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Sample records for acute brain damage

  1. Evolution of blood-brain barrier damage associated with changes in brain metabolites following acute ischemia.

    PubMed

    Yan, Gen; Xuan, Yinghua; Dai, Zhuozhi; Zhang, Guishan; Xu, Haiyun; Mikulis, David; Wu, Renhua

    2015-11-11

    Stroke is a serious medical condition that requires emergency care. In the case of ischemic stroke, ischemia may lead to damage to the blood-brain barrier (BBB); the damage in turn may exacerbate the condition. Therefore, noninvasive detection of BBB damage represents a challenge for experimental and clinical researchers. In this study, we assessed the onset of BBB disruption by means of T1-weighted images with administration of the contrast enhancement agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and related BBB breakdown to brain metabolite changes in proton magnetic resonance spectrum (H-MRS) in the infarcted site following middle cerebral artery occlusion (MCAO) in rats. It was shown that MCAO for 30 min and 1.5 h caused no Gd-DTPA signal change in the T1-weighted images, whereas MCAO for 1 h significantly altered some of H-MRS brain metabolites, suggesting that brain metabolite changes occurred earlier than BBB damage after ischemic stroke. MCAO for 2 h caused BBB breakdown, which was related to changes in the levels of some brain metabolites detected by H-MRS. Between the second and the third hour after MCAO, brain metabolite changes continued as the result of BBB breakdown and the concurrent overperfusion to the infarcted site, which may ameliorate the metabolite changes, thus compensating for the functional failures of the brain after stroke. PMID:26366833

  2. Right Hemisphere Brain Damage

    MedlinePlus

    ... Language and Swallowing / Disorders and Diseases Right Hemisphere Brain Damage [ en Español ] What is right hemisphere brain ... right hemisphere brain damage ? What is right hemisphere brain damage? Right hemisphere brain damage (RHD) is damage ...

  3. Neuroprotection by gonadal steroid hormones in acute brain damage requires cooperation with astroglia and microglia.

    PubMed

    Johann, Sonja; Beyer, Cordian

    2013-09-01

    The neuroactive steroids 17β-estradiol and progesterone control a broad spectrum of neural functions. Besides their roles in the regulation of classical neuroendocrine loops, they strongly influence motor and cognitive systems, behavior, and modulate brain performance at almost every level. Such a statement is underpinned by the widespread and lifelong expression pattern of all types of classical and non-classical estrogen and progesterone receptors in the CNS. The life-sustaining power of neurosteroids for tattered or seriously damaged neurons aroused interest in the scientific community in the past years to study their ability for therapeutic use under neuropathological challenges. Documented by excellent studies either performed in vitro or in adequate animal models mimicking acute toxic or chronic neurodegenerative brain disorders, both hormones revealed a high potency to protect neurons from damage and saved neural systems from collapse. Unfortunately, neurons, astroglia, microglia, and oligodendrocytes are comparably target cells for both steroid hormones. This hampers the precise assignment and understanding of neuroprotective cellular mechanisms activated by both steroids. In this article, we strive for a better comprehension of the mutual reaction between these steroid hormones and the two major glial cell types involved in the maintenance of brain homeostasis, astroglia and microglia, during acute traumatic brain injuries such as stroke and hypoxia. In particular, we attempt to summarize steroid-activated cellular signaling pathways and molecular responses in these cells and their contribution to dampening neuroinflammation and neural destruction. This article is part of a Special Issue entitled 'CSR 2013'. PMID:23196064

  4. Autophagy in acute brain injury.

    PubMed

    Galluzzi, Lorenzo; Bravo-San Pedro, José Manuel; Blomgren, Klas; Kroemer, Guido

    2016-08-01

    Autophagy is an evolutionarily ancient mechanism that ensures the lysosomal degradation of old, supernumerary or ectopic cytoplasmic entities. Most eukaryotic cells, including neurons, rely on proficient autophagic responses for the maintenance of homeostasis in response to stress. Accordingly, autophagy mediates neuroprotective effects following some forms of acute brain damage, including methamphetamine intoxication, spinal cord injury and subarachnoid haemorrhage. In some other circumstances, however, the autophagic machinery precipitates a peculiar form of cell death (known as autosis) that contributes to the aetiology of other types of acute brain damage, such as neonatal asphyxia. Here, we dissect the context-specific impact of autophagy on non-infectious acute brain injury, emphasizing the possible therapeutic application of pharmacological activators and inhibitors of this catabolic process for neuroprotection. PMID:27256553

  5. Coping with brain damage

    NASA Technical Reports Server (NTRS)

    Waring, W.

    1974-01-01

    Two neurological disorders, cerebral palsy, and traumatic brain damage as from an accident, are considered. The discussion covers the incidence of disabilities, their characteristics, and what is now being done to deal with them, particularly in reference to areas in which the capabilities of the engineer can be effectively applied.

  6. Inhibition of the group I mGluRs reduces acute brain damage and improves long-term histological outcomes after photothrombosis-induced ischaemia

    PubMed Central

    Li, Hailong; Zhang, Nannan; Sun, Grace; Ding, Shinghua

    2013-01-01

    Group I mGluRs (metabotropic glutamate receptors), including mGluR1 and mGluR5, are GPCRs (G-protein coupled receptors) and play important roles in physiology and pathology. Studies on their role in cerebral ischaemia have provided controversial results. In this study, we used a PT (photothrombosis)-induced ischaemia model to investigate whether antagonists to the group I mGluRs may offer acute and long-term protective effects in adult mice. Our results demonstrated that administration with mGluR5 antagonist MPEP [2-methyl-6-(phenylethynyl)-pyridine] or mGluR1 antagonist LY367385 by intraperitoneal injection at 3 h after PT decreased brain infarct volume evaluated one day after ischaemia. Additive effects on infarct volume were observed upon co-injection with MPEP and LY367385. These antagonists also significantly alleviated neurodegeneration and apoptosis in the penumbra. In addition, when evaluated 2 weeks after PT, they reduced infarct volume and tissue loss, attenuated glial scar formation, and inhibited cell proliferation in the penumbra. Importantly, co-injection with MPEP and LY367385 reduced the expression levels of calpain, a Ca2+-activated protease known to mediate ischaemia-induced neuronal death. Injection of calpeptin, a calpain inhibitor, could inhibit neuronal death and brain damage after PT but injection of calpeptin together with MPEP and LY367385 did not further improve the protective effects mediated by MPEP and LY367385. These results suggest that inhibition of group I mGluRs is sufficient to protect ischaemic damage through the calpain pathway. Taken together, our results demonstrate that inhibition of group I mGluRs can mitigate PT-induced brain damage through attenuating the effects of calpain, and improve long-term histological outcomes. PMID:23772679

  7. Acute Methamphetamine Intoxication: Brain Hyperthermia, Blood-Brain Barrier and Brain Edema

    PubMed Central

    Kiyatkin, Eugene A.; Sharma, Hari S.

    2011-01-01

    Methamphetamine (METH) is a powerful and often abused stimulant with potent addictive and neurotoxic properties. While it is generally assumed that multiple chemical substances released in the brain following METH-induced metabolic activation (or oxidative stress) are primary factors underlying damage of neural cells, in this work we will present data suggesting a role of brain hyperthermia and associated leakage of the brain-blood barrier (BBB) in acute METH-induced toxicity. First, we show that METH induces a dose-dependent brain and body hyperthermia, which is strongly potentiated by associated physiological activation and in warm environments that prevent proper heat dissipation to the external environment. Second, we demonstrate that acute METH intoxication induces robust, widespread but structure-specific leakage of the BBB, acute glial activation, and increased water content (edema), which are related to drug-induced brain hyperthermia. Third, we document widespread morphological abnormalities of brain cells, including neurons, glia, epithelial and endothelial cells developing rapidly during acute METH intoxication. These structural abnormalities are tightly related to the extent of brain hyperthermia, leakage of the BBB, and brain edema. While it is unclear whether these rapidly developed morphological abnormalities are reversible, this study demonstrates that METH induces multiple functional and structural perturbations in the brain, determining its acute toxicity and possibly contributing to neurotoxicity. PMID:19897075

  8. Acute lysine overload provokes protein oxidative damage and reduction of antioxidant defenses in the brain of infant glutaryl-CoA dehydrogenase deficient mice: a role for oxidative stress in GA I neuropathology.

    PubMed

    Seminotti, Bianca; Ribeiro, Rafael Teixeira; Amaral, Alexandre Umpierrez; da Rosa, Mateus Struecker; Pereira, Carolina Coffi; Leipnitz, Guilhian; Koeller, David M; Goodman, Stephen; Woontner, Michael; Wajner, Moacir

    2014-09-15

    We evaluated the antioxidant defense system and protein oxidative damage in the brain and liver of 15-day-old GCDH deficient knockout (Gcdh(-/-)) mice following an acute intraperitoneal administration of Lys (8 μmol/g). We determined reduced glutathione (GSH) concentrations, sulfhydryl content, carbonyl formation and the activities of the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) in the brain and liver of these animals. 2',7'-dihydrodichlorofluorescein (DCFH) oxidation was also measured as an index of free radical formation. The only parameters altered in Gcdh(-/-) compared to wild type (Gcdh(+/+)) mice were a reduction of liver GSH concentrations and of brain sulfhydryl content. Acute Lys injection provoked a decrease of GSH concentration in the brain and sulfhydryl content in the liver, and an increase in carbonyl formation in the brain and liver of Gcdh(-/-) mice. Lys administration also induced a decrease of all antioxidant enzyme activities in the brain, as well as an increase of the activities of SOD and CAT in the liver of Gcdh(-/-) mice. Finally, Lys elicited a marked increase of DCFH oxidation in the brain and liver. It is concluded that Lys overload compromises the brain antioxidant defenses and induces protein oxidation probably secondary to reactive species generation in infant Gcdh(+/+) mice. PMID:24996493

  9. A Brain-Damage Advantage for Lefties?

    ERIC Educational Resources Information Center

    Bower, B.

    1985-01-01

    Reports that people who are predominantly left-handed apparently are able to withstand moderate brain damage with relatively few of the motor problems observed in right-handed victims of brain damage. Other brain-related differences between left- and right-handed individuals are also noted. (JN)

  10. Genetic damage in multiple organs of acutely exercised rats.

    PubMed

    Pozzi, Renan; Rosa, Jose C; Eguchi, Ricardo; Oller do Nascimento, Claudia M; Oyama, Lila M; Aguiar, Odair; Chaves, Marcelo D; Ribeiro, Daniel A

    2010-12-01

    The aim of this study was to investigate the effects of acute exercise on genomic damage in an animal model. Male adult Wistar rats were divided into the following groups: control and acute exercised (experimental). For this purpose, 15 animals were accustomed to running on a rodent treadmill for 15 min per day for 5 days (10-20 m min(-1); 08 grade). After 4 days at rest, active animals ran on the treadmill (22 m min(-1), 58 grade) till exhaustion. Cells from peripheral blood, liver, heart, and brain were collected after 0, 2, and 6 h after exercise. The results showed that acute exercise was able to induce genetic damage in peripheral blood cells after 2 and 6 h of exercise, whereas liver pointed out genetic damage for all periods evaluated. No genetic damage was induced either in brain or in heart cells. In conclusion, our results suggest that acute exercise could contribute to the genetic damage in peripheral blood and liver cells. It seems that liver is a sensitive organ to the genotoxic insult after acute exercise. PMID:20979236

  11. Neglect severity after left and right brain damage

    PubMed Central

    Suchan, Julia; Rorden, Chris; Karnath, Hans-Otto

    2012-01-01

    While unilateral spatial neglect after left brain damage is undoubtly less common than spatial neglect after a right hemisphere lesion, it is also assumed to be less severe. Here we directly test this latter hypothesis using a continuous measure of neglect severity: the so-called Center of Cancellation (CoC). Rorden and Karnath (2010) recently validated this index for right brain damaged neglect patients. A first aim of the present study was to evaluate this new measure for spatial neglect after left brain damage. In a group of 48 left-sided stroke patients with and without neglect, a score greater than −0.086 on the Bells Test and greater than −0.024 on the Letter Cancellation Task turned out to indicate neglect behavior for left brain damaged patients. A second aim was to directly compare the severity of spatial neglect after left versus right brain injury by using the new CoC measure. While neglect is less frequent following left than right hemisphere injury, we found that when this symptom occurs it is of similar severity in acute left brain injury as in patients after acute right brain injury. PMID:22230231

  12. Effects of Cannabidiol and Hypothermia on Short-Term Brain Damage in New-Born Piglets after Acute Hypoxia-Ischemia.

    PubMed

    Lafuente, Hector; Pazos, Maria R; Alvarez, Antonia; Mohammed, Nagat; Santos, Martín; Arizti, Maialen; Alvarez, Francisco J; Martinez-Orgado, Jose A

    2016-01-01

    Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection. Cannabidiol could be a good candidate. Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets. Hypoxic-ischemic animals were randomly divided into four groups receiving 30 min after the insult: (1) normothermia and vehicle administration; (2) normothermia and cannabidiol administration; (3) hypothermia and vehicle administration; and (4) hypothermia and cannabidiol administration. Six hours after treatment, brains were processed to quantify the number of damaged neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate) and excitotoxicity (glutamate/Nacetyl-aspartate). Western blot studies were performed to quantify protein nitrosylation (oxidative stress), content of caspase-3 (apoptosis) and TNFα (inflammation). Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels in newborn piglets subjected to hypoxic-ischemic insult. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on cell damage, was greater than either hypothermia or cannabidiol alone. The present study demonstrated that cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage if applied shortly after the insult. PMID:27462203

  13. Effects of Cannabidiol and Hypothermia on Short-Term Brain Damage in New-Born Piglets after Acute Hypoxia-Ischemia

    PubMed Central

    Lafuente, Hector; Pazos, Maria R.; Alvarez, Antonia; Mohammed, Nagat; Santos, Martín; Arizti, Maialen; Alvarez, Francisco J.; Martinez-Orgado, Jose A.

    2016-01-01

    Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection. Cannabidiol could be a good candidate. Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets. Hypoxic-ischemic animals were randomly divided into four groups receiving 30 min after the insult: (1) normothermia and vehicle administration; (2) normothermia and cannabidiol administration; (3) hypothermia and vehicle administration; and (4) hypothermia and cannabidiol administration. Six hours after treatment, brains were processed to quantify the number of damaged neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate) and excitotoxicity (glutamate/Nacetyl-aspartate). Western blot studies were performed to quantify protein nitrosylation (oxidative stress), content of caspase-3 (apoptosis) and TNFα (inflammation). Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels in newborn piglets subjected to hypoxic-ischemic insult. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on cell damage, was greater than either hypothermia or cannabidiol alone. The present study demonstrated that cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage if applied shortly after the insult. PMID:27462203

  14. Body representations and brain damage.

    PubMed

    Rousseaux, M; Honoré, J; Saj, A

    2014-01-01

    We review changes in body representation in patients with brain hemisphere damage and discuss their relationship with impaired limb movements in peripersonal space, navigation between objects/obstacles and control of the body's general posture and balance. The egocentric representation of the body's median sagittal axis (considered as the main zone around which movements are anchored) has been studied in most detail. This reference is distorted in patients with spatial neglect and involves a combination of ipsilesional translation and contralesional tilt. There are clear links with the patients' difficulties in egocentric tasks, activities of daily living and postural control. In both healthy subjects and patients, this reference axis can be modulated by somaesthetic, vestibular and visual stimulations; these phenomena have been used in rehabilitation programmes to reduce disease-induced deviations. A few studies have analyzed other lateral body reference (at the shoulders, in particular). These references were found to be more severely affected than the body midline (notably on the contralesional side). The severity of the distortion was related to the presence of lesions that mainly affected the parietal, somatosensory and multimodal association cortex (notably around the intraparietal sulcus) and, to a lesser extent, the middle temporal and frontal dorsolateral premotor cortex. These convergent results suggested that patients (notably those with neglect) have a complex distortion of the body schema and the perceptive representations of the body, that does not simply correspond to poor awareness of the contralateral hemicorpus. PMID:24502906

  15. Interleukin-1 and acute brain injury

    PubMed Central

    Murray, Katie N.; Parry-Jones, Adrian R.; Allan, Stuart M.

    2015-01-01

    Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection) have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL)-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review. PMID:25705177

  16. Involvement of leukotrienes in acute gastric damage.

    PubMed

    Boughton-Smith, N K

    1989-01-01

    The leukotrienes have potent inflammatory actions which could be of importance in gastric mucosal integrity. In animals, LTC4 produces vasoconstriction in the gastric mucosa. Furthermore, acute gastric damage produced by ethanol is accompanied by marked increases in the mucosal formation of LTC4 and LTB4. Depending on the extent of protection, prostaglandins either have no effect or prevent the increases in leukotriene formation which accompany ethanol-induced damage. Various non-specific inhibitors of leukotriene synthesis prevent ethanol and indomethacin-induced damage to the gastric mucosa. However, a novel selective 5-lipoxygenase inhibitor (BW A4C) had no effect on these models of acute gastric damage at doses which completely inhibited gastric mucosal leukotriene synthesis. These studies cast doubt on the role of the leukotrienes in these models of acute gastric damage. However, the potent biological actions of the leukotrienes may be of importance in the pathogenesis of other forms of gastric damage, or as mediators of chronic gastric ulceration or inflammation. PMID:2657289

  17. Brain Damage in Commercial Breath-Hold Divers

    PubMed Central

    Kohshi, Kiyotaka; Tamaki, Hideki; Lemaître, Frédéric; Okudera, Toshio; Ishitake, Tatsuya; Denoble, Petar J.

    2014-01-01

    Background Acute decompression illness (DCI) involving the brain (Cerebral DCI) is one of the most serious forms of diving-related injuries which may leave residual brain damage. Cerebral DCI occurs in compressed air and in breath-hold divers, likewise. We conducted this study to investigate whether long-term breath-hold divers who may be exposed to repeated symptomatic and asymptomatic brain injuries, show brain damage on magnetic resonance imaging (MRI). Subjects and Methods Our study subjects were 12 commercial breath-hold divers (Ama) with long histories of diving work in a district of Japan. We obtained information on their diving practices and the presence or absence of medical problems, especially DCI events. All participants were examined with MRI to determine the prevalence of brain lesions. Results Out of 12 Ama divers (mean age: 54.9±5.1 years), four had histories of cerebral DCI events, and 11 divers demonstrated ischemic lesions of the brain on MRI studies. The lesions were situated in the cortical and/or subcortical area (9 cases), white matters (4 cases), the basal ganglia (4 cases), and the thalamus (1 case). Subdural fluid collections were seen in 2 cases. Conclusion These results suggest that commercial breath-hold divers are at a risk of clinical or subclinical brain injury which may affect the long-term neuropsychological health of divers. PMID:25115903

  18. Brain Damage in School Age Children.

    ERIC Educational Resources Information Center

    Haywood, H. Carl, Ed.

    The product of a professional workshop, 10 papers discuss brain damage. An introduction to clinical neuropsychology is presented by H. Carl Haywood. A section on neurological foundations includes papers on the organization of the central nervous system by Jack T. Tapp and Lance L. Simpson, on epilepsy by Angela T. Folsom, and on organic language…

  19. Cognitive Development in Children with Brain Damage.

    ERIC Educational Resources Information Center

    Bortner, Morton

    Presented is a report on a cross-sectional and longitudinal study concerned with the course of intellectual development in 210 children (6-12 years old) educationally designated as brain damaged (learning disabled and/or behavior problems) and assigned to special school placement. The report is divided into four sections which focus on…

  20. The dose-response effect of acute intravenous transplantation of human umbilical cord blood cells on brain damage and spatial memory deficits in neonatal hypoxia-ischemia.

    PubMed

    de Paula, S; Greggio, S; Marinowic, D R; Machado, D C; DaCosta, J Costa

    2012-05-17

    Despite the beneficial effects of cell-based therapies on brain repair shown in most studies, there has not been a consensus regarding the optimal dose of human umbilical cord blood cells (HUCBC) for neonatal hypoxia-ischemia (HI). In this study, we compared the long-term effects of intravenous administration of HUCBC at three different doses on spatial memory and brain morphological changes after HI in newborn Wistar rats. In addition, we tested whether the transplanted HUCBC migrate to the injured brain after transplantation. Seven-day-old animals underwent right carotid artery occlusion and were exposed to 8% O(2) inhalation for 2 h. After 24 h, randomly selected animals were assigned to four different experimental groups: HI rats administered with vehicle (HI+vehicle), HI rats treated with 1×10(6) (HI+low-dose), 1×10(7) (HI+medium-dose), and 1×10(8) (HI+high-dose) HUCBC into the jugular vein. A control group (sham-operated) was also included in this study. After 8 weeks of transplantation, spatial memory performance was assessed using the Morris water maze (MWM), and subsequently, the animals were euthanized for brain morphological analysis using stereological methods. In addition, we performed immunofluorescence and polymerase chain reaction (PCR) analyses to identify HUCBC in the rat brain 7 days after transplantation. The MWM test showed a significant spatial memory recovery at the highest HUCBC dose compared with HI+vehicle rats (P<0.05). Furthermore, the brain atrophy was also significantly lower in the HI+medium- and high-dose groups compared with the HI+vehicle animals (P<0.01; 0.001, respectively). In addition, HUCBC were demonstrated to be localized in host brains by immunohistochemistry and PCR analyses 7 days after intravenous administration. These results revealed that HUCBC transplantation has the dose-dependent potential to promote robust tissue repair and stable cognitive improvement after HI brain injury. PMID:22441035

  1. Brain damage in alcoholism: current concepts.

    PubMed

    Lishman, W A; Jacobson, R R; Acker, C

    1987-01-01

    Current views concerning the brain damage occasioned by alcohol abuse are reviewed. Diffuse cerebral changes appear to be common and partially reversible with prolonged abstinence. The possible determinants of such changes, and their relevance to functional deficits are discussed, with illustrations from work currently proceeding at the Institute of Psychiatry. Possible interactions between cortical and subcortical pathologies in contributing to the cognitive deficits shown by alcoholic patients are emphasised. PMID:3478970

  2. Medical Perspectives on Brain Damage and Development. Revised.

    ERIC Educational Resources Information Center

    McCrae, Marcia Q.

    The author describes damage and normal development of the brain, as well as assessment and intervention with brain-damaged children. After a brief introduction on the complex and delicate process of brain development and a review of incidence, aspects of etiology such as genetic and postnatal causes are discussed. Brain development is examined…

  3. Clinical and pathological features of alcohol-related brain damage.

    PubMed

    Zahr, Natalie M; Kaufman, Kimberley L; Harper, Clive G

    2011-05-01

    One of the sequelae of chronic alcohol abuse is malnutrition. Importantly, a deficiency in thiamine (vitamin B(1)) can result in the acute, potentially reversible neurological disorder Wernicke encephalopathy (WE). When WE is recognized, thiamine treatment can elicit a rapid clinical recovery. If WE is left untreated, however, patients can develop Korsakoff syndrome (KS), a severe neurological disorder characterized by anterograde amnesia. Alcohol-related brain damage (ARBD) describes the effects of chronic alcohol consumption on human brain structure and function in the absence of more discrete and well-characterized neurological concomitants of alcoholism such as WE and KS. Through knowledge of both the well-described changes in brain structure and function that are evident in alcohol-related disorders such as WE and KS and the clinical outcomes associated with these changes, researchers have begun to gain a better understanding of ARBD. This Review examines ARBD from the perspective of WE and KS, exploring the clinical presentations, postmortem brain pathology, in vivo MRI findings and potential molecular mechanisms associated with these conditions. An awareness of the consequences of chronic alcohol consumption on human behavior and brain structure can enable clinicians to improve detection and treatment of ARBD. PMID:21487421

  4. Blood-brain barrier damage in vascular dementia.

    PubMed

    Ueno, Masaki; Chiba, Yoichi; Matsumoto, Koichi; Murakami, Ryuta; Fujihara, Ryuji; Kawauchi, Machi; Miyanaka, Hiroshi; Nakagawa, Toshitaka

    2016-04-01

    New findings on flow or drainage pathways of brain interstitial fluid and cerebrospinal fluid have been made. The interstitial fluid flow has an effect on the passage of blood-borne substances in the brain parenchyma, especially in areas near blood-brain barrier (BBB)-free regions. Actually, blood-borne substances can be transferred in areas with intact BBB function, such as the hippocampus, the corpus callosum, periventricular areas, and medial portions of the amygdala, presumably through leaky vessels in the subfornical organs or the choroid plexus. Increasing evidence indicates that dysfunction of the BBB function may play a significant role in the pathogenesis of vascular dementia. Accordingly, we have examined which insults seen in patients suffering from vascular dementia have an effect on the BBB using experimental animal models exhibiting some phenotypes of vascular dementia. The BBB in the hippocampus was clearly deteriorated in Mongolian gerbils exposed to acute ischemia followed by reperfusion and also in stroke-prone spontaneously hypertensive rats (SHRSP) showing hypertension. The BBB in the corpus callosum was clearly deteriorated in Wistar rats with permanent ligation of the bilateral common carotid arteries showing chronic hypoperfusion. The BBB in the hippocampus and the olfactory bulb was mildly deteriorated in aged senescence accelerated prone mice (SAMP8) showing cognitive dysfunction. The BBB in the hippocampus was mildly deteriorated in aged animals with hydrocephalus. Mild endothelial damage was seen in hyperglycemic db/db mice. In addition, mRNA expression of osteopontin, matrix metalloproteinase-13 (MMP-13), and CD36 was increased in vessels showing BBB damage in hypertensive SHRSP. As osteopontin, MMP-13 and CD36 are known to be related to brain injury and amyloid β accumulation or clearance, BBB damage followed by increased gene expression of these molecules not only contributes to the pathogenesis of vascular dementia, but also bridges

  5. Endoplasmic reticulum stress in brain damage.

    PubMed

    Raghubir, Ram; Nakka, Venkata Prasuja; Mehta, Suresh L

    2011-01-01

    The efficient functioning of the ER is indispensable for most of the cellular activities and survival. Disturbances in the physiological functions of the ER result in the activation of a complex set of signaling pathways from the ER to the cytosol and nucleus, and these are collectively known as unfolded protein response (UPR), which is aimed to compensate damage and can eventually trigger cell death if ER stress is severe or persists for a longer period. The precise molecular mechanisms that facilitate this switch in brain damage have yet to be understood completely with multiple potential participants involved. The ER stress-associated cell death pathways have been recognized in the numerous pathophysiological conditions, such as diabetes, hypoxia, ischemia/reperfusion injury, and neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and bipolar disorder. Hence, there is an emerging need to study the basic molecular mechanisms of ER stress-mediating multiple cell survival/death signaling pathways. These molecules that regulate the ER stress response would be potential drug targets in brain diseases. PMID:21266235

  6. Animal imaging studies of potential brain damage

    NASA Astrophysics Data System (ADS)

    Gatley, S. J.; Vazquez, M. E.; Rice, O.

    To date, animal studies have not been able to predict the likelihood of problems in human neurological health due to HZE particle exposure during space missions outside the Earth's magnetosphere. In ongoing studies in mice, we have demonstrated that cocaine stimulated locomotor activity is reduced by a moderate dose (120 cGy) of 1 GeV 56Fe particles. We postulate that imaging experiments in animals may provide more sensitive and earlier indicators of damage due to HZE particles than behavioral tests. Since the small size of the mouse brain is not well suited to the spatial resolution offered by microPET, we are now repeating some of our studies in a rat model. We anticipate that this will enable us to identify imaging correlates of behavioral endpoints. A specific hypothesis of our studies is that changes in the metabolic rate for glucose in striatum of animals will be correlated with alterations in locomotor activity. We will also evaluate whether the neuroprotective drug L-deprenyl reduces the effect of radiation on locomotor activity. In addition, we will conduct microPET studies of brain monoamine oxidase A and monoamine oxidase B in rats before and at various times after irradiation with HZE particles. The hypothesis is that monoamine oxidase A, which is located in nerve terminals, will be unchanged or decreased after irradiation, while monoamine oxidase B, which is located in glial cells, will be increased after irradiation. Neurochemical effects that could be measured using PET could in principle be applied in astronauts, in terms of detecting and monitoring subtle neurological damage that might have occurred during long space missions. More speculative uses of PET are in screening candidates for prolonged space missions (for example, for adequate reserve in critical brain circuits) and in optimizing medications to treat impairments after missions.

  7. Extending the viability of acute brain slices.

    PubMed

    Buskila, Yossi; Breen, Paul P; Tapson, Jonathan; van Schaik, André; Barton, Matthew; Morley, John W

    2014-01-01

    The lifespan of an acute brain slice is approximately 6-12 hours, limiting potential experimentation time. We have designed a new recovery incubation system capable of extending their lifespan to more than 36 hours. This system controls the temperature of the incubated artificial cerebral spinal fluid (aCSF) while continuously passing the fluid through a UVC filtration system and simultaneously monitoring temperature and pH. The combination of controlled temperature and UVC filtering maintains bacteria levels in the lag phase and leads to the dramatic extension of the brain slice lifespan. Brain slice viability was validated through electrophysiological recordings as well as live/dead cell assays. This system benefits researchers by monitoring incubation conditions and standardizing this artificial environment. It further provides viable tissue for two experimental days, reducing the time spent preparing brain slices and the number of animals required for research. PMID:24930889

  8. Alcohol-Related Brain Damage in Humans

    PubMed Central

    Erdozain, Amaia M.; Morentin, Benito; Bedford, Lynn; King, Emma; Tooth, David; Brewer, Charlotte; Wayne, Declan; Johnson, Laura; Gerdes, Henry K.; Wigmore, Peter; Callado, Luis F.; Carter, Wayne G.

    2014-01-01

    Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann’s area (BA) 9) from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE) proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in α-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in β-spectrin protein levels, and a significant increase in transmembranous α3 (catalytic) subunit of the Na+,K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of α-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic α- and β-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics. PMID:24699688

  9. Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

    NASA Astrophysics Data System (ADS)

    Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

    2015-03-01

    Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

  10. Brain protection therapy in acute cerebral infarction.

    PubMed

    Katsura, Ken-ichiro; Suda, Satoshi; Abe, Arata; Kanamaru, Takuya; Toda, Yusuke; Katayama, Yasuo

    2012-01-01

    Many drugs for cerebral infarction that were shown to be effective in animal experiments have shown negative results in human clinical trials. For this reason, a completely new approach is needed to develop brain protection therapies against cerebral infarction. Brain protection therapies can be categorized into 3 types: 1) lengthening the therapeutic time window for thrombolytic therapy, 2) reducing the side effects of thrombolytic therapy, and 3) brain protection drug therapy for patients with contraindications for thrombolytic therapy (including combination therapy). Here, we show our recent results of brain protection therapy. First, combination therapy with 2 effective drugs was tried, and time-lag administration was performed. Combination therapy was effective and lengthened the therapeutic time window. Next, a completely new approach to improve cerebral ischemic damage, namely, H2 gas inhalation therapy, was tried. This therapy was also effective, even in the ischemic core. PMID:22687352

  11. BRAIN DAMAGE IN CHILDREN, THE BIOLOGICAL AND SOCIAL ASPECTS.

    ERIC Educational Resources Information Center

    BIRCH, HERBERT G., ED.

    PAPERS AND DISCUSSION SUMMARIES ARE PRESENTED FROM A CONFERENCE ON THE BIOLOGICAL AND SOCIAL PROBLEMS OF CHILDHOOD BRAIN DAMAGE, HELD AT THE CHILDREN'S HOSPITAL OF PHILADELPHIA IN NOVEMBER 1962. A VARIETY OF DISCIPLINES IS REPRESENTED, AND THE FOLLOWING TOPICS ARE CONSIDERED--(1) "THE PROBLEM OF 'BRAIN DAMAGE' IN CHILDREN" BY HERBERT G. BIRCH, (2)…

  12. Electrophysiologic monitoring in acute brain injury.

    PubMed

    Claassen, Jan; Vespa, Paul

    2014-12-01

    To determine the optimal use and indications of electroencephalography (EEG) in critical care management of acute brain injury (ABI). An electronic literature search was conducted for articles in English describing electrophysiological monitoring in ABI from January 1990 to August 2013. A total of 165 studies were included. EEG is a useful monitor for seizure and ischemia detection. There is a well-described role for EEG in convulsive status epilepticus and cardiac arrest (CA). Data suggest EEG should be considered in all patients with ABI and unexplained and persistent altered consciousness and in comatose intensive care unit (ICU) patients without an acute primary brain condition who have an unexplained impairment of mental status. There remain uncertainties about certain technical details, e.g., the minimum duration of EEG studies, the montage, and electrodes. Data obtained from both EEG and EP studies may help estimate prognosis in ABI patients, particularly following CA and traumatic brain injury. Data supporting these recommendations is sparse, and high quality studies are needed. EEG is used to monitor and detect seizures and ischemia in ICU patients and indications for EEG are clear for certain disease states, however, uncertainty remains on other applications. PMID:25208668

  13. The Involvement of Secondary Neuronal Damage in the Development of Neuropsychiatric Disorders Following Brain Insults

    PubMed Central

    Chen, Yun; Garcia, Gregory E.; Huang, Wei; Constantini, Shlomi

    2014-01-01

    Neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people. Previous publications have demonstrated that neuropsychiatric disorders can cause histomorphological damage in particular regions of the brain. By using a clinical symptom-comparing approach, 55 neuropsychiatric signs or symptoms related usually to 14 types of acute and chronic brain insults were identified and categorized in the present study. Forty percent of the 55 neuropsychiatric signs and symptoms have been found to be commonly shared by the 14 brain insults. A meta-analysis supports existence of the same neuropsychiatric signs or symptoms in all brain insults. The results suggest that neuronal damage might be occurring in the same or similar regions or structures of the brain. Neuronal cell death, neural loss, and axonal degeneration in some parts of the brain (the limbic system, basal ganglia system, brainstem, cerebellum, and cerebral cortex) might be the histomorphological basis that is responsible for the neuropsychiatric symptom clusters. These morphological alterations may be the result of secondary neuronal damage (a cascade of progressive neural injury and neuronal cell death that is triggered by the initial insult). Secondary neuronal damage causes neuronal cell death and neural injury in not only the initial injured site but also remote brain regions. It may be a major contributor to subsequent neuropsychiatric disorders following brain insults. PMID:24653712

  14. Experience-Dependent Neural Plasticity in the Adult Damaged Brain

    ERIC Educational Resources Information Center

    Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

    2011-01-01

    Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper…

  15. Tool use disorders after left brain damage

    PubMed Central

    Baumard, Josselin; Osiurak, François; Lesourd, Mathieu; Le Gall, Didier

    2014-01-01

    In this paper we review studies that investigated tool use disorders in left-brain damaged (LBD) patients over the last 30 years. Four tasks are classically used in the field of apraxia: Pantomime of tool use, single tool use, real tool use and mechanical problem solving. Our aim was to address two issues, namely, (1) the role of mechanical knowledge in real tool use and (2) the cognitive mechanisms underlying pantomime of tool use, a task widely employed by clinicians and researchers. To do so, we extracted data from 36 papers and computed the difference between healthy subjects and LBD patients. On the whole, pantomime of tool use is the most difficult task and real tool use is the easiest one. Moreover, associations seem to appear between pantomime of tool use, real tool use and mechanical problem solving. These results suggest that the loss of mechanical knowledge is critical in LBD patients, even if all of those tasks (and particularly pantomime of tool use) might put differential demands on semantic memory and working memory. PMID:24904487

  16. Rehabilitation of damage to the visual brain.

    PubMed

    Ajina, S; Kennard, C

    2012-10-01

    Homonymous visual field loss is a common consequence of stroke and traumatic brain injury. It is associated with an adverse functional prognosis and has implications on day-to-day activities such as driving, reading, and safe navigation. Early recovery is expected in around half of cases, and may be associated with a return in V1 activity. In stable disease, recovery is unlikely beyond 3 and certainly 6 months. Rehabilitative approaches generally target three main areas, encompassing a range of techniques with variable success: visual aids aim to expand or relocate the affected visual field; eye movement training builds upon compensatory strategies to improve explorative saccades; visual field restitution aims to improve visual processing within the damaged field itself. All these approaches seem to offer modest improvements with repeated practice, with none clearly superior to the rest. However, a number of areas are demonstrating particular promise currently, including simple web-based training initiatives, and work on neuroimaging and learning. The research interest in this area is encouraging, and it is to be hoped that future trials can better untangle and control for the number of complicated confounds, so that we will be in a much better position to evaluate and select the most appropriate therapy for patients. PMID:22981268

  17. Acute and chronic administration of gold nanoparticles cause DNA damage in the cerebral cortex of adult rats.

    PubMed

    Cardoso, Eria; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rodriguez, Juan Carlos Ortiz; Benavides, Roberto; da Silva, Luciano; Andrade, Vanessa M; da Silva Paula, Marcos Marques

    2014-01-01

    The use of gold nanoparticles is increasing in medicine; however, their toxic effects remain to be elucidated. Studies show that gold nanoparticles can cross the blood-brain barrier, as well as accumulate in the brain. Therefore, this study was undertaken to better understand the effects of gold nanoparticles on rat brains. DNA damage parameters were evaluated in the cerebral cortex of adult rats submitted to acute and chronic administration of gold nanoparticles of two different diameters: 10 and 30nm. During acute administration, adult rats received a single intraperitoneal injection of either gold nanoparticles or saline solution. During chronic administration, adult rats received a daily single injection for 28 days of the same gold nanoparticles or saline solution. Twenty-four hours after either single (acute) or last injection (chronic), the rats were euthanized by decapitation, their brains removed, and the cerebral cortices isolated for evaluation of DNA damage parameters. Our study showed that acute administration of gold nanoparticles in adult rats presented higher levels of damage frequency and damage index in their DNA compared to the control group. It was also observed that gold nanoparticles of 30nm presented higher levels of damage frequency and damage index in the DNA compared to the 10nm ones. When comparing the effects of chronic administration of gold nanoparticles of 10 and 30nm, we observed that occurred significant different index and frequency damage, comparing with control group. However, there is no difference between the 10 and 30nm groups in the levels of DNA damage for both parameters of the Comet assay. Results suggest that gold nanoparticles for both sizes cause DNA damage for chronic as well as acute treatments, although a higher damage was observed for the chronic one. PMID:25847268

  18. The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain?

    PubMed

    Harper, C

    1998-02-01

    The aim of this review is to identify neuropathological changes that are directly related to the long-term use of excessive amounts of alcohol (ethanol). There is still debate as to whether alcohol per se causes brain damage. The main problem has been to identify those lesions caused by alcohol itself and those caused by other common alcohol-related factors, principally thiamin deficiency. Careful selection and classification of alcoholic cases into those with and without these complications, together with detailed quantitative neuropathological analyses, has provided us with useful data. There is brain shrinkage in uncomplicated alcoholics which can largely be accounted for by loss of white matter. Some of this damage appears to be reversible. However, alcohol-related neuronal loss has been documented in specific regions of the cerebral cortex (superior frontal association cortex), hypothalamus (supraoptic and paraventricular nuclei), and cerebellum. The data is conflicting for several regions: the hippocampus, amygdala and locus ceruleus. No change is found in the basal ganglia, nucleus basalis, or serotonergic raphe nuclei. Many of the regions that are normal in uncomplicated alcoholics are damaged in those with the Wernicke-Korsakoff syndrome. Dendritic and synaptic changes have been documented in uncomplicated alcoholics and these, together with receptor and transmitter changes, may explain functional changes and cognitive deficits that precede the more severe structural neuronal changes. The pattern of damage appears to be somewhat different and species-specific in animal models of alcohol toxicity. Pathological changes that have been found to correlate with alcohol intake include white matter loss and neuronal loss in the hypothalamus and cerebellum. PMID:9600202

  19. Acute Brain Trauma in Mice Followed By Longitudinal Two-photon Imaging

    PubMed Central

    Paveliev, Mikhail; Kislin, Mikhail; Molotkov, Dmitry; Yuryev, Mikhail; Rauvala, Heikki; Khiroug, Leonard

    2014-01-01

    Although acute brain trauma often results from head damage in different accidents and affects a substantial fraction of the population, there is no effective treatment for it yet. Limitations of currently used animal models impede understanding of the pathology mechanism. Multiphoton microscopy allows studying cells and tissues within intact animal brains longitudinally under physiological and pathological conditions. Here, we describe two models of acute brain injury studied by means of two-photon imaging of brain cell behavior under posttraumatic conditions. A selected brain region is injured with a sharp needle to produce a trauma of a controlled width and depth in the brain parenchyma. Our method uses stereotaxic prick with a syringe needle, which can be combined with simultaneous drug application. We propose that this method can be used as an advanced tool to study cellular mechanisms of pathophysiological consequences of acute trauma in mammalian brain in vivo. In this video, we combine acute brain injury with two preparations: cranial window and skull thinning. We also discuss advantages and limitations of both preparations for multisession imaging of brain regeneration after trauma. PMID:24748024

  20. Acute parotitis and hyperamylasemia following whole-brain radiation therapy

    SciTech Connect

    Cairncross, J.G.; Salmon, J.; Kim, J.H.; Posner, J.B.

