrant) compared with sham-operated controls (p<0.05). In this neonatal rat model of HI, myelination deficiency induced by activated astrocytes and microglia during the early phase with subsequent glial scarring was associated with long-term spatial learning and memory dysfunction.

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Analysis of Variance; Animals; Animals, Newborn; Antigens, CD; Antigens, Differentiation, Myelomonocytic; CA1 Region, Hippocampal; Cell Count; Cognition Disorders; Demyelinating Diseases; Exploratory Behavior; Female; Gliosis; Hypoxia-Ischemia, Brain; Immunohistochemistry; Male; Maze Learning; Myelin Basic Protein; Nerve Fibers, Myelinated; Neuroglia; Rats; Space Perception; Time Factors

The aim of the study was evaluation of usefulness of cerebrospinal fluid (CSF) myelin basic protein (MBP) level examination in diagnostics of Lyme neuroborreliosis. The study was performed in 24 subjects. In all individuals CSF MBP concentration was estimated on the 1st day of hospitalization. In patients with depressive and cognitive impairments, proved in neuropsychological tests (group I), mean CSF MBP concentration was 3.1 ng/mL, whereas in subjects without abnormalities in tests (group II), respectively, 1.2 ng/mL. The difference of mean CSF MBP levels was statistically significant (p<0.01). The obtained results indicate usefulness of this CSF parameter, besides neuropsychological tests, in objective evaluation of clinical state in patients with chronic Lyme neuroborreliosis.

Topics: Adult; Aged; Antibodies, Bacterial; Cognition Disorders; Depression; Female; Humans; Immunoglobulin G; Lyme Neuroborreliosis; Male; Middle Aged; Myelin Basic Protein; Neuropsychological Tests; Poland; Sensitivity and Specificity; Severity of Illness Index

Neurological sequelae (NS) is a common complication of carbon monoxide (CO) poisoning and structural alterations of myelin basic protein have been proven to initiate immunological reactions leading to NS. To determine whether xanthine oxidoreductase (XOR) participates in the pathophysiology of CO-mediated NS, we examined myelin basic protein in CO poisoned XOR-depleted rats and performed radial maze studies to evaluate the alteration of cognitive function. Carbon monoxide poisoned XOR-depleted rats did not exhibit myelin basic protein alterations or impaired cognitive function, both found in CO poisoned control rats. These results indicate that XOR is essential to the pathological cascade of CO-mediated NS.

Topics: Animals; Brain; Carbon Monoxide; Carbon Monoxide Poisoning; Cognition Disorders; Male; Maze Learning; Myelin Basic Protein; Rats; Rats, Wistar; Xanthine Dehydrogenase

The structural substrates for age-associated cognitive and motor slowing are not known, but age-related white matter changes, such as ubiquitin (UBQ)-immunoreactive granular degeneration of myelin, might contribute to this slowing. To address this hypothesis we measured immunoreactivity for UBQ and myelin basic protein (MBP) in frontal white matter of age-, sex- and postmortem interval-matched cases with no cognitive impairment (NCI; N=12), mild cognitive impairment (MCI; N=14) and Alzheimer disease (AD; N=12). There were no significant correlations between UBQ in white matter and cognitive measures, but MBP was significantly lower in AD compared with NCI and MCI. MBP correlated with overall cognition as assessed by neuropsychological summary scores, as well as with timed cognitive tests and those that reflect frontal functions. An age-related decrease in MBP immunoreactivity was detected in NCI cases (r=0.71). These results support the hypothesis that white matter pathology may contribute to age-associated decline in cognition.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Blotting, Western; Chi-Square Distribution; Cognition Disorders; Female; Frontal Lobe; Humans; Immunoblotting; Immunohistochemistry; Male; Myelin Basic Protein; Neurologic Examination; Neuropsychological Tests; Statistics, Nonparametric; Ubiquitin

The neuropathological sequelae of carbon monoxide (CO) poisoning cannot be explained by hypoxic stress alone. CO poisoning also causes adduct formation between myelin basic protein (MBP) and malonylaldehyde, a reactive product of lipid peroxidation, resulting in an immunological cascade. MBP loses its normal cationic characteristics, and antibody recognition of MBP is altered. Immunohistochemical evidence of degraded MBP occurs in brain over days, along with influx of macrophages and CD-4 lymphocytes. Lymphocytes from CO-poisoned rats subsequently exhibit an auto-reactive proliferative response to MBP, and there is a significant increase in the number of activated microglia in brain. Rats rendered immunologically tolerant to MBP before CO poisoning exhibit acute biochemical changes in MBP but no lymphocyte proliferative response or brain microglial activation. CO poisoning causes a decrement in learning that is not observed in immunologically tolerant rats. These results demonstrate that delayed CO-mediated neuropathology is linked to an adaptive immunological response to chemically modified MBP.

Topics: Animals; Brain; Carbon Monoxide; Carbon Monoxide Poisoning; Cognition Disorders; Hydrogen-Ion Concentration; Immunohistochemistry; Lymphocyte Activation; Lymphocytes; Male; Malondialdehyde; Maze Learning; Microglia; Myelin Basic Protein; Neurons; Protein Isoforms; Rats; Rats, Wistar

Cognitive dysfunction and histological changes in the brain were investigated following irradiation in 20 Fischer 344 rats aged 6 months treated with whole brain irradiation (WBR) (25 Gy/single dose), and compared with the same number of sham-irradiated rats as controls. Performance of the Morris water maze task and the passive avoidance task were examined one year after WBR. Finally, histological and immunohistochemical examinations using antibodies to myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and neurofilament (NF) were performed of the rat brains. The irradiated rats continued to gain weight 7 months after WBR whereas the control rats stopped gaining weight. Cognitive functions in both the water maze task and the passive avoidance task were lower in the irradiated rats than in the control rats. Brain damage consisting of demyelination only or with necrosis was found mainly in the body of the corpus callosum and the parietal white matter near the corpus callosum in the irradiated rats. Immunohistochemical examination of the brains without necrosis found MBP-positive fibers were markedly decreased in the affected areas by irradiation; NF-positive fibers were moderately decreased and irregularly dispersed in various shapes in the affected areas; and GFAP-positive fibers were increased, with gliosis in those areas. These findings are similar to those in clinically accelerated brain aging in conditions such as Alzheimer's disease, Binswanger's disease, and multiple sclerosis.

Topics: Animals; Avoidance Learning; Brain; Cognition Disorders; Cranial Irradiation; Glial Fibrillary Acidic Protein; Male; Maze Learning; Myelin Basic Protein; Neurofilament Proteins; Radiation Injuries, Experimental; Rats; Rats, Inbred F344