    1980-04-01

    Parotitis, an infrequent, previously unreported complication of whole-brain radiation therapy, was observed in 4 patients. The acute symptoms, which include fever, dry mouth, pain, swelling, and tenderness, are accompanied by hyperamylasemia. Among 10 patients receiving whole-brain irradiation, 8 had serum amylase elevations without symptoms. Both acute parotitis and asymptomatic hyperamylasemia result from irradiation of the parotid glands.

  1. Neural Stability, Sparing, and Behavioral Recovery Following Brain Damage

    ERIC Educational Resources Information Center

    LeVere, T. E.

    1975-01-01

    The present article discusses the possibility that behavioral recovery following brain damage is not dependent on the functional reorganization of neural tissue but is rather the result of the continued normal operation of spared neural mechanisms. (Editor)

  2. Immunomodulation by poly-YE reduces organophosphate-induced brain damage.

    PubMed

    Finkelstein, Arseny; Kunis, Gilad; Berkutzki, Tamara; Ronen, Ayal; Krivoy, Amir; Yoles, Eti; Last, David; Mardor, Yael; Van Shura, Kerry; McFarland, Emylee; Capacio, Benedict A; Eisner, Claire; Gonzales, Mary; Gregorowicz, Danise; Eisenkraft, Arik; McDonough, John H; Schwartz, Michal

    2012-01-01

    Accidental organophosphate poisoning resulting from environmental or occupational exposure, as well as the deliberate use of nerve agents on the battlefield or by terrorists, remain major threats for multi-casualty events, with no effective therapies yet available. Even transient exposure to organophosphorous compounds may lead to brain damage associated with microglial activation and to long-lasting neurological and psychological deficits. Regulation of the microglial response by adaptive immunity was previously shown to reduce the consequences of acute insult to the central nervous system (CNS). Here, we tested whether an immunization-based treatment that affects the properties of T regulatory cells (Tregs) can reduce brain damage following organophosphate intoxication, as a supplement to the standard antidotal protocol. Rats were intoxicated by acute exposure to the nerve agent soman, or the organophosphate pesticide, paraoxon, and after 24 h were treated with the immunomodulator, poly-YE. A single injection of poly-YE resulted in a significant increase in neuronal survival and tissue preservation. The beneficial effect of poly-YE treatment was associated with specific recruitment of CD4(+) T cells into the brain, reduced microglial activation, and an increase in the levels of brain derived neurotrophic factor (BDNF) in the piriform cortex. These results suggest therapeutic intervention with poly-YE as an immunomodulatory supplementary approach against consequences of organophosphate-induced brain damage. PMID:21925261

  3. Childhood Aphasia and Brain Damage: Volume II, Differential Diagnosis.

    ERIC Educational Resources Information Center

    Rappaport, Sheldon R., Ed.

    Addressing itself to factors leading to the misdiagnosis of the brain damaged child and the aphasic child, the Pathway School's Second Annual Institute considered the differences between the following: the aphasic and the aphasoid child; the sensory aphasic and the deaf child; the psychotic and the psychotic aphasic child; childhood brain damage…

  4. Transgenic overexpression of neuroglobin attenuates formation of smoke-inhalation-induced oxidative DNA damage, in vivo, in the mouse brain.

    PubMed

    Lee, Heung Man; Greeley, George H; Englander, Ella W

    2011-12-15

    Acute inhalation of combustion smoke causes neurological deficits in survivors. Inhaled smoke includes carbon monoxide, noxious gases, and a hypoxic environment, which disrupt oxygenation and generate free radicals. To replicate a smoke-inhalation scenario, we developed an experimental model of acute exposure to smoke for the awake mouse/rat and detected induction of biomarkers of oxidative stress. These include inhibition of mitochondrial respiratory complexes and formation of oxidative DNA damage in the brain. DNA damage is likely to contribute to neuronal dysfunction and progression of brain injury. In the search for strategies to attenuate the smoke-initiated brain injury, we produced a transgenic mouse overexpressing the neuronal globin protein neuroglobin. Neuroglobin was neuroprotective in diverse models of ischemic/hypoxic/toxic brain injuries. Here, we report lesser inhibition of respiratory complex I and reduced formation of smoke-induced DNA damage in neuroglobin transgenic compared to wild-type mouse brain. DNA damage was assessed using the standard comet assay, as well as a modified comet assay done in conjunction with an enzyme that excises oxidized guanines that form readily under conditions of oxidative stress. Both comet assays revealed that overexpressed neuroglobin attenuates the formation of oxidative DNA damage, in vivo, in the brain. These findings suggest that elevated neuroglobin exerts neuroprotection, in part, by decreasing the impact of acute smoke inhalation on the integrity of neuronal DNA. PMID:22001746

  5. Anemia management after acute brain injury.

    PubMed

    Lelubre, Christophe; Bouzat, Pierre; Crippa, Ilaria Alice; Taccone, Fabio Silvio

    2016-01-01

    Anemia is frequent among brain-injured patients, where it has been associated with an increased risk of poor outcome. The pathophysiology of anemia in this patient population remains multifactorial; moreover, whether anemia merely reflects a higher severity of the underlying disease or is a significant determinant of the neurological recovery of such patients remains unclear. Interestingly, the effects of red blood cell transfusions (RBCT) in moderately anemic patients remain controversial; although hemoglobin levels are increased, different studies observed only a modest and inconsistent improvement in cerebral oxygenation after RBCT and raised serious concerns about the risk of increased complications. Thus, considering this "blood transfusion anemia paradox", the optimal hemoglobin level to trigger RBCT in brain-injured patients has not been defined yet; also, there is insufficient evidence to provide strong recommendations regarding which hemoglobin level to target and which associated transfusion strategy (restrictive versus liberal) to select in this patient population. We summarize in this review article the more relevant studies evaluating the effects of anemia and RBCT in patients with an acute neurological condition; also, we propose some potential strategies to optimize transfusion management in such patients. PMID:27311626

  6. Decreased myeloperoxidase expressing cells in the aged rat brain after excitotoxic damage.

    PubMed

    Campuzano, Oscar; Castillo-Ruiz, Maria del Mar; Acarin, Laia; Gonzalez, Berta; Castellano, Bernardo

    2011-09-01

    Brain aging is associated to several morphological and functional alterations that influence the evolution and outcome of CNS damage. Acute brain injury such as an excitotoxic insult induces initial tissue damage followed by associated inflammation and oxidative stress, partly attributed to neutrophil recruitment and the expression of oxidative enzymes such as myeloperoxidase (MPO), among others. However, to date, very few studies have focused on how age can influence neutrophil infiltration after acute brain damage. Therefore, to evaluate the age-dependent pattern of neutrophil cell infiltration following an excitotoxic injury, intrastriatal injection of N-methyl-d-aspartate was performed in young and aged male Wistar rats. Animals were sacrificed at different times between 12h post-lesion (hpl) to 14 days post-lesion (dpl). Cryostat sections were processed for myeloperoxidase (MPO) immunohistochemistry, and double labeling for either neuronal cells (NeuN), astrocytes (GFAP), perivascular macrophages (ED-2), or microglia/macrophages (tomato lectin histochemistry). Our observations showed that MPO + cells were observed in the injured striatum from 12 hpl (when maximum values were found) until 7 dpl, when cell density was strongly diminished. However, at all survival times analyzed, the overall density of MPO + cells was lower in the aged versus the adult injured striatum. MPO + cells were mainly identified as neutrophils (especially at 12 hpl and 1 dpl), but it should be noted that MPO + neurons and microglia/macrophages were also found. MPO + neurons were most commonly observed at 12 hpl and reduced in the aged. MPO + microglia/macrophages were the main population expressing MPO from 3 dpl, when density was also reduced in aged subjects. These results point to neutrophil infiltration as another important factor contributing to the different responses of the adult and aged brain to damage, highlighting the need of using aged animals for the study of acute age

  7. The neuropathology of alcohol-related brain damage.

    PubMed

    Harper, Clive

    2009-01-01

    Excessive alcohol use can cause structural and functional abnormalities of the brain and this has significant health, social and economic implications for most countries in the world. Even heavy social drinkers who have no specific neurological or hepatic problems show signs of regional brain damage and cognitive dysfunction. Changes are more severe and other brain regions are damaged in patients who have additional vitamin B1 (thiamine) deficiency (Wernicke-Korsakoff syndrome). Quantitative studies and improvements in neuroimaging have contributed significantly to the documentation of these changes but mechanisms underlying the damage are not understood. A human brain bank targeting alcohol cases has been established in Sydney, Australia, and tissues can be used for structural and molecular studies and to test hypotheses developed from animal models and in vivo studies. The recognition of potentially reversible changes and preventative medical approaches are important public health issues. PMID:19147798

  8. Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase

    SciTech Connect

    Read, David J.; Li Yong; Chao, Moses V.; Cavanagh, John B.; Glynn, Paul

    2010-05-15

    Single doses of organophosphorus compounds (OP) which covalently inhibit neuropathy target esterase (NTE) can induce lower-limb paralysis and distal damage in long nerve axons. Clinical signs of neuropathy are evident 3 weeks post-OP dose in humans, cats and chickens. By contrast, clinical neuropathy in mice following acute dosing with OPs or any other toxic compound has never been reported. Moreover, dosing mice with ethyloctylphosphonofluoridate (EOPF) - an extremely potent NTE inhibitor - causes a different (subacute) neurotoxicity with brain oedema. These observations have raised the possibility that mice are intrinsically resistant to neuropathies induced by acute toxic insult, but may incur brain oedema, rather than distal axonal damage, when NTE is inactivated. Here we provide the first report that hind-limb dysfunction and extensive axonal damage can occur in mice 3 weeks after acute dosing with a toxic compound, bromophenylacetylurea. Three weeks after acutely dosing mice with neuropathic OPs no clinical signs were observed, but distal lesions were present in the longest spinal sensory axons. Similar lesions were evident in undosed nestin-cre:NTEfl/fl mice in which NTE had been genetically-deleted from neural tissue. The extent of OP-induced axonal damage in mice was related to the duration of NTE inactivation and, as reported in chickens, was promoted by post-dosing with phenylmethanesulfonylfluoride. However, phenyldipentylphosphinate, another promoting compound in chickens, itself induced in mice lesions different from the neuropathic OP type. Finally, EOPF induced subacute neurotoxicity with brain oedema in both wild-type and nestin-cre:NTEfl/fl mice indicating that the molecular target for this effect is not neural NTE.

  9. Pathological display of affect in patients with depression and right frontal brain damage. An alternative mechanism.

    PubMed

    Ross, E D; Stewart, R S

    1987-03-01

    Two patients are reported with the acute onset of pathological crying following right inferior frontal brain damage. Both had severe endogenous depression and neither had pseudobulbar palsy. These and other cases argue that two organic brain diseases--one structural and the other "physiopharmacological"--may interact to produce pathological display of affect that cannot be accounted for by traditional neurological explanations. A pharmacological mechanism for the rapid amelioration of pathological affect by tricyclic medications and its possible relationship to the newly discovered descending motor systems of the brain that use norepinephrine and serotonin as neurotransmitters is offered. These cases also suggest that pathological affect is a valuable clinical indicator of an underlying major depression in some brain-injured patients. PMID:3819712

  10. Damage and repair of irradiated mammalian brain

    SciTech Connect

    Frankel, K.; Lo, E.; Phillips, M.; Fabrikant, J.; Brennan, K.; Valk, P.; Poljak, A.; Delapaz, R.; Woodruff, K.; Stanford Univ., CA . Medical Center; Brookside Hospital, San Pablo, CA )

    1989-07-01

    We have demonstrated that focal charged particle irradiation of the rabbit brain can create well-defined lesions which are observable by nuclear magnetic resonance imaging (NMR) and positron emission tomography (PET) imaging techniques. These are similar, in terms of location and characteristic NMR and PET features, to those that occur in the brain of about 10% of clinical research human subjects, who have been treated for intracranial vascular malformations with stereotactic radiosurgery. These lesions have been described radiologically as vasogenic edema of the deep white matter,'' and the injury is of variable intensity and temporal duration, can recede or progress to serious neurologic sequelae, and persist for a considerable period of time, frequently 18 mon to 3 yr. 8 refs., 6 figs.

  11. Brain perfusion in acute and chronic hyperglycemia in rats

    SciTech Connect

    Kikano, G.E.; LaManna, J.C.; Harik, S.I. )

    1989-08-01

    Recent studies show that acute and chronic hyperglycemia cause a diffuse decrease in regional cerebral blood flow and that chronic hyperglycemia decreases the brain L-glucose space. Since these changes can be caused by a decreased density of perfused brain capillaries, we used 30 adult male Wistar rats to study the effect of acute and chronic hyperglycemia on (1) the brain intravascular space using radioiodinated albumin, (2) the anatomic density of brain capillaries using alkaline phosphatase histochemistry, and (3) the fraction of brain capillaries that are perfused using the fluorescein isothiocyanate-dextran method. Our results indicate that acute and chronic hyperglycemia do not affect the brain intravascular space nor the anatomic density of brain capillaries. Also, there were no differences in capillary recruitment among normoglycemic, acutely hyperglycemic, and chronically hyperglycemic rats. These results suggest that the shrinkage of the brain L-glucose space in chronic hyperglycemia is more likely due to changes in the blood-brain barrier permeability to L-glucose.

  12. Measuring consciousness in severely damaged brains.

    PubMed

    Gosseries, Olivia; Di, Haibo; Laureys, Steven; Boly, Mélanie

    2014-01-01

    Significant advances have been made in the behavioral assessment and clinical management of disorders of consciousness (DOC). In addition, functional neuroimaging paradigms are now available to help assess consciousness levels in this challenging patient population. The success of these neuroimaging approaches as diagnostic markers is, however, intrinsically linked to understanding the relationships between consciousness and the brain. In this context, a combined theoretical approach to neuroimaging studies is needed. The promise of such theoretically based markers is illustrated by recent findings that used a perturbational approach to assess the levels of consciousness. Further research on the contents of consciousness in DOC is also needed. PMID:25002279

  13. Altered Spontaneous Brain Activity in Patients with Acute Spinal Cord Injury Revealed by Resting-State Functional MRI

    PubMed Central

    Zhu, Ling; Wu, Guangyao; Zhou, Xin; Li, Jielan; Wen, Zhi; Lin, Fuchun

    2015-01-01

    Background Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging. Methods A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity. Results Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores. Conclusion Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as

  14. Predicting aphasia type from brain damage measured with structural MRI.

    PubMed

    Yourganov, Grigori; Smith, Kimberly G; Fridriksson, Julius; Rorden, Chris

    2015-12-01

    Chronic aphasia is a common consequence of a left-hemisphere stroke. Since the early insights by Broca and Wernicke, studying the relationship between the loci of cortical damage and patterns of language impairment has been one of the concerns of aphasiology. We utilized multivariate classification in a cross-validation framework to predict the type of chronic aphasia from the spatial pattern of brain damage. Our sample consisted of 98 patients with five types of aphasia (Broca's, Wernicke's, global, conduction, and anomic), classified based on scores on the Western Aphasia Battery (WAB). Binary lesion maps were obtained from structural MRI scans (obtained at least 6 months poststroke, and within 2 days of behavioural assessment); after spatial normalization, the lesions were parcellated into a disjoint set of brain areas. The proportion of damage to the brain areas was used to classify patients' aphasia type. To create this parcellation, we relied on five brain atlases; our classifier (support vector machine - SVM) could differentiate between different kinds of aphasia using any of the five parcellations. In our sample, the best classification accuracy was obtained when using a novel parcellation that combined two previously published brain atlases, with the first atlas providing the segmentation of grey matter, and the second atlas used to segment the white matter. For each aphasia type, we computed the relative importance of different brain areas for distinguishing it from other aphasia types; our findings were consistent with previously published reports of lesion locations implicated in different types of aphasia. Overall, our results revealed that automated multivariate classification could distinguish between aphasia types based on damage to atlas-defined brain areas. PMID:26465238

  15. Clinical Relevance of Discourse Characteristics after Right Hemisphere Brain Damage

    ERIC Educational Resources Information Center

    Blake, Margaret Lehman

    2006-01-01

    Purpose: Discourse characteristics of adults with right hemisphere brain damage are similar to those reported for healthy older adults, prompting the question of whether changes are due to neurological lesions or normal aging processes. The clinical relevance of potential differences across groups was examined through ratings by speech-language…

  16. Training of Perceptual Motor Skills in Minimally Brain Damaged Children.

    ERIC Educational Resources Information Center

    Glazer, Hilda Ruth; Cox, David L.

    Twenty-five male (aged 7 years, 6 months to 10 years, 7 months) and five female (aged 9 years, 3 months to 10 years, 2 months) minimally brain damaged children were examined to determine feasibility of perceptual motor training on the pursuit rotor (which requires Ss to track a light as it revolves under a pattern on a turntable). Experimental Ss…

  17. Bilirubin and its oxidation products damage brain white matter.

    PubMed

    Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

    2014-11-01

    Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

  18. Bilirubin and its oxidation products damage brain white matter

    PubMed Central

    Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

    2014-01-01

    Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

  19. Pathogenesis of brain damage produced in sheep by Clostridium perfringens type D epsilon toxin: a review.

    PubMed

    Finnie, J W

    2003-04-01

    Microvascular endothelial damage by the epsilon toxin of Clostridium perfringens type D appears to be the fundamental cause of cerebral parenchymal injury and lesions occur in a seemingly dose- and time-dependent manner. Large doses of circulating toxin produce a severe, generalised, vasogenic cerebral oedema and an acute or peracute clinical course to death. With lower doses of toxin, or in partially immune sheep, focal necrosis, often bilaterally symmetrical, occurs in certain selectively vulnerable brain regions, which appear to become fewer as the toxin dose is reduced. These cases follow a more protracted clinical course, but death is the usual outcome. The precise pathogenesis of the focal brain damage found in subacutely intoxicated sheep is unresolved, but several possible mechanisms are discussed. PMID:15080445

  20. Neurocomputational models of the remote effects of focal brain damage.

    PubMed

    Reggia, James A

    2004-11-01

    Sudden localized brain damage, such as occurs in stroke, produces neurological deficits directly attributable to the damaged site. In addition, other clinical deficits occur due to secondary "remote" effects that functionally impair the remaining intact brain regions (e.g., due to their sudden disconnection from the damaged area), a phenomenon known as diaschisis. The underlying mechanisms of these remote effects, particularly those involving interactions between the left and right cerebral hemispheres, have proven somewhat difficult to understand in the context of current theories of hemispheric specialization. This article describes some recent neurocomputational models done in the author's research group that try to explain diaschisis qualitatively. These studies show that both specialization and diaschisis can be accounted for with a single model of hemispheric interactions. Further, the results suggest that left-right subcortical influences may be much more important in influencing hemispheric specialization than is generally recognized. PMID:15564108

  1. Hyperschematia after right brain damage: a meaningful entity?

    PubMed

    Rode, Gilles; Ronchi, Roberta; Revol, Patrice; Rossetti, Yves; Jacquin-Courtois, Sophie; Rossi, Irene; Vallar, Giuseppe

    2014-01-01

    In recent years we reported three right-brain-damaged patients, who exhibited a left-sided disprortionate expansion of drawings, both by copying and from memory, contralateral to the side of the hemispheric lesion (Neurology, 67: 1801, 2006, Neurocase 14: 369, 2008). We proposed the term "hyperschematia" for such an expansion, with reference to an interpretation in terms of a lateral leftward distortion of the representation of extra-personal space, with a leftward anisometric expansion (relaxation) of the spatial medium. The symptom-complex shown by right-brain-damaged patients with "hyperschematia" includes: (1) a disproportionate leftward expansion of drawings (with possible addition of details), by copy and from memory (also in clay modeling, in one patient); (2) an overestimation of left lateral extent, when a leftward movement is required, associated in some patients with a perceptual underestimation; (3) unawareness of the disorder; (4) no unilateral spatial neglect. In most right-brain-damaged patients, left "hyperschematia" involves extra-personal space. In one patient the deficit was confined to a body part (left half-face: personal "hyperschematia"). The neural underpinnings of the disorder include damage to the fronto-temporo-parietal cortices, and subcortical structures in the right cerebral hemisphere, in the vascular territory of the middle cerebral artery. Here, four novel additional patients are reported. Finally, "hypeschematia" is reconsidered, in its clinical components, the underlying pathological mechanisms, as well as its neural underpinnings. PMID:24478674

  2. Hyperschematia after right brain damage: a meaningful entity?

    PubMed Central

    Rode, Gilles; Ronchi, Roberta; Revol, Patrice; Rossetti, Yves; Jacquin-Courtois, Sophie; Rossi, Irene; Vallar, Giuseppe

    2014-01-01

    In recent years we reported three right-brain-damaged patients, who exhibited a left-sided disprortionate expansion of drawings, both by copying and from memory, contralateral to the side of the hemispheric lesion (Neurology, 67: 1801, 2006, Neurocase 14: 369, 2008). We proposed the term “hyperschematia” for such an expansion, with reference to an interpretation in terms of a lateral leftward distortion of the representation of extra-personal space, with a leftward anisometric expansion (relaxation) of the spatial medium. The symptom-complex shown by right-brain-damaged patients with “hyperschematia” includes: (1) a disproportionate leftward expansion of drawings (with possible addition of details), by copy and from memory (also in clay modeling, in one patient); (2) an overestimation of left lateral extent, when a leftward movement is required, associated in some patients with a perceptual underestimation; (3) unawareness of the disorder; (4) no unilateral spatial neglect. In most right-brain-damaged patients, left “hyperschematia” involves extra-personal space. In one patient the deficit was confined to a body part (left half-face: personal “hyperschematia”). The neural underpinnings of the disorder include damage to the fronto-temporo-parietal cortices, and subcortical structures in the right cerebral hemisphere, in the vascular territory of the middle cerebral artery. Here, four novel additional patients are reported. Finally, “hypeschematia” is reconsidered, in its clinical components, the underlying pathological mechanisms, as well as its neural underpinnings. PMID:24478674

  3. Cortical activity evoked by an acute painful tissue-damaging stimulus in healthy adult volunteers

    PubMed Central

    Williams, Gemma; Lee, Amy; Meek, Judith; Slater, Rebeccah; Olhede, Sofia; Fitzgerald, Maria

    2013-01-01

    Everyday painful experiences are usually single events accompanied by tissue damage, and yet most experimental studies of cutaneous nociceptive processing in the brain use repeated laser, thermal, or electrical stimulations that do not damage the skin. In this study the nociceptive activity in the brain evoked by tissue-damaging skin lance was analyzed with electroencephalography (EEG) in 20 healthy adult volunteers (13 men and 7 women) aged 21–40 yr. Time-frequency analysis of the evoked activity revealed a distinct late event-related vertex potential (lance event-related potential, LERP) at 100–300 ms consisting of a phase-locked energy increase between 1 and 20 Hz (delta-beta bands). A pairwise comparison between lance and sham control stimulation also revealed a period of ultralate stronger desynchronization after lance in the delta band (1–5 Hz). Skin application of mustard oil before lancing, which sensitizes a subpopulation of nociceptors expressing the cation channel TRPA1, did not affect the ultralate desynchronization but reduced the phase-locked energy increase in delta and beta bands, suggesting a central interaction between different modalities of nociceptive inputs. Verbal descriptor screening of individual pain experience revealed that lance pain is predominantly due to Aδ fiber activation, but when individuals describe lances as C fiber mediated, an ultralate delta band event-related desynchronization occurs in the brain-evoked activity. We conclude that pain evoked by acute tissue damage is associated with distinct Aδ and C fiber-mediated patterns of synchronization and desynchronization of EEG oscillations in the brain. PMID:23427303

  4. L-tyrosine induces DNA damage in brain and blood of rats.

    PubMed

    De Prá, Samira D T; Ferreira, Gabriela K; Carvalho-Silva, Milena; Vieira, Júlia S; Scaini, Giselli; Leffa, Daniela D; Fagundes, Gabriela E; Bristot, Bruno N; Borges, Gabriela D; Ferreira, Gustavo C; Schuck, Patrícia F; Andrade, Vanessa M; Streck, Emilio L

    2014-01-01

    Mutations in the tyrosine aminotransferase gene have been identified to cause tyrosinemia type II which is inherited in an autosomal recessive manner. Studies have demonstrated that an excessive production of ROS can lead to reactions with macromolecules, such as DNA, lipids, and proteins. Considering that the L-tyrosine may promote oxidative stress, the main objective of this study was to investigate the in vivo effects of L-tyrosine on DNA damage determined by the alkaline comet assay, in brain and blood of rats. In our acute protocol, Wistar rats (30 days old) were killed 1 h after a single intraperitoneal L-tyrosine injection (500 mg/kg) or saline. For chronic administration, the animals received two subcutaneous injections of L-tyrosine (500 mg/kg, 12-h intervals) or saline administered for 24 days starting at postnatal day (PD) 7 (last injection at PD 31), 12 h after the last injection, the animals were killed by decapitation. We observed that acute administration of L-tyrosine increased DNA damage frequency and damage index in cerebral cortex and blood when compared to control group. Moreover, we observed that chronic administration of L-tyrosine increased DNA damage frequency and damage index in hippocampus, striatum, cerebral cortex and blood when compared to control group. In conclusion, the present work demonstrated that DNA damage can be encountered in brain from animal models of hypertyrosinemia, DNA alterations may represent a further means to explain neurological dysfunction in this inherited metabolic disorder and to reinforce the role of oxidative stress in the pathophysiology of tyrosinemia type II. PMID:24297753

  5. Accumulation of oxidatively generated DNA damage in the brain: a mechanism of neurotoxicity.

    PubMed

    Chen, Liuji; Lee, Heung M; Greeley, George H; Englander, Ella W

    2007-02-01

    Unrepaired or erroneously repaired DNA lesions drive genomic instability and contribute to cellular and organ decline. Since delayed neuropathologies are common in survivors of smoke inhalation injuries, we asked whether the integrity of brain DNA might be compromised by acute exposure to combustion smoke. Although many studies demonstrate that the brain is equipped to repair oxidatively damaged DNA, to date, the capacity for accurate DNA repair under conditions of disrupted oxygenation and oxidative stress has not been defined. We show that DNA adducts detectable by their ability to block PCR amplification form in the rat hippocampus after acute exposure to smoke. To identify the different types of adducts and to dissect their temporal formation and repair profiles in vivo in the brain, we used DNA-modifying enzymes to convert specific adducts into strand breaks prior to PCR amplification. Using this strategy, we detected formation of oxidative DNA adducts early on after smoke inhalation, while mismatched bases emerged at the later recovery times, potentially due to an erroneous DNA repair process. Erroneous repair can be mutagenic and because the initial smoke-induced oxidative damage to DNA is extensive, compromised fidelity of DNA repair may underlie neurotoxicity and contribute to delayed death of hippocampal neurons. PMID:17210451

  6. Influence of Age on Brain Edema Formation, Secondary Brain Damage and Inflammatory Response after Brain Trauma in Mice

    PubMed Central

    Timaru-Kast, Ralph; Luh, Clara; Gotthardt, Philipp; Huang, Changsheng; Schäfer, Michael K.; Engelhard, Kristin; Thal, Serge C.

    2012-01-01

    After traumatic brain injury (TBI) elderly patients suffer from higher mortality rate and worse functional outcome compared to young patients. However, experimental TBI research is primarily performed in young animals. Aim of the present study was to clarify whether age affects functional outcome, neuroinflammation and secondary brain damage after brain trauma in mice. Young (2 months) and old (21 months) male C57Bl6N mice were anesthetized and subjected to a controlled cortical impact injury (CCI) on the right parietal cortex. Animals of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the end of the observation periods, contusion volume, brain water content, neurologic function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory cytokine expression in brain and lung, blood differential cell count) were determined. Old animals showed worse neurological function 72 h after CCI and a high mortality rate (19.2%) compared to young (0%). This did not correlate with histopathological damage, as contusion volumes were equal in both age groups. Although a more pronounced brain edema formation was detected in old mice 24 hours after TBI, lack of correlation between brain water content and neurological deficit indicated that brain edema formation is not solely responsible for age-dependent differences in neurological outcome. Brains of old naïve mice were about 8% smaller compared to young naïve brains, suggesting age-related brain atrophy with possible decline in plasticity. Onset of cerebral inflammation started earlier and primarily ipsilateral to damage in old mice, whereas in young mice inflammation was delayed and present in both hemispheres with a characteristic T cell migration pattern. Pulmonary interleukin 1β expression was up-regulated after cerebral injury only in young, not aged mice. The results therefore indicate that old animals are prone to functional deficits and strong ipsilateral cerebral inflammation

  7. [Organ damage and cardiorenal syndrome in acute heart failure].

    PubMed

    Casado Cerrada, Jesús; Pérez Calvo, Juan Ignacio

    2014-03-01

    Heart failure is a complex syndrome that affects almost all organs and systems of the body. Signs and symptoms of organ dysfunction, in particular kidney dysfunction, may be accentuated or become evident for the first time during acute decompensation of heart failure. Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney, regardless of which of the two organs may have suffered the initial damage and regardless also of their previous functional status. Research into the mechanisms regulating the complex relationship between the two organs is prompting the search for new biomarkers to help physicians detect renal damage in subclinical stages. Hence, a preventive approach to renal dysfunction may be adopted in the clinical setting in the near future. This article provides a general overview of cardiorenal syndrome and an update of the physiopathological mechanisms involved. Special emphasis is placed on the role of visceral congestion as an emergent mechanism in this syndrome. PMID:24930080

  8. Acute blast injury reduces brain abeta in two rodent species.

    PubMed

    De Gasperi, Rita; Gama Sosa, Miguel A; Kim, Soong Ho; Steele, John W; Shaughness, Michael C; Maudlin-Jeronimo, Eric; Hall, Aaron A; Dekosky, Steven T; McCarron, Richard M; Nambiar, Madhusoodana P; Gandy, Sam; Ahlers, Stephen T; Elder, Gregory A

    2012-01-01

    Blast-induced traumatic brain injury (TBI) has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI). The β-amyloid (Aβ) peptide associated with the development of Alzheimer's disease is elevated acutely following TBI in humans as well as in experimental animal models of nbTBI. We examined levels of brain Aβ following experimental blast injury using enzyme-linked immunosorbent assays for Aβ 40 and 42. In both rat and mouse models of blast injury, rather than being increased, endogenous rodent brain Aβ levels were decreased acutely following injury. Levels of the amyloid precursor protein (APP) were increased following blast exposure although there was no evidence of axonal pathology based on APP immunohistochemical staining. Unlike the findings in nbTBI animal models, levels of the β-secretase, β-site APP cleaving enzyme 1, and the γ-secretase component presenilin-1 were unchanged following blast exposure. These studies have implications for understanding the nature of blast injury to the brain. They also suggest that strategies aimed at lowering Aβ production may not be effective for treating acute blast injury to the brain. PMID:23267342

  9. Nonverbal dialogue with the brain-damaged elderly.

    PubMed

    Fischer, T; Fischer, R

    1977-01-01

    In a population of twelve 63- to 89-year-old residents of a nursing home, rank-ordered scores of copying errors on the revised Benton visual retention test were found to be significantly correlated with the rotational shifts in the Minnesota percepto-diagnostic test. Residents on both ends of the continuum of brain damage could paint interesting, expressive and/or original pictures, in spite of the fact that the first eight residents were on psychotropic medication and the last four were occasionally handicapped by constructional apraxia. Ten adjudicators ranked pairs of figure drawings for each resident in decreasing order of 'aesthetic pleasingness' and 'originality'. Degree of brain damage was found unrelated to both measures. Interadjudicator agreement was stronger on 'originality' than on 'aesthetic pleasingness'. Some of the beneficial and provocative results of art therapy with the elderly are elaborated ans a plea made for accepting their observed creative performance as part of the realm of legitimate art. PMID:923239

  10. Brain Damage and the Moral Significance of Consciousness

    PubMed Central

    kahane, Guy

    2009-01-01

    Neuroimaging studies of brain-damaged patients diagnosed as in the vegetative state suggest that the patients might be conscious. This might seem to raise no new ethical questions given that in related disputes both sides agree that evidence for consciousness gives strong reason to preserve life. We question this assumption. We clarify the widely held but obscure principle that consciousness is morally significant. It is hard to apply this principle to difficult cases given that philosophers of mind distinguish between a range of notions of consciousness and that is unclear which of these is assumed by the principle. We suggest that the morally relevant notion is that of phenomenal consciousness and then use our analysis to interpret cases of brain damage. We argue that enjoyment of consciousness might actually give stronger moral reasons not to preserve a patient's life and, indeed, that these might be stronger when patients retain significant cognitive function. PMID:19193694

  11. Blood-brain barrier in acute liver failure

    PubMed Central

    Nguyen, Justin H.

    2011-01-01

    Brain edema remains a challenging obstacle in the management of acute liver failure (ALF). Cytotoxic mechanisms associated with brain edema have been well recognized, but evidence for vasogenic mechanisms in the pathogenesis of brain edema in ALF has been lacking. Recent reports have not only shown a role of matrix metalloproteinase-9 in the pathogenesis of brain edema in experimental ALF but have also found significant alterations in the tight junction elements including occludin and claudin-5, suggesting a vasogenic injury in the blood-brain barrier (BBB) integrity. This article reviews and explores the role of the paracellular tight junction proteins in the increased selective BBB permeability that leads to brain edema in ALF. PMID:22100566

  12. Study Suggests Brain Damage in 40 Percent of Ex-NFL Players

    MedlinePlus

    ... gov/medlineplus/news/fullstory_158243.html Study Suggests Brain Damage in 40 Percent of Ex-NFL Players ... National Football League players may suffer from traumatic brain injuries, a small study suggests. Brain scans of ...

  13. [Pharmacological neuroprotection against brain damage in ischemiai/reperfusion experiment].

    PubMed

    Petrov, V I; Ponomarev, É A; Maskin, S S; Strepetov, N N

    2011-01-01

    Experiment carried out on laboratory animals (rats) were aimed at comparative evaluation of the effect of several neuroprotective drugs under the conditions of model brain ischemia-reperfusion. The experimental methods included staining of brain tissue sections by hematoxiline-eosine, Nissl staining, and expression of NOS1, NOS3, TRAIL by imunnohistological means. The intensity of damage in various parts of brain and the nature of apoptosis without neuroprotection and with popular neuroprotectors (cytoflavin, actovegin, mexidol) and a test drug at the stage ofpreclinical trial (AKF-90-7) were evaluated. Characteristic cytotoxic (coagulative pycnomorphic and colliquative necrosis of neurons) and vascular (hemostasia, erythropedesis) changes were revealed. The neuroprotective effectof drugs decreases in the following order: AKF-90-7 > cytoflavin > actovegin > mexidol. PMID:22232908

  14. Alcohol-induced vascular damage of brain can be ameliorated by administration of magnesium

    SciTech Connect

    Altura, B.M.; Altura, B.T.; Gebrewold, A.

    1986-03-01

    Long-term as well as short-term administration of alcohol can cause neuronal and vascular damage in the brain. The authors have reported that acute administration of ethyl alcohol (ALC), either directly into the rat brain, IV or locally, can produce concentration-dependent spasms of cerebral arterioles, venules, arteries and veins followed by irreversible rupture of capillaries and veins followed by irreversible rupture of capillaries and venules. Several experiments have suggested that administration of magnesium ions (Mg/sup 2 +/) can modify vascular tone. Whether Mg/sup 2 +/ can exert direct actions on the intact cerebral microcirculation is not known. Using the above intact rat brain model, and TV-image intensification, the authors determine whether administration of Mg/sup 2 +/ : 1) exerts actions on cerebral (coritical) arterioles (A) and venules (V) (12-40..mu..m); 2) directly into the brain alters arterial blood pressure (BP); and 3) could ameliorate or prevent some of the detrimental cerebral-vascular actions ALC exerts in the brain. The data show that infusion of Mg/sup 7 +/ : 1) into the rat brain result in a rapid dose-dependent lowering of systolic and diastolic and BP; 2) IV or intra-arterially (IA) produces dose-dependent vaso-dilation of A and V; 3) IV or IA prevents spasms and rupture of A and V induced by 10% ALC. The cerebral vascular actions of Mg/sup 2 +/ may prove to be useful in treatment and prevention of ALC-induced brain damage.

  15. Brain and Muscle Redox Imbalance Elicited by Acute Ethylmalonic Acid Administration

    PubMed Central

    Schuck, Patrícia Fernanda; Milanez, Ana Paula; Felisberto, Francine; Galant, Leticia Selinger; Machado, Jéssica Luca; Furlanetto, Camila Brulezi; Petronilho, Fabricia; Dal-Pizzol, Felipe; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-01-01

    Ethylmalonic acid (EMA) accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections) and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2’,7’-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers), and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy. PMID:26010931

  16. Brain and muscle redox imbalance elicited by acute ethylmalonic acid administration.

    PubMed

    Schuck, Patrícia Fernanda; Milanez, Ana Paula; Felisberto, Francine; Galant, Leticia Selinger; Machado, Jéssica Luca; Furlanetto, Camila Brulezi; Petronilho, Fabricia; Dal-Pizzol, Felipe; Streck, Emilio Luiz; Ferreira, Gustavo Costa

    2015-01-01

    Ethylmalonic acid (EMA) accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections) and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2',7'-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers), and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy. PMID:26010931

  17. Anosognosia for Motor Impairment Following Left Brain Damage

    PubMed Central

    Cocchini, Gianna; Beschin, Nicoletta; Cameron, Annette; Fotopoulou, Aikaterini; Sala, Sergio Della

    2009-01-01

    Anosognosia for motor impairment has been linked to lesions of the right hemisphere. However, left hemisphere damaged patients have often been excluded from investigation because of their associated language deficits. In this study we assessed anosognosia for motor disorders in a group of left hemisphere damaged patients using 2 tools that assess the presence of unawareness—a structured interview that is a common method of assessment of anosognosia in clinical settings, and a new tool, the Visual-Analogue Test for Anosognosia for Motor Impairment (VATAm; Della Sala, Cocchini, Beschin, & Cameron, in press). The structured interview relies heavily on language and enquires about general motor ability whereas the VATAm is less dependent on language abilities and enquires about specific motor tasks. Results suggest that the frequency of anosognosia in left brain damaged patients may have been underestimated due to methodological reasons, and that anosognosia for motor impairment can also be associated with lesions of the left hemisphere. PMID:19254095

  18. Endothelial Glycocalyx Damage Is Associated with Leptospirosis Acute Kidney Injury

    PubMed Central

    Libório, Alexandre Braga; Braz, Marcelo Boecker Munoz; Seguro, Antonio Carlos; Meneses, Gdayllon C.; Neves, Fernanda Macedo de Oliveira; Pedrosa, Danielle Carvalho; Cavalcanti, Luciano Pamplona de Góes; Martins, Alice Maria Costa; Daher, Elizabeth de Francesco

    2015-01-01

    Leptospirosis is a common disease in tropical countries, and the kidney is one of the main target organs. Membrane proteins of Leptospira are capable of causing endothelial damage in vitro, but there have been no studies in humans evaluating endothelial glycocalyx damage and its correlation with acute kidney injury (AKI). We performed a cohort study in an outbreak of leptospirosis among military personnel. AKI was diagnosed in 14 of 46 (30.4%) patients. Leptospirosis was associated with higher levels of intercellular adhesion molecule-1 (ICAM-1; 483.1 ± 31.7 versus 234.9 ± 24.4 mg/L, P < 0.001) and syndecan-1 (73.7 ± 15.9 versus 21.2 ± 7.9 ng/mL, P < 0.001) compared with exposed controls. Patients with leptospirosis-associated AKI had increased level of syndecan-1 (112.1 ± 45.4 versus 41.5 ± 11.7 ng/mL, P = 0.021) and ICAM-1 (576.9 ± 70.4 versus 434.9 ± 35.3, P = 0.034) compared with leptospirosis patients with no AKI. Association was verified between syndecan-1 and ICAM-1 with serum creatinine elevation and neutrophil gelatinase-associated lipocalin (NGAL) levels. This association remained even after multivariate analysis including other AKI-associated characteristics. Endothelial injury biomarkers are associated with leptospirosis-associated renal damage. PMID:25624405

  19. [Definition and biomarkers of acute renal damage: new perspectives].

    PubMed

    Seijas, M; Baccino, C; Nin, N; Lorente, J A

    2014-01-01

    The RIFLE and AKIN criteria have definitely help out to draw attention to the relationship between a deterioration of renal function that produces a small increase in serum creatinine and a worse outcome. However, the specific clinical utility of using these criteria remains to be well-defined. It is believed that the main use of these criteria is for the design of epidemiological studies and clinical trials to define inclusion criteria and objectives of an intervention. AKI adopting term, re-summoning former ARF terminology, it is appropriate to describe the clinical condition characterized by damage to kidney, in the same way as the term is used to describe acute lung damage where the lung injury situation still has not increased to a situation of organ failure (dysfunction). The serum and urine biomarkers (creatinine, urea, and diuresis) currently in use are not sensitive or specific for detecting kidney damage, limiting treatment options and potentially compromising the outcome. New biomarkers are being studied in order to diagnose an earlier and more specific AKI, with the potential to change the definition criteria of AKI with different stages, currently based in diuresis and serum creatinine. PMID:24880198

  20. Hyponatraemia and death or permanent brain damage in healthy children.

    PubMed Central

    Arieff, A. I.; Ayus, J. C.; Fraser, C. L.

    1992-01-01

    OBJECTIVE--To determine if hyponatraemia causes permanent brain damage in healthy children and, if so, if the disorder is primarily limited to females, as occurs in adults. DESIGN--Prospective clinical case study of 16 affected children and a review of 24,412 consecutive surgical admissions at one medical centre. PATIENTS--16 children (nine male, seven female; age 7 (SD 5) years) with generally minor illness were electively hospitalised for primary care. Consultation was obtained for the combination of respiratory arrest with symptomatic hyponatraemia (serum sodium concentration less than or equal to 128 mmol/l). MAIN OUTCOME MEASURES--Presence, gender distribution, and classification of permanent brain damage in children with symptomatic hyponatraemia in both prospective and retrospective studies. RESULTS--By retrospective evaluation the incidence of postoperative hyponatraemia among 24,412 patients was 0.34% (83 cases) and mortality of those afflicted was 8.4% (seven deaths). In the prospective population the serum sodium concentration on admission was 138 (SD 2) mmol/l. From three to 120 inpatient hours after hypotonic fluid administration patients developed progressive lethargy, headache, nausea, and emesis with an explosive onset of respiratory arrest. At the time serum sodium concentration was 115 (7) mmol/l and arterial oxygen tension 6 (1.5) kPa. The hyponatraemia was primarily caused by extrarenal loss of electrolytes with replacement by hypotonic fluids. All 16 patients had cerebral oedema detected at either radiological or postmortem examination. All 15 patients not treated for their hyponatraemia in a timely manner either died or were permanently incapacitated by brain damage. The only patient treated in a timely manner was alive but mentally retarded. CONCLUSIONS--Symptomatic hyponatraemia can result in high morbidity in children of both genders, which is due in large part to inadequate brain adaptation and lack of timely treatment. PMID:1515791

  1. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats

    PubMed Central

    Zhao, Jinbing; Chen, Zhi; Xi, Guohua; Keep, Richard F.; Hua, Ya

    2014-01-01

    Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron level in brain may relate to hydrocephalus development after intracranial hemorrhage. However, the role of iron in the development of post-traumatic hydrocephalus is still unclear. This study was to determine whether or not iron has a role in hydrocephalus development after TBI. TBI was induced by lateral fluid-percussion in male Sprague-Dawley rats. Some rats had intraventricular injection of iron. Acute hydrocephalus was measured by magnetic resonance T2-weighted imaging and brain hemorrhage was determined by T2* gradient-echo sequence imaging and brain hemoglobin levels. The effect of deferoxamine on TBI-induced hydrocephalus was examined. TBI resulted in acute hydrocephalus at 24 hours (lateral ventricle volume: 24.1±3.0 vs. 9.9±0.2 mm3 in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm3 in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI. PMID:24935175

  2. Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage.

    PubMed

    Puentes, Sandra; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Yoshimoto, Yuhei; Mikuni, Masahiko; Imai, Hideaki; Ishizaki, Yasuki

    2012-08-21

    Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia. PMID:22771710

  3. Induction of acute brain injury in mice by irradiation with high-LET charged particles

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Zhang, Hong

    The present study was performed to evaluate the induction of acute brain injury in mice after 235 Mev/u carbon ion irradiation. In our study, young outbred Kunming mice were divided into four treatment groups according to the penetration depth of carbon ions. Animals were irradiated with a sublethal dose of carbon ion beams prior to the Bragg curve. An experiment was performed to evaluate the acute alterations in histology, DNA double-strand breaks (DNA DSBs) as well as p53and Bax expression in the brain 96 h post-irradiation. The results demonstrated that various histopathological changes, a significant number of DNA DSBs and elevated p53 and Bax protein expression were induced in the brain following exposure to carbon ions. This was particularly true for mice irradiated with ions having a 9.1 cm-pentration depth, indicating that carbon ions can led to deleterious lesions in the brain of young animals within 96 h. Moreover, there was a remarkable increase in DNA DSBs and in the severity of histopathological changes as the penetration depths of ions increased, which may be associated with the complex track structure of heavy ions. These data reveal that carbon ions can promote serious neuropathological degeneration in the cerebral cortex of young mice. Given that damaged neurons cannot regenerate, these findings warrant further investigation of the adverse effects of the space radiation and the passage of a therapeutic heavy ion beam in the plateau region of the Bragg curve through healthy brain tissue.

  4. Restoration of function after brain damage using a neural prosthesis

    PubMed Central

    Guggenmos, David J.; Azin, Meysam; Barbay, Scott; Mahnken, Jonathan D.; Dunham, Caleb; Mohseni, Pedram; Nudo, Randolph J.

    2013-01-01

    Neural interface systems are becoming increasingly more feasible for brain repair strategies. This paper tests the hypothesis that recovery after brain injury can be facilitated by a neural prosthesis serving as a communication link between distant locations in the cerebral cortex. The primary motor area in the cerebral cortex was injured in a rat model of focal brain injury, disrupting communication between motor and somatosensory areas and resulting in impaired reaching and grasping abilities. After implantation of microelectrodes in cerebral cortex, a neural prosthesis discriminated action potentials (spikes) in premotor cortex that triggered electrical stimulation in somatosensory cortex continuously over subsequent weeks. Within 1 wk, while receiving spike-triggered stimulation, rats showed substantially improved reaching and grasping functions that were indistinguishable from prelesion levels by 2 wk. Post hoc analysis of the spikes evoked by the stimulation provides compelling evidence that the neural prosthesis enhanced functional connectivity between the two target areas. This proof-of-concept study demonstrates that neural interface systems can be used effectively to bridge damaged neural pathways functionally and promote recovery after brain injury. PMID:24324155

  5. Areas of Brain Damage Underlying Increased Reports of Behavioral Disinhibition.

    PubMed

    Knutson, Kristine M; Dal Monte, Olga; Schintu, Selene; Wassermann, Eric M; Raymont, Vanessa; Grafman, Jordan; Krueger, Frank

    2015-01-01

    Disinhibition, the inability to inhibit inappropriate behavior, is seen in frontal-temporal degeneration, Alzheimer's disease, and stroke. Behavioral disinhibition leads to social and emotional impairments, including impulsive behavior and disregard for social conventions. The authors investigated the effects of lesions on behavioral disinhibition measured by the Neuropsychiatric Inventory in 177 veterans with traumatic brain injuries. The authors performed voxel-based lesion-symptom mapping using MEDx. Damage in the frontal and temporal lobes, gyrus rectus, and insula was associated with greater behavioral disinhibition, providing further evidence of the frontal lobe's involvement in behavioral inhibition and suggesting that these regions are necessary to inhibit improper behavior. PMID:25959040

  6. Interdependence of priming performance and brain-damage.

    PubMed

    Markowitsch, H J; Härting, C

    1996-04-01

    Basically, two hospitalized patient groups were a variety of different learning situations which are subdividable into conventional and experimental tests and which covered so-called implicit and explicit memory tests. Furthermore, data from other cases were used for comparison and for support of the proposed hypotheses. The main sample consisted of 15 focal brain-damaged patients (group N) and 15 patients after surgical interventions outside the nervous system (group O). Aside from affective behavior and intelligence, memory tests were used. These included the WMS-r, picture and face recognition tests, the Tower of Hanoi, the Wisconsin Card Sorting Test (WCST), a Concept Comprehensive Test, and word and picture priming tests. A number of significant differences were obtained between the two age, sex, and education matched groups. Above all, intelligence and memory were reduced in parallel in the cortically damaged compared to the well-matched orthopedic group, while attention and concentration did not differ. Even performance in tests such as the Tower of Hanoi and the WCST differed, perhaps explainable by the proportion of frontal lobe damaged patients and the overall decrease in intelligence in group N. Verbal priming was found to a similar degree in both groups. On the other hand, priming of incomplete pictures was significantly poorer in group N than in group O; furthermore, results from MQ- and IQ-based group splitting (independent of their previous N or O affiliations) suggested a direct relation between mnemonic and other cognitive abilities and success in priming. As perceptual, but not verbal priming differed between groups, and explanation of group N results, based primarily on explicit memory processing, is unlikely. It is concluded that non-brain damaged patients in general are able to use a wider repertoire of information encoding strategies which at least in part is memory and intelligence correlated. PMID:8734566

  7. Targeted Lipid Profiling Discovers Plasma Biomarkers of Acute Brain Injury

    PubMed Central

    Sheth, Sunil A.; Iavarone, Anthony T.; Liebeskind, David S.; Won, Seok Joon; Swanson, Raymond A.

    2015-01-01

    Prior efforts to identify a blood biomarker of brain injury have relied almost exclusively on proteins; however their low levels at early time points and poor correlation with injury severity have been limiting. Lipids, on the other hand, are the most abundant molecules in the brain and readily cross the blood-brain barrier. We previously showed that certain sphingolipid (SL) species are highly specific to the brain. Here we examined the feasibility of using SLs as biomarkers for acute brain injury. A rat model of traumatic brain injury (TBI) and a mouse model of stroke were used to identify candidate SL species though our mass-spectrometry based lipid profiling approach. Plasma samples collected after TBI in the rat showed large increases in many circulating SLs following injury, and larger lesions produced proportionately larger increases. Plasma samples collected 24 hours after stroke in mice similarly revealed a large increase in many SLs. We constructed an SL score (sum of the two SL species showing the largest relative increases in the mouse stroke model) and then evaluated the diagnostic value of this score on a small sample of patients (n = 14) who presented with acute stroke symptoms. Patients with true stroke had significantly higher SL scores than patients found to have non-stroke causes of their symptoms. The SL score correlated with the volume of ischemic brain tissue. These results demonstrate the feasibility of using lipid biomarkers to diagnose brain injury. Future studies will be needed to further characterize the diagnostic utility of this approach and to transition to an assay method applicable to clinical settings. PMID:26076478

  8. Brain damage from sup 125 I brachytherapy evaluated by MR imaging, a blood-brain barrier tracer, and light and electron microscopy in a rat model

    SciTech Connect

    Bernstein, M.; Marotta, T.; Stewart, P.; Glen, J.; Resch, L.; Henkelman, M. )

    1990-10-01

    Changes in normal rat brain were studied acutely, and at 3, 6, 9, and 12 months following interstitial brachytherapy with high-activity {sup 125}I seeds. An 80-Gy radiation dose was administered to an area with a 5.5-mm radius. Effects were measured with magnetic resonance (MR) imaging (with and without gadolinium enhancement), leakage of horseradish peroxidase (HRP), electron microscopy, and light microscopy. Significant histological damage was seen at radiation doses above 295 Gy, and breakdown of the blood-brain barrier was observed only in tissue receiving a dose of 165 Gy or greater. Blood-brain barrier breakdown increased up to the 6-month time point, and thereafter appeared to stabilize or decrease. The area of blood-brain barrier disruption indicated by gadolinium-enhanced MR imaging was greater than that indicated by leakage of HRP.

  9. Reversing brain damage in former NFL players: implications for traumatic brain injury and substance abuse rehabilitation.

    PubMed

    Amen, Daniel G; Wu, Joseph C; Taylor, Derek; Willeumier, Kristen

    2011-01-01

    Brain injuries are common in professional American football players. Finding effective rehabilitation strategies can have widespread implications not only for retired players but also for patients with traumatic brain injury and substance abuse problems. An open label pragmatic clinical intervention was conducted in an outpatient neuropsychiatric clinic with 30 retired NFL players who demonstrated brain damage and cognitive impairment. The study included weight loss (if appropriate); fish oil (5.6 grams a day); a high-potency multiple vitamin; and a formulated brain enhancement supplement that included nutrients to enhance blood flow (ginkgo and vinpocetine), acetylcholine (acetyl-l-carnitine and huperzine A), and antioxidant activity (alpha-lipoic acid and n-acetyl-cysteine). The trial average was six months. Outcome measures were Microcog Assessment of Cognitive Functioning and brain SPECT imaging. In the retest situation, corrected for practice effect, there were statistically significant increases in scores of attention, memory, reasoning, information processing speed and accuracy on the Microcog. The brain SPECT scans, as a group, showed increased brain perfusion, especially in the prefrontal cortex, parietal lobes, occipital lobes, anterior cingulate gyrus and cerebellum. This study demonstrates that cognitive and cerebral blood flow improvements are possible in this group with multiple interventions. PMID:21615001

  10. Experimental models of perinatal hypoxic-ischemic brain damage.

    PubMed

    Vannucci, R C

    1993-01-01

    Animal research has provided important information on the pathogenesis of and neuropathologic responses to perinatal cerebral hypoxia-ischemia. In experimental animals, structural brain damage from hypoxia-ischemia has been produced in immature rats, rabbits, guinea pigs, sheep and monkeys (18, 20, 24, 25, 38). Of the several available animal models, the fetal and newborn rhesus monkey and immature rat have been studied most extensively because of their similarities to humans in respect to the physiology of reproduction and their neuroanatomy at or shortly following birth. Given the frequency of occurrence of human perinatal hypoxic-ischemic brain damage and the multiple, often severe neurologic handicaps which ensue in infants and children, it is not surprising that the above described animal models have been developed. These models have provided the basis for investigations to clarify not only physiologic and biochemical mechanisms of tissue injury but also the efficacy of specific management strategies. Hopefully, such animal research will continue to provide important information regarding how best to prevent or minimize the devastating consequences of perinatal cerebral hypoxia-ischemia. PMID:8311995

  11. [Caffeinol: a neuroprotective action in ischemic brain damage].

    PubMed

    Bednarski, Jerzy; Gasińska, Karolina; Straszewski, Tomasz; Godek, Magdalena; Tutka, Piotr

    2015-01-01

    Caffeinol--a combination of ethanol and caffeine in appropriate concentrations--exerts neuroprotective and anticonvulsive action. Research conducted on rats in models of ischemic brain damage have shown that caffeinol decreases the size of cortical damage by about 80%, improves motional coordination and memory. The sooner caffeinol was administered, the better were beneficial therapeutic effects. What is more, the medicine may be safely combined with other methods used in stroke treatment, such as hypothermia and thrombolysis, what additionally increases its neuroprotective influence. Research on people have shown that caffeinol is less effective as neuroprotective agent in patients abusing alcohol, while chronic intake of caffeine does not influence its activity. Mechanism of its activity is not known yet, however, it is assumed that it bases on an antagonism of NMDA receptors. Regarding the fact that the most of strokes in humans concern subcortical areas, it is justified to conduct further research on caffeinol, which would involve other brain structures, thus allowing to define its use in clinical practice. PMID:27012130

  12. Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke

    PubMed Central

    Zavaglia, Melissa; Forkert, Nils D.; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C.

    2015-01-01

    Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a ‘map of stroke’. PMID:26448908

  13. Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke.

    PubMed

    Zavaglia, Melissa; Forkert, Nils D; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C

    2015-01-01

    Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a 'map of stroke'. PMID:26448908

  14. Pediatric traumatic brain injury: acute and rehabilitation costs.

    PubMed

    Jaffe, K M; Massagli, T L; Martin, K M; Rivara, J B; Fay, G C; Polissar, N L

    1993-07-01

    Pediatric traumatic brain injury constitutes an enormous public health problem, but little is known about the economic costs of such injury. Using charges as a proxy for cost, we prospectively collected data on initial hospital charges and professional fees for emergency department services, acute inpatient care, and acute inpatient rehabilitation for 96 patients with mild, moderate, and severe traumatic brain injuries. We also examined the relationship between these costs and injury severity and etiology. Acute care and rehabilitation median costs were $5,233 per child, $11,478 for hospitalized children, and $230 for those only seen in the emergency department. Median costs for injuries due to motor vehicles, bicycles, and falls were $15,213, $6,311, and $792, respectively. Using Glasgow Coma Scale criteria, median cost of mild, moderate, and severe traumatic brain injuries were $598, $12,022, and $53,332, respectively. Injury etiology added modestly but significantly to the prediction of cost over and above that predicted by injury severity alone. Rehabilitation costs accounted for 37% of the total for all children, but 45% of those with the most severe injuries. PMID:8328886

  15. Oxidative stress, inflammation, and DNA damage in multiple organs of mice acutely exposed to amorphous silica nanoparticles

    PubMed Central

    Nemmar, Abderrahim; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Kazzam, Elsadig E; Ali, Badreldin H

    2016-01-01

    The use of amorphous silica (SiO2) in biopharmaceutical and industrial fields can lead to human exposure by injection, skin penetration, ingestion, or inhalation. However, the in vivo acute toxicity of amorphous SiO2 nanoparticles (SiNPs) on multiple organs and the mechanisms underlying these effects are not well understood. Presently, we investigated the acute (24 hours) effects of intraperitoneally administered 50 nm SiNPs (0.25 mg/kg) on systemic toxicity, oxidative stress, inflammation, and DNA damage in the lung, heart, liver, kidney, and brain of mice. Lipid peroxidation was significantly increased by SiNPs in the lung, liver, kidney, and brain, but was not changed in the heart. Similarly, superoxide dismutase and catalase activities were significantly affected by SiNPs in all organs studied. While the concentration of tumor necrosis factor α was insignificantly increased in the liver and brain, its increase was statistically significant in the lung, heart, and kidney. SiNPs induced a significant elevation in pulmonary and renal interleukin 6 and interleukin-1 beta in the lung, liver, and brain. Moreover, SiNPs caused a significant increase in DNA damage, assessed by comet assay, in all the organs studied. SiNPs caused leukocytosis and increased the plasma activities of lactate dehydrogenase, creatine kinase, alanine aminotranferase, and aspartate aminotransferase. These results indicate that acute systemic exposure to SiNPs causes oxidative stress, inflammation, and DNA damage in several major organs, and highlight the need for thorough evaluation of SiNPs before they can be safely used in human beings. PMID:27022259

  16. Neuroglobin mitigates mitochondrial impairments induced by acute inhalation of combustion smoke in the mouse brain

    PubMed Central

    Gorgun, Falih Murat; Zhuo, Ming; Singh, Shilpee; Englander, Ella W.

    2014-01-01

    Context Acute inhalation of combustion smoke adversely affects brain homeostasis and energy metabolism. We previously showed that overexpressed neuroglobin (neuron specific globin protein) attenuates the formation of smoke inhalation-induced oxidative DNA damage, in vivo, in the mouse brain, while others reported protection by neuroglobin in diverse models of brain injury, mainly involving oxidative stress and hypoxic/ischemic insults. Objective To determine to what extent elevated neuroglobin ameliorates post smoke-inhalation brain bioenergetics and homeostasis in neuroglobin overexpressing transgenic mouse. Methods Smoke inhalation induced changes in bioenergetics were measured in the wild type and neuroglobin transgene mouse brain. Modulations of mitochondrial respiration were analyzed using the Seahorse XF24 flux analyzer and changes in cytoplasmic energy metabolism were assessed by measuring enzymatic activities and lactate in the course of post smoke recovery. Results Cortical mitochondria from neuroglobin transgene, better maintained ATP synthesis-linked oxygen consumption and unlike wild type mitochondria did not increase futile oxygen consumption feeding the proton leak, reflecting lesser smoke-induced mitochondrial compromise. Measurements revealed lesser reduction of mitochondrial ATP content and lesser compensatory increases in cytosolic energy metabolism, involving pyruvate kinase and lactate dehydrogenase activities as well as cytosolic lactate levels. Additionally, induction of c-Fos, the early response gene and key neuronal stress sensor, was attenuated in neuroglobin transgene compared to wild type brain after smoke. Conclusion Considered together, these differences reflect lesser perturbations produced by acute inhalation of combustion smoke in the neuroglobin overexpressing mouse, suggesting that neuroglobin mitigates mitochondrial dysfunction and neurotoxicity and raises the threshold of smoke inhalation-induced brain injury. PMID:24730682

  17. Brain damage in a large cohort of solvent abusers.

    PubMed

    Al-Hajri, Zahra; Del Bigio, Marc R

    2010-04-01

    The neuropathology of solvent inhalation consists of patchy myelin loss with white matter macrophages that contain granular inclusions. It has been described only in a small number of cases. We sought to characterize the abnormalities in greater detail. In a retrospective study from 1995 to 2009, we encountered 88 autopsy cases with documented history of solvent abuse by inhalation and 1 with industrial exposure. Among these are 6 fetuses and infants with maternal exposure, 23 children (12-17 years), and 60 adults (18-66 years). Available brain samples from 75 cases were stained with solochrome cyanein (to demonstrate myelin) and periodic acid-Schiff (PAS) (to highlight the inclusions). Forty brains of ethanol and/or illicit drug exposed individuals and ten cases of multiple sclerosis were examined as controls. We found that 16 cases (age 23-49, median 37 years) had well-established leukoencephalopathy with multifocal myelin loss and abundant macrophages that stain with PAS and which contain birefringent inclusions. Six cases (age 15-55, median 27 years) had early leukoencephalopathy with scattered macrophages but no obvious myelin changes. Clusters of PAS-staining but non-birefringent macrophages were seen in 2/10 cases of (active) multiple sclerosis and in none of the ethanol/drug exposed brains. Ultrastructurally, inclusions from solvent cases differed from multiple sclerosis cases. Although exposure to solvents is impossible to quantify, there appears to be a duration-dependent effect. Brain damage related to solvent abuse can begin within only a few years of the onset. In the context of substance abuse, the changes are relatively specific for solvent inhalation and do not appear to result from demyelination alone. Interaction with ethanol cannot be excluded as a compounding risk factor. PMID:20300918

  18. AMBIENT PARTICULATE MATTER STIMULATES OXIDATIVE STRESS IN BRAIN MICROGLIA AND DAMAGES NEURONS IN CULTURE.

    EPA Science Inventory

    Ambient particulate matter (PM) damages biological targets through oxidative stress (OS) pathways. Several reports indicate that the brain is one of those targets. Since microglia (brain macrophage) are critical to OS-mediated neurodegeneration, their response to concentrated amb...

  19. Cardiac troponins as indicators of acute myocardial damage in dogs.

    PubMed

    Burgener, Iwan A; Kovacevic, Alan; Mauldin, G Neal; Lombard, Christophe W

    2006-01-01

    Cardiac troponin I (cTnI) and T (cTnT) have a high sequence homology across phyla and are sensitive and specific markers of myocardial damage. The purpose of this study was to evaluate the Cardiac Reader, a human point-of-care system for the determination of cTnT and myoglobin, and the Abbott Axsym System for the determination of cTnI and creatine kinase isoenzyme MB (CK-MB) in healthy dogs and in dogs at risk for acute myocardial damage because of gastric dilatation-volvulus (GDV) and blunt chest trauma (BCT). In healthy dogs (n = 56), cTnI was below detection limits (<0.1 microg/L) in 35 of 56 dogs (reference range 0-0.7 microg/L), and cTnT was not measurable (<0.05 ng/mL) in all but 1 dog. At presentation, cTnI, CK-MB, myoglobin, and lactic acid were all significantly higher in dogs with GDV (n = 28) and BCT (n = 8) than in control dogs (P < .001), but cTnT was significantly higher only in dogs with BCT (P = .033). Increased cTnI or cTnT values were found in 26 of 28 (highest values 1.1-369 microg/L) and 16 of 28 dogs (0.1-1.7 ng/mL) with GDV, and in 6 of 8 (2.3-82.4 microg/L) and 3 of 8 dogs (0.1-0.29 ng/mL) with BCT, respectively. In dogs suffering from GDV, cTnI and cTnT increased further within the first 48 hours (P < .001). Increased cardiac troponins suggestive of myocardial damage occurred in 93% of dogs with GDV and 75% with BCT. cTnI appeared more sensitive, but cTnT may be a negative prognostic indicator in GDV. Both systems tested seemed applicable for the measurement of canine cardiac troponins, with the Cardiac Reader particularly suitable for use in emergency settings. PMID:16594583

  20. Biomarkers and acute brain injuries: interest and limits

    PubMed Central

    2014-01-01

    For patients presenting with acute brain injury (such as traumatic brain injury, subarachnoid haemorrhage and stroke), the diagnosis and identification of intracerebral lesions and evaluation of the severity, prognosis and treatment efficacy can be challenging. The complexity and heterogeneity of lesions after brain injury are most probably responsible for this difficulty. Patients with apparently comparable brain lesions on imaging may have different neurological outcomes or responses to therapy. In recent years, plasmatic and cerebrospinal fluid biomarkers have emerged as possible tools to distinguish between the different pathophysiological processes. This review aims to summarise the plasmatic and cerebrospinal fluid biomarkers evaluated in subarachnoid haemorrhage, traumatic brain injury and stroke, and to clarify their related interests and limits for diagnosis and prognosis. For subarachnoid haemorrhage, particular interest has been focused on the biomarkers used to predict vasospasm and cerebral ischaemia. The efficacy of biomarkers in predicting the severity and outcome of traumatic brain injury has been stressed. The very early diagnostic performance of biomarkers and their ability to discriminate ischaemic from haemorrhagic stroke were studied. PMID:25029344

  1. Endogenous recovery after brain damage: molecular mechanisms that balance neuronal life/death fate.

    PubMed

    Tovar-y-Romo, Luis B; Penagos-Puig, Andrés; Ramírez-Jarquín, Josué O

    2016-01-01

    Neuronal survival depends on multiple factors that comprise a well-fueled energy metabolism, trophic input, clearance of toxic substances, appropriate redox environment, integrity of blood-brain barrier, suppression of programmed cell death pathways and cell cycle arrest. Disturbances of brain homeostasis lead to acute or chronic alterations that might ultimately cause neuronal death with consequent impairment of neurological function. Although we understand most of these processes well when they occur independently from one another, we still lack a clear grasp of the concerted cellular and molecular mechanisms activated upon neuronal damage that intervene in protecting damaged neurons from death. In this review, we summarize a handful of endogenously activated mechanisms that balance molecular cues so as to determine whether neurons recover from injury or die. We center our discussion on mechanisms that have been identified to participate in stroke, although we consider different scenarios of chronic neurodegeneration as well. We discuss two central processes that are involved in endogenous repair and that, when not regulated, could lead to tissue damage, namely, trophic support and neuroinflammation. We emphasize the need to construct integrated models of neuronal degeneration and survival that, in the end, converge in neuronal fate after injury. Under neurodegenerative conditions, endogenously activated mechanisms balance out molecular cues that determine whether neurons contend toxicity or die. Many processes involved in endogenous repair may as well lead to tissue damage depending on the strength of stimuli. Signaling mediated by trophic factors and neuroinflammation are examples of these processes as they regulate different mechanisms that mediate neuronal demise including necrosis, apoptosis, necroptosis, pyroptosis and autophagy. In this review, we discuss recent findings on balanced regulation and their involvement in neuronal death. PMID:26376102

  2. Mapping neuroplastic potential in brain-damaged patients.

    PubMed

    Herbet, Guillaume; Maheu, Maxime; Costi, Emanuele; Lafargue, Gilles; Duffau, Hugues

    2016-03-01

    It is increasingly acknowledged that the brain is highly plastic. However, the anatomic factors governing the potential for neuroplasticity have hardly been investigated. To bridge this knowledge gap, we generated a probabilistic atlas of functional plasticity derived from both anatomic magnetic resonance imaging results and intraoperative mapping data on 231 patients having undergone surgery for diffuse, low-grade glioma. The atlas includes detailed level of confidence information and is supplemented with a series of comprehensive, connectivity-based cluster analyses. Our results show that cortical plasticity is generally high in the cortex (except in primary unimodal areas and in a small set of neural hubs) and rather low in connective tracts (especially associative and projection tracts). The atlas sheds new light on the topological organization of critical neural systems and may also be useful in predicting the likelihood of recovery (as a function of lesion topology) in various neuropathological conditions-a crucial factor in improving the care of brain-damaged patients. PMID:26912646

  3. Acetylcholine facilitates recovery of episodic memory after brain damage

    PubMed Central

    Croxson, Paula L.; Browning, Philip G. F.; Gaffan, David; Baxter, Mark G.

    2012-01-01

    Episodic memory depends on a network of interconnected brain structures including the inferior temporal cortex, hippocampus, fornix and mammillary bodies. We have previously shown that a moderate episodic memory impairment in monkeys with transection of the fornix is exacerbated by prior depletion of acetylcholine from inferotemporal cortex. This is despite the fact that depletion of acetylcholine from inferotemporal cortex on its own has no effect on episodic memory. Here we now show that this effect occurs because inferotemporal acetylcholine facilitates recovery of function following structural damage within the neural circuit for episodic memory. Episodic memory impairment caused by lesions of the mammillary bodies, like fornix transection, was exacerbated by prior removal of temporal cortical acetylcholine. However, removing temporal cortical acetylcholine after the lesion of the fornix or mammillary bodies did not increase the severity of the impairment. This lesion order effect suggests that acetylcholine within the inferior temporal cortex ordinarily facilitates functional recovery after structural lesions that impair episodic memory. In the absence of acetylcholine innervation to inferotemporal cortex, this recovery is impaired and the amnesia caused by the structural lesion is more severe. These results suggest that humans with loss of cortical acetylcholine function, for example in Alzheimer’s disease, may be less able to adapt to memory impairments caused by structural neuronal damage to areas in the network important for episodic memory. PMID:23035090

  4. Neonatal `Brain Damage'—An Analysis of 250 Claims

    PubMed Central

    Cornblath, Marvin; Clark, Russell L.

    1984-01-01

    Advances in perinatal care have resulted in decreased neonatal mortality. Increasingly, damage in survivors has been attributed to alleged negligence. We analyzed the 250 claims (1957 to 1982) from one major insurance company for factors to characterize high-risk pregnancies and then to distinguish preventable from nonpreventable causes within the group. Using predetermined criteria, 77 (31%) were classified preventable, 105 (42%) nonpreventable and 68 (27%) indeterminate. Preventable actions could be attributed to family members as well as health care providers. Twenty risk factors were significantly increased in the study group compared with those in a general population and included maternal, gestational, delivery and postdelivery risks. Furthermore, 13 of 25 factors differed significantly between preventable and nonpreventable cases. Those with significantly higher prevalence in preventable cases included prolonged gestation, the use of mid or high forceps, cesarean sections, meconium staining, low one- and five-minute Apgar scores, birth weight exceeding 4.5 kg (10 lb), poor tone, seizures and transfers to neonatal intensive care units. Increased in prevalence in the nonpreventable cases were congenital infections and malformations and the late onset of neurologic abnormalities. These findings suggest preventive measures to reduce unwarranted litigation and certain cases of neonatal brain damage. PMID:6730485

  5. Acute brain slice methods for adult and aging animals: application of targeted patch clampanalysis and optogenetics

    PubMed Central

    Daigle, Tanya L.; Chen, Qian; Feng, Guoping

    2014-01-01

    Summary The development of the living acute brain slice preparation for analyzing synaptic function roughly a half century ago was a pivotal achievement that greatly influenced the landscape of modern neuroscience. Indeed, many neuroscientists regard brain slices as the gold-standard model system for detailed cellular, molecular, and circuitry level analysis and perturbation of neuronal function. A critical limitation of this model system is the difficulty in preparing slices from adult and aging animals, and over the past several decades few substantial methodological improvements have emerged to facilitate patch clamp analysis in the mature adult stage. In this chapter we describe a robust and practical protocol for preparing brain slices from mature adult mice that are suitable for patch clamp analysis. This method reduces swelling and damage in superficial layers of the slices and improves the success rate for targeted patch clamp recordings, including recordings from fluorescently labeled populations in slices derived from transgenic mice. This adult brain slice method is suitable for diverse experimental applications, including both monitoring and manipulating neuronal activity with genetically encoded calcium indicators and optogenetic actuators, respectively. We describe the application of this adult brain slice platform and associated methods for screening kinetic properties of Channelrhodopsin (ChR) variants expressed in genetically-defined neuronal subtypes. PMID:25023312

  6. Intraoperative Targeted Temperature Management in Acute Brain and Spinal Cord Injury.

    PubMed

    Kraft, Jacqueline; Karpenko, Anna; Rincon, Fred

    2016-02-01

    Acute brain and spinal cord injuries affect hundreds of thousands of people worldwide. Though advances in pre-hospital and emergency and neurocritical care have improved the survival of some to these devastating diseases, very few clinical trials of potential neuro-protective strategies have produced promising results. Medical therapies such as targeted temperature management (TTM) have been trialed in traumatic brain injury (TBI), spinal cord injury (SCI), acute ischemic stroke (AIS), subarachnoid hemorrhage (SAH), and intracranial hemorrhage (ICH), but in no study has a meaningful effect on outcome been demonstrated. To this end, patient selection for potential neuro-protective therapies such as TTM may be the most important factor to effectively demonstrate efficacy in clinical trials. The use of TTM as a strategy to treat and prevent secondary neuronal damage in the intraoperative setting is an area of ongoing investigation. In this review we will discuss recent and ongoing studies that address the role of TTM in combination with surgical approaches for different types of brain injury. PMID:26759319

  7. Regulation of brain anandamide by acute administration of ethanol

    PubMed Central

    Ferrer, Belen; Bermúdez-Silva, Francisco Javier; Bilbao, Ainhoa; Alvarez-Jaimes, Lily; Sanchez-Vera, Irene; Giuffrida, Andrea; Serrano, Antonia; Baixeras, Elena; Khaturia, Satishe; Navarro, Miguel; Parsons, Loren H.; Piomelli, Daniele; Rodríguez de Fonseca, Fernando

    2007-01-01

    The endogenous cannabinoid acylethanolamide AEA (arachidonoylethanolamide; also known as anandamide) participates in the neuroadaptations associated with chronic ethanol exposure. However, no studies have described the acute actions of ethanol on AEA production and degradation. In the present study, we investigated the time course of the effects of the intraperitoneal administration of ethanol (4 g/kg of body mass) on the endogenous levels of AEA in central and peripheral tissues. Acute ethanol administration decreased AEA in the cerebellum, the hippocampus and the nucleus accumbens of the ventral striatum, as well as in plasma and adipose tissue. Parallel decreases of a second acylethanolamide, PEA (palmitoylethanolamide), were observed in the brain. Effects were observed 45–90 min after ethanol administration. In vivo studies revealed that AEA decreases were associated with a remarkable inhibition of the release of both anandamide and glutamate in the nucleus accumbens. There were no changes in the expression and enzymatic activity of the main enzyme that degrades AEA, the fatty acid amidohydrolase. Acute ethanol administration did not change either the activity of N-acyltransferase, the enzyme that catalyses the synthesis of the AEA precursor, or the expression of NAPE-PLD (N-acylphosphatidylethanolamine-hydrolysing phospholipase D), the enzyme that releases AEA from membrane phospholipid precursors. These results suggest that receptor-mediated release of acylethanolamide is inhibited by the acute administration of ethanol, and that this effect is not derived from increased fatty acid ethanolamide degradation. PMID:17302558

  8. Acute moderate exercise enhances compensatory brain activation in older adults.

    PubMed

    Hyodo, Kazuki; Dan, Ippeita; Suwabe, Kazuya; Kyutoku, Yasushi; Yamada, Yuhki; Akahori, Mitsuya; Byun, Kyeongho; Kato, Morimasa; Soya, Hideaki

    2012-11-01

    A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (incongruent-neutral) as Stroop performance. Though activation for Stroop interference was found in the bilateral prefrontal area before the acute bout of exercise, activation of the right frontopolar area (R-FPA) was enhanced after exercise. In the majority of participants, this coincided with improved performance reflected in Stroop interference results. Thus, an acute bout of moderate exercise improved Stroop performance in older adults, and this was associated with contralateral compensatory activation. PMID:22300952

  9. Interhemispheric and Intrahemispheric Control of Emotion: A Focus on Unilateral Brain Damage.

    ERIC Educational Resources Information Center

    Borod, Joan C.

    1992-01-01

    Discusses neocortical contributions to emotional processing. Examines parameters critical to neuropsychological study of emotion: interhemispheric and intrahemispheric factors, processing mode, and communication channel. Describes neuropsychological theories of emotion. Reviews studies of right-brain-damaged, left-brain-damaged, and normal adults,…

  10. Sex Differences in the Effects of Unilateral Brain Damage on Intelligence.

    ERIC Educational Resources Information Center

    Inglis, James; Lawson, J. S.

    1981-01-01

    A sexual dimorphism in the functional asymmetry of the damaged human brain is reflected in a test-specific laterality effect in male patients, explaining some contradictions concerning the effects of unilateral brain damage on intelligence in studies in which the influence of sex was overlooked. (Author/SK)

  11. Changes in Connectivity after Visual Cortical Brain Damage Underlie Altered Visual Function

    ERIC Educational Resources Information Center

    Bridge, Holly; Thomas, Owen; Jbabdi, Saad; Cowey, Alan

    2008-01-01

    The full extent of the brain's ability to compensate for damage or changed experience is yet to be established. One question particularly important for evaluating and understanding rehabilitation following brain damage is whether recovery involves new and aberrant neural connections or whether any change in function is due to the functional…

  12. Sex Differences in the Effects of Unilateral Brain Damage on Intelligence

    NASA Astrophysics Data System (ADS)

    Inglis, James; Lawson, J. S.

    1981-05-01

    A sexual dimorphism in the functional asymmetry of the damaged human brain is reflected in a test-specific laterality effect in male but not in female patients. This sex difference explains some contradictions concerning the effects of unilateral brain damage on intelligence in studies in which the influence of sex was overlooked.

  13. Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

    PubMed Central

    Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

    2012-01-01

    Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

  14. Acute iron overload and oxidative stress in brain.

    PubMed

    Piloni, Natacha E; Fermandez, Virginia; Videla, Luis A; Puntarulo, Susana

    2013-12-01

    An in vivo model in rat was developed by intraperitoneally administration of Fe-dextran to study oxidative stress triggered by Fe-overload in rat brain. Total Fe levels, as well as the labile iron pool (LIP) concentration, in brain from rats subjected to Fe-overload were markedly increased over control values, 6h after Fe administration. In this in vivo Fe overload model, the ascorbyl (A)/ascorbate (AH(-)) ratio, taken as oxidative stress index, was assessed. The A/AH(-) ratio in brain was significantly higher in Fe-dextran group, in relation to values in control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactive substances (TBARS) generation rate and lipid radical (LR) content detected by Electron Paramagnetic Resonance (EPR), in Fe-dextran supplemented rats were similar to control values. However, values of nuclear factor-kappaB deoxyribonucleic acid (NFκB DNA) binding activity were significantly increased (30%) after 8h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21h after Fe administration. Significant enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold) and striatum (2.9 fold), were found at 6h after Fe administration. CAT activity was significantly increased after 8h of Fe administration in cortex, hippocampus and striatum (1.4 fold, 86, and 47%, respectively). Fe response in the whole brain seems to lead to enhanced NF-κB DNA binding activity, which may contribute to limit oxygen reactive species-dependent damage by effects on the antioxidant enzyme CAT activity. Moreover, data shown here clearly indicate that even though Fe increased in several isolated brain areas, this parameter was more drastically enhanced in striatum than in cortex and hippocampus. However, comparison among the net increase in LR generation rate, in different brain areas, showed enhancements in cortex lipid peroxidation, without changes in striatum and hippocampus LR generation rate after 6h of Fe overload

  15. Methamphetamine causes acute hyperthermia-dependent liver damage.

    PubMed

    Halpin, Laura E; Gunning, William T; Yamamoto, Bryan K

    2013-10-01

    Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug. PMID:25505562

  16. Methamphetamine causes acute hyperthermia-dependent liver damage

    PubMed Central

    Halpin, Laura E; Gunning, William T; Yamamoto, Bryan K

    2013-01-01

    Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug. PMID:25505562

  17. Death rates reflect accumulating brain damage in arthropods.

    PubMed

    Fonseca, Duane B; Brancato, Carolina L; Prior, Andrew E; Shelton, Peter M J; Sheehy, Matt R J

    2005-09-22

    We present the results of the first quantitative, whole-lifespan study of the relationship between age-specific neurolipofuscin concentration and natural mortality rate in any organism. In a convenient laboratory animal, the African migratory locust, Locusta migratoria, we find an unusual delayed-onset neurolipofuscin accumulation pattern that is highly correlated with exponentially accelerating age-specific Gompertz-Makeham death rates in both males (r=0.93, p=0.0064) and females (r=0.97, p=0.0052). We then test the conservation of this association by aggregating the locust results with available population-specific data for a range of other terrestrial, freshwater, marine, tropical and temperate arthropods whose longevities span three orders of magnitude. This synthesis shows that the strong association between neurolipofuscin deposition and natural mortality is a phylogenetically and environmentally widespread phenomenon (r=0.96, p < 0.0001). These results highlight neurolipofuscin as a unique and outstanding integral biomarker of ageing. They also offer compelling evidence for the proposal that, in vital organs like the brain, either the accumulation of toxic garbage in the form of lipofuscin itself, or the particular molecular reactions underlying lipofuscinogenesis, including free-radical damage, are the primary events in senescence. PMID:16191601

  18. Acute traumatic anterior glenohumeral dislocation complicated by axillary nerve damage: a case report

    PubMed Central

    Kazemi, Mohsen

    1998-01-01

    An elite soccer player presented with a classic acute anterior dislocation of the glenohumeral joint complicated by axillary nerve damage. The incidence, mechanism of injury, clinical presentation, conservative treatment and rehabilitation of the anterior glenohumeral joint dislocation and associated axillary nerve damage are discussed in this paper. ImagesFigure 3

  19. Acute and long term respiratory damage following inhalation of ammonia.

    PubMed Central

    Leduc, D; Gris, P; Lheureux, P; Gevenois, P A; De Vuyst, P; Yernault, J C

    1992-01-01

    A lifelong non-smoker who was the victim of a massive accidental exposure to anhydrous ammonia gas was followed up for 10 years. In the acute phase the patient presented with severe tracheobronchitis and respiratory failure, caused by very severe burns of the respiratory mucosa. After some improvement he was left with severe and fixed airways obstruction. Isotope studies of mucociliary clearance, computed tomography, and bronchography showed mild bronchiectasis. It is concluded that acute exposure to high concentrations of ammonia may lead to acute respiratory injury but also to long term impairment of respiratory function. Images PMID:1440475

  20. [Effects of total saponins of semen ziziphi Spinosae on brain damages and brain biochemical parameters under cerebral ischemia of rats].

    PubMed

    Bai, X; Huang, Z; Mo, Z; Pan, H; Ding, H

    1996-02-01

    Total saponins of Semen Ziziphi Spinosae (ZS) can reduce the contents of water and MDA in ischemic rat's brain tissues, elevate the activity of SOD, CK and LDH, cut down the content of lactate and alleviate the damages of nerve cells in brain. The study shows that ZS possesses protective effects on cerebral ischemic injuries. PMID:8758767

  1. Psychiatric Disease and Post-Acute Traumatic Brain Injury.

    PubMed

    Zgaljardic, Dennis J; Seale, Gary S; Schaefer, Lynn A; Temple, Richard O; Foreman, Jack; Elliott, Timothy R

    2015-12-01

    Psychiatric disorders are common following traumatic brain injury (TBI) and can include depression, anxiety, and psychosis, as well as other maladaptive behaviors and personality changes. The epidemiologic data of psychiatric disorders post-TBI vary widely, although the incidence and prevalence rates typically are higher than in the general population. Although the experience of psychiatric symptoms may be temporary and may resolve in the acute period, many patients with TBI can experience psychopathology that is persistent or that develops in the post-acute period. Long-term psychiatric disorder, along with cognitive and physical sequelae and greater risk for substance use disorders, can pose a number of life-long challenges for patients and their caregivers, as they can interfere with participation in rehabilitation as well as limit functional independence in the community. The current review of the literature considers the common psychiatric problems affecting individuals with TBI in the post-acute period, including personality changes, psychosis, executive dysfunction, depression, anxiety, and substance misuse. Although treatment considerations (pharmacological and nonpharmacological) are referred to, an extensive description of such protocols is beyond the scope of the current review. The impact of persistent psychiatric symptoms on perceived caregiver burden and distress is also discussed. PMID:25629222

  2. Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

    PubMed

    Peng, Kaiwei; Tan, Danfeng; He, Miao; Guo, Dandan; Huang, Juan; Wang, Xia; Liu, Chentao; Zheng, Xiangrong

    2016-08-17

    Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase. PMID:27362436

  3. Retinal Ganglion Cell Damage in an Experimental Rodent Model of Blast-Mediated Traumatic Brain Injury

    PubMed Central

    Mohan, Kabhilan; Kecova, Helga; Hernandez-Merino, Elena; Kardon, Randy H.; Harper, Matthew M.

    2013-01-01

    Purpose. To evaluate retina and optic nerve damage following experimental blast injury. Methods. Healthy adult mice were exposed to an overpressure blast wave using a custom-built blast chamber. The effects of blast exposure on retina and optic nerve function and structure were evaluated using the pattern electroretinogram (pERG), spectral domain optical coherence tomography (OCT), and the chromatic pupil light reflex. Results. Assessment of the pupil response to light demonstrated decreased maximum pupil constriction diameter in blast-injured mice using red light or blue light stimuli 24 hours after injury compared with baseline in the eye exposed to direct blast injury. A decrease in the pupil light reflex was not observed chronically following blast exposure. We observed a biphasic pERG decrease with the acute injury recovering by 24 hours postblast and the chronic injury appearing at 4 months postblast injury. Furthermore, at 3 months following injury, a significant decrease in the retinal nerve fiber layer was observed using OCT compared with controls. Histologic analysis of the retina and optic nerve revealed punctate regions of reduced cellularity in the ganglion cell layer and damage to optic nerves. Additionally, a significant upregulation of proteins associated with oxidative stress was observed acutely following blast exposure compared with control mice. Conclusions. Our study demonstrates that decrements in retinal ganglion cell responses can be detected after blast injury using noninvasive functional and structural tests. These objective responses may serve as surrogate tests for higher CNS functions following traumatic brain injury that are difficult to quantify. PMID:23620426

  4. Induction of acute phase gene expression by brain irradiation

    SciTech Connect

    Hong, Ji-Hong |; Sun, Ji-Rong; Withers, H.R.

    1995-10-15

    To investigate the in vivo acute phase molecular response of the brain to ionizing radiation, C3Hf/Sed/Kam mice were given midbrain or whole-body irradiation. Cerebral expression of interleukins (IL-1{alpha}, IL-1{beta}, IL-2, IL-3, IL-4, IL-5, IL-6), interferon (IFN-{gamma}), tumor necrosis factors (TNF-{alpha} and TNF-{beta}), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthetase (iNOS), von Willebrand factor (vWF), {alpha}1-antichymotrypsin (EB22/5.3), and glial fibrillary acidic protein (GFAP) was measured at various times after various radiation doses by ribonuclease (RNase) protection assay. The effects of dexamethasone or pentoxifylline treatment of mice on radiation-induced gene expression were also examined. Levels of TNF-{alpha}, IL-1{beta}, ICAM-1, EB22/5.3, and to a lesser extent IL-1{alpha} and GFAP, messenger RNA were increased in the brain after irradiation, whether the dose was delivered to the whole body or only to the midbrain. Responses were radiation dose dependent, but were not found below 7 Gy; the exception being ICAM-1, which was increased by doses as low as 2 Gy. Most responses were rapid, peaking within 4-8 h, but antichymotrypsin and GFAP responses were delayed and still elevated at 24 h, by which time the others had subsided. Pretreatment of mice with dexamethasone or pentoxifylline suppressed radiation-induced gene expression, either partially or completely. Dexamethasone was more inhibitory than pentoxifylline at the doses chosen. The initial response of the brain to irradiation involves expression of inflammatory gene products, which are probably responsible for clinically observed early symptoms of brain radiotherapy. This mechanism explains the beneficial effects of the clinical use of steroids in such circumstances. 64 refs., 4 figs.

  5. Optimizing sedation in patients with acute brain injury.

    PubMed

    Oddo, Mauro; Crippa, Ilaria Alice; Mehta, Sangeeta; Menon, David; Payen, Jean-Francois; Taccone, Fabio Silvio; Citerio, Giuseppe

    2016-01-01

    Daily interruption of sedative therapy and limitation of deep sedation have been shown in several randomized trials to reduce the duration of mechanical ventilation and hospital length of stay, and to improve the outcome of critically ill patients. However, patients with severe acute brain injury (ABI; including subjects with coma after traumatic brain injury, ischaemic/haemorrhagic stroke, cardiac arrest, status epilepticus) were excluded from these studies. Therefore, whether the new paradigm of minimal sedation can be translated to the neuro-ICU (NICU) is unclear. In patients with ABI, sedation has 'general' indications (control of anxiety, pain, discomfort, agitation, facilitation of mechanical ventilation) and 'neuro-specific' indications (reduction of cerebral metabolic demand, improved brain tolerance to ischaemia). Sedation also is an essential therapeutic component of intracranial pressure therapy, targeted temperature management and seizure control. Given the lack of large trials which have evaluated clinically relevant endpoints, sedative selection depends on the effect of each agent on cerebral and systemic haemodynamics. Titration and withdrawal of sedation in the NICU setting has to be balanced between the risk that interrupting sedation might exacerbate brain injury (e.g. intracranial pressure elevation) and the potential benefits of enhanced neurological function and reduced complications. In this review, we provide a concise summary of cerebral physiologic effects of sedatives and analgesics, the advantages/disadvantages of each agent, the comparative effects of standard sedatives (propofol and midazolam) and the emerging role of alternative drugs (ketamine). We suggest a pragmatic approach for the use of sedation-analgesia in the NICU, focusing on some practical aspects, including optimal titration and management of sedation withdrawal according to ABI severity. PMID:27145814

  6. Categorization skills and recall in brain damaged children: a multiple case study.

    PubMed

    Mello, Claudia Berlim de; Muszkat, Mauro; Xavier, Gilberto Fernando; Bueno, Orlando Francisco Amodeo

    2009-09-01

    During development, children become capable of categorically associating stimuli and of using these relationships for memory recall. Brain damage in childhood can interfere with this development. This study investigated categorical association of stimuli and recall in four children with brain damages. The etiology, topography and timing of the lesions were diverse. Tasks included naming and immediate recall of 30 perceptually and semantically related figures, free sorting, delayed recall, and cued recall of the same material. Traditional neuropsychological tests were also employed. Two children with brain damage sustained in middle childhood relied on perceptual rather than on categorical associations in making associations between figures and showed deficits in delayed or cued recall, in contrast to those with perinatal lesions. One child exhibited normal performance in recall despite categorical association deficits. The present results suggest that brain damaged children show deficits in categorization and recall that are not usually identified in traditional neuropsychological tests. PMID:19722038

  7. BHT blocks NfkB activation and Ethanol-Induced Brain Damage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Binge ethanol administration causes corticolimbic brain damage that models alcoholic neurodegeneration. The mechanism of binge ethanol induced degeneration is unknown, but is not glutamate neurotoxicity. To test the hypothesis that oxidative stress and inflammation are mechanisms of binge ethanol ...

  8. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    PubMed Central

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-01-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries. PMID:27351915

  9. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    NASA Astrophysics Data System (ADS)

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-06-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

  10. Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke.

    PubMed

    Silva, Bruno; Sousa, Larissa; Miranda, Aline; Vasconcelos, Anilton; Reis, Helton; Barcelos, Lucíola; Arantes, Rosa; Teixeira, Antonio; Rachid, Milene Alvarenga

    2015-08-01

    The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO), a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia. PMID:26222355

  11. Radiation-Induced Astrogliosis and Blood-Brain Barrier Damage Can Be Abrogated Using Anti-TNF Treatment

    SciTech Connect

    Wilson, Christy M.; Gaber, M. Waleed Sabek, Omaima M.; Zawaski, Janice A.; Merchant, Thomas E.

    2009-07-01

    Purpose: In this article, we investigate the role of tumor necrosis factor-alpha (TNF) in the initiation of acute damage to the blood-brain barrier (BBB) and brain tissue following radiotherapy (RT) for CNS tumors. Methods and Materials: Intravital microscopy and a closed cranial window technique were used to measure quantitatively BBB permeability to FITC-dextran 4.4-kDa molecules, leukocyte adhesion (Rhodamine-6G) and vessel diameters before and after 20-Gy cranial radiation with and without treatment with anti-TNF. Immunohistochemistry was used to quantify astrogliosis post-RT and immunofluorescence was used to visualize protein expression of TNF and ICAM-1 post-RT. Recombinant TNF (rTNF) was used to elucidate the role of TNF in leukocyte adhesion and vessel diameter. Results: Mice treated with anti-TNF showed significantly lower permeability and leukocyte adhesion at 24 and 48 h post-RT vs. RT-only animals. We observed a significant decrease in arteriole diameters at 48 h post-RT that was inhibited in TNF-treated animals. We also saw a significant increase in activated astrocytes following RT that was significantly lower in the anti-TNF-treated group. In addition, immunofluorescence showed protein expression of TNF and ICAM-1 in the cerebral cortex that was inhibited with anti-TNF treatment. Finally, administration of rTNF induced a decrease in arteriole diameter and a significant increase in leukocyte adhesion in venules and arterioles. Conclusions: TNF plays a significant role in acute changes in BBB permeability, leukocyte adhesion, arteriole diameter, and astrocyte activation following cranial radiation. Treatment with anti-TNF protects the brain's microvascular network from the acute damage following RT.

  12. Pharmacotherapy in rehabilitation of post-acute traumatic brain injury.

    PubMed

    Bhatnagar, Saurabha; Iaccarino, Mary Alexis; Zafonte, Ross

    2016-06-01

    There are nearly 1.8 million annual emergency room visits and over 289,000 annual hospitalizations related to traumatic brain injury (TBI). The goal of this review article is to highlight pharmacotherapies that we often use in the clinic that have been shown to benefit various sequelae of TBI. We have decided to focus on sequelae that we commonly encounter in our practice in the post-acute phase after a TBI. These symptoms are hyper-arousal, agitation, hypo-arousal, inattention, slow processing speed, memory impairment, sleep disturbance, depression, headaches, spasticity, and paroxysmal sympathetic hyperactivity. In this review article, the current literature for the pharmacological management of these symptoms are mentioned, including medications that have not had success and some ongoing trials. It is clear that the pharmacological management specific to those with TBI is often based on small studies and that often treatment is based on assumptions of how similar conditions are managed when not relating to TBI. As the body of the literature expands and targeted treatments start to emerge for TBI, the function of pharmacological management will need to be further defined. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26801831

  13. Brain damage in a new hemorrhagic shock model in the rat using long-term recovery

    SciTech Connect

    Yamauchi, Y.; Kato, H.; Kogure, K. )

    1990-03-01

    A new shock model in the rat using hemorrhagic hypotension for production of brain damage is described. Hemorrhagic shock was induced by lowering arterial blood pressure with bleeding. The MABP was maintained at approximately 25 mm Hg, accompanied by isoelectric EEG, and then shed blood was retransfused. At 1 week of recovery, morphological and 45Ca autoradiographic changes were examined. No brain damage was observed in rats after 1 min of isoelectric EEG. Mild neuronal damage in the hippocampal CA1 subfield was seen in some animals after 2 min of isoelectric EEG. Severe and consistent neuronal loss in the hippocampal CA1 subfield was recognized after 3 min of isoelectric EEG. Additional damage was also seen in the dentate hilus and the thalamus in some animals. This model can be used to study the pathophysiology of postshock brain damage and to assess new therapies following shock.

  14. Brain damage in methylmalonic aciduria: 2-methylcitrate induces cerebral ammonium accumulation and apoptosis in 3D organotypic brain cell cultures

    PubMed Central

    2013-01-01

    Background Methylmalonic aciduria is an inborn error of metabolism characterized by accumulation of methylmalonate (MMA), propionate and 2-methylcitrate (2-MCA) in body fluids. Early diagnosis and current treatment strategies aimed at limiting the production of these metabolites are only partially effective in preventing neurological damage. Methods To explore the metabolic consequences of methylmalonic aciduria on the brain, we used 3D organotypic brain cell cultures from rat embryos. We challenged the cultures at two different developmental stages with 1 mM MMA, propionate or 2-MCA applied 6 times every 12 h. In a dose–response experiment cultures were challenged with 0.01, 0.1, 0.33 and 1 mM 2-MCA. Immunohistochemical staining for different brain cell markers were used to assess cell viability, morphology and differentiation. Significant changes were validated by western blot analysis. Biochemical markers were analyzed in culture media. Apoptosis was studied by immunofluorescence staining and western blots for activated caspase-3. Results Among the three metabolites tested, 2-MCA consistently produced the most pronounced effects. Exposure to 2-MCA caused morphological changes in neuronal and glial cells already at 0.01 mM. At the biochemical level the most striking result was a significant ammonium increase in culture media with a concomitant glutamine decrease. Dose–response studies showed significant and parallel changes of ammonium and glutamine starting from 0.1 mM 2-MCA. An increased apoptosis rate was observed by activation of caspase-3 after exposure to at least 0.1 mM 2-MCA. Conclusion Surprisingly, 2-MCA, and not MMA, seems to be the most toxic metabolite in our in vitro model leading to delayed axonal growth, apoptosis of glial cells and to unexpected ammonium increase. Morphological changes were already observed at 2-MCA concentrations as low as 0.01 mM. Increased apoptosis and ammonium accumulation started at 0.1 mM thus suggesting that ammonium

  15. Recurrent Moderate Hypoglycemia Ameliorates Brain Damage and Cognitive Dysfunction Induced by Severe Hypoglycemia

    PubMed Central

    Puente, Erwin C.; Silverstein, Julie; Bree, Adam J.; Musikantow, Daniel R.; Wozniak, David F.; Maloney, Susan; Daphna-Iken, Dorit; Fisher, Simon J.

    2010-01-01

    OBJECTIVE Although intensive glycemic control achieved with insulin therapy increases the incidence of both moderate and severe hypoglycemia, clinical reports of cognitive impairment due to severe hypoglycemia have been highly variable. It was hypothesized that recurrent moderate hypoglycemia preconditions the brain and protects against damage caused by severe hypoglycemia. RESEARCH DESIGN AND METHODS Nine-week-old male Sprague-Dawley rats were subjected to either 3 consecutive days of recurrent moderate (25–40 mg/dl) hypoglycemia (RH) or saline injections. On the fourth day, rats were subjected to a hyperinsulinemic (0.2 units · kg−1 · min−1) severe hypoglycemic (∼11 mg/dl) clamp for 60 or 90 min. Neuronal damage was subsequently assessed by hematoxylin-eosin and Fluoro-Jade B staining. The functional significance of severe hypoglycemia–induced brain damage was evaluated by motor and cognitive testing. RESULTS Severe hypoglycemia induced brain damage and striking deficits in spatial learning and memory. Rats subjected to recurrent moderate hypoglycemia had 62–74% less brain cell death and were protected from most of these cognitive disturbances. CONCLUSIONS Antecedent recurrent moderate hypoglycemia preconditioned the brain and markedly limited both the extent of severe hypoglycemia–induced neuronal damage and associated cognitive impairment. In conclusion, changes brought about by recurrent moderate hypoglycemia can be viewed, paradoxically, as providing a beneficial adaptive response in that there is mitigation against severe hypoglycemia–induced brain damage and cognitive dysfunction. PMID:20086229

  16. Connectomic and Surface-Based Morphometric Correlates of Acute Mild Traumatic Brain Injury.

    PubMed

    Dall'Acqua, Patrizia; Johannes, Sönke; Mica, Ladislav; Simmen, Hans-Peter; Glaab, Richard; Fandino, Javier; Schwendinger, Markus; Meier, Christoph; Ulbrich, Erika J; Müller, Andreas; Jäncke, Lutz; Hänggi, Jürgen

    2016-01-01

    Reduced integrity of white matter (WM) pathways and subtle anomalies in gray matter (GM) morphology have been hypothesized as mechanisms in mild traumatic brain injury (mTBI). However, findings on structural brain changes in early stages after mTBI are inconsistent and findings related to early symptoms severity are rare. Fifty-one patients were assessed with multimodal neuroimaging and clinical methods exclusively within 7 days following mTBI and compared to 53 controls. Whole-brain connectivity based on diffusion tensor imaging was subjected to network-based statistics, whereas cortical surface area, thickness, and volume based on T1-weighted MRI scans were investigated using surface-based morphometric analysis. Reduced connectivity strength within a subnetwork of 59 edges located predominantly in bilateral frontal lobes was significantly associated with higher levels of self-reported symptoms. In addition, cortical surface area decreases were associated with stronger complaints in five clusters located in bilateral frontal and postcentral cortices, and in the right inferior temporal region. Alterations in WM and GM were localized in similar brain regions and moderately-to-strongly related to each other. Furthermore, the reduction of cortical surface area in the frontal regions was correlated with poorer attentive-executive performance in the mTBI group. Finally, group differences were detected in both the WM and GM, especially when focusing on a subgroup of patients with greater complaints, indicating the importance of classifying mTBI patients according to severity of symptoms. This study provides evidence that mTBI affects not only the integrity of WM networks by means of axonal damage but also the morphology of the cortex during the initial post-injury period. These anomalies might be greater in the acute period than previously believed and the involvement of frontal brain regions was consistently pronounced in both findings. The dysconnected subnetwork

  17. Connectomic and Surface-Based Morphometric Correlates of Acute Mild Traumatic Brain Injury

    PubMed Central

    Dall'Acqua, Patrizia; Johannes, Sönke; Mica, Ladislav; Simmen, Hans-Peter; Glaab, Richard; Fandino, Javier; Schwendinger, Markus; Meier, Christoph; Ulbrich, Erika J.; Müller, Andreas; Jäncke, Lutz; Hänggi, Jürgen

    2016-01-01

    Reduced integrity of white matter (WM) pathways and subtle anomalies in gray matter (GM) morphology have been hypothesized as mechanisms in mild traumatic brain injury (mTBI). However, findings on structural brain changes in early stages after mTBI are inconsistent and findings related to early symptoms severity are rare. Fifty-one patients were assessed with multimodal neuroimaging and clinical methods exclusively within 7 days following mTBI and compared to 53 controls. Whole-brain connectivity based on diffusion tensor imaging was subjected to network-based statistics, whereas cortical surface area, thickness, and volume based on T1-weighted MRI scans were investigated using surface-based morphometric analysis. Reduced connectivity strength within a subnetwork of 59 edges located predominantly in bilateral frontal lobes was significantly associated with higher levels of self-reported symptoms. In addition, cortical surface area decreases were associated with stronger complaints in five clusters located in bilateral frontal and postcentral cortices, and in the right inferior temporal region. Alterations in WM and GM were localized in similar brain regions and moderately-to-strongly related to each other. Furthermore, the reduction of cortical surface area in the frontal regions was correlated with poorer attentive-executive performance in the mTBI group. Finally, group differences were detected in both the WM and GM, especially when focusing on a subgroup of patients with greater complaints, indicating the importance of classifying mTBI patients according to severity of symptoms. This study provides evidence that mTBI affects not only the integrity of WM networks by means of axonal damage but also the morphology of the cortex during the initial post-injury period. These anomalies might be greater in the acute period than previously believed and the involvement of frontal brain regions was consistently pronounced in both findings. The dysconnected subnetwork

  18. White Matter Damage and Cognitive Impairment after Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Kinnunen, Kirsi Maria; Greenwood, Richard; Powell, Jane Hilary; Leech, Robert; Hawkins, Peter Charlie; Bonnelle, Valerie; Patel, Maneesh Chandrakant; Counsell, Serena Jane; Sharp, David James

    2011-01-01

    White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury…

  19. The Use of Computers and Video Games in Brain Damage Therapy.

    ERIC Educational Resources Information Center

    Lorimer, David

    The use of computer assisted therapy (CAT) in the rehabilitation of individuals with brain damage is examined. Hardware considerations are explored, and the variety of software programs available for brain injury rehabilitation is discussed. Structured testing and treatment programs in time measurement, memory, and direction finding are described,…

  20. Unilateral Brain Damage Effects on Processing Homonymous and Polysemous Words

    ERIC Educational Resources Information Center

    Klepousniotou, E.; Baum, S.R.

    2005-01-01

    Using an auditory semantic priming paradigm, the present study investigated the abilities of left-hemisphere-damaged (LHD) non-fluent aphasic, right-hemisphere-damaged (RHD) and normal control individuals to access, out of context, the multiple meanings of three types of ambiguous words, namely homonyms (e.g., ''punch''), metonymies (e.g.,…

  1. Perceptual Asymmetry for Chimeric Stimuli in Children with Early Unilateral Brain Damage

    ERIC Educational Resources Information Center

    Bava, Sunita; Ballantyne, Angela O.; May, Susanne J.; Trauner, Doris A.

    2005-01-01

    The present study used a chimeric stimuli task to assess the magnitude of the left-hemispace bias in children with congenital unilateral brain damage (n=46) as compared to typically developing matched controls (n=46). As would be expected, controls exhibited a significant left-hemispace bias. In the presence of left hemisphere (LH) damage, the…

  2. Expression Profile of DNA Damage Signaling Genes in Proton Exposed Mouse Brain

    NASA Astrophysics Data System (ADS)

    Ramesh, Govindarajan; Wu, Honglu

    Exposure of living systems to radiation results in a wide assortment of lesions, the most signif-icant of is damage to genomic DNA which induce several cellular functions such as cell cycle arrest, repair, apoptosis etc. The radiation induced DNA damage investigation is one of the im-portant area in biology, but still the information available regarding the effects of proton is very limited. In this report, we investigated the differential gene expression pattern of DNA damage signaling genes particularly, damaged DNA binding, repair, cell cycle arrest, checkpoints and apoptosis using quantitative real-time RT-PCR array in proton exposed mouse brain tissues. The expression profiles showed significant changes in DNA damage related genes in 2Gy proton exposed mouse brain tissues as compared with control brain tissues. Furthermore, we also show that significantly increased levels of apoptotic related genes, caspase-3 and 8 activities in these cells, suggesting that in addition to differential expression of DNA damage genes, the alteration of apoptosis related genes may also contribute to the radiation induced DNA damage followed by programmed cell death. In summary, our findings suggest that proton exposed brain tissue undergo severe DNA damage which in turn destabilize the chromatin stability.

  3. Acute and late gastrointestinal toxicity after radiotherapy in prostate cancer patients: Consequential late damage

    SciTech Connect

    Heemsbergen, Wilma D. . E-mail: w.heemsbergen@nki.nl; Peeters, Stephanie T.H.; Koper, Peter; Hoogeman, Mischa S.; Lebesque, Joos V.

    2006-09-01

    Purpose: Late gastrointestinal (GI) toxicity after radiotherapy can be partly explained by late effects of acute toxicity (consequential late damage). We studied whether there is a direct relationship between acute and late GI toxicity. Patients and Methods: A total of 553 evaluable patients from the Dutch dose escalation trial (68 Gy vs. 78 Gy) were included. We defined three outcomes for acute reactions: 1) maximum Radiation Therapy Oncology Group acute toxicity, 2) maximum acute mucous discharge (AMD), and 3) maximum acute proctitis. Within a multivariable model, late endpoints (overall toxicity and five toxicity indicators) were studied as a function of acute toxicity, pretreatment symptoms, and relevant dose parameters. Results: At multivariable analysis, AMD and acute proctitis were strong predictors for overall toxicity, 'intermittent bleeding,' and 'incontinence pads' (p {<=} 0.01). For 'stools {>=}6/day' all three were strong predictors. No significant associations were found for 'severe bleeding' and 'use of steroids.' The predictive power of the dose parameters remained at the same level or became weaker for most late endpoints. Conclusions: Acute GI toxicity is an independent significant predictor of late GI toxicity. This suggests a significant consequential component in the development of late GI toxicity.

  4. Alteration in rectification of potassium channels in perinatal hypoxia ischemia brain damage.

    PubMed

    Chen, Penghui; Wang, Liyan; Deng, Qiyue; Ruan, Huaizhen; Cai, Wenqin

    2015-01-15

    Oligodendrocyte progenitor cells (OPCs) are susceptible to perinatal hypoxia ischemia brain damage (HIBD), which results in infant cerebral palsy due to the effects on myelination. The origin of OPC vulnerability in HIBD, however, remains controversial. In this study, we defined the HIBD punctate lesions by MRI diffuse excessive high signal intensity (DEHSI) in postnatal 7-day-old rats. The electrophysiological functional properties of OPCs in HIBD were recorded by patch-clamp in acute cerebral cortex slices. The slices were intracellularly injected with Lucifer yellow and immunohistochemically labeled with NG2 antibody to identify local OPCs. Passive membrane properties and K(+) channel functions in OPCs were analyzed to estimate the onset of vulnerability in HIBD. The resting membrane potential, membrane resistance, and membrane capacitance of OPCs were increased in both the gray and white matter of the cerebral cortex. OPCs in both the gray and white matter exhibited voltage-dependent K(+) currents, which consisted of the initiated rectified potassium currents (IA) and the sustained rectified currents (IK). The significant alternation in membrane resistance was influenced by the diversity of potassium channel kinetics. These findings suggest that the rectification of IA and IK channels may play a significant role in OPC vulnerability in HIBD. PMID:25355958

  5. A clinical study on closing-in in focal brain-damaged individuals.

    PubMed

    De Lucia, Natascia; Grossi, Dario; Trojano, Luigi

    2016-04-15

    In visuo-constructional assessment, brain-damaged individuals may copy figures near to or superimposed on the model, showing the Closing-in (CI). CI has been largely investigated in dementia, and often ascribed to impairments of the attention/executive abilities ("Attraction hypothesis"). Only a few dated studies investigated frequency of CI in brain-damaged individuals, without clarifying the genesis of the phenomenon. We aimed at testing the "Attraction hypothesis" in 27 individuals with focal frontal cortical or sub-cortical brain lesions by a dual-task experimental paradigm. The participants underwent a neuropsychological battery and a copying task to be performed alone (single task condition), or concurrently with a simple or a complex verbal secondary task (dual-task conditions). CI was found in 66% of frontal-damaged individuals, who scored significantly lower than healthy adults on all neuropsychological measures; brain-damaged individuals showing CI performed worse than frontal-damaged individuals without CI on frontal and visuo-constructional measures. In the dual-task condition with the complex secondary task CI was significantly enhanced, with a weaker tendency to self-correction, in individuals with CI compared to individuals without CI. These findings would confirm that the CI in brain-damaged individuals is related to reduction of attentional resources, consistently with the "Attraction hypothesis". PMID:27000246

  6. Expression of heat shock protein (HSP 72 kD) during acute methamphetamine intoxication depends on brain hyperthermia: neurotoxicity or neuroprotection?

    PubMed Central

    Kiyatkin, Eugene A.; Sharma, Hari S.

    2011-01-01

    In the present study, light and electron microscopy were used to examine heat shock protein (HSP 72kD) expression during acute methamphetamine (METH) intoxication in rats and evaluate its relationships with brain temperature and alterations in a number of other histochemical and morphological parameters. Freely moving rats received METH at the same dose (9 mg/kg, sc) but at different ambient temperatures (23 and 29°C), showing a wide range of brain temperature elevations (37.6–42.5°C); brains were taken for histochemical and morphological evaluations at peak of brain temperature increase. We found that acute METH intoxication induces massive and wise-spread HSP expression in neural and glial cells examined in details in the cortex, hippocampus, thalamus, and hypothalamus. In each of these structures, the number of HSP-positive cells tightly correlated with brain temperature elevation. The changes in HSP immunoreactivity were also tightly related to alterations in permeability of the blood-brain barrier, acute glial activation and brain edema assessed by albumin and GFAP immunoreactivity and measuring tissue water content, respectively. While robust and generalized HSP production normally appears to be the part of an adaptive brain response associated with METH-induced metabolic activation, activation of this protective mechanism has its natural limits and could not counteract the damaging effects of oxidative stress, high temperature and edema – the leading factors of METH-induced neurotoxicity. PMID:20931246

  7. Systems approach to the study of brain damage in the very preterm newborn

    PubMed Central

    Leviton, Alan; Gressens, Pierre; Wolkenhauer, Olaf; Dammann, Olaf

    2015-01-01

    Background: A systems approach to the study of brain damage in very preterm newborns has been lacking. Methods: In this perspective piece, we offer encephalopathy of prematurity as an example of the complexity and interrelatedness of brain-damaging molecular processes that can be initiated inflammatory phenomena. Results: Using three transcription factors, nuclear factor-kappa B (NF-κB), Notch-1, and nuclear factor erythroid 2 related factor 2 (NRF2), we show the inter-connectedness of signaling pathways activated by some antecedents of encephalopathy of prematurity. Conclusions: We hope that as biomarkers of exposures and processes leading to brain damage in the most immature newborns become more readily available, those who apply a systems approach to the study of neuroscience can be persuaded to study the pathogenesis of brain disorders in the very preterm newborn. PMID:25926780

  8. Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model

    PubMed Central

    Hacioglu, Gulay; Senturk, Ayse; Ince, Imran; Alver, Ahmet

    2016-01-01

    Objective(s): Exposing to stress may be associated with increased production of reactive oxygen species (ROS). Therefore, high level of oxidative stress may eventually give rise to accumulation of oxidative damage and development of numerous neurodegenerative diseases. It has been presented that brain-derived neurotrophic factor (BDNF) supports neurons against various neurodegenerative conditions. Lately, there has been growing evidence that changes in the cerebral neurotrophic support and especially in the BDNF expression and its engagement with ROS might be important in various disorders and neurodegenerative diseases. Hence, we aimed to investigate protective effects of BDNF against stress-induced oxidative damage. Materials and Methods: Five- to six-month-old male wild-type and BDNF knock-down mice were used in this study. Activities of catalase (CAT) and superoxide dismutase (SOD) enzymes, and the amount of malondialdehyde (MDA) were assessed in the cerebral homogenates of studied groups in response to acute restraint stress. Results: Exposing to acute physiological stress led to significant elevation in the markers of oxidative stress in the cerebral cortexes of experimental groups. Conclusion: As BDNF-deficient mice were observed to be more susceptible to stress-induced oxidative damage, it can be suggested that there is a direct interplay between oxidative stress indicators and BDNF levels in the brain. PMID:27279982

  9. Effort test performance in clinical acute brain injury, community brain injury, and epilepsy populations.

    PubMed

    Hampson, Natalie E; Kemp, Steven; Coughlan, Anthony K; Moulin, Chris J A; Bhakta, Bipin B

    2014-01-01

    Effort tests have become commonplace within medico-legal and forensic contexts and their use is rising within clinical settings. It is recognized that some patients may fail effort tests due to cognitive impairment and not because of poor effort. However, investigation of the base rate of failure among clinical populations other than dementia is limited. Forty-seven clinical participants were recruited and comprised three subgroups: acute brain injury (N = 11), community brain injury (N = 20), and intractable epilepsy (N = 16). Base rates of failure on the Word Memory Test (WMT; Green, 2003 ) and six other less well-validated measures were investigated. A significant minority of patients failed effort tests according to standard cutoff scores, particularly patients with severe traumatic brain injury and marked frontal-executive features. The WMT was able to identify failures associated with significant cognitive impairment through the application of profile analysis and/or lowered cutoff levels. Implications for clinical assessment, effort test interpretation, and future research are discussed. PMID:25084843

  10. Contralateral and ipsilateral disorders of visual attention in patients with unilateral brain damage.

    PubMed

    Gainotti, G; Giustolisi, L; Nocentini, U

    1990-05-01

    To explain the prevalence of unilateral spatial neglect in patients with right brain damage, Heilman et al have suggested that the attentional neurons of the right parietal lobe might have bilateral receptive fields, whereas the homologous cells of the left hemisphere would have strictly contralateral receptive fields. One implication of this theory is that patients with right brain damage should show a prevalence of disorders of visual attention not only in the half space contralateral to the damaged hemisphere, but also in the ipsilateral one. To check this theory, 50 control subjects, 102 right and 125 left brain-damaged patients were given a drawing completion task in which patients were requested to complete the missing parts of a star, a cube and a house. Omissions of lines lying on the sides of the models contralateral and ipsilateral to the damaged hemisphere were taken separately into account. Results did not confirm the hypothesis, since right brain-damaged patients failed to complete the contralateral sides of the models much more frequently than patients with left brain injury, but no difference was found between the two hemispheric groups when ipsilateral disorders of visual attention were taken into account. Furthermore, no correlation was found between omissions of lines lying on the sides of the models contralateral and ipsilateral to the damaged hemisphere. This finding suggests that contralateral and ipsilateral disorders of visual attention are not due to the same mechanism in right brain-damaged patients. The alternative hypothesis viewing ipsilateral disorders as resulting from a widespread lowering of general attention (and only contralateral neglect reflecting a specific disorder of visual attention) was supported by results obtained on a verbal memory test, used to evaluate the general cognitive and attention level of the patients. Patients with clear-cut ipislateral inattention obtained very low scores on this test, whereas patients with

  11. Magnetic resonance analysis of the effects of acute ammonia intoxication on rat brain. Role of NMDA receptors.

    PubMed

    Cauli, Omar; López-Larrubia, Pilar; Rodrigues, Tiago B; Cerdán, Sebastián; Felipo, Vicente

    2007-11-01

    Acute ammonia intoxication leads to rapid death, which is prevented by blocking N-methyl-d-aspartate (NMDA) receptors. The subsequent mechanisms leading to death remain unclear. Brain edema seems an important step. The aim of this work was to study the effects of acute ammonia intoxication on different cerebral parameters in vivo using magnetic resonance and to assess which effects are mediated by NMDA receptors activation. To assess edema induction, we injected rats with ammonium acetate and measured apparent diffusion coefficient (ADC) in 16 brain areas. We also analyzed the effects on T1, T2, and T2* maps and whether these effects are prevented by blocking NMDA receptors. The effects of acute ammonia intoxication are different in different brain areas. T1 relaxation time is reduced in eight areas. T2 relaxation time is reduced only in ventral thalamus and globus pallidus. ADC values increased in hippocampus, caudate-putamen, substantia nigra and cerebellar cortex, reflecting vasogenic edema. ADC decreased in hypothalamus, reflecting cytotoxic edema. Myo-inositol increased in cerebellum and substantia nigra, reflecting vasogenic edema. N-acetyl-aspartate decreased in cerebellum, reflecting neuronal damage. Changes in N-acetyl-aspartate, T1 and T2 are prevented by blocking NMDA receptors with MK-801 while changes in ADC or myo-inositol (induction of edema) are not. PMID:17727627

  12. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

    PubMed

    Shin, Jin A; Jeong, Sae Im; Kim, Minsuk; Yoon, Joo Chun; Kim, Hee-Sun; Park, Eun-Mi

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population. PMID:26184082

  13. Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

    PubMed

    Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

    2014-06-01

    Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration. PMID:24338618

  14. Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

    PubMed

    Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

    2015-01-01

    Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI. PMID:26064794

  15. Thaliporphine derivative improves acute lung injury after traumatic brain injury.

    PubMed

    Chen, Gunng-Shinng; Huang, Kuo-Feng; Huang, Chien-Chu; Wang, Jia-Yi

    2015-01-01

    Acute lung injury (ALI) occurs frequently in patients with severe traumatic brain injury (TBI) and is associated with a poor clinical outcome. Aquaporins (AQPs), particularly AQP1 and AQP4, maintain water balances between the epithelial and microvascular domains of the lung. Since pulmonary edema (PE) usually occurs in the TBI-induced ALI patients, we investigated the effects of a thaliporphine derivative, TM-1, on the expression of AQPs and histological outcomes in the lung following TBI in rats. TM-1 administered (10 mg/kg, intraperitoneal injection) at 3 or 4 h after TBI significantly reduced the elevated mRNA expression and protein levels of AQP1 and AQP4 and diminished the wet/dry weight ratio, which reflects PE, in the lung at 8 and 24 h after TBI. Postinjury TM-1 administration also improved histopathological changes at 8 and 24 h after TBI. PE was accompanied with tissue pathological changes because a positive correlation between the lung injury score and the wet/dry weight ratio in the same animal was observed. Postinjury administration of TM-1 improved ALI and reduced PE at 8 and 24 h following TBI. The pulmonary-protective effect of TM-1 may be attributed to, at least in part, downregulation of AQP1 and AQP4 expression after TBI. PMID:25705683

  16. Early glycoxidation damage in brains from Down's syndrome.

    PubMed

    Odetti, P; Angelini, G; Dapino, D; Zaccheo, D; Garibaldi, S; Dagna-Bricarelli, F; Piombo, G; Perry, G; Smith, M; Traverso, N; Tabaton, M

    1998-02-24

    In Down's syndrome, the presence of three copies of chromosome 21 is associated with premature aging and progressive mental retardation sharing the pathological features of Alzheimer disease. Early cortical dysgenesis and late neuronal degeneration are probably caused by an overproduction of amyloid beta-peptide, followed by an increased cellular oxidation. Interestingly, chromosome 21 codes for superoxide-dismutase and amyloid beta precursor resulting, in Down's syndrome, in an overflow of these gene products and metabolites. We studied Down's fetal brain cortex to evaluate the presence and amount of lipid and protein oxidation markers; moreover, we quantified two forms of glycation end products that are known to be involved in the process of cellular oxidation. All these parameters are significantly increased in Down's fetal brains in comparison to controls, providing the evidence that accelerated brain glycoxidation occurs very early in the life of Down's syndrome subjects. PMID:9501012

  17. Pharmacological mitigation of tissue damage during brain microdialysis.

    PubMed

    Nesbitt, Kathryn M; Jaquins-Gerstl, Andrea; Skoda, Erin M; Wipf, Peter; Michael, Adrian C

    2013-09-01

    Microdialysis sampling in the brain is employed frequently in the chemical analysis of neurological function and disease, but implanting the probes, which are substantially larger than the size and spacing of brain cells and blood vessels, is injurious and triggers ischemia, gliosis, and cell death at the sampling site. The nature of the interface between the brain and the microdialysis probe is critical to the use of microdialysis as a neurochemical analysis technique. The objective of the work reported here was to investigate the potential of two compounds, dexamethasone, a glucocorticoid anti-inflammatory agent, and XJB-5-131, a mitochondrially targeted reactive oxygen species scavenger, to mitigate the penetration injury. Measurements were performed in the rat brain striatum, which is densely innervated by axons that release dopamine, an electroactive neurotransmitter. We used voltammetry to measure electrically evoked dopamine release next to microdialysis probes during the retrodialysis of dexamethasone or XJB-5-131. After the in vivo measurements, the brain tissue containing the microdialysis probe tracks was examined by fluorescence microscopy using markers for ischemia, neuronal nuclei, macrophages, and dopamine axons and terminals. Dexamethasone and XJB-5-131 each diminished the loss of evoked dopamine activity, diminished ischemia, diminished the loss of neuronal nuclei, diminished the appearance of extravasated macrophages, and diminished the loss of dopamine axons and terminals next to the probes. Our findings confirm the ability of dexamethasone and XJB-5-131 to mitigate, but not eliminate, the effects of the penetration injury caused by implanting microdialysis probes into brain tissue. PMID:23927692

  18. Lipopolysaccharide hyporesponsiveness: protective or damaging response to the brain?

    PubMed

    Pardon, Marie Christine

    2015-01-01

    Lipopolysaccharide (LPS) endotoxins are widely used as experimental models of systemic bacterial infection and trigger robust inflammation by potently activating toll-like receptors 4 (TLR4) expressed on innate immune cells. Their ability to trigger robust neuroinflammation despite poor brain penetration can prove useful for the understanding of how inflammation induced by viral infections contributes to the pathogenesis of neurodegenerative diseases. A single LPS challenge often result in a blunted inflammatory response to subsequent stimulation by LPS and other TLR ligands, but the extent to which endotoxin tolerance occur in the brain requires further clarification. LPS is also thought to render the brain transiently resistant to subsequent brain injuries by attenuating the concomitant pro-inflammatory response. While LPS hyporesponsiveness and preconditioning are classically seen as protective mechanisms limiting the toxic effects of sustained inflammation, recent research casts doubt as to whether they have beneficial or detrimental roles on the brain and in neurodegenerative disease. These observations suggest that spatio-temporal aspects of the immune responses to LPS and the disease status are determinant factors. Endotoxin tolerance may lead to a late pro-inflammatory response with potential harmful consequences. And while reduced TLR4 signaling reduces the risk of neurodegenerative diseases, up-regulation of anti-inflammatory cytokines associated with LPS hyporesponsiveness can have deleterious consequences to the brain by inhibiting the protective phenotype of microglia, aggravating the progression of some neurodegenerative conditions such as Alzheimer's disease. Beneficial effects of LPS preconditioning, however appear to require a stimulation of anti-inflammatory mediators rather than an attenuation of the pro-inflammatory response. PMID:26662122

  19. Trans-Differentiation of Neural Stem Cells: A Therapeutic Mechanism Against the Radiation Induced Brain Damage

    PubMed Central

    Kang, Bong Gu; Lee, Se Jeong; Kim, Kang Ho; Yang, Heekyoung; Lee, Young-Ae; Cho, Yu Jin; Im, Yong-Seok; Lee, Dong-Sup; Lim, Do-Hoon; Kim, Dong Hyun; Um, Hong-Duck; Lee, Sang-Hun; Lee, Jung-II; Nam, Do-Hyun

    2012-01-01

    Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases. PMID:22347993

  20. Relationship of plasma S100B and MBP with brain damage in preterm infants

    PubMed Central

    Zhou, Wei; Li, Wei; Qu, Liu-Hong; Tang, Juan; Chen, Shan; Rong, Xiao

    2015-01-01

    To study the relationships of MBP and S100B with PVH-IVH and PVL in preterm infants. 385 cases of preterm infants, whose gestational age was less than 34 weeks, were enrolled in the study. The plasma levels of S100B and MBP were detected within 24 hours and on the 3rd, 7th, 14th day after birth. Cranial ultrasound was preformed 2-3 d, 1 week, 2 weeks, 3 weeks and 4 weeks after birth. They also received Cranial MRI examination before discharge or when the correct gestational age reached 40 weeks. According to the exclusion standard, 73 cases were excluded. The included 312 cases were divided into 3 groups (no brain damage group, PVH-IVH group and PVL group) according to the result of cranial ultrasound and MRI. The differences of plasma levels of S100B and MBP among groups were compared, and the relationships of the plasma levels of S100B and MBP with gestational age in no brain damage group were analyzed. The results of cranial ultrasound and/or MRI showed: 204 cases had no brain damage (enrolled in no brain damage group); 69 cases had PVH-IVH (enrolled in PVH-IVH group); 27 cases had PVL and 12 cases had PVL and PVH-IVH (both enrolled in PVL group). The plasma level of S100B: within 24 h and on the 3rd d after birth, the serum levels of S100B in PVH-IVH group were significantly higher than those in no brain damage group (P < 0.05); and the plasma levels of S100B in PVL group were significantly higher than those in no brain damage group and PVH-IVH group (all P < 0.05). On 7th d and 14th d after birth, there were no significant differences between PVH-IVH group and no brain damage group (P > 0.05); and the plasma levels of S100B in PVL group were still significantly higher than those in no brain damage group and PVH-IVH group (all P < 0.05). The plasma levels of MBP: within 24 h and on the 3rd d, 7th d and 14th d after birth, there were no significant differences between PVH-IVH group and no brain damage group (all P > 0.05); and the plasma levels of MBP in PVL

  1. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response.

    PubMed

    Yang, Yang; Zhang, Yan; Wang, Zhaotao; Wang, Shanshan; Gao, Mou; Xu, Ruxiang; Liang, Chunyang; Zhang, Hongtian

    2016-04-01

    The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability. PMID:26498936

  2. Conformational Change in Transfer RNA Is an Early Indicator of Acute Cellular Damage

    PubMed Central

    Mishima, Eikan; Inoue, Chisako; Saigusa, Daisuke; Inoue, Ryusuke; Ito, Koki; Suzuki, Yusuke; Jinno, Daisuke; Tsukui, Yuri; Akamatsu, Yosuke; Araki, Masatake; Araki, Kimi; Shimizu, Ritsuko; Shinke, Haruka; Suzuki, Takehiro; Takeuchi, Yoichi; Shima, Hisato; Akiyama, Yasutoshi; Toyohara, Takafumi; Suzuki, Chitose; Saiki, Yoshikatu; Tominaga, Teiji; Miyagi, Shigehito; Kawagisihi, Naoki; Soga, Tomoyoshi; Ohkubo, Takayoshi; Yamamura, Kenichi; Imai, Yutaka; Masuda, Satohiro; Sabbisetti, Venkata; Ichimura, Takaharu; Mount, David B.; Bonventre, Joseph V.; Ito, Sadayoshi; Tomioka, Yoshihisa; Itoh, Kunihiko

    2014-01-01

    Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases, including AKI and CKD. Thus, early detection of oxidative tissue damage is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we show that oxidative stress induces a direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation and occurs much earlier than DNA damage. In various models of tissue damage (ischemic reperfusion, toxic injury, and irradiation), the levels of circulating tRNA derivatives increased rapidly. In humans, the levels of circulating tRNA derivatives also increased under conditions of acute renal ischemia, even before levels of other known tissue damage markers increased. Notably, the level of circulating free m1A correlated with mortality in the general population (n=1033) over a mean follow-up of 6.7 years. Compared with healthy controls, patients with CKD had higher levels of circulating free m1A, which were reduced by treatment with pitavastatin (2 mg/d; n=29). Therefore, tRNA damage reflects early oxidative stress damage, and detection of tRNA damage may be a useful tool for identifying organ damage and forming a clinical prognosis. PMID:24833129

  3. Accumulation of oxidative DNA damage in brain mitochondria in mouse model of hereditary ferritinopathy.

    PubMed

    Deng, Xiaoling; Vidal, Ruben; Englander, Ella W

    2010-07-19

    Tissue iron content is strictly regulated to concomitantly satisfy specialized metabolic requirements and avoid toxicity. Ferritin, a multi-subunit iron storage protein, is central to maintenance of iron homeostasis in the brain. Mutations in the ferritin light chain (FTL)-encoding gene underlie the autosomal dominant, neurodegenerative disease, neuroferritinopathy/hereditary ferritinopathy (HF). HF is characterized by progressive accumulation of ferritin and iron. To gain insight into mechanisms by which FTL mutations promote neurodegeneration, a transgenic mouse, expressing human mutant form of FTL, was recently generated. The FTL mouse exhibits buildup of iron in the brain and presents manifestations of oxidative stress reminiscent of the human disease. Here, we asked whether oxidative DNA damage accumulates in the FTL mouse brain. Long-range PCR (L-PCR) amplification-mediated DNA damage detection assays revealed that the integrity of mitochondrial DNA (mtDNA) in the brain was significantly compromised in the 12- but not 6-month-old FTL mice. Furthermore, L-PCR employed in conjunction with DNA modifying enzymes, which target specific DNA adducts, revealed the types of oxidative adducts accumulating in mtDNA in the FTL brain. Consistently with DNA damage predicted to form under conditions of excessive oxidative stress, detected adducts include, oxidized guanines, abasic sites and strand breaks. Elevated mtDNA damage may impair mitochondrial function and brain energetics and in the long term contribute to neuronal loss and exacerbate neurodegeneration in HF. PMID:20478358

  4. Insight into Pre-Clinical Models of Traumatic Brain Injury Using Circulating Brain Damage Biomarkers: Operation Brain Trauma Therapy.

    PubMed

    Mondello, Stefania; Shear, Deborah A; Bramlett, Helen M; Dixon, C Edward; Schmid, Kara E; Dietrich, W Dalton; Wang, Kevin K W; Hayes, Ronald L; Glushakova, Olena; Catania, Michael; Richieri, Steven P; Povlishock, John T; Tortella, Frank C; Kochanek, Patrick M

    2016-03-15

    Operation Brain Trauma Therapy (OBTT) is a multicenter pre-clinical drug screening consortium testing promising therapies for traumatic brain injury (TBI) in three well-established models of TBI in rats--namely, parasagittal fluid percussion injury (FPI), controlled cortical impact (CCI), and penetrating ballistic-like brain injury (PBBI). This article presents unique characterization of these models using histological and behavioral outcomes and novel candidate biomarkers from the first three treatment trials of OBTT. Adult rats underwent CCI, FPI, or PBBI and were treated with vehicle (VEH). Shams underwent all manipulations except trauma. The glial marker glial fibrillary acidic protein (GFAP) and the neuronal marker ubiquitin C-terminal hydrolase (UCH-L1) were measured by enzyme-linked immunosorbent assay in blood at 4 and 24 h, and their delta 24-4 h was calculated for each marker. Comparing sham groups across experiments, no differences were found in the same model. Similarly, comparing TBI + VEH groups across experiments, no differences were found in the same model. GFAP was acutely increased in injured rats in each model, with significant differences in levels and temporal patterns mirrored by significant differences in delta 24-4 h GFAP levels and neuropathological and behavioral outcomes. Circulating GFAP levels at 4 and 24 h were powerful predictors of 21 day contusion volume and tissue loss. UCH-L1 showed similar tendencies, albeit with less robust differences between sham and injury groups. Significant differences were also found comparing shams across the models. Our findings (1) demonstrate that TBI models display specific biomarker profiles, functional deficits, and pathological consequence; (2) support the concept that there are different cellular, molecular, and pathophysiological responses to TBI in each model; and (3) advance our understanding of TBI, providing opportunities for a successful translation and holding promise for theranostic

  5. An introduction to alcohol-induced brain damage and its causes.

    PubMed

    Harper, C; Kril, J

    1994-01-01

    The aim of the symposium on alcohol-induced brain damage is to review current opinion and recent advances concerning factors which are thought to play a significant role in this disorder. The three principal factors are: alcohol specific neurotoxicity, associated vitamin B1 (thiamine) deficiency (the Wernicke-Korsakoff syndrome) and liver failure secondary to alcoholic cirrhosis. There is a complex interaction of these and other factors and it is difficult to dissect out the relative importance of each in the pathogenesis of alcohol-related brain damage. Moreover recent molecular and biochemical studies suggest that several of these factors may have pathogenetic mechanisms in common-for example, excitotoxicity, mitric oxide and free radicals. The application of new technologies in neuropathological studies of carefully selected groups of alcoholic cases is beginning to reveal a far more complex pattern of damage than current view holds. Quantitative morphometry and immunohistochemistry can be combined to create three dimensional images of various anatomical regions of the brain together with detailed analyses of neuronal counts, sizes and neurochemical type. In the Wernicke-Korsakoff syndrome (WKS) there is good evidence (in support of neuropsychological and neuroradiological data) to suggest that specific populations of neurons are damaged in cortical and subcortical regions. In those cases with the WKS there is also evidence of pathological damage in cortical and subcortical regions other than the well described periventricular distributions. These more detailed studies provide us with a more comprehensive understanding of alcohol-related brain damage. PMID:8974342

  6. Unilateral brain damage effects on processing homonymous and polysemous words.

    PubMed

    Klepousniotou, Ekaterini; Baum, Shari R

    2005-06-01

    Using an auditory semantic priming paradigm, the present study investigated the abilities of left-hemisphere-damaged (LHD) non-fluent aphasic, right-hemisphere-damaged (RHD) and normal control individuals to access, out of context, the multiple meanings of three types of ambiguous words, namely homonyms (e.g., "punch"), metonymies (e.g., "rabbit"), and metaphors (e.g., "star"). In addition, the study tested certain predictions of the "suppression deficit" and "coarse semantic coding" hypotheses that have been proposed to account for the linguistic deficits typically observed after RH damage. Homonymous, metonymous, and metaphorical words were used as primes followed after a short (100 ms) or a long (1000 ms) inter-stimulus interval (ISI) by dominant-meaning-related, subordinate-meaning-related or unrelated target words. No significant group effects were found, and for both ISIs, dominant- and subordinate-related targets were facilitated relative to unrelated control targets for the homonymy and metonymy conditions. In contrast, for the metaphor condition, only targets related to the dominant meaning were facilitated. These findings provide only partial support for the "suppression deficit" hypothesis and no support for the "coarse semantic coding" hypothesis (as interpreted herein) indicating that patients with focal LH or RH damage can access the multiple meanings of ambiguous words and exhibit processing abilities comparable to those of older normal control subjects, at least at the single-word level. PMID:15862856

  7. Inferencing Processes after Right Hemisphere Brain Damage: Maintenance of Inferences

    ERIC Educational Resources Information Center

    Blake, Margaret Lehman

    2009-01-01

    Purpose: This study was designed to replicate and extend a previous study of inferencing in which some adults with right hemisphere damage (RHD) generated but did not maintain predictive inferences over time (M. Lehman-Blake & C. Tompkins, 2001). Two hypotheses were tested: (a) inferences were deactivated, and (b) selection of previously generated…

  8. Brain capacity for repair of oxidatively damaged DNA and preservation of neuronal function.

    PubMed

    Englander, Ella W

    2008-01-01

    Accumulation of oxidative DNA damage in the human brain has been implicated in etiologies of post-traumatic and age-associated declines in neuronal function. In neurons, because of high metabolic rates and prolonged life span, exposure to free radicals is intense and risk for accumulation of damaged DNA is amplified. While data indicate that the brain is equipped to repair nuclear and mitochondrial DNA, it is unclear whether repair is executed by distinct subsets of the DNA-repair machinery. Likewise, there are no firm assessments of brain capacity for accurate DNA repair under normal and more so compromised conditions. Consequently, the scope of DNA repair in the brain and the impact of resolution of oxidative lesions on neuronal survival and function remain largely unknown. This review considers evidences for brain levels and activities of the base excision repair (BER) pathway in the context of newly available, comprehensive in situ hybridization analyses of genes encoding repair enzymes. These analyses suggest that not all subsets of BER are equally represented in the brain. Because BER is the major repair process for oxidatively damaged DNA, to what extent parsimonious BER may contribute to development of neuronal dysfunction and brain injury under compromised conditions, is discussed. PMID:18374390

  9. Protective and damaging effects of stress mediators: central role of the brain

    PubMed Central

    McEwen, Bruce S.

    2006-01-01

    The mind involves the whole body, and two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms. Stress is a condition of the mind-body interaction, and a factor in the expression of disease that differs among individuals. It is not just the dramatic stressful events that exact their toll, but rather the many events of daily life that elevate and sustain activities of physiological systems and cause sleep deprivation, overeating, and other health-damaging behaviors, producing the feeling of being “stressed out.” Over time, this results in wear and tear on the body, which is called “allostatic load,” and it reflects not only the impact of life experiences but also of genetic load, individual lifestyle habits reflecting items such as diet, exercise, and substance abuse, and developmental experiences that set life-long patterns of behavior and physiological reactivity. Hormones associated with stress and allostatic load protect the body in the short run and promote adaptation by the process known as allostasis, but in the long run allostatic load causes changes in the body that can lead to disease. The brain is the key organ of stress, allostasis, and allostatic load, because it determines what is threatening and therefore stressful, and also determines the physiological and behavioral responses. Brain regions such as the hippocampus, amygdala, and prefrontal cortex respond to acute and chronic stress by undergoing structural remodeling, which alters behavioral and physiological responses. Translational studies in humans with structural and functional imaging reveal smaller hippocampal volume in stress-related conditions, such as mild cognitive impairment in aging and prolonged major depressive illness, as well as in individuals with low self-esteem. Alterations in amygdala and prefrontal cortex are also reported. Besides Pharmaceuticals, approaches to alleviate chronic stress and reduce

  10. Emotional and non-emotional facial behaviour in patients with unilateral brain damage.

    PubMed Central

    Borod, J C; Koff, E; Lorch, M P; Nicholas, M; Welkowitz, J

    1988-01-01

    Aspects of emotional facial expression (responsivity, appropriateness, intensity) were examined in brain-damaged adults with right or left hemisphere cerebrovascular lesions and in normal controls. Subjects were videotaped during experimental procedures designed to elicit emotional facial expression and non-emotional facial movement (paralysis, mobility, praxis). On tasks of emotional facial expression, patients with right hemisphere pathology were less responsive and less appropriate than patients with left hemisphere pathology or normal controls. These results corroborate other research findings that the right cerebral hemisphere is dominant for the expression of facial emotion. Both brain-damaged groups had substantial facial paralysis and impairment in muscular mobility on the hemiface contralateral to site of lesion, and the left brain-damaged group had bucco-facial apraxia. Performance measures of emotional expression and non-emotional movement were uncorrelated, suggesting a dissociation between these two systems of facial behaviour. PMID:3404189

  11. Brain damage following prophylactic cranial irradiation in lung cancer survivors.

    PubMed

    Simó, Marta; Vaquero, Lucía; Ripollés, Pablo; Jové, Josep; Fuentes, Rafael; Cardenal, Felipe; Rodríguez-Fornells, Antoni; Bruna, Jordi

    2016-03-01

    Long-term toxic effects of prophylactic cranial irradiation (PCI) on cognition in small cell lung cancer (SCLC) patients have not yet been well-established. The aim of our study was to examine the cognitive toxic effects together with brain structural changes in a group of long-term SCLC survivors treated with PCI. Eleven SCLC patients, who underwent PCI ≥ 2 years before, were compared with an age and education matched healthy control group. Both groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging. Voxel-based morphometry and Tract-based Spatial Statistics were used to study gray matter density (GMD) and white matter (WM) microstructural changes. Cognitive deterioration was correlated with GMD and Fractional Anisotropy (FA). Finally, we carried out a single-subject analysis in order to evaluate individual structural brain changes. Nearly half of the SCLC met criteria for cognitive impairment, all exhibiting a global worsening of cognitive functioning. Patients showed significant decreases of GMD in basal ganglia bilaterally (putamen and caudate), bilateral thalamus and right insula, together with WM microstructural changes of the entire corpus callosum. Cognitive deterioration scores correlated positively with mean FA values in the corpus callosum. Single-subject analysis revealed that GMD and WM changes were consistently observed in nearly all patients. This study showed neuropsychological deficits together with brain-specific structural differences in long-term SCLC survivors. Our results suggest that PCI therapy, possibly together with platinum-based chemotherapy, was associated to permanent long-term cognitive and structural brain effects in a SCLC population. PMID:26015269

  12. Protection of the blood-brain barrier by hypercapnia during acute hypertension

    SciTech Connect

    Baumbach, G.L.; Mayhan, W.G.; Heistad, D.D.

    1986-08-01

    The purpose of this study was to examine effects of hypercapnia on susceptibility of the blood-brain barrier to disruption during acute hypertension. Two methods were used to test the hypothesis that cerebral vasodilation during hypercapnia increases disruption of the blood-brain barrier. First, permeability of the blood-brain barrier was measured in anesthetized cats with SVI-labeled serum albumin. Severe hypertension markedly increased permeability of the blood-brain barrier during normocapnia, but not during hypercapnia. The protective effect of hypercapnia was not dependent on sympathetic nerves. Second, in anesthetized rats, permeability of the barrier was quantitated by clearance of fluorescent dextran. Disruption of the blood-brain barrier during hypertension was decreased by hypercapnia. Because disruption of the blood-brain barrier occurred primarily in pial venules, the authors also measured pial venular diameter and pressure. Acute hypertension increased pial venular pressure and diameter in normocapnic rats. Hypercapnia alone increased pial venular pressure and pial venular diameter, and acute hypertension during hypercapnia further increased venular pressure. The magnitude of increase in pial venular pressure during acute hypertension was significantly less in hypercapnic than in normocapnic rats. They conclude that hypercapnia protects the blood-brain barrier. Possible mechanisms of this effect include attenuation of the incremental increase in pial venular pressure by hypercapnia or a direct effect on the blood-brain barrier not related to venous pressure.

  13. Contrasting Acute and Slow-Growing Lesions: A New Door to Brain Plasticity

    ERIC Educational Resources Information Center

    Desmurget, Michel; Bonnetblanc, FranCois; Duffau, Hugues

    2007-01-01

    The concept of plasticity describes the mechanisms that rearrange cerebral organization following a brain injury. During the last century, plasticity has been mainly investigated in humans with acute strokes. It was then shown: (i) that the brain is organized into highly specialized functional areas, often designated "eloquent" areas and (ii) that…

  14. Jaw opening and swallow triggering method for bilateral-brain-damaged patients: K-point stimulation.

    PubMed

    Kojima, Chieko; Fujishima, Ichiro; Ohkuma, Ruri; Maeda, Hiroshi; Shibamoto, Isamu; Hojo, Kyoko; Arai, Motoko

    2002-01-01

    The aim of this study was to confirm the response in patients stimulated at the trigger point (K-point). Since we have already clinically encountered patients with hyperactive bite reflexes who were able to open their mouth and swallow after stimulation of the trigger point, we investigated this response in other brain-damaged patients. The trigger point lies on the mucosa lateral to the palatoglossal arch and medial to the pterygomandibular fold at the height of the postretromolar pad. A total of 57 brain-damaged patients, including patients with pseudobulbar palsy due to bilateral upper motor neuron disease and bulbar palsy due to medulla oblongate. Other supratentorial brain-damaged patients and 20 non-brain-damaged subjects were also examined. The subjects were gently stimulated at the trigger point by a finger or a tongue depressor. We found that the pseudobulbar palsy patients with a hyperactive bite reflex responded by mouth opening and swallowing after a jaw movement similar to mastication elicited by the stimulation. The other pseudobulbar palsy patients, who did not have hyperactive bite reflexes and could open their mouth spontaneously, responded by swallowing with jaw movements similar to mastication after the stimulation. The bulbar palsy patients and the supratentorial brain-damaged patients showed no response to the stimulation. The non-brain-damaged subjects also did not respond, but all of the subjects reported a strange sensation after the stimulation. We concluded that stimulating the trigger point was useful for opening the mouth and facilitating swallowing in pseudobulbar palsy patients and that this technique may be of help in these patients in terms of oral health care and feeding. PMID:12355142

  15. Propagation of damage in brain tissue: coupling the mechanics of oedema and oxygen delivery.

    PubMed

    Lang, Georgina E; Vella, Dominic; Waters, Sarah L; Goriely, Alain

    2015-11-01

    Brain tissue swelling, or oedema, is a dangerous consequence of traumatic brain injury and stroke. In particular, a locally swollen region can cause the injury to propagate further through the brain: swelling causes mechanical compression of the vasculature in the surrounding tissue and so can cut off that tissue's oxygen supply. We use a triphasic mathematical model to investigate this propagation, and couple tissue mechanics with oxygen delivery. Starting from a fully coupled, finite elasticity, model, we show that simplifications can be made that allow us to express the volume of the propagating region of damage analytically in terms of key parameters. Our results show that performing a craniectomy, to alleviate pressure in the brain and allow the tissue to swell outwards, reduces the propagation of damage; this finding agrees with experimental observations. PMID:25822263

  16. Primary gonadal damage following treatment of brain tumors in childhood

    SciTech Connect

    Ahmed, S.R.; Shalet, S.M.; Campbell, R.H.; Deakin, D.P.

    1983-10-01

    Gonadal function was studied in two groups of children previously treated for medulloblastoma with surgery followed by postoperative craniospinal irradiation. In group 1 but not in group 2, the children also received adjuvant chemotherapy for one to two years. All children in group 1 received a nitrosourea (BCNU or CCNU), plus vincristine in four and procarbazine in three patients. The nine children in group 1 showed clinical and biochemical evidence of gonadal damage with elevated serum FSH concentrations and, in the boys, small testes for their stage of pubertal development. In group 2 (n . 8), each child had completed pubertal development normally, the boys had adult sized testes and the girls regular menses. Gonadotropin values were normal in all eight children. We conclude that nitrosoureas were responsible for the gonadal damage in the children in group 1, with procarbazine also contributing to the damage in the three children who received this drug. In view of the limited proved value of adjuvant chemotherapy with nitrosoureas in the treatment of medulloblastoma, recognition of this serious complication of cytotoxic drug therapy may necessitate reassessing in which subgroups of children with medulloblastoma the benefits of adjuvant chemotherapy outweigh the complications.

  17. Synthesis of a novel photopolymerized nanocomposite hydrogel for the treatment of acute mechanical damage to cartilage

    NASA Astrophysics Data System (ADS)

    Schlichting, Kathryn; Copeland-Johnson, Trishelle; Goodman, Matthew; Lipert, Robert; McKinley, Todd; Martin, James; Mallapragada, Surya; Lin, Zhiqun

    2011-03-01

    Posttraumatic osteoarthritis is caused by a cascade of pathobiologic and pathomechanical events starting with intraarticular fractures in the cartilage. Currently, treatment of fractures is completely focused on restoration of the macroanatomy of the joint. The premise is that restoring the macroanatomy will prevent ongoing stresses and in turn prevent cartilage degeneration. However, current treatment ignores acute mechanical damage sustained by cartilage at the time of injury. This study describes the initial development of a novel nanocomposite photopolymerizing copolymer that has potential to restore local structural integrity to acutely injured cartilage, and subsequently act as a carrier for chondrocyte-enhancing bioactive agents.

  18. The effects of acute alcohol administration on the human brain: Insights from neuroimaging

    PubMed Central

    Bjork, James M.; Gilman, Jodi M.

    2014-01-01

    Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. PMID:23978384

  19. Vorinostat Induces Reactive Oxygen Species and DNA Damage in Acute Myeloid Leukemia Cells

    PubMed Central

    Pettersson, Filippa; Retrouvey, Hélène; Skoulikas, Sophia; Miller, Wilson H.

    2011-01-01

    Histone deacetylase inhibitors (HDACi) are promising anti-cancer agents, however, their mechanisms of action remain unclear. In acute myeloid leukemia (AML) cells, HDACi have been reported to arrest growth and induce apoptosis. In this study, we elucidate details of the DNA damage induced by the HDACi vorinostat in AML cells. At clinically relevant concentrations, vorinostat induces double-strand breaks and oxidative DNA damage in AML cell lines. Additionally, AML patient blasts treated with vorinostat display increased DNA damage, followed by an increase in caspase-3/7 activity and a reduction in cell viability. Vorinostat-induced DNA damage is followed by a G2-M arrest and eventually apoptosis. We found that pre-treatment with the antioxidant N-acetyl cysteine (NAC) reduces vorinostat-induced DNA double strand breaks, G2-M arrest and apoptosis. These data implicate DNA damage as an important mechanism in vorinostat-induced growth arrest and apoptosis in both AML cell lines and patient-derived blasts. This supports the continued study and development of vorinostat in AMLs that may be sensitive to DNA-damaging agents and as a combination therapy with ionizing radiation and/or other DNA damaging agents. PMID:21695163

  20. Monitoring stroke progression: in vivo imaging of cortical perfusion, blood-brain barrier permeability and cellular damage in the rat photothrombosis model.

    PubMed

    Schoknecht, Karl; Prager, Ofer; Vazana, Udi; Kamintsky, Lyn; Harhausen, Denise; Zille, Marietta; Figge, Lena; Chassidim, Yoash; Schellenberger, Eyk; Kovács, Richard; Heinemann, Uwe; Friedman, Alon

    2014-11-01

    Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood-brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood-brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex. PMID:25160672

  1. Monitoring stroke progression: in vivo imaging of cortical perfusion, blood–brain barrier permeability and cellular damage in the rat photothrombosis model

    PubMed Central

    Schoknecht, Karl; Prager, Ofer; Vazana, Udi; Kamintsky, Lyn; Harhausen, Denise; Zille, Marietta; Figge, Lena; Chassidim, Yoash; Schellenberger, Eyk; Kovács, Richard; Heinemann, Uwe; Friedman, Alon

    2014-01-01

    Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood–brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood–brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex. PMID:25160672

  2. Melanocortin MC4 receptor agonists alleviate brain damage in abdominal compartment syndrome in the rat.

    PubMed

    Liu, Dong; Zhang, Hong-Guang; Zhao, Zi-Ai; Chang, Ming-Tao; Li, Yang; Yu, Jian; Zhang, Ye; Zhang, Lian-Yang

    2015-02-01

    Intra-abdominal hypertension (IAH) is accompanied by high morbidity and mortality in surgical departments and ICUs. However, its specific pathophysiology is unclear. IAH not only leads to intra-abdominal tissue damage but also causes dysfunction in distal organs, such as the brain. In this study, we explore the protective effects of melanocortin 4 receptor agonists in IAH-induced brain injury. The IAH rat models were induced by hemorrhagic shock/resuscitation (with the mean arterial pressure (MAP) maintained at 30 mm Hg for 90 min followed by the reinfusion of the withdrawn blood with lactated Ringer's solution). Then, air was injected into the peritoneal cavity of the rats to maintain an intra-abdominal pressure of 20 mm Hg for 4 h. The effects of the melanocortin 4 receptor agonist RO27-3225 in alleviating the rats' IAH brain injuries were observed, which indicated that RO27-3225 could reduce brain edema, the expressions of the IL-1β and TNF-α inflammatory cytokines, the blood-brain barrier's permeability and the aquaporin4 (AQP4) and matrix metalloproteinase 9 (MMP9) levels. Moreover, the nicotinic acetylcholine receptor antagonist chlorisondamine and the selective melanocortin 4 receptor antagonist HS024 can negate the protective effects of the RO27-3225. The MC4R agonist can effectively reduce the intracerebral proinflammatory cytokine gene expression and alleviate the brain injury caused by blood-brain barrier damage following IAH. PMID:25616531

  3. The Acute Phase of Mild Traumatic Brain Injury Is Characterized by a Distance-Dependent Neuronal Hypoactivity

    PubMed Central

    Johnstone, Victoria P.A.; Shultz, Sandy R.; Yan, Edwin B.; O'Brien, Terence J.

    2014-01-01

    Abstract The consequences of mild traumatic brain injury (TBI) on neuronal functionality are only now being elucidated. We have now examined the changes in sensory encoding in the whisker-recipient barrel cortex and the brain tissue damage in the acute phase (24 h) after induction of TBI (n=9), with sham controls receiving surgery only (n=5). Injury was induced using the lateral fluid percussion injury method, which causes a mixture of focal and diffuse brain injury. Both population and single cell neuronal responses evoked by both simple and complex whisker stimuli revealed a suppression of activity that decreased with distance from the locus of injury both within a hemisphere and across hemispheres, with a greater extent of hypoactivity in ipsilateral barrel cortex compared with contralateral cortex. This was coupled with an increase in spontaneous output in Layer 5a, but only ipsilateral to the injury site. There was also disruption of axonal integrity in various regions in the ipsilateral but not contralateral hemisphere. These results complement our previous findings after mild diffuse-only TBI induced by the weight-drop impact acceleration method where, in the same acute post-injury phase, we found a similar depth-dependent hypoactivity in sensory cortex. This suggests a common sequelae of events in both diffuse TBI and mixed focal/diffuse TBI in the immediate post-injury period that then evolve over time to produce different long-term functional outcomes. PMID:24927383

  4. Transketolase: observations in alcohol-related brain damage research.

    PubMed

    Alexander-Kaufman, Kimberley; Harper, Clive

    2009-04-01

    Thiamin, or vitamin B1, is crucial for brain function. In its active form, thiamin pyrophosphate (TPP), it is a co-enzyme for several enzymes, including transketolase. Transketolase is an important enzyme in the non-oxidative branch of the pentose phosphate pathway (PPP), a pathway responsible for generating reducing equivalents, which is essential for energy transduction and for generating ribose for nucleic acid synthesis. Transketolase also links the PPP to glycolysis, allowing a cell to adapt to a variety of energy needs, depending on its environment. Abnormal transketolase expression and/or activity have been implicated in a number of diseases where thiamin availability is low, including Wernicke-Korsakoff's Syndrome and alcoholism. Yet, the precise mechanism by which this enzyme is involved in the pathophysiology of these disorders remains controversial. PMID:18490188

  5. Use of EPO as an adjuvant in PDT of brain tumors to reduce damage to normal brain

    NASA Astrophysics Data System (ADS)

    Rendon, Cesar A.; Lilge, Lothar

    2004-10-01

    In order to reduce damage to surrounding normal brain in the treatment of brain tumors with photodynamic therapy (PDT), we have investigated the use of the cytokine erythropoietin (EPO) to exploit its well-established role as a neuroprotective agent. In vitro experiments demonstrated that EPO does not confer protection from PDT to rat glioma cells. In vivo testing of the possibility of EPO protecting normal brain tissue was carried out. The normal brains of Lewis rats were treated with Photofrin mediated PDT (6.25 mg/Kg B.W. 22 hours pre irradiation) and the outcome of the treatment compared between animals that received EPO (5000 U/Kg B.W. 22 hours pre irradiation) and controls. This comparison was made based on the volume of necrosis, as measured with the viability stain 2,3,5- Triphenyl tetrazoium chloride (TTC), and incidence of apoptosis, as measured with in situ end labeling assay (ISEL). Western blotting showed that EPO reaches the normal brain and activates the anti-apoptotic protein PKB/AKT1 within the brain cortex. The comparison based on volume of necrosis showed no statistical significance between the two groups. No clear difference was observed in the ISEL staining between the groups. A possible lack of responsivity in the assays that give rise to these results is discussed and future corrections are described.

  6. Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome

    PubMed Central

    De Felice, Claudio; Della Ragione, Floriana; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Ciccoli, Lucia; Scalabrì, Francesco; Marracino, Federico; Madonna, Michele; Belmonte, Giuseppe; Ricceri, Laura; De Filippis, Bianca; Laviola, Giovanni; Valacchi, Giuseppe; Durand, Thierry; Galano, Jean-Marie; Oger, Camille; Guy, Alexandre; Bultel-Poncé, Valérie; Guy, Jacky; Filosa, Stefania; Hayek, Joussef; D'Esposito, Maurizio

    2014-01-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder affecting almost exclusively females, caused in the overwhelming majority of the cases by loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). High circulating levels of oxidative stress (OS) markers in patients suggest the involvement of OS in the RTT pathogenesis. To investigate the occurrence of oxidative brain damage in Mecp2 mutant mouse models, several OS markers were evaluated in whole brains of Mecp2-null (pre-symptomatic, symptomatic, and rescued) and Mecp2-308 mutated (pre-symptomatic and symptomatic) mice, and compared to those of wild type littermates. Selected OS markers included non-protein-bound iron, isoprostanes (F2-isoprostanes, F4-neuroprostanes, F2-dihomo-isoprostanes) and 4-hydroxy-2-nonenal protein adducts. Our findings indicate that oxidative brain damage 1) occurs in both Mecp2-null (both −/y and stop/y) and Mecp2-308 (both 308/y males and 308/+ females) mouse models of RTT; 2) precedes the onset of symptoms in both Mecp2-null and Mecp2-308 models; and 3) is rescued by Mecp2 brain specific gene reactivation. Our data provide direct evidence of the link between Mecp2 deficiency, oxidative stress and RTT pathology, as demonstrated by the rescue of the brain oxidative homeostasis following brain-specifically Mecp2-reactivated mice. The present study indicates that oxidative brain damage is a previously unrecognized hallmark feature of murine RTT, and suggests that Mecp2 is involved in the protection of the brain from oxidative stress. PMID:24769161

  7. An Evidence-Based Systematic Review on Communication Treatments for Individuals with Right Hemisphere Brain Damage

    ERIC Educational Resources Information Center

    Blake, Margaret Lehman; Frymark, Tobi; Venedictov, Rebecca

    2013-01-01

    Purpose: The purpose of this review is to evaluate and summarize the research evidence related to the treatment of individuals with right hemisphere communication disorders. Method: A comprehensive search of the literature using key words related to right hemisphere brain damage and communication treatment was conducted in 27 databases (e.g.,…

  8. Perspectives on Treatment for Communication Deficits Associated with Right Hemisphere Brain Damage

    ERIC Educational Resources Information Center

    Blake, Margaret Lehman

    2007-01-01

    Purpose: To describe the current treatment research for communication (prosodic, discourse, and pragmatic) deficits associated with right hemisphere brain damage and to provide suggestions for treatment selection given the paucity of evidence specifically for this population. Method: The discussion covers (a) clinical decision processes and…

  9. Principles of Experience-Dependent Neural Plasticity: Implications for Rehabilitation after Brain Damage

    ERIC Educational Resources Information Center

    Kleim, Jeffrey A.; Jones, Theresa A.

    2008-01-01

    Purpose: This paper reviews 10 principles of experience-dependent neural plasticity and considerations in applying them to the damaged brain. Method: Neuroscience research using a variety of models of learning, neurological disease, and trauma are reviewed from the perspective of basic neuroscientists but in a manner intended to be useful for the…

  10. The rodent endovascular puncture model of subarachnoid hemorrhage: mechanisms of brain damage and therapeutic strategies

    PubMed Central

    2014-01-01

    Subarachnoid hemorrhage (SAH) represents a considerable health problem. To date, limited therapeutic options are available. In order to develop effective therapeutic strategies for SAH, the mechanisms involved in SAH brain damage should be fully explored. Here we review the mechanisms of SAH brain damage induced by the experimental endovascular puncture model. We have included a description of similarities and distinctions between experimental SAH in animals and human SAH pathology. Moreover, several novel treatment options to diminish SAH brain damage are discussed. SAH is accompanied by cerebral inflammation as demonstrated by an influx of inflammatory cells into the cerebral parenchyma, upregulation of inflammatory transcriptional pathways and increased expression of cytokines and chemokines. Additionally, various cell death pathways including cerebral apoptosis, necrosis, necroptosis and autophagy are involved in neuronal damage caused by SAH. Treatment strategies aiming at inhibition of inflammatory or cell death pathways demonstrate the importance of these mechanisms for survival after experimental SAH. Moreover, neuroregenerative therapies using stem cells are discussed as a possible strategy to repair the brain after SAH since this therapy may extend the window of treatment considerably. We propose the endovascular puncture model as a suitable animal model which resembles the human pathology of SAH and which could be applied to investigate novel therapeutic therapies to combat this debilitating insult. PMID:24386932

  11. Magnetic resonance imaging of the brain in survivors of childhood acute lymphoblastic leukemia

    PubMed Central

    BADR, MOHAMED AHMED; HASSAN, TAMER HASAN; EL-GERBY, KHALED MOHAMED; LAMEY, MOHAMED EL-SAYED

    2013-01-01

    The issue of delayed neurological damage as a result of treatment is becoming increasingly important now that an increased number of children survive treatment for acute lymphoblastic leukemia (ALL). Following modification of the treatment protocols, severe symptomatic late effects are rare, and most adverse effects are detected by sensitive imaging methods such as magnetic resonance imaging (MRI) or by neuropsychological testing. In this study we aimed to determine the prevalence and characteristics of late central nervous system (CNS) damage by MRI and clinical examination in children treated for ALL. A cross-sectional study was carried out at the pediatric oncology unit of Zagazig University, Egypt, and included 25 patients who were consecutively enrolled and treated according to the modified Children’s Cancer Group (CCG) 1991 protocol for standard risk ALL and the modified CCG 1961 protocol for high-risk ALL and who had survived more than 5 years from the diagnosis. All relevant data were collected from patients’ medical records; particularly the data concerning the initial clinical presentation and initial brain imaging. All patients were subjected to thorough history and full physical examination with special emphasis on the neurological system. MRI of the brain was performed for all patients. The mean age of patients was 6.9±3.04 years at diagnosis and was 12.9±3.2 years at the time of study. The patients comprised 14 boys and 11 girls. Abnormal MRI findings were detected in six patients (24%). They were in the form of leukoencephalopathy in two patients (8%), brain atrophy in two patients (8%), old infarct in one patient (4%) and old hemorrhage in one patient (4%). The number of abnormal MRI findings was significantly higher in high-risk patients, patients who had CNS manifestations at diagnosis and patients who had received cranial irradiation. We concluded that cranial irradiation is associated with higher incidence of MRI changes in children

  12. A Brain Signature to Differentiate Acute and Chronic Pain in Rats

    PubMed Central

    Guo, Yifei; Wang, Yuzheng; Sun, Yabin; Wang, Jin-Yan

    2016-01-01

    The transition from acute pain to chronic pain entails considerable changes of patients at multiple levels of the nervous system and in psychological states. An accurate differentiation between acute and chronic pain is essential in pain management as it may help optimize analgesic treatments according to the pain state of patients. Given that acute and chronic pain could modulate brain states in different ways and that brain states could greatly shape the neural processing of external inputs, we hypothesized that acute and chronic pain would show differential effects on cortical responses to non-nociceptive sensory information. Here by analyzing auditory-evoked potentials (AEPs) to pure tones in rats with acute or chronic pain, we found opposite influences of acute and chronic pain on cortical responses to auditory inputs. In particular, compared to no-pain controls, the N100 wave of rat AEPs was significantly enhanced in rats with acute pain but significantly reduced in rats with chronic pain, indicating that acute pain facilitated cortical processing of auditory information while chronic pain exerted an inhibitory effect. These findings could be justified by the fact that individuals suffering from acute or chronic pain would have different vigilance states, i.e., the vigilance level to external sensory stimuli would be increased with acute pain, but decreased with chronic pain. Therefore, this auditory response holds promise of being a brain signature to differentiate acute and chronic pain. Instead of investigating the pain system per se, the study of pain-induced influences on cortical processing of non-nocicpetive sensory information might represent a potential strategy to monitor the progress of pain chronification in clinical applications. PMID:27199727

  13. Dexamethasone and betamethasone protect against LPS-induced brain damage in the neonatal rats

    PubMed Central

    Pang, Yi; Fan, Lir-Wan; Zheng, Baoying; Campbell, Leigh R.; Cai, Zhengwei; Rhodes, Philip G.

    2013-01-01

    The aim of this study is to test whether dexamethasone (Dex) and betamethasone (Beta), two of the most commonly used corticosteroids, protect against lipopolysaccharide (LPS)-induced white matter damage and neurobehavioral dysfunction. LPS or sterile saline was injected into the brain white matter of rat pups at postnatal day 5 (P5) and Dex or Beta was given intraperitoneally to the rat pups 1 h before the LPS microinjection. Brain inflammatory response, brain damage, and myelination were examined at P6, P8 and P14. Neurobehavioral tests were performed from P3 through P22. Our results demonstrate that Dex and Beta markedly diminish the LPS-induced brain inflammatory response, restore myelin basic protein (MBP) expression and alleviate lateral ventricle dilation. Both corticosteroids demonstrate significant protection against most of LPS-induced behavioral deficits, including those in rearing, vibrissa-elicited forelimb-placing, beam walking, learning and elevated plus-maze test. Notably, only Beta improved the locomotion and stereotype dysfunction. In contrast to their beneficial effects, neither drug prevented LPS-induced delay in body weight gain from P6 through P21. Our study suggests that if their adverse effects are minimized, corticosteroids may be the potential candidate drugs to prevent brain damage in premature infants. PMID:22314662

  14. Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage

    PubMed Central

    Hou, Sheng Tao; Nilchi, Ladan; Li, Xuesheng; Gangaraju, Sandhya; Jiang, Susan X.; Aylsworth, Amy; Monette, Robert; Slinn, Jacqueline

    2015-01-01

    Semaphorin 3A (Sema3A) increased significantly in mouse brain following cerebral ischemia. However, the role of Sema3A in stroke brain remains unknown. Our aim was to determine wether Sema3A functions as a vascular permeability factor and contributes to ischemic brain damage. Recombinant Sema3A injected intradermally to mouse skin, or stereotactically into the cerebral cortex, caused dose- and time-dependent increases in vascular permeability, with a degree comparable to that caused by injection of a known vascular permeability factor vascular endothelial growth factor receptors (VEGF). Application of Sema3A to cultured endothelial cells caused disorganization of F-actin stress fibre bundles and increased endothelial monolayer permeability, confirming Sema3A as a permeability factor. Sema3A-mediated F-actin changes in endothelial cells were through binding to the neuropilin2/VEGFR1 receptor complex, which in turn directly activates Mical2, a F-actin modulator. Down-regulation of Mical2, using specific siRNA, alleviated Sema3A-induced F-actin disorganization, cellular morphology changes and endothelial permeability. Importantly, ablation of Sema3A expression, cerebrovascular permeability and brain damage were significantly reduced in response to transient middle cerebral artery occlusion (tMCAO) and in a mouse model of cerebral ischemia/haemorrhagic transformation. Together, these studies demonstrated that Sema3A is a key mediator of cerebrovascular permeability and contributes to brain damage caused by cerebral ischemia. PMID:25601765

  15. Utility of EEG measures of brain function in patients with acute stroke.

    PubMed

    Wu, Jennifer; Srinivasan, Ramesh; Burke Quinlan, Erin; Solodkin, Ana; Small, Steven L; Cramer, Steven C

    2016-06-01

    EEG has been used to study acute stroke for decades; however, because of several limitations EEG-based measures rarely inform clinical decision-making in this setting. Recent advances in EEG hardware, recording electrodes, and EEG software could overcome these limitations. The present study examined how well dense-array (256 electrodes) EEG, acquired with a saline-lead net and analyzed with whole brain partial least squares (PLS) modeling, captured extent of acute stroke behavioral deficits and varied in relation to acute brain injury. In 24 patients admitted for acute ischemic stroke, 3 min of resting-state EEG was acquired at bedside, including in the ER and ICU. Traditional quantitative EEG measures (power in a specific lead, in any frequency band) showed a modest association with behavioral deficits [NIH Stroke Scale (NIHSS) score] in bivariate models. However, PLS models of delta or beta power across whole brain correlated strongly with NIHSS score (R(2) = 0.85-0.90) and remained robust when further analyzed with cross-validation models (R(2) = 0.72-0.73). Larger infarct volume was associated with higher delta power, bilaterally; the contralesional findings were not attributable to mass effect, indicating that EEG captures significant information about acute stroke effects not available from MRI. We conclude that 1) dense-array EEG data are feasible as a bedside measure of brain function in patients with acute stroke; 2) high-dimension EEG data are strongly correlated with acute stroke behavioral deficits and are superior to traditional single-lead metrics in this regard; and 3) EEG captures significant information about acute stroke injury not available from structural brain imaging. PMID:26936984

  16. Relationships between acute imaging biomarkers and theory of mind impairment in post-acute pediatric traumatic brain injury: A prospective analysis using susceptibility weighted imaging (SWI).

    PubMed

    Ryan, Nicholas P; Catroppa, Cathy; Cooper, Janine M; Beare, Richard; Ditchfield, Michael; Coleman, Lee; Silk, Timothy; Crossley, Louise; Rogers, Kirrily; Beauchamp, Miriam H; Yeates, Keith O; Anderson, Vicki A

    2015-01-01

    Theory of Mind (ToM) forms an integral component of socially skilled behavior, and is critical for attaining developmentally appropriate goals. The protracted development of ToM is mediated by increasing connectivity between regions of the anatomically distributed 'mentalizing network', and may be vulnerable to disruption from pediatric traumatic brain injury (TBI). The present study aimed to evaluate the post-acute effects of TBI on first-order ToM, and examine relations between ToM and both local and global indices of macrostructural damage detected using susceptibility-weighted imaging (SWI). 104 children and adolescents with TBI and 43 age-matched typically developing (TD) controls underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks post-injury and were assessed on cognitive ToM tasks at 6-months after injury. Compared to TD controls and children with mild-moderate injuries, children with severe TBI showed significantly poorer ToM. Moreover, impairments in ToM were related to diffuse neuropathology, and parietal lobe lesions. Our findings support the vulnerability of the immature social brain network to disruption from TBI, and suggest that global macrostructural damage commonly associated with traumatic axonal injury (TAI) may contribute to structural disconnection of anatomically distributed regions that underlie ToM. This study suggests that SWI may be a valuable imaging biomarker to predict outcome and recovery of social cognition after pediatric TBI. PMID:25445779

  17. Processing of Basic Speech Acts Following Localized Brain Damage: A New Light on the Neuroanatomy of Language

    ERIC Educational Resources Information Center

    Soroker, N.; Kasher, A.; Giora, R.; Batori, G.; Corn, C.; Gil, M.; Zaidel, E.

    2005-01-01

    We examined the effect of localized brain lesions on processing of the basic speech acts (BSAs) of question, assertion, request, and command. Both left and right cerebral damage produced significant deficits relative to normal controls, and left brain damaged patients performed worse than patients with right-sided lesions. This finding argues…

  18. Brain Injury in Chronically Ventilated Preterm Neonates: Collateral Damage Related to Ventilation Strategy

    PubMed Central

    Albertine, Kurt H.

    2012-01-01

    Synopsis Brain injury is a frequent co-morbidity in chronically ventilated preterm infants. However, the molecular basis of the brain injury remains incompletely understood. The focus of this paper is the subtler (diffuse) form of brain injury that has white matter and gray matter lesions, without germinal matrix hemorrhage-intraventricular hemorrhage, posthemorrhagic hydrocephalus, or cystic periventricular leukomalacia. The purpose of this review is to synthesize data that suggest diffuse lesions to white matter and gray matter are collateral damage related to ventilator strategy. Evidence is introduced from the two large-animal, physiological models of evolving neonatal chronic lung disease that suggest an epigenetic mechanism may underlie the collateral damage. PMID:22954278

  19. Calcium-dependent neuroepithelial contractions expel damaged cells from the developing brain

    PubMed Central

    Herrgen, Leah; Voss, Oliver P.; Akerman, Colin J.

    2016-01-01

    Summary Both developing and adult organisms need efficient strategies for wound repair. In adult mammals, wounding triggers an inflammatory response that can exacerbate tissue injury and lead to scarring. In contrast, embryonic wounds heal quickly and with minimal inflammation, but how this is achieved remains incompletely understood. Using in vivo imaging in the developing brain of Xenopus laevis, we show that ATP release from damaged cells and subsequent activation of purinergic receptors induce long-range calcium waves in neural progenitor cells. Cytoskeletal reorganization, and activation of the actomyosin contractile machinery in a Rho kinase-dependent manner, then lead to rapid and pronounced apical-basal contractions of the neuroepithelium. These contractions drive the expulsion of damaged cells into the brain ventricle within seconds. Successful cell expulsion prevents the death of nearby cells and an exacerbation of the injury. Cell expulsion through neuroepithelial contraction represents a novel mechanism for rapid wound healing in the developing brain. PMID:25468753

  20. Calcium-dependent neuroepithelial contractions expel damaged cells from the developing brain.

    PubMed

    Herrgen, Leah; Voss, Oliver P; Akerman, Colin J

    2014-12-01

    Both developing and adult organisms need efficient strategies for wound repair. In adult mammals, wounding triggers an inflammatory response that can exacerbate tissue injury and lead to scarring. In contrast, embryonic wounds heal quickly and with minimal inflammation, but how this is achieved remains incompletely understood. Using in vivo imaging in the developing brain of Xenopus laevis, we show that ATP release from damaged cells and subsequent activation of purinergic receptors induce long-range calcium waves in neural progenitor cells. Cytoskeletal reorganization and activation of the actomyosin contractile machinery in a Rho kinase-dependent manner then lead to rapid and pronounced apical-basal contractions of the neuroepithelium. These contractions drive the expulsion of damaged cells into the brain ventricle within seconds. Successful cell expulsion prevents the death of nearby cells and an exacerbation of the injury. Cell expulsion through neuroepithelial contraction represents a mechanism for rapid wound healing in the developing brain. PMID:25468753

  1. A protective effect of musical expertise on cognitive outcome following brain damage?

    PubMed

    Omigie, Diana; Samson, Severine

    2014-12-01

    The current review examines the possibility that training-related changes that take place in the brains of musicians may have a beneficial effect on their cognitive outcome and recovery following neurological damage. First, we propose three different mechanisms by which training-related brain changes might result in relatively preserved function in musicians as compared to non-musicians with cerebral lesions. Next, we review the neuropsychological literature examining musical ability in professional musicians following brain damage, specifically of vascular, tumoral and epileptic aetiology. Finally, given that assessment of musician patients can greatly inform our understanding of the influence of premorbid experience on postmorbid recovery, we suggest some basic guidelines for the future evaluation of relevant patients. PMID:25380766

  2. Acute liver damage induced by 2-nitropropane in rats: effect of diphenyl diselenide on antioxidant defenses.

    PubMed

    Borges, Lysandro P; Nogueira, Cristina Wayne; Panatieri, Rodrigo B; Rocha, João Batista Teixeira; Zeni, Gilson

    2006-03-25

    The effect of post-treatment with diphenyl diselenide on liver damage induced by 2-nitropropane (2-NP) was examined in male rats. Rats were pre-treated with a single dose of 2-NP (100 mg/kg body weight dissolved in canola oil). Afterward, the animals were post-treated with a dose of diphenyl diselenide (10, 50 or 100 micromol/kg). The parameters that indicate tissue damage such as liver histopathology, plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), urea and creatinine were determined. Since the liver damage induced by 2-NP is related to oxidative damage, lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and ascorbic acid level were also evaluated. Diphenyl diselenide (50 and 100 micromol/kg) effectively restored the increase of ALT and AST activities and urea level when compared to the 2-NP group. At the higher dose, diphenyl diselenide decreased GGT activity. Treatment with diphenyl diselenide, at all doses, effectively ameliorated the increase of hepatic and renal lipid peroxidation when compared to 2-NP group. 2-NP reduced CAT activity and neither alter SOD activity nor ascorbic acid level. This study points out the involvement of CAT activity in 2-NP-induced acute liver damage and suggests that the post-treatment with diphenyl diselenide was effective in restoring the hepatic damage induced by 2-NP. PMID:16445897

  3. [Acute lymphoblastic leukemia presenting with multiple hemorrhagic brain metastases (case report)].

    PubMed

    Halefoğlu, Ahmet M; Ertürk, Mehmet; Ozel, Alper; Calişkan, K Can

    2004-06-01

    Intracranial metastases represent 7-17% of all brain tumors. Renal cell carcinoma, thyroid cancer, choriocarcinoma, melanoma, retinoblastoma, lung cancer and breast cancer have a propensity for producing hemorrhagic brain metastases. Leukemias have also been rarely reported to cause hemorrhagic brain metastases. We describe an 18-year-old girl diagnosed as acute lymphoblastic leukemia presenting with multiple hemorrhagic brain metastases. MRI demonstrated high signal intensity lesions on both T1- and T2-weighted images which were characteristic for extracellular methemoglobin and consistent with hemorrhagic metastases. PMID:15236125

  4. What role does the blood brain barrier play in acute mountain sickness?

    PubMed

    Baneke, Alex

    2010-07-01

    As high altitude travel increases, acute mountain sickness (AMS) and life threatening high altitude cerebral oedema (HACE) are becoming more prevalent. Acute mountain sickness occurs in 45% of lowlanders above 4250 m. Predisposing factors are still unknown and its development is more complex than the original "tight fit" hypothesis. This review examines evidence relating to a possible role of the blood brain barrier in AMS as suggested by MRI studies. Underlying mechanisms may involve vascular endothelial growth factor and free radicals in addition to increases in hydrostatic pressure. An increased understanding is important in advising patients planning high altitude adventures. Current studies have linked increased blood brain barrier permeability to high altitude cerebral oedema, but the role of the blood brain barrier in acute mountain sickness is less clear; varied symptoms include headache. MRI shows vasogenic oedema occurs in high altitude cerebral oedema, suggesting blood brain barrier permeability increases, and acute mountain sickness typically precedes high altitude cerebral oedema. Hypoxia leads to increased hydrostatic pressure, and blood brain barrier permeability has been shown to increase in stroke patients. Vascular endothelial growth factor is upregulated in hypoxia, and may increase blood brain barrier permeability. PMID:20952272

  5. Altered Cerebellar White Matter Integrity in Patients with Mild Traumatic Brain Injury in the Acute Stage

    PubMed Central

    Wang, Zhongqiu; Wu, Wenzhong; Liu, Yongkang; Wang, Tianyao; Chen, Xiao; Zhang, Jianhua; Zhou, Guoxing; Chen, Rong

    2016-01-01

    Background and Purpose Imaging studies of traumatic brain injury demonstrate that the cerebellum is often affected. We aim to examine fractional anisotropy alteration in acute-phase mild traumatic brain injury patients in cerebellum-related white matter tracts. Materials and Methods This prospective study included 47 mild traumatic brain injury patients in the acute stage and 37 controls. MR imaging and neurocognitive tests were performed in patients within 7 days of injury. White matter integrity was examined by using diffusion tensor imaging. We used three approaches, tract-based spatial statistics, graphical-model-based multivariate analysis, and region-of-interest analysis, to detect altered cerebellar white matter integrity in mild traumatic brain injury patients. Results Results from three analysis methods were in accordance with each other, and suggested fractional anisotropy in the middle cerebellar peduncle and the pontine crossing tract was changed in the acute-phase mild traumatic brain injury patients, relative to controls (adjusted p-value < 0.05). Higher fractional anisotropy in the middle cerebellar peduncle was associated with worse performance in the fluid cognition composite (r = -0.289, p-value = 0.037). Conclusion Altered cerebellar fractional anisotropy in acute-phase mild traumatic brain injury patients is localized in specific regions and statistically associated with cognitive deficits detectable on neurocognitive testing. PMID:26967320

  6. Effect of acute and chronic cholinesterase inhibition on biogenic amines in rat brain.

    PubMed

    Soininen, H; Unni, L; Shillcutt, S

    1990-12-01

    The effects of five cholinesterase inhibitors on forebrain monoamine and their metabolite levels, and on forebrain and plasma cholinesterase (ChE) activity in rat were studied in acute and chronic conditions. Acute tetrahydroaminoacridine (THA) dosing caused lower brain (68%) and higher plasma (90%) ChE inhibition than the other drugs studied and increased levels of brain dihydroxyphenylacetic acid (DOPAC) (236%), homovanillic acid (HVA) (197%) and 5-hydroxyindoleacetic acid (5-HIAA) (130%). Acute physostigmine (PHY) administration caused a 215% increase in brain DOPAC content. Despite high brain ChE inhibition induced by metrifonate (MTF), dichlorvos (DDVP) or naled no changes in brain noradrenaline (NA), dopamine (DA) or serotonin (5-HT) occurred due to treatment with the study drugs in the acute study. In the chronic 10-day study THA or PHY caused no substantial ChE inhibition in brain when measured 18 hours after the last dose, whereas MTF induced 74% ChE inhibition. Long-term treatment with THA or MTF caused no changes in monoamine levels, but PHY treatment resulted in slightly increased 5-HT values. These results suggest that MTF, DDVP and naled seem to act solely by cholinergic mechanisms. However, the central neuropharmacological mechanism of action of THA and PHY may involve changes in cholinergic as well as dopaminergic and serotoninergic systems. PMID:1711162

  7. Do hyperbaric oxygen-induced seizures cause brain damage?

    PubMed

    Domachevsky, Liran; Pick, Chaim G; Arieli, Yehuda; Krinsky, Nitzan; Abramovich, Amir; Eynan, Mirit

    2012-06-01

    It is commonly accepted that hyperbaric oxygen-induced seizures, the most severe manifestation of central nervous system oxygen toxicity, are harmless. However, this hypothesis has not been investigated in depth. We used apoptotic markers to determine whether cells in the cortex and hippocampus were damaged by hyperbaric oxygen-induced seizures in mice. Experimental animals were exposed to a pressure of 6 atmospheres absolute breathing oxygen, and were randomly assigned to two groups sacrificed 1h after the appearance of seizures or 7 days later. Control groups were not exposed to hyperbaric oxygen. Caspase 9, caspase 3, and cytochrome c were used as apoptotic markers. These were measured in the cortex and the hippocampus, and compared between the groups. Levels of caspase 3, cytochrome c, and caspase 9 in the hippocampus were significantly higher in the hyperbaric oxygenexposed groups compared with the control groups 1 week after seizures (p<0.01). The levels of two fragments of caspase 9 in the cortex were higher in the control group compared with the hyperbaric oxygen-exposed group 1h after seizures (p<0.01). Hyperbaric oxygen-induced seizures activate apoptosis in the mouse hippocampus. The reason for the changes in the cortex is not understood. Further investigation is necessary to elucidate the mechanism underlying these findings and their significance. PMID:22293507

  8. Brain damages in ketamine addicts as revealed by magnetic resonance imaging

    PubMed Central

    Wang, Chunmei; Zheng, Dong; Xu, Jie; Lam, Waiping; Yew, D. T.

    2013-01-01

    Ketamine, a known antagonist of N-methyl-D-aspartic (NMDA) glutamate receptors, had been used as an anesthetic particularly for pediatric or for cardiac patients. Unfortunately, ketamine has become an abusive drug in many parts of the world while chronic and prolonged usage led to damages of many organs including the brain. However, no studies on possible damages in the brains induced by chronic ketamine abuse have been documented in the human via neuroimaging. This paper described for the first time via employing magnetic resonance imaging (MRI) the changes in ketamine addicts of 0.5–12 years and illustrated the possible brain regions susceptible to ketamine abuse. Twenty-one ketamine addicts were recruited and the results showed that the lesions in the brains of ketamine addicts were located in many regions which appeared 2–4 years after ketamine addiction. Cortical atrophy was usually evident in the frontal, parietal or occipital cortices of addicts. Such study confirmed that many brain regions in the human were susceptible to chronic ketamine injury and presented a diffuse effect of ketamine on the brain which might differ from other central nervous system (CNS) drugs, such as cocaine, heroin, and methamphetamine. PMID:23882190

  9. Elevated metals compromise repair of oxidative DNA damage via the base excision repair pathway: implications of pathologic iron overload in the brain on integrity of neuronal DNA.

    PubMed

    Li, Hui; Swiercz, Rafal; Englander, Ella W

    2009-09-01

    Tissue-specific iron content is tightly regulated to simultaneously satisfy specialized metabolic needs and avoid cytotoxicity. In the brain, disruption of iron homeostasis may occur in acute as well as progressive injuries associated with neuronal dysfunction and death. We hypothesized that adverse effects of disrupted metal homeostasis on brain function may involve impairment of DNA repair processes. Because in the brain, the base excision repair (BER) pathway is central for handling oxidatively damaged DNA, we investigated effects of elevated iron and zinc on key BER enzymes. In vitro DNA repair assays revealed inhibitory effects of metals on BER activities, including the incision of abasic sites, 5'-flap cleavage, gap filling DNA synthesis and ligation. Using the comet assay, we showed that while metals at concentrations which inhibit BER activities in in vitro assays, did not induce direct genomic damage in cultured primary neurons, they significantly delayed repair of genomic DNA damage induced by sublethal exposure to H(2)O(2). Thus, in the brain even a mild transient metal overload, may adversely affect the DNA repair capacity and thereby compromise genomic integrity and initiate long-term deleterious sequelae including neuronal dysfunction and death. PMID:19619136

  10. Dapsone improves functional deficit and diminishes brain damage evaluated by 3-Tesla magnetic resonance image after transient cerebral ischemia and reperfusion in rats.

    PubMed

    Diaz-Ruiz, Araceli; Roldan-Valadez, Ernesto; Ortiz-Plata, Alma; Mondragón-Lozano, Rodrigo; Heras-Romero, Yessica; Mendez-Armenta, Marisela; Osorio-Rico, Laura; Nava-Ruiz, Concepción; Ríos, Camilo

    2016-09-01

    Stroke is a frequent cause of death and the first of disability in the world population. We have shown that dapsone acts as an antioxidant, antiinflammatory and antiapoptotic agent after brain Ischemia reperfusion (I/R) in rats; however, its therapeutic efficacy, measured by imaging has not been characterized. In this context, the aim of this study was to evaluate the neuroprotective effect of dapsone by magnetic resonance imaging (MRI) and to correlate imaging markers with motor function and oxidative stress after transient cerebral ischemia and reperfusion (I/R). We used male rats throughout the experiment. Functional deficit after I/R was assessed by using Longa scale. The area of brain tissue damage was measured by histology. The nuclear factor erythroid 2-related factor 2 (Nrf-2) and the amount of reactive oxygen species (ROS) were measured as biomarkers of oxidative stress. Finally, difussion tensor MRI was employed to measure the fractional anisotropy (FA), as a MRI marker of the pathophysiologic brain status. Results showed a better functional recovery and less damaged tissue in animals treated with dapsone vs control group. The values of FA were higher in animals receiving treatment, indicating a better preservation of brain structure. At early stages of the damage, dapsone was able to reduce both oxidative markers (Nrf-2 and ROS). Our findings provide new evidence for the efficacy of dapsone when administered during the acute phase after I/R and that quantitative sequences of MRI are useful for characterizing its potential therapeutic benefits after stroke. PMID:27321157

  11. Sympathoadrenal Activation is Associated with Acute Traumatic Coagulopathy and Endotheliopathy in Isolated Brain Injury

    PubMed Central

    Di Battista, Alex P.; Rizoli, Sandro B.; Lejnieks, Brandon; Min, Arimie; Shiu, Maria Y.; Peng, Henry T.; Baker, Andrew J.; Hutchison, Michael G.; Churchill, Nathan; Inaba, Kenji; Nascimento, Bartolomeu B.; de Oliveira Manoel, Airton Leonardo; Beckett, Andrew; Rhind, Shawn G.

    2016-01-01

    ABSTRACT Background: Acute coagulopathy after traumatic brain injury (TBI) involves a complex multifactorial hemostatic response that is poorly characterized. Objectives: To examine early posttraumatic alterations in coagulofibrinolytic, endothelial, and inflammatory blood biomarkers in relation to sympathetic nervous system (SNS) activation and 6-month patient outcomes, using multivariate partial least-squares (PLS) analysis. Patients and Methods: A multicenter observational study of 159 adult isolated TBI patients admitted to the emergency department at an urban level I trauma center, was performed. Plasma concentrations of 6 coagulofibrinolytic, 10 vascular endothelial, 19 inflammatory, and 2 catecholamine biomarkers were measured by immunoassay on admission and 24 h postinjury. Neurological outcome at 6 months was assessed using the Extended Glasgow Outcome Scale. PLS-discriminant analysis was used to identify salient biomarker contributions to unfavorable outcome, whereas PLS regression analysis was used to evaluate the covariance between SNS correlates (catecholamines) and biomarkers of coagulopathy, endotheliopathy, and inflammation. Results: Biomarker profiles in patients with an unfavorable outcome displayed procoagulation, hyperfibrinolysis, glycocalyx and endothelial damage, vasculature activation, and inflammation. A strong covariant relationship was evident between catecholamines and biomarkers of coagulopathy, endotheliopathy, and inflammation at both admission and 24 h postinjury. Conclusions: Biomarkers of coagulopathy and endotheliopathy are associated with poor outcome after TBI. Catecholamine levels were highly correlated with endotheliopathy and coagulopathy markers within the first 24 h after injury. Further research is warranted to characterize the pathogenic role of SNS-mediated hemostatic alterations in isolated TBI. PMID:27206278

  12. Preventing Flow-Metabolism Uncoupling Acutely Reduces Axonal Injury after Traumatic Brain Injury

    PubMed Central

    Mironova, Yevgeniya A.; Chen, Szu-Fu; Richards, Hugh K.; Pickard, John D.

    2012-01-01

    Abstract We have previously presented evidence that the development of secondary traumatic axonal injury is related to the degree of local cerebral blood flow (LCBF) and flow-metabolism uncoupling. We have now tested the hypothesis that augmenting LCBF in the acute stages after brain injury prevents further axonal injury. Data were acquired from rats with or without acetazolamide (ACZ) that was administered immediately following controlled cortical impact injury to increase cortical LCBF. Local cerebral metabolic rate for glucose (LCMRglc) and LCBF measurements were obtained 3 h post-trauma in the same rat via 18F-fluorodeoxyglucose and 14C-iodoantipyrine co-registered autoradiographic images, and compared to the density of damaged axonal profiles in adjacent sections, and in additional groups at 24 h used to assess different populations of injured axons stereologically. ACZ treatment significantly and globally elevated LCBF twofold above untreated-injured rats at 3 h (p<0.05), but did not significantly affect LCMRglc. As a result, ipsilateral LCMRglc:LCBF ratios were reduced by twofold to sham-control levels, and the density of β-APP-stained axons at 24 h was significantly reduced in most brain regions compared to the untreated-injured group (p<0.01). Furthermore, early LCBF augmentation prevented the injury-associated increase in the number of stained axons from 3–24 h. Additional robust stereological analysis of impaired axonal transport and neurofilament compaction in the corpus callosum and cingulum underlying the injury core confirmed the amelioration of β-APP axon density, and showed a trend, but no significant effect, on RMO14-positive axons. These data underline the importance of maintaining flow-metabolism coupling immediately after injury in order to prevent further axonal injury, in at least one population of injured axons. PMID:22321027

  13. Acute radiation-induced pulmonary damage: a clinical study on the response to fractionated radiation therapy.

    PubMed

    Mah, K; Van Dyk, J; Keane, T; Poon, P Y

    1987-02-01

    Acute radiation-induced pulmonary damage can be a significant cause of morbidity in radiation therapy of the thorax. A prospective, clinical study was conducted to obtain dose-response data on acute pulmonary damage caused by fractionated radiation therapy. The endpoint was a visible increase in lung density within the irradiated volume on a computed tomographic (CT) examination as observed independently by three diagnostic radiologists. Fifty-four patients with various malignancies of the thorax completed the study. CT chest scans were taken before and at preselected times following radiotherapy. To represent different fractionation schedules of equivalent biological effect, the estimated single dose (ED) model, ED = D X N-0.377 X T-0.058 was used in which D was the average lung dose within the high dose region in cGy, N was the number of fractions, and T was the overall treatment time in days. Patients were grouped according to ED and the percent incidence of pulmonary damage for each group was determined. Total average lung doses ranged from 29.8 Gy to 53.6 Gy given in 10 to 30 fractions over a range of 12 to 60 days. Five patient groups with incidence ranging from 30% (ED of 930) to 90% (ED of 1150) were obtained. The resulting dose-response curve predicted a 50% incidence level at an ED value (ED50) of 1000 +/- 40 ED units. This value represents fractionation schedules equivalent to a total average lung dose of 32.9 Gy given in 15 fractions over 19 days. Over the linear portion of the dose-response curve, a 5% increase in ED (or total dose if N and T remain constant), predicts a 12% increase in the incidence of acute radiation-induced pulmonary damage. PMID:3818385

  14. Single-stranded DNA as an immunohistochemical marker of neuronal damage in human brain: an analysis of autopsy material with regard to the cause of death.

    PubMed

    Michiue, Tomomi; Ishikawa, Takaki; Quan, Li; Li, Dong-Ri; Zhao, Dong; Komatsu, Ayumi; Zhu, Bao-Li; Maeda, Hitoshi

    2008-07-01

    Single-stranded DNA (ssDNA) is a marker of apoptosis and programmed cell death, which appears prior to DNA fragmentation during delayed neuronal death. The present study investigated the immunohistochemical distribution of ssDNA in the brain to investigate apoptotic neuronal damage with regard to the cause of death in medicolegal autopsy cases (n=305). Neuronal immunopositivity for ssDNA was globally detected in the brain, independent of the age, gender of subjects and postmortem interval, and depended on the cause of death. Higher positivity was typically found in the pallidum for delayed brain injury death and fatal carbon monoxide intoxication, and in the cerebral cortex, pallidum and substantia nigra for drug intoxication. For mechanical asphyxiation, a high positivity was detected in the cerebral cortex and pallidum, while the positivity was low in the substantia nigra. The neuronal ssDNA increased during the survival period within about 24h at each site, depending on the type of brain injury, and in the substantia nigra for other blunt injuries. The neuronal positivity was usually lower for drowning and acute ischemic disease. Topographical analysis of ssDNA-positive neurons may contribute to investigating the cause of brain damage and survival period after a fatal insult. PMID:18462896

  15. Uptake of radiolabeled ions in normal and ischemia-damaged brain.

    PubMed

    Dienel, G A; Pulsinelli, W A

    1986-05-01

    The regional concentrations of nine radiochemicals were measured in rat brain after induction of cerebral ischemia to identify tracers concentrated by brain undergoing selective neuronal necrosis. Transient (30 minute) forebrain ischemia was produced in the rat; 24 hours after cerebral recirculation the radiochemicals were injected intravenously and allowed to circulate for 5 hours. The brain concentrations of the radiochemicals in dissected regions were determined by scintillation counting. Forebrain ischemia of this nature will produce extensive injury to striatal neurons but will spare the great majority of neocortical neurons at 24 hours. The regional concentrations of these radiochemicals varied considerably in both control and ischemic animals. In postischemic animals, 4 radionuclides (63Ni, 99TcO4, 22Na, and [3H]tetracycline) were concentrated in the irreversibly damaged striatum in amounts ranging from 1.4 to 2.4 times greater than in normal tissue. The concentrations of 65Zn, 59Fe, 32PO4, and 147Pm in postischemic brain were similar to or less than those in normal brain. The concentration of [14C]EDTA was increased in injured and uninjured brain of postischemic rats. Autoradiographic analysis of the distribution patterns of some of these ions in normal animals showed that 99TcO4, 22Na, 65Zn, and 59Fe were distributed more uniformly throughout the brain than were 32PO4, 63Ni, and 147Pm. At 24 or 48 hours after ischemia, 63Ni, 99TcO4, and 22Na were preferentially concentrated in the damaged striatum and hippocampus, whereas 65Zn, 59Fe, 32PO4, and 147Pm did not accumulate in irreversibly injured tissue. Of the radiochemicals tested to date, Ni, TcO4, and tetracycline may be useful for diagnosing ischemic brain injury in humans, using positron emission tomography. PMID:3013076

  16. The effects of chronic smoking on the pathology of alcohol-related brain damage.

    PubMed

    McCorkindale, A N; Sheedy, D; Kril, J J; Sutherland, G T

    2016-06-01

    Both pathological and neuroimaging studies demonstrate that chronic alcohol abuse causes brain atrophy with widespread white matter loss limited gray matter loss. Recent neuroimaging studies suggest that tobacco smoking also causes brain atrophy in both alcoholics and neurologically normal individuals; however, this has not been confirmed pathologically. In this study, the effects of smoking and the potential additive effects of concomitant alcohol and tobacco consumption were investigated in autopsied human brains. A total of 44 cases and controls were divided into four groups: 16 non-smoking controls, nine smoking controls, eight non-smoking alcoholics, and 11 smoking alcoholics. The volumes of 26 gray and white matter regions were measured using an established point-counting technique. The results showed trends for widespread white matter loss in alcoholics (p < 0.007) but no effect on gray matter regions. In contrast, smoking alone had no effect on brain atrophy and the combination of smoking and alcohol showed no additional effect. Neuronal density was analyzed as a more sensitive assay of gray matter integrity. Similar to the volumetric analysis, there was a reduction in neurons (29%) in the prefrontal cortex of alcoholics, albeit this was only a trend when adjusted for potential confounders (p < 0.06). There were no smoking or combinatorial effects on neuronal density in any of the three regions examined. These results do not support the hypothesis that smoking exacerbates alcohol-related brain damage. The trends here support previous studies that alcohol-related brain damage is characterized by focal neuronal loss and generalized white matter atrophy. These disparate effects suggest that two different pathogenic mechanisms may be operating in the alcoholic brain. Future studies using ultrastructural or molecular techniques will be required to determine if smoking has more subtle effects on the brain and how chronic alcohol consumption leads to

  17. Neuroprotective actions of taurine on hypoxic-ischemic brain damage in neonatal rats.

    PubMed

    Zhu, Xiao-Yun; Ma, Peng-Sheng; Wu, Wei; Zhou, Ru; Hao, Yin-Ju; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

    2016-06-01

    Taurine is an abundant amino acid in the nervous system, which has been proved to possess antioxidation, osmoregulation and membrane stabilization. Previously it has been demonstrated that taurine exerts ischemic brain injury protective effect. This study was designed to investigate whether the protective effect of taurine has the possibility to be applied to treat neonatal hypoxic-ischemic brain damage. Seven-day-old Sprague-Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen to generate the experimental group. The cerebral damage area was measured after taurine post-treatment with 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxyline-Eosin (HE) staining and Nissl staining. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), myeloperoxtidase (MPO), ATP and Lactic Acid productions were assayed with ipsilateral hemisphere homogenates. Western-blot and immunofluorescence assay were processed to detect the expressions of AIF, Cyt C, Bax, Bcl-2 in brain. We found that taurine significantly reduced brain infarct volume and ameliorated morphological injury obviously reversed the changes of SOD, MDA, GSH-Px, T-AOC, ATP, MPO, and Lactic Acid levels. Compared with hypoxic-ischemic group, it showed marked reduction of AIF, Cyt C and Bax expressions and increase of Bcl-2 after post-treatment. We conclude that taurine possesses an efficacious neuroprotective effect after cerebral hypoxic-ischemic damage in neonatal rats. PMID:27345710

  18. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age

    PubMed Central

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2013-01-01

    The New South Wales Tissue Resource Centre (NSW TRC) at the University of Sydney, Australia is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain disease (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951–61) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539–52). PMID:24033426

  19. Brain edema in acute liver failure. Insight from experimental studies.

    PubMed

    Andres, T; Blei, M D; Judy, R; Cho, M D

    1990-07-01

    Brain edema is a leading cause of death in fulminant hepatic failure (FHP). Animal studies are needed to gain further insight into its pathogenesis. The authors describe and analyze the results of brain studies in two animal models of FHF, the rabbit with galactosamine induced hepatitis and the anhepatic model of liver desvascularization. A gravimetric technique is used to determine water content in brain samples as small as 10 mg in weight. Results showed that water content is increased and correlates with the severity of encephalopathy in both experimental models of encephalopathy. The possible pathogenic role of ammonia and octanoic acid are discussed. PMID:19256151

  20. Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

    NASA Astrophysics Data System (ADS)

    Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

    2013-05-01

    Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

  1. Exendin-4 attenuates brain death-induced liver damage in the rat.

    PubMed

    Carlessi, Rodrigo; Lemos, Natalia E; Dias, Ana L; Brondani, Leticia A; Oliveira, Jarbas R; Bauer, Andrea C; Leitão, Cristiane B; Crispim, Daisy

    2015-11-01

    The majority of liver grafts destined for transplantation originate from brain dead donors. However, significantly better posttransplantation outcomes are achieved when organs from living donors are used, suggesting that brain death (BD) causes irreversible damage to the liver tissue. Recently, glucagon-like peptide-1 (GLP1) analogues were shown to possess interesting hepatic protection effects in different liver disease models. We hypothesized that donor treatment with the GLP1 analogue exendin-4 (Ex-4) could alleviate BD-induced liver damage. A rat model of BD was employed in order to estimate BD-induced liver damage and Ex-4's potential protective effects. Liver damage was assessed by biochemical determination of circulating hepatic markers. Apoptosis in the hepatic tissue was assessed by immunoblot and immunohistochemistry using an antibody that only recognizes the active form of caspase-3. Gene expression changes in inflammation and stress response genes were monitored by quantitative real-time polymerase chain reaction. Here, we show that Ex-4 administration to the brain dead liver donors significantly reduces levels of circulating aspartate aminotransferase and lactate dehydrogenase. This was accompanied by a remarkable reduction in hepatocyte apoptosis. In this model, BD caused up-regulation of tumor necrosis factor and stress-related genes, confirming previous findings in clinical and animal studies. In conclusion, treatment of brain dead rats with Ex-4 reduced BD-induced liver damage. Further investigation is needed to determine the molecular basis of the observed liver protection. After testing in a randomized clinical trial, the inclusion of GLP1 analogues in organ donor management might help to improve organ quality, maximize organ donation, and possibly increase liver transplantation success rates. PMID:26334443

  2. Effect of acute thioacetamide administration on rat brain phospholipid metabolism

    SciTech Connect

    Osada, J.; Aylagas, H.; Miro-Obradors, M.J.; Arce, C.; Palacios-Alaiz, E.; Cascales, M. )

    1990-09-01

    Brain phospholipid composition and the ({sup 32}P)orthophosphate incorporation into brain phospholipids of control and rats treated for 3 days with thioacetamide were studied. Brain phospholipid content, phosphatidylcholine, phosphatidylethanolamine, lysolecithin and phosphatidic acid did not show any significant change by the effect of thioacetamide. In contrast, thioacetamide induced a significant decrease in the levels of phosphatidylserine, sphingomyelin, phosphatidylinositol and diphosphatidylglycerol. After 75 minutes of intraperitoneal label injection, specific radioactivity of all the above phospholipids with the exception of phosphatidylethanolamine and phosphatidylcholine significantly increased. After 13 hours of isotope administration the specific radioactivity of almost all studied phospholipid classes was elevated, except for phosphatidic acid, the specific radioactivity of which did not change and for diphosphatidylglycerol which showed a decrease in specific radioactivity. These results suggest that under thioacetamide treatment brain phospholipids undergo metabolic transformations that may contribute to the hepatic encephalopathy induced by thioacetamide.

  3. Effect of Pentoxifylline on Ischemia- induced Brain Damage and Spatial Memory Impairment in Rat

    PubMed Central

    Movassaghi, Shabnam; Nadia Sharifi, Zahra; Soleimani, Mansooreh; Joghataii, Mohammad Taghi; Hashemi, Mehrdad; Shafaroodi, Hamed; Mehdizadeh, Mehdi

    2012-01-01

    Objective(s) The brief interruption of cerebral blood flow causes permanent brain damage and behavioral dysfunction. The hippocampus is highly vulnerable to ischemic insults, particularly the CA1 pyramidal cell layer. There is no effective pharmacological strategy for improving brain tissue damage induced by cerebral ischemia. Previous studies reported that pentoxifylline (PTX) has a neuroprotective effect on brain trauma. The possible neuroprotector effects of PTX on behavioral deficit were studied in male Wistar rats subjected to a model of transient global brain ischemia. Materials and Methods Animals (n= 32) were assigned to control, sham-operated, vehicle, and PTX- treated (200 mg/kg IP) groups. PTX administered at 1hr before and 3 hr after ischemia. Global cerebral ischemia was induced by bilateral common carotid artery occlusion, followed by reperfusion. Results Morris Water maze testing revealed that PTX administration in cerebral ischemia significantly improved hippocampal-dependent memory and cognitive spatial abilities after reperfusion as compared to sham-operated and vehicle-treated animals. After the behavioral test, the rats were sacrificed and brain sections were stained with Nissl staining. There were no significant differences between number of pyramidal cells in both control and PTX groups. Conclusion Our study demonstrated that pentoxifylline had a protective effect on rats with transient global ischemia and could reduce cognitive impairment. PMID:23493977

  4. Intranasal Delivery of Umbilical Cord-Derived Mesenchymal Stem Cells Preserves Myelination in Perinatal Brain Damage.

    PubMed

    Oppliger, Byron; Joerger-Messerli, Marianne; Mueller, Martin; Reinhart, Ursula; Schneider, Philipp; Surbek, Daniel V; Schoeberlein, Andreina

    2016-08-15

    Preterm white matter injury (WMI) is an important cause for long-term disability. Stem cell transplantation has been proposed as a novel therapeutic approach. However, intracerebral transplantation is not feasible for clinical purpose in newborns. Intranasal delivery of cells to the brain might be a promising, noninvasive therapeutic approach to restore the damaged brain. Therefore, our goal is to study the remyelinating potential of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) after intranasal delivery. Wistar rat pups, previously brain-damaged by a combined hypoxic-ischemic and inflammatory insult, received hWJ-MSC (150,000 cells in 3 μL) that were intranasally delivered twice to each nostril (600,000 cells total). WMI was assessed by immunohistochemistry and western blot for myelination, astrogliosis, and microgliosis. The expression of preoligodendrocyte markers, and neurotrophic factors, was analyzed by real-time polymerase chain reaction. Animals treated with intranasally delivered hWJ-MSC showed increased myelination and decreased gliosis compared to untreated animals. hWJ-MSC may, therefore, modulate the activation of microglia and astrocytes, resulting in a change of the brain microenvironment, which facilitates the maturation of oligodendrocyte lineage cells. This is the first study to show that intranasal delivery of hWJ-MSC in rats prevented hypomyelination and microgliosis in a model of WMI in the premature rat brain. Further studies should address the dose and frequency of administration. PMID:27392671

  5. Brain oxidative damage restored by Sesbania grandiflora in cigarette smoke-exposed rats.

    PubMed

    Ramesh, Thiyagarajan; Sureka, Chandrabose; Bhuvana, Shanmugham; Begum, Vavamohaideen Hazeena

    2015-08-01

    Cigarette smoking has been associated with high risk of neurological diseases such as stroke, Alzheimer's disease, multiple sclerosis, etc., The present study was designed to evaluate the restorative effects of Sesbania grandiflora (S. grandiflora) on oxidative damage induced by cigarette smoke exposure in the brain of rats. Adult male Wistar-Kyoto rats were exposed to cigarette smoke for a period of 90 days and consecutively treated with S. grandiflora aqueous suspension (SGAS, 1000 mg/kg body weight per day by oral gavage) for a period of 3 weeks. The levels of protein carbonyl, nitric oxide, and activities of cytochrome P450, NADPH oxidase and xanthine oxidase were significantly increased, whereas the levels of total thiol, protein thiol, non-protein thiol, nucleic acids, tissue protein and the activities of Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase were significantly diminished in the brain of rats exposed to cigarette smoke as compared with control rats. Also cigarette smoke exposure resulted in a significant alteration in brain total lipid, total cholesterol, triglycerides and phospholipids content. Treatment of SGAS is regressed these alterations induced by cigarette smoke. The results of our study suggest that S. grandiflora restores the brain from cigarette smoke induced oxidative damage. S. grandiflora could have rendered protection to the brain by stabilizing their cell membranes and prevented the protein oxidation, probably through its free radical scavenging and anti-peroxidative effect. PMID:25620659

  6. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed

    Xu, Feng; Liu, Peiying; Pekar, James J; Lu, Hanzhang

    2015-04-15

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain's response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine's effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  7. Quantitation of heavy ion damage to the mammalian brain - Some preliminary findings

    NASA Technical Reports Server (NTRS)

    Cox, A. B.; Kraft, L. M.

    1984-01-01

    For several years, studies have been conducted regarding late effects of particulate radiations in mammalian tissues, taking into account the brains of rodents and lagomorphs. Recently, it has become feasible to quantify pathological damage and morpho-physiologic alterations accurately in large numbers of histological specimens. New investigative procedures make use of computer-assisted automated image analysis systems. Details regarding the employed methodology are discussed along with the results of the information. The radiations of high linear energy transfer (LET) cause apparently earlier and more dramatic shrinkage of olfactory glomeruli in exposed rabbit brains than comparable doses of Co-60 gamma photons.

  8. Interfacing brain with computer to improve communication and rehabilitation after brain damage.

    PubMed

    Riccio, A; Pichiorri, F; Schettini, F; Toppi, J; Risetti, M; Formisano, R; Molinari, M; Astolfi, L; Cincotti, F; Mattia, D

    2016-01-01

    Communication and control of the external environment can be provided via brain-computer interfaces (BCIs) to replace a lost function in persons with severe diseases and little or no chance of recovery of motor abilities (ie, amyotrophic lateral sclerosis, brainstem stroke). BCIs allow to intentionally modulate brain activity, to train specific brain functions, and to control prosthetic devices, and thus, this technology can also improve the outcome of rehabilitation programs in persons who have suffered from a central nervous system injury (ie, stroke leading to motor or cognitive impairment). Overall, the BCI researcher is challenged to interact with people with severe disabilities and professionals in the field of neurorehabilitation. This implies a deep understanding of the disabled condition on the one hand, and it requires extensive knowledge on the physiology and function of the human brain on the other. For these reasons, a multidisciplinary approach and the continuous involvement of BCI users in the design, development, and testing of new systems are desirable. In this chapter, we will focus on noninvasive EEG-based systems and their clinical applications, highlighting crucial issues to foster BCI translation outside laboratories to eventually become a technology usable in real-life realm. PMID:27590975

  9. αKlotho deficiency in acute kidney injury contributes to lung damage.

    PubMed

    Ravikumar, Priya; Li, Liping; Ye, Jianfeng; Shi, Mingjun; Taniguchi, Masatomo; Zhang, Jianning; Kuro-O, Makoto; Hu, Ming Chang; Moe, Orson W; Hsia, Connie C W

    2016-04-01

    αKlotho is a circulating protein that originates predominantly from the kidney and exerts cytoprotective effects in distant sites. We previously showed in rodents that the lung is particularly vulnerable to αKlotho deficiency. Because acute lung injury is a common and serious complication of acute kidney injury (AKI), we hypothesized that αKlotho deficiency in AKI contributes to lung injury. To test the hypothesis, we created AKI by renal artery ischemia-reperfusion in rats and observed the development of alveolar interstitial edema and increased pulmonary oxidative damage to DNA, protein, and lipids. Administration of αKlotho-containing conditioned media 6 h post-AKI did not alter plasma creatinine but improved recovery of endogenous αKlotho production 3 days post-AKI, reduced lung edema and oxidative damage, and increased endogenous antioxidative capacity in the lung. Intravenously injected αKlotho rapidly exits alveolar capillaries as a macromolecule, suggesting transcytosis and direct access to the epithelium. To explore the epithelial action of αKlotho, we simulated oxidative stress in vitro by adding hydrogen peroxide to cultured A549 lung epithelial cells. Purified recombinant αKlotho directly protected cells at 20 pM with half-maximal effects at 40-50 pM, which is compatible with circulating αKlotho levels. Addition of recombinant αKlotho activated an antioxidant response element reporter and increased the levels of target proteins of the nuclear factor erythroid-derived 2 related factor system. In summary, αKlotho deficiency in AKI contributes to acute lung injury by reducing endogenous antioxidative capacity and increasing oxidative damage in the lung. αKlotho replacement partially reversed these abnormalities and mitigated pulmonary complications in AKI. PMID:26718784

  10. Role of microvascular disruption in brain damage from traumatic brain injury

    PubMed Central

    Logsdon, Aric F.; Lucke-Wold, Brandon P.; Turner, Ryan C.; Huber, Jason D.; Rosen, Charles L.; Simpkins, James W.

    2015-01-01

    Traumatic brain injury (TBI) is acquired from an external force, which can inflict devastating effects to the brain vasculature and neighboring neuronal cells. Disruption of vasculature is a primary effect that can lead to a host of secondary injury cascades. The primary effects of TBI are rapidly occurring while secondary effects can be activated at later time points and may be more amenable to targeting. Primary effects of TBI include diffuse axonal shearing, changes in blood brain barrier (BBB) permeability, and brain contusions. These mechanical events, especially changes to the BBB, can induce calcium perturbations within brain cells producing secondary effects, which include cellular stress, inflammation, and apoptosis. These secondary effects can be potentially targeted to preserve the tissue surviving the initial impact of TBI. In the past, TBI research had focused on neurons without any regard for glial cells and the cerebrovasculature. Now a greater emphasis is being placed on the vasculature and the neurovascular unit following TBI. A paradigm shift in the importance of the vascular response to injury has opened new avenues of drug treatment strategies for TBI. However, a connection between the vascular response to TBI and the development of chronic disease has yet to be elucidated. Long-term cognitive deficits are common amongst those sustaining severe or multiple mild TBIs. Understanding the mechanisms of cellular responses following TBI is important to prevent the development of neuropsychiatric symptoms. With appropriate intervention following TBI, the vascular network can perhaps be maintained and the cellular repair process possibly improved to aid in the recovery of cellular homeostasis. PMID:26140712

  11. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed Central

    Xu, Feng; Liu, Peiying; Pekar, James J.; Lu, Hanzhang

    2015-01-01

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain’s response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine’s effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  12. DNA damage in organs of mice treated acutely with patulin, a known mycotoxin.

    PubMed

    de Melo, Flávia Terezinha; de Oliveira, Iuri Marques; Greggio, Samuel; Dacosta, Jaderson Costa; Guecheva, Temenouga Nikolova; Saffi, Jenifer; Henriques, João Antonio Pêgas; Rosa, Renato Moreira

    2012-10-01

    Patulin, a known mycotoxin, is considered a significant contaminant in apples, apple-derived products and feeds. This study investigated the genotoxic effects of patulin in multiple organs (brain, kidney, liver and urinary bladder) of mice using an in vivo comet assay. We assessed the mechanism underlying this genotoxicity by measuring the GSH content and the thiobarbituric acid-reactive species (TBARS) level. Male CF-1 mice were given 1.0-3.75 mg/kg patulin intraperitoneally. The effect of patulin was dose-dependent and the highest patulin dose induced DNA strand breaks in the brain (damage index, DI, in hippocampus increased from 36.2 in control animals to 127.5), liver (44.3-138.4) and kidneys (31.5-99); decreased levels of GSH (hippocampus--from 46.9 to 18.4 nmol/mg protein); and an increase in lipid peroxidation (hippocampus--from 5.8 to 20.3 MDA equivalents/mg protein). This finding establishes an interrelationship between the pro-oxidant and genotoxic effects of patulin. Pre-treatment administration of N-acetyl-cysteine reduced patulin-induced DNA damage (hippocampus--DI from 127.5 to 39.8) and lipid peroxidation (hippocampus--20.3 to 12.8 MDA equivalents/mg protein) by restoring cellular GSH levels, reinforcing the positive relationship between patulin-induced GSH depletion and DNA damage caused by systemic administration of this mycotoxin. PMID:22222931

  13. [Pharmacological correction of toxic liver damage in patients with heavy forms of acute ethanol intoxication].

    PubMed

    Shikalova, I A; Shilov, V V; Vasil'ev, S A; Batotsyrenov, B V; Loladze, A T

    2012-01-01

    The efficiency of using remaxol and ademethionine in the therapy of patients with heavy acute alcohol intoxication on the background of toxic liver damage has been studied. The administration of remaxol led to improvement of the clinical treatment of alcohol intoxication, which is manifested by a decrease in the rate and duration of delirium tremens (from 33.9 to 10.8%), frequency of secondary lung disorders (from 18.5 to 3.1%), duration of stay in hospital (from 7.3 +/- 0.6 to 5.6 +/- 0.3 days), and total therapy duration (from 11.8 +/- 1.05 to 5.6 +/- 0.3 days). The results of biochemical investigations confirmed that remaxol and ademethionine provide effective treatment of the toxic liver damage. Remaxol decreases the degree of metabolic disorders to a greater extent than does ademethionine. PMID:22702109

  14. The impact of unilateral brain damage on weight perception, sensorimotor anticipation, and fingertip force adaptation.

    PubMed

    Buckingham, Gavin; Bieńkiewicz, Marta; Rohrbach, Nina; Hermsdörfer, Joachim

    2015-10-01

    Damage to the left parietal cortex can lead to apraxia - a selective deficit in tool use and action planning. There is conflicting evidence as to whether this disorder affects more fundamental motor parameters, such as applying the appropriate forces to lift objects based upon how heavy they look. Here we examined how individuals with left and right-lateralized brain damage lift and perceive the weight of objects of the same mass which vary in their size and material properties. No clear differences emerged between the groups in terms of how visual material properties affected their perceptions of object weight or their initial application of grip and load forces. There was, however, some evidence that unilateral brain injury impaired the use of size cues for the parameterization of grip forces. PMID:25711977

  15. Nutritional management of a patient with brain damage and spinal cord injury.

    PubMed

    Bildsten, C; Lamid, S

    1983-08-01

    Few reports on nutritional management of patients with both brain damage and spinal-cord-injury appear in the literature. We present a case of a 20-year-old male quadriplegic, C4 complete, who also sustained brain damage secondary to cerebral anoxia. When the patient was transferred to our rehabilitation unit, deterioration in nutritional status was noted, as evidenced by weight loss and depressed serum albumin and hemoglobin. Nutritional rehabilitation consisted of weaning from nasogastric tube feedings to an oral diet providing snacks and commercial supplements. This resulted in a positive nitrogen balance. Other factors, such as mobilization, exercises, and closure of a pressure sore, contributed favorably to improvement of nutritional status. PMID:6411046

  16. [Progress on Hypoxic-ischemic Brain Damage Associated with CCR2 and CCL2].

    PubMed

    Luo, Yu-jia; Li, Ru-bo; Ma, Shi-yu; Lü, Meng-yan

    2016-02-01

    Hypoxic-ischemic brain damage (HIBD) is referred to a common type of cerebral damage, which is caused by injury, leading to shallow bleeding in the cortex with intact cerebral pia mater. In recent years, studies show that a various kinds of immune cells and immune cellular factors are involved in the occurrence of HIBD. CC chemokine receptor 2 (CCR2) is a representative of CC chemokine receptor, and is widely distributed in cerebral neuron, astrocyte, and microglial cells, and is the main chemo-tactic factor receptor in brain tissue. CC chemokine ligand 2 (CCL2) is a kind of basophilic protein and the ligand of CCR2, and plays an important role in inflammation. In order to provide evidence for correlational studies in HIBD, this review will introduce the biological characteristics of CCR2 and CCL2, and illustrate the relationship between the immunoreactivity and HIBD. PMID:27295859

  17. Platelet microparticle number is associated with the extent of myocardial damage in acute myocardial infarction

    PubMed Central

    Puspitawati, Ira; Gharini, Putrika Prastuti Ratna; Setianto, Budi Yuli

    2016-01-01

    Introduction Activated platelets generate microparticles. Increased platelet microparticles occur in acute myocardial infarction (AMI) and contribute to intracoronary thrombosis and subsequent myocardial injury. This study aimed to investigate the impact of platelet microparticles on intracoronary thrombosis by assessing the relationship between platelet microparticles and the extent of myocardial damage in AMI. Material and methods This was a cross sectional study. The subjects were patients with acute coronary syndrome (ACS). Forty-one consecutive subjects with ACS admitted to intensive cardiovascular care unit were enrolled. The clinical spectrum of ACS comprised AMI (n = 26), both ST-elevation AMI (STEMI) and non-ST-elevation AMI (NSTEMI), and unstable angina (n = 15). Platelet microparticles were isolated from peripheral venous blood and detected with anti-CD42b-PE by the flow cytometry method. The extent of myocardial damage was determined by measuring the peak level of serial cardiac enzymes within 24 h of admission. Results Subjects with AMI had a significantly higher number of platelet microparticles than those with unstable angina (4855 ±4509/µl vs. 2181 ±1923/µl respectively; p = 0.036). Subjects with STEMI had the highest number of platelet microparticles, but no significant difference was detected as compared to those with NSTEMI (5775 ±5680/µl vs. 3601 ±1632/µl). The number of platelet microparticles in AMI was positively associated with the extent of myocardial damage (peak CK-MB: r = 0.408, p = 0.019 and peak GOT: r = 0.384, p = 0.026). Conclusions The number of platelet microparticles was increased in AMI as compared to unstable angina and associated with the extent of myocardial damage. PMID:27279844

  18. Brain Abscesses Complicating Acute Pneumococcal Meningitis During Etanercept Therapy

    PubMed Central

    Kasirye, Yusuf; Epperla, Narendranath; Manne, Janaki Ram; Bapani, Sowjanya; Garcia-Montilla, Romel J

    2012-01-01

    Brain abscess formation as a sequelae of community-acquired pneumococcal meningitis is extremely rare, accounting for less than 1% of all meningitis complications. Although metastatic seeding from a distal peripheral septic focus has been observed, this phenomenon most commonly occurs in the context of ear, nose and throat infections, post-cranial neurosurgical procedures, traumatic open cranial injury, or immunosuppression. We present the case of a man, 61 years old, on etanercept therapy for ankylosing spondylitis who developed multiple brain abscesses as a complication of pneumococcal meningitis. We believe that the predisposition to this extremely rare complication of a particularly aggressive pneumococcal meningitis was most likely due to the underlying immunosuppression resulting from etanercept therapy. As far as we know, this case is the first report linking multiple brain abscess formation in a patient with community-acquired pneumococcal meningitis with etanercept therapy. PMID:22634540

  19. Clinical significance of elevated serum A-FABP and free fatty acid in neonates with hypoxic ischemic brain damage

    PubMed Central

    Li, Mei; Jiang, Lian; Zhang, Huifen; Wang, Dandan; Zhang, Min; Zhang, Lianshan

    2016-01-01

    The main function of adipocyte fatty acid-binding protein (A-FABP) is to regulate fatty acid metabolism as its molecular chaperone. The clinical significance of A-FABP in hypoxic-ischemic brain damage (HIBD) neonates is not yet clear. Free fatty acid (FFA) in cerebral cortex increases along with hypoxia ischemia degree. Thus, we aimed to investigate whether FFA can induce A-FABP expression and elevate the serum A-FABP level in HIBD neonates. In the present study, 42 HIBD neonates were selected including 11 cases as mild, 16 cases as moderate and 15 cases as severe. The serum was collected from peripheral vein at 72 h after the first visit (acute stage) and 7 days after birth (recovery stage), and the serum from 10 normal neonates was used as the control. The serum level of A-FABP and FFA in 42 neonates with acute phase and recovery phase HIBD were detected using ELISA and copper colorimetric method. The overall serum A-FABP content in HIBD neonates at the acute stage was significantly higher compared to the normal neonates (P<0.05). The serum A-FABP level in severe HIBD neonates was significantly higher than that in mild HIBD, moderate HIBD and normal neonates (P<0.05). The serum FFA level in HIBD neonates at the acute stage was 1,521.57±605.63 µmol/l, which was significantly higher than that in the normal neonates 838.24±294.22 µmol/l. The serum FFA levels in mild, moderate and severe HIBD neonates were significantly higher than those in the normal neonates. The overall A-FABP level in HIBD neonates at the recovery stage was significantly lower compared to the acute stage, which was significant in severe HIBD neonates. A-FABP levels in mild and moderate HIBD neonates at recovery stage were decreased compared with the acute stage, although there was no statistical difference. There was a positive correlation between serum A-FABP and FFA in HIBD neonates at acute stage (r=0.369, P<0.05). In conclusion, serum A-FABP and FFA levels were signifcantly increased in

  20. Traumatic brain injury in children: acute care management.

    PubMed

    Geyer, Kristen; Meller, Karen; Kulpan, Carol; Mowery, Bernice D

    2013-01-01

    The care of the pediatric patient with a severe traumatic brain injury (TBI) is an all-encompassing nursing challenge. Nursing vigilance is required to maintain a physiological balance that protects the injured brain. From the time a child and family first enter the hospital, they are met with the risk of potential death and an uncertain future. The family is subjected to an influx of complex medical and nursing terminology and interventions. Nurses need to understand the complexities of TBI and the modalities of treatment, as well as provide patients and families with support throughout all phases of care. PMID:24640314

  1. Melatonin Improves Outcomes of Heatstroke in Mice by Reducing Brain Inflammation and Oxidative Damage and Multiple Organ Dysfunction

    PubMed Central

    Hsu, Shu-Fen; Lin, Mao-Tsun

    2013-01-01

    We report here that when untreated mice underwent heat stress, they displayed thermoregulatory deficit (e.g., animals display hypothermia during room temperature exposure), brain (or hypothalamic) inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment (e.g., decreased plasma levels of both adrenocorticotrophic hormone and corticosterone during heat stress), multiple organ dysfunction or failure, and lethality. Melatonin therapy significantly reduced the thermoregulatory deficit, brain inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment, multiple organ dysfunction, and lethality caused by heat stroke. Our data indicate that melatonin may improve outcomes of heat stroke by reducing brain inflammation, oxidative damage, and multiple organ dysfunction. PMID:24369441

  2. Neuronal PPARγ Deficiency Increases Susceptibility to Brain Damage after Cerebral Ischemia

    PubMed Central

    Zhao, Xiurong; Strong, Roger; Zhang, Jie; Sun, Guanghua; Tsien, Joe Z; Cui, Zhenzhong; Grotta, James C.; Aronowski, Jaroslaw

    2009-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) plays a role in regulating a myriad of biological processes in virtually all brain cell types, including neurons. We and others have reported recently that drugs which activate PPARγ are effective in reducing damage to brain in distinct models of brain disease, including ischemia. However, the cell type responsible for PPARγ-mediated protection has not been established. In response to ischemia, PPARγ gene is robustly upregulated in neurons, suggesting that neuronal PPARγ may be a primary target for PPARγ-agonist mediated neuroprotection. To understand the contribution of neuronal PPARγ to ischemic injury, we generated conditional neuron-specific PPARγ knockout mice (N-PPARγ-KO). These mice are viable and appeared to be normal with respect to their gross behavior and brain anatomy. However, neuronal PPARγ deficiency caused these mice to experience significantly more brain damage and oxidative stress in response to middle cerebral artery occlusion. The primary cortical neurons harvested from N-PPARγ-KO mice, but not astroglia, exposed to ischemia in vitro demonstrated more damage and a reduced expression of numerous key gene products that could explain increased vulnerability, including: SOD1, catalase, glutathione S-transferase (GST), uncoupling protein-1 or transcription factor liver X receptor-alpha (LXRα). Also, PPARγ agonist based neuroprotective effect was lost in neurons from N-PPARγ neurons. Therefore, we conclude that PPARγ in neurons play an essential protective function, and that PPARγ agonists may have utility in neuronal self-defense, in addition to their well-established anti-inflammatory effect. PMID:19439596

  3. Perinatal hypoxic-ischemic brain damage: evolution of an animal model.

    PubMed

    Vannucci, Robert C; Vannucci, Susan J

    2005-01-01

    Early research in the Vannucci laboratory prior to 1981 focused largely on brain energy metabolism in the developing rat. At that time, there was no experimental model to study the effects of perinatal hypoxia-ischemia in the rodent, despite the tremendous need to investigate the pathophysiology of perinatal asphyxial brain damage in infants. Accordingly, we developed such a model in the postnatal day 7 rat, using a modification of the Levine preparation in the adult rat. Rat pups underwent unilateral common carotid artery ligation followed by exposure to systemic hypoxia (8% oxygen) at a constant temperature of 37 degrees C. Brain damage, seen histologically, was generally confined to the cerebral hemisphere ipsilateral to the arterial occlusion, and consisted of selective neuronal death or infarction, depending on the duration of the systemic hypoxia. Tissue injury was observed in the cerebral cortex, hippocampus, striatum, and thalamus. Subcortical and periventricular white matter injury was also observed. This model was originally described in the Annals of Neurology in 1981, and during the more than 20 years since that publication numerous investigations utilizing the model have been conducted in our laboratories as well as laboratories around the world. Cerebral blood flow and metabolic correlates have been fully characterized. Physiologic and pharmacologic manipulations have been applied to the model in search of neuroprotective strategies. More recently, molecular biologic alterations during and following the hypoxic-ischemic stress have been ascertained and the model has been adapted to the immature mouse for specific use in genetically altered animals. As predicted in the original article, the model has proven useful for the study of the short- and long-term effects of hypoxic-ischemic brain damage on motor activity, behavior, seizure incidence, and the process of maturation in the brain and other organ systems. PMID:16046840

  4. Thiamine utilization in the pathogenesis of alcohol-induced brain damage.

    PubMed

    Martin, P R; Pekovich, S R; McCool, B A; Whetsell, W O; Singleton, C K

    1994-01-01

    There is increasing evidence for the role of thiamine deficiency in ethanol neurotoxicity and in development of alcoholic organic brain disorders other than Wernicke-Korsakoff syndrome [WKS] and cerebellar degeneration. Investigations in humans and in animal models have implicated a reduction in the activities of thiamine-utilizing enzymes as the metabolic basis of tissue injury due to thiamine deficiency. We have investigated the interactions of the thiamine-utilizing enzyme transketolase [Tk], derived from human fibroblasts, lymphoblasts, and various brain regions, with its cofactor, thiamine pyrophosphate [TPP], in an attempt to elucidate the molecular basis of selective brain damage in alcoholism-associated thiamine deficiency. There were no significant differences in the isoelectric pattern of Tk among the nine brain regions (white matter and grey matter) examined. However, Tk activity/mg protein, increase in Tk activity with addition of excess TPP (TPP effect), and TPP-dependent rate of formation of active Tk holoenzyme (tau) varied 2.5-, 6-, and 4-fold, respectively, among these brain regions. These differences in tissue requirements for TPP may contribute to the selective vulnerability of certain brain regions to alcoholism-associated thiamine deficiency, and may influence the pattern of clinical impairment in the individual patient. PMID:8974347

  5. Carnosine pretreatment protects against hypoxia-ischemia brain damage in the neonatal rat model.

    PubMed

    Zhang, Xiangmin; Song, Lili; Cheng, Xiuyong; Yang, Yi; Luan, Bin; Jia, Liting; Xu, Falin; Zhang, Zhan

    2011-09-30

    Perinatal hypoxia-ischemia brain injury is a major cause of mortality and morbidity in neonates and lacks an effective treatment thus far. Carnosine has been demonstrated to play a neuroprotective role in the adult brain injuries. However, there is no information available concerning its neuroprotective role in the immature brains after hypoxia-ischemia insults. Therefore, we investigated whether carnosine could also confer neuroprotective effects in a neonatal rat hypoxia-ischemia model. Hypoxia-ischemia was induced in rats on postnatal day 7 (P7). Carnosine (250 mg/kg) was administered intraperitoneally, 30 min prior to hypoxia-ischemia induction. Morphological brain injury and biochemical markers of apoptosis and oxidative stress were evaluated 24 h after hypoxia-ischemia induction. Cognitive performance was evaluated by the Morris Water Maze test on P28-P33. We found that pretreatment with carnosine significantly reduced the infarct volume and the number of terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the hypoxia-ischemia brain. Carnosine also inhibited mRNA expression of apoptosis-inducing factor(AIF) and caspase-3, which was accompanied by an increase in superoxide dismutase(SOD)activity and a decrease in the malondialdehyde(MDA)level in carnosine-treated rats. Furthermore, carnosine also improved the spatial learning and memory abilities of rats declined due to hypoxia-ischemia. These results demonstrate that carnosine can protect rats against hypoxia-ischemia-induced brain damage by antioxidation. PMID:21693116

  6. Cognitive Impairment and Whole Brain Diffusion in Patients with Neuromyelitis Optica after Acute Relapse

    ERIC Educational Resources Information Center

    He, Diane; Wu, Qizhu; Chen, Xiuying; Zhao, Daidi; Gong, Qiyong; Zhou, Hongyu

    2011-01-01

    The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive…

  7. Age-related changes in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats

    PubMed Central

    LI, YALI; LIU, JIAN; GAO, DENGFENG; WEI, JIN; YUAN, HAIFENG; NIU, XIAOLIN; ZHANG, QIAOJUN

    2016-01-01

    The aim of the present study was to investigate the age-related alterations in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats (SHR) and the underlying mechanisms. Aging resulted in a significant increase in the number of activated astrocytes and apoptotic cells in the SHR group, which was accompanied by increased expression of oxidative stress markers (iNOS and gp47phox) and apoptotic regulatory proteins (Bax and caspase-3). In addition, the expression of PPAR-γ and Bcl-2 were progressively reduced with increasing age in the SHR group. The 32 and 64-week-old SHRs exhibited significantly increased numbers of apoptotic cells, oxidative stress markers and pro-apoptotic proteins compared with age-matched WKY rats, which was accompanied by reduced expression of PPAR-γ. Compared with the 16 and 32-week-old WKY group, the 64-week-old WKY rats exhibited increased oxidative stress and pro-apoptotic markers, and increased levels apoptotic cells. In conclusion, the present study indicated that both aging and hypertension enhanced brain damage and oxidative stress injury in the hippocampi of SHRs, indicated by an increased presence of apoptotic cells and astrocytes. In addition, reduced expression of PPAR-γ may contribute to the age-related brain damage in SHRs. PMID:26846626

  8. Age-related changes in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats.

    PubMed

    Li, Yali; Liu, Jian; Gao, Dengfeng; Wei, Jin; Yuan, Haifeng; Niu, Xiaolin; Zhang, Qiaojun

    2016-03-01

    The aim of the present study was to investigate the age‑related alterations in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats (SHR) and the underlying mechanisms. Aging resulted in a significant increase in the number of activated astrocytes and apoptotic cells in the SHR group, which was accompanied by increased expression of oxidative stress markers (iNOS and gp47phox) and apoptotic regulatory proteins (Bax and caspase‑3). In addition, the expression of PPAR‑γ and Bcl‑2 were progressively reduced with increasing age in the SHR group. The 32 and 64‑week‑old SHRs exhibited significantly increased numbers of apoptotic cells, oxidative stress markers and pro‑apoptotic proteins compared with age‑matched WKY rats, which was accompanied by reduced expression of PPAR‑γ. Compared with the 16 and 32‑week‑old WKY group, the 64‑week‑old WKY rats exhibited increased oxidative stress and pro‑apoptotic markers, and increased levels apoptotic cells. In conclusion, the present study indicated that both aging and hypertension enhanced brain damage and oxidative stress injury in the hippocampi of SHRs, indicated by an increased presence of apoptotic cells and astrocytes. In addition, reduced expression of PPAR‑γ may contribute to the age‑related brain damage in SHRs. PMID:26846626

  9. Focal brain damage protects against post-traumatic stress disorder in combat veterans.

    PubMed

    Koenigs, Michael; Huey, Edward D; Raymont, Vanessa; Cheon, Bobby; Solomon, Jeffrey; Wassermann, Eric M; Grafman, Jordan

    2008-02-01

    Post-traumatic stress disorder (PTSD) is an often debilitating mental illness that is characterized by recurrent distressing memories of traumatic events. PTSD is associated with hypoactivity in the ventromedial prefrontal cortex (vmPFC), hyperactivity in the amygdala and reduced volume in the hippocampus, but it is unknown whether these neuroimaging findings reflect the underlying cause or a secondary effect of the disorder. To investigate the causal contribution of specific brain areas to PTSD symptoms, we studied a unique sample of Vietnam War veterans who suffered brain injury and emotionally traumatic events. We found a substantially reduced occurrence of PTSD among those individuals with damage to one of two regions of the brain: the vmPFC and an anterior temporal area that included the amygdala. These results suggest that the vmPFC and amygdala are critically involved in the pathogenesis of PTSD. PMID:18157125

  10. Blueberry treatment decreased D-galactose-induced oxidative stress and brain damage in rats.

    PubMed

    Çoban, Jale; Doğan-Ekici, Işın; Aydın, A Fatih; Betül-Kalaz, Esra; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2015-06-01

    D-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of whole fresh blueberry (BB) (Vaccinium corymbosum L.) treatment on oxidative stress in age-related brain damage model. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with 5 % (BB1) and 10 % (BB2) BB containing chow for two months. Malondialdehyde (MDA),protein carbonyl (PC) and glutathione (GSH) levels, and Cu Zn-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities as well as acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brain by immunohistochemistry. MDA and PC levels and AChE activity increased, but GSH levels, SOD and GSH-Px activities decreased together with histopathological structural damage in the brain of GAL-treated rats. BB treatments, especially BB2 reduced MDA and PC levels and AChE activity and elevated GSH levels and GSH-Px activity. BB1 and BB2 treatments diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. These results indicate that BB partially prevented the shift towards an imbalanced prooxidative status and apoptosis together with histopathological amelioration by acting as an antioxidant (radical scavenger) itself in GAL-treated rats. PMID:25511550

  11. The expression of DNA damage checkpoint proteins and prognostic implication in metastatic brain tumors.

    PubMed

    Seol, Ho Jun; Yoo, Hae Yong; Jin, Juyoun; Joo, Kyeung Min; Kim, Hyeong-Seok; Yoon, Su Jin; Choi, Seung Ho; Kim, Yonghyun; Pyo, Hong Ryull; Lim, Do-Hoon; Kim, Wook; Um, Hong-Duck; Kim, Jong Hyun; Lee, Jung-Ii; Nam, Do-Hyun

    2011-01-01

    The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, DNA damage checkpoint signaling pathway activation after irradiation has received increasing attention. The association between the expression levels and survival outcome was evaluated to find possible therapeutic targets in brain metastasis. Radiosensitivity of human non-small cell lung cancer cell lines was determined by checking their viability after treatment with varying doses of ionizing radiation (IR). The expression of DNA checkpoint proteins was analyzed by Western blots and immunohistochemistry. On the basis of the clinical data for the patients, the association between the expression of the components and patients' survival was investigated. The expression levels of TopBP1 and phosphorylated Chk1 (P-Chk1) protein were higher in radioresistant lung cancer cell lines compared to radiosensitive cell lines. We previously assessed radiation survival of lung cancer cell lines after treating them with Chk1 inhibitor, AZD7762. AZD7762 significantly sensitized both radioresistant and radiosensitive cells to IR. We also observed a strong inverse relationship between progression-free survival (PFS) and expression level of P-Chk1 and TopBP1. This study, which is the first clinical report that connects DNA damage checkpoints and prognosis of brain metastasis, supports these two proteins to be promising targets for overcoming the radioresistance in brain metastasis. PMID:22329197

  12. [Histomorphometric characteristic of human brain in acute alcoholic intoxication].

    PubMed

    Shormanov, S V; Shormanova, N S

    2005-01-01

    Different brain sections were studied in 20 subjects, who died of ethanol intoxication and in 14 subjects who died of injuries of the heart and main vessels, in order to detect histological changes in the brain and for the purpose of defining spatial and quantitative ratios between cerebral tissue structures in alcoholic intoxication. Different histological, stereometric and morphometric tools were made use of. It was demonstrated that, in alcoholic intoxication, there occur severe disorders of the circulation with affection of vessels in the brain; there are also dystrophic and necrotic changes in neurocytes, glial cells and white substance. The square of neurons shrinks due to death of some of them in the cortex of hemispheres, thalamus and cerebellum. As for the medulla, they are more resistant, there, to ethanol. The diameter of capillaries in the studied brain sections diminishes due to a reduced tonus of cerebral arteries; the quantity of such vessels increases within a standard area, which is conditioned by the compensatory opening of reserve capillaries. All this can be important in dealing with issues of thanatogenesis and of forensic medical diagnosis in death of alcoholic intoxication. PMID:15881135

  13. Hyperbaric oxygen can induce neuroplasticity and improve cognitive functions of patients suffering from anoxic brain damage

    PubMed Central

    Hadanny, A.; Golan, H.; Fishlev, G.; Bechor, Y.; Volkov, O.; Suzin, G.; Ben-Jacob, E.; Efrati, S.

    2015-01-01

    Abstract Purpose: Cognitive impairment may occur in 42–50% of cardiac arrest survivors. Hyperbaric oxygen therapy (HBO2) has recently been shown to have neurotherapeutic effects in patients suffering from chronic cognitive impairments (CCI) consequent to stroke and mild traumatic brain injury. The objective of this study was to assess the neurotherapeutic effect of HBO2 in patients suffering from CCI due to cardiac arrest. Methods: Retrospective analysis of patients with CCI caused by cardiac arrest, treated with 60 daily sessions of HBO2. Evaluation included objective computerized cognitive tests (NeuroTrax), Activity of Daily Living (ADL) and Quality of life questionnaires. The results of these tests were compared with changes in brain activity as assessed by single photon emission computed tomography (SPECT) brain imaging. Results: The study included 11 cases of CCI patients. Patients were treated with HBO2, 0.5–7.5 years (mean 2.6 ± 0.6 years) after the cardiac arrest. HBO2 was found to induce modest, but statistically significant improvement in memory, attention and executive function (mean scores) of 12% , 20% and 24% respectively. The clinical improvements were found to be well correlated with increased brain activity in relevant brain areas as assessed by computerized analysis of the SPECT imaging. Conclusions: Although further research is needed, the results demonstrate the beneficial effects of HBO2 on CCI in patients after cardiac arrest, even months to years after the acute event. PMID:26409406

  14. Association of seizures with cortical spreading depression and peri-infarct depolarisations in the acutely injured human brain

    PubMed Central

    Fabricius, Martin; Fuhr, Susanne; Willumsen, Lisette; Dreier, Jens P; Bhatia, Robin; Boutelle, Martyn G.; Hartings, Jed A; Bullock, Ross; Strong, Anthony J; Lauritzen, Martin

    2008-01-01

    Objective To test the co-occurrence and interrelation of ictal activity and cortical spreading depressions (CSDs) - including the related periinfarct depolarisations in acute brain injury caused by trauma, and spontaneous subarachnoid and/or intracerebral haemorrhage. Methods 63 patients underwent craniotomy and electrocorticographic (ECoG) recordings were taken near foci of damaged cortical tissue for up to 10 days. Results 32 of 63 patients exhibited CSDs (5 to 75 episodes), and 11 had ECoGraphic seizure activity (1-81 episodes). Occurrence of seizures was significantly associated with CSD, as 10 of 11 patients with seizures also had CSD (p=0.007, 2-tailed Fishers exact test). Clinically overt seizures were only observed in one patient. Each patient with CSD and seizures displayed one of four different patterns of interaction between CSD and seizures. In four patients CSD was immediately preceded by prolonged seizure activity. In three patients the two phenomena were separated in time: multiple CSDs were replaced by ictal activity. In one patient seizures appeared to trigger repeated CSDs at the adjacent electrode. In two patients ongoing repeated seizures were interrupted each time CSD occurred. Conclusions Seizure activity occurs in association with CSD in the injured human brain. Significance ECoG recordings in brain injury patients provide insight into pathophysiological mechanisms that is not accessible by scalp EEG recordings. PMID:18621582

  15. Rapid manifestation of reactive astrogliosis in acute hippocampal brain slices

    PubMed Central

    Takano, Takahiro; He, Wei; Han, Xiaoning; Wang, Fushun; Xu, Qiwu; Wang, Xiaohai; Oberheim Bush, Nancy Ann; Cruz, Nancy; Dienel, Gerald A.; Nedergaard, Maiken

    2014-01-01

    A flurry of studies over the past decade has shown that astrocytes play a more active role in neural function than previously recognized. Hippocampal slices prepared from young rodent pups have served as a popular model for studying the pathways by which astrocytes participate in synaptic transmission. It is, however, not known how well astrocytes tolerate traumatic injury and hypoxia, which are unavoidable when preparing acute slices. We here show that astrocytes exhibit striking changes in expression of several receptors and structural proteins, including re-expression of the developmental marker nestin within 90 min following preparation of live vibratome slices. Moreover, immunoelectron microscopy showed a 2.7-fold loss of astrocytic processes in acute hippocampal slices prepared from GFAP-GFP reporter mice. A sharp decrease in the number of mitochondria was also noted in acute slices, concurrently with an increase in mitochondrial size. Glycogen content decreased 3-fold upon slice preparation and did not recover despite stable recordings of field EPSC. Analysis of Ca2+ signaling showed that astrocytic responses to purine receptor and mGluR5 agonists differed in slice vs. in vivo. These observations suggest that the functional properties and the fine structure of astrocytes in slices may be reflective of early stages of reactive gliosis and should be confirmed in vivo when possible. PMID:24272704

  16. Rapid manifestation of reactive astrogliosis in acute hippocampal brain slices.

    PubMed

    Takano, Takahiro; He, Wei; Han, Xiaoning; Wang, Fushun; Xu, Qiwu; Wang, Xiaohai; Oberheim Bush, Nancy Ann; Cruz, Nancy; Dienel, Gerald A; Nedergaard, Maiken

    2014-01-01

    A flurry of studies over the past decade has shown that astrocytes play a more active role in neural function than previously recognized. Hippocampal slices prepared from young rodent pups have served as a popular model for studying the pathways by which astrocytes participate in synaptic transmission. It is, however, not known how well astrocytes tolerate traumatic injury and hypoxia, which are unavoidable when preparing acute slices. We here showed that astrocytes exhibit striking changes in expression of several receptors and structural proteins, including re-expression of the developmental marker nestin within 90 min following preparation of live vibratome slices. Moreover, immunoelectron microscopy showed a 2.7-fold loss of astrocytic processes in acute hippocampal slices prepared from glial fibrillary acidic protein-green fluorescent protein reporter mice. A sharp decrease in the number of mitochondria was also noted in acute slices, concurrently with an increase in mitochondrial size. Glycogen content decreased 3-fold upon slice preparation and did not recover despite stable recordings of field excitatory postsynaptic current. Analysis of Ca(2+) signaling showed that astrocytic responses to purine receptor and mGluR5 agonists differed in slice versus in vivo. These observations suggest that the functional properties and the fine structure of astrocytes in slices may be reflective of early stages of reactive gliosis and should be confirmed in vivo when possible. PMID:24272704

  17. Acute Reduction of Microglia Does Not Alter Axonal Injury in a Mouse Model of Repetitive Concussive Traumatic Brain Injury

    PubMed Central

    Bennett, Rachel E.

    2014-01-01

    Abstract The pathological processes that lead to long-term consequences of multiple concussions are unclear. Primary mechanical damage to axons during concussion is likely to contribute to dysfunction. Secondary damage has been hypothesized to be induced or exacerbated by inflammation. The main inflammatory cells in the brain are microglia, a type of macrophage. This research sought to determine the contribution of microglia to axon degeneration after repetitive closed-skull traumatic brain injury (rcTBI) using CD11b-TK (thymidine kinase) mice, a valganciclovir-inducible model of macrophage depletion. Low-dose (1 mg/mL) valganciclovir was found to reduce the microglial population in the corpus callosum and external capsule by 35% after rcTBI in CD11b-TK mice. At both acute (7 days) and subacute (21 days) time points after rcTBI, reduction of the microglial population did not alter the extent of axon injury as visualized by silver staining. Further reduction of the microglial population by 56%, using an intermediate dose (10 mg/mL), also did not alter the extent of silver staining, amyloid precursor protein accumulation, neurofilament labeling, or axon injury evident by electron microscopy at 7 days postinjury. Longer treatment of CD11b-TK mice with intermediate dose and treatment for 14 days with high-dose (50 mg/mL) valganciclovir were both found to be toxic in this injury model. Altogether, these data are most consistent with the idea that microglia do not contribute to acute axon degeneration after multiple concussive injuries. The possibility of longer-term effects on axon structure or function cannot be ruled out. Nonetheless, alternative strategies directly targeting injury to axons may be a more beneficial approach to concussion treatment than targeting secondary processes of microglial-driven inflammation. PMID:24797413

  18. Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats

    PubMed Central

    Chen, Jiann-Hwa; Kuo, Hsing-Chun; Lee, Kam-Fai; Tsai, Tung-Hu

    2015-01-01

    Ischemia-reperfusion injury resulting from arterial occlusion or hypotension in patients leads to tissue hypoxia with glucose deprivation, which causes endoplasmic reticulum (ER) stress and neuronal death. A proteomic approach was used to identify the differentially expressed proteins in the brain of rats following a global ischemic stroke. The mechanisms involved the action in apoptotic and ER stress pathways. Rats were treated with ischemia-reperfusion brain injuries by the bilateral occlusion of the common carotid artery. The cortical neuron proteins from the stroke animal model (SAM) and the control rats were separated using two-dimensional gel electrophoresis (2-DE) to purify and identify the protein profiles. Our results demonstrated that the SAM rats experienced brain cell death in the ischemic core. Fifteen proteins were expressed differentially between the SAM rats and control rats, which were assayed and validated in vivo and in vitro. Interestingly, the set of differentially expressed, down-regulated proteins included catechol O-methyltransferase (COMT) and cathepsin D (CATD), which are implicated in oxidative stress, inflammatory response and apoptosis. After an ischemic stroke, one protein spot, namely the calretinin (CALB2) protein, showed increased expression. It mediated the effects of SAM administration on the apoptotic and ER stress pathways. Our results demonstrate that the ischemic injury of neuronal cells increased cell cytoxicity and apoptosis, which were accompanied by sustained activation of the IRE1-alpha/TRAF2, JNK1/2, and p38 MAPK pathways. Proteomic analysis suggested that the differential expression of CALB2 during a global ischemic stroke could be involved in the mechanisms of ER stress-induced neuronal cell apoptosis, which occurred via IRE1-alpha/TRAF2 complex formation, with activation of JNK1/2 and p38 MAPK. Based on these results, we also provide the molecular evidence supporting the ischemia-reperfusion-related neuronal injury

  19. Neuronal Interleukin-4 as a Modulator of Microglial Pathways and Ischemic Brain Damage

    PubMed Central

    Zhao, Xiurong; Wang, Huan; Sun, Guanghua; Zhang, Jie; Edwards, Nancy J.

    2015-01-01

    After ischemic stroke, various damage-associated molecules are released from the ischemic core and diffuse to the ischemic penumbra, activating microglia and promoting proinflammatory responses that may cause damage to the local tissue. Here we demonstrate using in vivo and in vitro models that, during sublethal ischemia, local neurons rapidly produce interleukin-4 (IL-4), a cytokine with potent anti-inflammatory properties. One such anti-inflammatory property includes its ability to polarize macrophages away from a proinflammatory M1 phenotype to a “healing” M2 phenotype. Using an IL-4 reporter mouse, we demonstrated that IL-4 expression was induced preferentially in neurons in the ischemic penumbra but not in the ischemic core or in brain regions that were spared from ischemia. When added to cultured microglia, IL-4 was able to induce expression of genes typifying the M2 phenotype and peroxisome proliferator activated receptor γ (PPARγ) activation. IL-4 also enhanced expression of the IL-4 receptor on microglia, facilitating a “feedforward” increase in (1) their expression of trophic factors and (2) PPARγ-dependent phagocytosis of apoptotic neurons. Parenteral administration of IL-4 resulted in augmented brain expression of M2- and PPARγ-related genes. Furthermore, IL-4 and PPARγ agonist administration improved functional recovery in a clinically relevant mouse stroke model, even if administered 24 h after the onset of ischemia. We propose that IL-4 is secreted by ischemic neurons as an endogenous defense mechanism, playing a vital role in the regulation of brain cleanup and repair after stroke. Modulation of IL-4 and its associated pathways could represent a potential target for ischemic stroke treatment. SIGNIFICANCE STATEMENT Depending on the activation signal, microglia/macrophages (MΦ) can behave as “healing” (M2) or “harmful” (M1). In response to ischemia, damaged/necrotic brain cells discharge factors that polarize MΦ to a M1-like

  20. DNA Damage Focus Analysis in Blood Samples of Minipigs Reveals Acute Partial Body Irradiation

    PubMed Central

    Lamkowski, Andreas; Forcheron, Fabien; Agay, Diane; Ahmed, Emad A.; Drouet, Michel; Meineke, Viktor; Scherthan, Harry

    2014-01-01

    Radiation accidents frequently involve acute high dose partial body irradiation leading to victims with radiation sickness and cutaneous radiation syndrome that implements radiation-induced cell death. Cells that are not lethally hit seek to repair ionizing radiation (IR) induced damage, albeit at the expense of an increased risk of mutation and tumor formation due to misrepair of IR-induced DNA double strand breaks (DSBs). The response to DNA damage includes phosphorylation of histone H2AX in the vicinity of DSBs, creating foci in the nucleus whose enumeration can serve as a radiation biodosimeter. Here, we investigated γH2AX and DNA repair foci in peripheral blood lymphocytes of Göttingen minipigs that experienced acute partial body irradiation (PBI) with 49 Gy (±6%) Co-60 γ-rays of the upper lumbar region. Blood samples taken 4, 24 and 168 hours post PBI were subjected to γ-H2AX, 53BP1 and MRE11 focus enumeration. Peripheral blood lymphocytes (PBL) of 49 Gy partial body irradiated minipigs were found to display 1–8 DNA damage foci/cell. These PBL values significantly deceed the high foci numbers observed in keratinocyte nuclei of the directly γ-irradiated minipig skin regions, indicating a limited resident time of PBL in the exposed tissue volume. Nonetheless, PBL samples obtained 4 h post IR in average contained 2.2% of cells displaying a pan-γH2AX signal, suggesting that these received a higher IR dose. Moreover, dispersion analysis indicated partial body irradiation for all 13 minipigs at 4 h post IR. While dose reconstruction using γH2AX DNA repair foci in lymphocytes after in vivo PBI represents a challenge, the DNA damage focus assay may serve as a rapid, first line indicator of radiation exposure. The occurrence of PBLs with pan-γH2AX staining and of cells with relatively high foci numbers that skew a Poisson distribution may be taken as indicator of acute high dose partial body irradiation, particularly when samples are available early after

  1. DNA damage focus analysis in blood samples of minipigs reveals acute partial body irradiation.

    PubMed

    Lamkowski, Andreas; Forcheron, Fabien; Agay, Diane; Ahmed, Emad A; Drouet, Michel; Meineke, Viktor; Scherthan, Harry

    2014-01-01

    Radiation accidents frequently involve acute high dose partial body irradiation leading to victims with radiation sickness and cutaneous radiation syndrome that implements radiation-induced cell death. Cells that are not lethally hit seek to repair ionizing radiation (IR) induced damage, albeit at the expense of an increased risk of mutation and tumor formation due to misrepair of IR-induced DNA double strand breaks (DSBs). The response to DNA damage includes phosphorylation of histone H2AX in the vicinity of DSBs, creating foci in the nucleus whose enumeration can serve as a radiation biodosimeter. Here, we investigated γH2AX and DNA repair foci in peripheral blood lymphocytes of Göttingen minipigs that experienced acute partial body irradiation (PBI) with 49 Gy (± 6%) Co-60 γ-rays of the upper lumbar region. Blood samples taken 4, 24 and 168 hours post PBI were subjected to γ-H2AX, 53BP1 and MRE11 focus enumeration. Peripheral blood lymphocytes (PBL) of 49 Gy partial body irradiated minipigs were found to display 1-8 DNA damage foci/cell. These PBL values significantly deceed the high foci numbers observed in keratinocyte nuclei of the directly γ-irradiated minipig skin regions, indicating a limited resident time of PBL in the exposed tissue volume. Nonetheless, PBL samples obtained 4 h post IR in average contained 2.2% of cells displaying a pan-γH2AX signal, suggesting that these received a higher IR dose. Moreover, dispersion analysis indicated partial body irradiation for all 13 minipigs at 4 h post IR. While dose reconstruction using γH2AX DNA repair foci in lymphocytes after in vivo PBI represents a challenge, the DNA damage focus assay may serve as a rapid, first line indicator of radiation exposure. The occurrence of PBLs with pan-γH2AX staining and of cells with relatively high foci numbers that skew a Poisson distribution may be taken as indicator of acute high dose partial body irradiation, particularly when samples are available early after IR

  2. Uncoupling of the autonomic and cardiovascular systems in acute brain injury.

    PubMed

    Goldstein, B; Toweill, D; Lai, S; Sonnenthal, K; Kimberly, B

    1998-10-01

    We hypothesized that acute brain injury results in decreased heart rate (HR) variability and baroreflex sensitivity indicative of uncoupling of the autonomic and cardiovascular systems and that the degree of uncoupling should be proportional to the degree of neurological injury. We used HR and blood pressure (BP) power spectral analysis to measure neuroautonomic regulation of HR and BP and the transfer function magnitude (TF) between BP and HR as a measure of baroreflex modulation of HR. In 24 brain-injured patients [anoxic/ischemic injury (n = 7), multiple trauma (n = 6), head trauma (n = 5), central nervous system infection (n = 4), and intracranial hemorrhage (n = 2)], neurological injury and survival was associated with low-frequency (0.01-0.15 Hz) HR and BP power and TF. Brain-dead patients showed decreased low-frequency HR power [0. 51 +/- 0.36 (SE) vs. 2.54 +/- 0.14 beats/min2, P = 0.03] and TF [0. 61 +/- 0.16 (SE) vs. 1.29 +/- 0.07 beats . min-1 . mmHg-1, P = 0.05] compared with non-brain-dead patients. We conclude that 1) severity of neurological injury and outcome are inversely associated with HR and BP variability and 2) there is direct evidence for cardiovascular and autonomic uncoupling in acute brain injury with complete uncoupling during brain death. PMID:9756562

  3. Reduction in DNA damage in brain and peripheral blood lymphocytes of elderly dogs after treatment with dehydroepiandrosterone (DHEA).

    PubMed

    Shen, S; Cooley, D M; Glickman, L T; Glickman, N; Waters, D J

    2001-09-01

    Steady state levels of DNA damage are substantial in vertebrate animals as a consequence of exposure to endogenous and environmental mutagens. DNA damage may contribute to organismal senescence and an increased risk for specific age-related diseases. In this study, we determined if treatment with the neuroactive adrenal steroid, dehydroepiandrosterone (DHEA), which exhibits antioxidant and anticarcinogenic properties in rodents, would reduce DNA damage in the brain and peripheral blood lymphocytes (PBLs) of elderly dogs. Elderly male dogs, physiologically equivalent to 59-69-year-old men, were randomly assigned to receive no treatment (n=9 dogs) or DHEA at 100mg/kg PO daily (n=8 dogs). Extent of DNA damage in brain cells and PBLs was measured using alkaline comet assay. The effect of DHEA treatment on the susceptibility of PBLs to H(2)O(2)-induced DNA damage was also measured. We found that elderly male dogs receiving daily DHEA treatment for 7 months had significantly less DNA damage detectable in their brain compared to age-matched control dogs. After 7 months treatment, DHEA-treated dogs also had a significant reduction in DNA damage in PBLs compared to pre-treatment levels. We also found that PBLs of dogs treated with DHEA were more resistant to H(2)O(2)-induced DNA damage than PBLs of untreated dogs. Our results did not show that basal DNA damage in PBLs was strongly correlated with DNA damage within the brain. The results of this study suggest that DHEA supplementation can significantly reduce steady state levels of DNA damage in the mammalian brain. Further evaluation of DHEA as a neuroactive agent and its effects on DNA damage and gene expression in other tissues and species is warranted. PMID:11506809

  4. Acute crack cocaine exposure induces genetic damage in multiple organs of rats.

    PubMed

    Moretti, Eduardo Gregolin; Yujra, Veronica Quispe; Claudio, Samuel Rangel; Silva, Marcelo Jose Dias; Vilegas, Wagner; Pereira, Camilo Dias Seabra; de Oliveira, Flavia; Ribeiro, Daniel Araki

    2016-04-01

    Crack cocaine is a very toxic product derived from cocaine. The aim of this study was to evaluate genetic damage in multiple organs of rats following acute exposure to crack cocaine. A total of 20 Wistar rats were distributed into four groups (n = 5), as follows: 0, 4.5, 9, and 18 mg/kg body weight (b.w.) of crack cocaine administered by intraperitoneal route (i.p.). All animals were killed 24 h after intraperitoneal (i.p.) injection. The results showed that crack cocaine increased the number of micronucleated cells in bone marrow cells exposed to 18 mg/kg crack cocaine (p < 0.05). Peripheral blood and liver cells presented genetic damage as depicted by single cell gel (comet) assay at 9 and 18 mg/kg doses (p < 0.05). Immunohistochemistry data revealed significant increase in 8-hydroxy-20-deoxyguanosine (8-OHdG) immunoexpression in hepatocytes of animals exposed to crack cocaine at 9 and 18 mg/kg (p < 0.05) when compared with negative controls. Taken together, our results demonstrate that crack cocaine is able to induce genomic damage in multiple organs of Wistar rats. PMID:26825523

  5. Protective effect of diphenyl diselenide on acute liver damage induced by 2-nitropropane in rats.

    PubMed

    Borges, Lysandro P; Borges, Vanessa Corralo; Moro, Angelica Venturini; Nogueira, Cristina Wayne; Rocha, Joao Batista Teixeira; Zeni, Gilson

    2005-05-15

    The effect of diphenyl diselenide, (PhSe)2, administration on 2-nitropropane (2-NP)-induced hepatic damage was examined in male rats. Rats were pre-treated with a single dose of diphenyl diselenide (10, 50 or 100 micromol/kg). Afterward, they received only one dose of 2-NP (100 mg/kg body weight dissolved in olive oil). The parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alpha-fetoprotein (AFP), creatinine and urea were determined. Since toxicity induced by 2-NP is related to oxidative stress, lipid peroxidation was also evaluated. Diphenyl diselenide (100 micromol/kg) significantly reduced plasma ALT, gamma-GGT, AFP levels when compared to 2-NP group. Treatment with diphenyl diselenide, at all doses, effectively protects the increase of lipid peroxidation when compared to 2-NP group. Histological examination revealed that 2-NP treatment causes a moderate swelling and degenerative alterations on hepatocytes and diphenyl diselenide (100 micromol/kg) protects against these alterations. Diphenyl diselenide (50 and 100 micromol/kg) significantly decreased the urea level. This study evidences the protective effect of diphenyl diselenide by 2-NP-induced acute hepatic damage. PMID:15804453

  6. An Aminopyridazine Inhibitor of Death Associated Protein Kinase Attenuates Hypoxia-Ischemia Induced Brain Damage

    SciTech Connect

    Velentza, A.V.; Wainwright, M.S.; Zasadzki, M.; Mirzoeva, S.; Haiech, J.; Focia, P.J.; Egli, M.; Watterson, D.M.

    2010-03-08

    Death associated protein kinase (DAPK) is a calcium and calmodulin regulated enzyme that functions early in eukaryotic programmed cell death, or apoptosis. To validate DAPK as a potential drug discovery target for acute brain injury, the first small molecule DAPK inhibitor was synthesized and tested in vivo. A single injection of the aminopyridazine-based inhibitor administered 6 h after injury attenuated brain tissue or neuronal biomarker loss measured, respectively, 1 week and 3 days later. Because aminopyridazine is a privileged structure in neuropharmacology, we determined the high-resolution crystal structure of a binary complex between the kinase domain and a molecular fragment of the DAPK inhibitor. The co-crystal structure describes a structural basis for interaction and provides a firm foundation for structure-assisted design of lead compounds with appropriate molecular properties for future drug development.

  7. Mutations of the Thyroid Hormone Transporter MCT8 Cause Prenatal Brain Damage and Persistent Hypomyelination

    PubMed Central

    López-Espíndola, Daniela; Morales-Bastos, Carmen; Grijota-Martínez, Carmen; Liao, Xiao-Hui; Lev, Dorit; Sugo, Ella; Verge, Charles F.; Refetoff, Samuel

    2014-01-01

    Context: Mutations in the MCT8 (SLC16A2) gene, encoding a specific thyroid hormone transporter, cause an X-linked disease with profound psychomotor retardation, neurological impairment, and abnormal serum thyroid hormone levels. The nature of the central nervous system damage is unknown. Objective: The objective of the study was to define the neuropathology of the syndrome by analyzing brain tissue sections from MCT8-deficient subjects. Design: We analyzed brain sections from a 30th gestational week male fetus and an 11-year-old boy and as controls, brain tissue from a 30th and 28th gestational week male and female fetuses, respectively, and a 10-year-old girl and a 12-year-old boy. Methods: Staining with hematoxylin-eosin and immunostaining for myelin basic protein, 70-kDa neurofilament, parvalbumin, calbindin-D28k, and synaptophysin were performed. Thyroid hormone determinations and quantitative PCR for deiodinases were also performed. Results: The MCT8-deficient fetus showed a delay in cortical and cerebellar development and myelination, loss of parvalbumin expression, abnormal calbindin-D28k content, impaired axonal maturation, and diminished biochemical differentiation of Purkinje cells. The 11-year-old boy showed altered cerebellar structure, deficient myelination, deficient synaptophysin and parvalbumin expression, and abnormal calbindin-D28k expression. The MCT8-deficient fetal cerebral cortex showed 50% reduction of thyroid hormones and increased type 2 deiodinase and decreased type 3 deiodinase mRNAs. Conclusions: The following conclusions were reached: 1) brain damage in MCT8 deficiency is diffuse, without evidence of focal lesions, and present from fetal stages despite apparent normality at birth; 2) deficient hypomyelination persists up to 11 years of age; and 3) the findings are compatible with the deficient action of thyroid hormones in the developing brain caused by impaired transport to the target neural cells. PMID:25222753

  8. Bumetanide increases manganese accumulation in the brain of rats with liver damage.

    PubMed

    Montes, Sergio; Castro-Chávez, Armando; Florian-Soto, Circe; Heras-Romero, Yessica; Ríos, Camilo; Rivera-Mancía, Susana

    2016-03-01

    Hepatic encephalopathy is a common complication in cases of liver damage; it results from several factors, including the accumulation of toxic substances in the brain, e.g. manganese, ammonia and glutamine. We have previously reported that manganese favors ammonia and glutamine accumulation in the brain of cirrhotic rats, and we suggested that such effect could be mediated by manganese-elicited activation of the NKCC1 (Na(+)/K(+)/2Cl(-) cotransporter 1). To test this hypothesis, we used bumetanide, an NKCC1 blocker prescribed to treat ascites in cirrhotic patients; we expected that if NKCC1 was responsible for manganese-mediated ammonia buildup and the subsequent glutamine accumulation, bumetanide could counteract such effect and improve motor coordination. In addition, we considered essential to test the effect of bumetanide on manganese brain levels. We used a model of liver damage in rats, consisting in bile-duct ligation. Animals were exposed to manganese in the drinking water (1 mg/ml) for two weeks and ammonia in the food (20% w/w of ammonia acetate) during the second week after surgery. Bumetanide was administered intraperitoneally in the course of the ammonia treatment. We measured glutamine and manganese in three brain regions: frontal cortex, striatum and cerebellum. Bumetanide produced no effect on glutamine accumulation; however, because of bumetanide treatment, manganese was increased in the brain, and also the activity of gamma-glutamyl transferase in plasma; thus, we consider that the influence of bumetanide and similar diuretics on liver function and manganese homeostasis should be further studied. PMID:26851372

  9. The neuroprotective effects of preconditioning exercise on brain damage and neurotrophic factors after focal brain ischemia in rats.

    PubMed

    Otsuka, Shotaro; Sakakima, Harutoshi; Sumizono, Megumi; Takada, Seiya; Terashi, Takuto; Yoshida, Yoshihiro

    2016-04-15

    Preconditioning exercise can exert neuroprotective effects after stroke. However, the mechanism underlying these neuroprotective effects by preconditioning exercise remains unclear. We investigated the neuroprotective effects of preconditioning exercise on brain damage and the expression levels of the midkine (MK) and brain-derived neurotrophic factor (BDNF) after brain ischemia. Animals were assigned to one of 4 groups: exercise and ischemia (Ex), no exercise and ischemia (No-Ex), exercise and no ischemia (Ex-only), and no exercise and intact (Control). Rats ran on a treadmill for 30 min once a day at a speed of 25 m/min for 5 days a week for 3 weeks. After the exercise program, stroke was induced by a 60 min left middle cerebral artery occlusion using an intraluminal filament. The infarct volume, motor function, neurological deficits, and the cellular expressions levels of MK, BDNF, GFAP, PECAM-1, caspase 3, and nitrotyrosine (NT) were evaluated 48 h after the induction of ischemia. The infarct volume, neurological deficits and motor function in the Ex group were significantly improved compared to that of the No-Ex group. The expression levels of MK, BDNF, GFAP, and PECAM-1 were enhanced in the Ex group compared to the expression levels in the No-Ex group after brain ischemia, while the expression levels of activated caspase 3 and NT were reduced in the area surrounding the necrotic lesion. Our findings suggest that preconditioning exercise reduced the infract volume and ameliorated motor function, enhanced expression levels of MK and BDNF, increased astrocyte proliferation, increased angiogenesis, and reduced neuronal apoptosis and oxidative stress. PMID:26808606

  10. Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain

    PubMed Central

    Al-Mashhadi, Sufana; Simpson, Julie E.; Heath, Paul R.; Dickman, Mark; Forster, Gillian; Matthews, Fiona E.; Brayne, Carol; Ince, Paul G.; Wharton, Stephen B.

    2016-01-01

    White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2′-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. PMID:25311358

  11. Permanent brain damage and pertussis vaccination: is the end of the saga in sight?

    PubMed

    Griffith, A H

    1989-06-01

    The development and widespread uptake of a safe and efficacious aluminium adsorbed diphtheria-tetanus-pertussis vaccine (DTP) in the United States between 1933 and 1944 led to a gradual decline in whooping cough morbidity and instilled confidence in a vaccination programme which has been effectively maintained for over 40 years. T his contrasts with the turbulent history of pertussis vaccination in the United Kingdom where doubts as to the efficacy of available vaccines delayed their active national promotion until 1957, after which various reports resulted in further doubts over efficacy and safety. In 1974, the mass media became involved in the safety issue when the National Hospital for Sick Children case series of neurological events, which had occurred after DTP vaccination was made core material for a television documentary. The Department of Health and Social Security (DHSS) responded by establishing two retrospective studies of case records of post vaccination adverse events and two prospective studies. One of the latter, the National Childhood Encephalopathy Study (NCES) was regarded as the definitive case control study. A claim for damages, Loveday v Renton and The Wellcome Foundation, heard in the High Court of Justice in London, from early October 1987 until late February 1988 dealt with the general issue of whether, on the balance of probabilities, pertussis vaccine could cause permanent brain damage. The cornerstone of the claim that pertussis vaccine can cause permanent brain damage has always been the apparent clustering of onset of neurological disorders within the first 24-48 h after vaccination. One of the main finds of the NCES, however, which was not divulged in any published report but emerged in the course of the hearing, was that permanent brain damage did not occur within 48 h of DTP vaccination in any child in England, Scotland and Wales from mid-1976 to mid-1979 when 2 million doses of vaccine were used. The NCES, in this respect

  12. Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients.

    PubMed

    Vanhaudenhuyse, Audrey; Noirhomme, Quentin; Tshibanda, Luaba J-F; Bruno, Marie-Aurelie; Boveroux, Pierre; Schnakers, Caroline; Soddu, Andrea; Perlbarg, Vincent; Ledoux, Didier; Brichant, Jean-François; Moonen, Gustave; Maquet, Pierre; Greicius, Michael D; Laureys, Steven; Boly, Melanie

    2010-01-01

    The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than during attention-demanding tasks. Recent studies have shown that it is possible to reliably identify this network in the absence of any task, by resting state functional magnetic resonance imaging connectivity analyses in healthy volunteers. However, the functional significance of these spontaneous brain activity fluctuations remains unclear. The aim of this study was to test if the integrity of this resting-state connectivity pattern in the default network would differ in different pathological alterations of consciousness. Fourteen non-communicative brain-damaged patients and 14 healthy controls participated in the study. Connectivity was investigated using probabilistic independent component analysis, and an automated template-matching component selection approach. Connectivity in all default network areas was found to be negatively correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative then coma patients. Furthermore, precuneus connectivity was found to be significantly stronger in minimally conscious patients as compared with unconscious patients. Locked-in syndrome patient's default network connectivity was not significantly different from controls. Our results show that default network connectivity is decreased in severely brain-damaged patients, in proportion to their degree of consciousness impairment. Future prospective studies in a larger patient population are needed in order to evaluate the prognostic value of the presented methodology. PMID:20034928

  13. Genetic influences in emotional dysfunction and alcoholism-related brain damage

    PubMed Central

    Oscar-Berman, Marlene; Bowirrat, Abdalla

    2005-01-01

    Alcoholism is a complex, multifactorial disorder involving problematic ethanol ingestion; it results from the interplay between genetic and environmental factors. Personality, likewise, is formed from a combination of inherited and acquired influences. Because selected dimensions of emotional temperament are associated with distinct neurochemical substrates contributing to specific personality phenotypes, certain aspects of abnormal emotional traits in alcoholics may be inherited. Emotions involve complex subjective experiences engaging multiple brain regions, most notably the cortex, limbic system, and cerebellum. Results of in vivo magnetic resonance imaging and post-mortem neuropathological studies of alcoholics indicate that the greatest cortical loss occurs in the frontal lobes, with concurrent thinning of the corpus callosum. Additional damage has been documented for the amygdala and hippocampus, as well as in the white matter of the cerebellum. All of the critical areas of alcoholism-related brain damage are important for normal emotional functioning. When changes occur in these brain regions, either as a consequence of chronic ethanol abuse or from a genetic anomaly affecting temperament and/or a vulnerability to alcoholism, corresponding changes in emotional functions are to be expected. In alcoholics, such changes have been observed in their perception and evaluation of emotional facial expressions, interpretation of emotional intonations in vocal utterances, and appreciation of the meaning of emotional materials. PMID:18568071

  14. Two-Photon Excitation STED Microscopy in Two Colors in Acute Brain Slices

    PubMed Central

    Bethge, Philipp; Chéreau, Ronan; Avignone, Elena; Marsicano, Giovanni; Nägerl, U. Valentin

    2013-01-01

    Many cellular structures and organelles are too small to be properly resolved by conventional light microscopy. This is particularly true for dendritic spines and glial processes, which are very small, dynamic, and embedded in dense tissue, making it difficult to image them under realistic experimental conditions. Two-photon microscopy is currently the method of choice for imaging in thick living tissue preparations, both in acute brain slices and in vivo. However, the spatial resolution of a two-photon microscope, which is limited to ∼350 nm by the diffraction of light, is not sufficient for resolving many important details of neural morphology, such as the width of spine necks or thin glial processes. Recently developed superresolution approaches, such as stimulated emission depletion microscopy, have set new standards of optical resolution in imaging living tissue. However, the important goal of superresolution imaging with significant subdiffraction resolution has not yet been accomplished in acute brain slices. To overcome this limitation, we have developed a new microscope based on two-photon excitation and pulsed stimulated emission depletion microscopy, which provides unprecedented spatial resolution and excellent experimental access in acute brain slices using a long-working distance objective. The new microscope improves on the spatial resolution of a regular two-photon microscope by a factor of four to six, and it is compatible with time-lapse and simultaneous two-color superresolution imaging in living cells. We demonstrate the potential of this nanoscopy approach for brain slice physiology by imaging the morphology of dendritic spines and microglial cells well below the surface of acute brain slices. PMID:23442956

  15. Brain-peripheral cell crosstalk in white matter damage and repair.

    PubMed

    Hayakawa, Kazuhide; Lo, Eng H

    2016-05-01

    White matter damage is an important part of cerebrovascular disease and may be a significant contributing factor in vascular mechanisms of cognitive dysfunction and dementia. It is well accepted that white matter homeostasis involves multifactorial interactions between all cells in the axon-glia-vascular unit. But more recently, it has been proposed that beyond cell-cell signaling within the brain per se, dynamic crosstalk between brain and systemic responses such as circulating immune cells and stem/progenitor cells may also be important. In this review, we explore the hypothesis that peripheral cells contribute to damage and repair after white matter damage. Depending on timing, phenotype and context, monocyte/macrophage can possess both detrimental and beneficial effects on oligodendrogenesis and white matter remodeling. Endothelial progenitor cells (EPCs) can be activated after CNS injury and the response may also influence white matter repair process. These emerging findings support the hypothesis that peripheral-derived cells can be both detrimental or beneficial in white matter pathology in cerebrovascular disease. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26277436

  16. Mouse model of diffuse brain damage following anoxia, evaluated by a new assay of generalized arousal.

    PubMed

    Arrieta-Cruz, Isabel; Pfaff, Donald W; Shelley, Deborah N

    2007-06-01

    Diffuse brain damage following anoxia due to cardiac failure, drowning, carbon monoxide exposure or other accidents constitutes a major medical problem. We have created a novel mouse model using the breathing of pure nitrogen, followed by a recently developed assay that reflects an operational definition of generalized arousal. The operational definition is precise, complete, and leads to quantitative, physical measures in a genetically tractable animal. Exposure to pure nitrogen for controlled periods had a surprising bifurcate effect: about half the mice survived with neurological measures that were virtually normal while the other half died. The new assay detected behavioral deficits unrevealed by neurological screening. Two important features of the results were that (i) deficits were not equal across the circadian cycle, and (ii) deficits were not equal across all the measures within the operational definition of arousal. Specific voluntary motor measurements were decreased in a manner that depended on the phase of the circadian cycle. Sensory responses were also decreased, with an emphasis on vertical movement responses; but, interestingly, fear learning was not damaged. This study establishes the first useful approach to diffuse brain damage in a genetically tractable animal. The model and its outcome measurements will be useful during future attempts at amelioration of acquired neurological disabilities following hypoxic-ischemic injuries. PMID:17448465

  17. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice.

    PubMed

    Chang, Jianhui; Luo, Yi; Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  18. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice

    PubMed Central

    Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  19. Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices

    PubMed Central

    Varela, Juan A.; Dupuis, Julien P.; Etchepare, Laetitia; Espana, Agnès; Cognet, Laurent; Groc, Laurent

    2016-01-01

    Single-molecule imaging has changed the way we understand many biological mechanisms, particularly in neurobiology, by shedding light on intricate molecular events down to the nanoscale. However, current single-molecule studies in neuroscience have been limited to cultured neurons or organotypic slices, leaving as an open question the existence of fast receptor diffusion in intact brain tissue. Here, for the first time, we targeted dopamine receptors in vivo with functionalized quantum dots and were able to perform single-molecule tracking in acute rat brain slices. We propose a novel delocalized and non-inflammatory way of delivering nanoparticles (NPs) in vivo to the brain, which allowed us to label and track genetically engineered surface dopamine receptors in neocortical neurons, revealing inherent behaviour and receptor activity regulations. We thus propose a NP-based platform for single-molecule studies in the living brain, opening new avenues of research in physiological and pathological animal models. PMID:26971573

  20. Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices

    NASA Astrophysics Data System (ADS)

    Varela, Juan A.; Dupuis, Julien P.; Etchepare, Laetitia; Espana, Agnès; Cognet, Laurent; Groc, Laurent

    2016-03-01

    Single-molecule imaging has changed the way we understand many biological mechanisms, particularly in neurobiology, by shedding light on intricate molecular events down to the nanoscale. However, current single-molecule studies in neuroscience have been limited to cultured neurons or organotypic slices, leaving as an open question the existence of fast receptor diffusion in intact brain tissue. Here, for the first time, we targeted dopamine receptors in vivo with functionalized quantum dots and were able to perform single-molecule tracking in acute rat brain slices. We propose a novel delocalized and non-inflammatory way of delivering nanoparticles (NPs) in vivo to the brain, which allowed us to label and track genetically engineered surface dopamine receptors in neocortical neurons, revealing inherent behaviour and receptor activity regulations. We thus propose a NP-based platform for single-molecule studies in the living brain, opening new avenues of research in physiological and pathological animal models.

  1. Ultrastructure damage of oviduct telocytes in rat model of acute salpingitis

    PubMed Central

    Yang, Jian; Chi, Chi; Liu, Zhen; Yang, Gang; Shen, Zong-Ji; Yang, Xiao-Jun

    2015-01-01

    Acute salpingitis (AS) is an inflammatory disease which causes severe damage to a subset of classically described cells lining in oviduct wall and contributes to interstitial fibrosis and fertility problems. Telocytes (TCs), a newly discovered peculiar type of stromal cells, have been identified in many organs, including oviduct, with proposed multiple potential bio-functions. However, with recent increasing reports regarding TCs alterations in disease-affected tissues, there is still lack of evidence about TCs involvement in AS-affected oviduct tissues and potential pathophysiological roles. We presently identified normal TCs by their characteristic ultrastructural features and immunophenotype. However, in AS-affected oviduct tissues, TCs displayed multiple ultrastructural damage both in cellular body and prolongations, with obvious loss of TCs and development of tissue fibrosis. Furthermore, TCs lose their interstitial 3-D network connected by homocellular or heterocellular junctions between TCs and adjacent cells. And especially, TCs connected to the activated immunocytes (mononuclear cells, eosinophils) and affected local immune state (repression or activation). Meanwhile, massive neutrophils infiltration and overproduced Inducible Nitric Oxide Synthase (iNOS), COX-2, suggested mechanism of inflammatory-induced TCs damage. Consequently, TCs damage might contribute to AS-induced structural and reproductive functional abnormalities of oviduct, probably via: (i) substances, energy and functional insufficiency, presumably, e.g. TC-specific genetic material profiles, ion channels, cytoskeletal elements, Tps dynamics, etc., (ii) impaired TCs-mediated multicellular signalling, such as homeostasis/angiogenesis, tissue repair/regeneration, neurotransmission, (iii) derangement of 3-D network and impaired mechanical support for TCs-mediated multicellular signals within the stromal compartment, consequently induced interstitial fibrosis, (iv) involvement in local

  2. Free radical damage to protein and DNA: mechanisms involved and relevant observations on brain undergoing oxidative stress.

    PubMed

    Floyd, R A; Carney, J M

    1992-01-01

    Iron mediates damage to proteins and DNA. The mechanisms of damage not only involve iron but also oxygen free radical intermediates. Oxidative damage to DNA causes not only strand breaks, but also formation of specific base adducts, such as 8-hydroxy-2'-deoxyguanosine. Oxidative damage also inactivates certain enzymes such as glutamine synthetase. Novel methods of assessing oxidative damage to tissue, including quantitation of salicylate hydroxylation as an index of hydroxyl free radical flux as well as specific lesions to proteins and DNA, have yielded results that clearly show that ischemia/reperfusion injury to mongolian gerbil brain involves oxidatively damaging events. Aging in gerbil as well as human brain is also associated with increased oxidative damage. Recent novel observations have shown that the spin-trapping agent phenyl alpha-tert-butylnitrone (PBN) offers protection in gerbil brain during ischemia/reperfusion injury. We also show that oxidative damage to brain during aging is decreased by chronic administration of PBN. The mechanism of action of PBN may be related to its trapping of specific free radicals, which triggers a cascade of oxidative events that eventually lead to tissue injury. PMID:1510377

  3. Acute O3 damage on first year coppice sprouts of aspen and maple sprouts in an open-air experiment

    SciTech Connect

    Darbah, J.N.; Nagy, J.; Jones, W. S.; Burton, A. J.; Kubiske, M. E.

    2011-10-01

    We studied the effect of high ozone (O{sub 3}) concentration (110-490 nmol mol{sup -1}) on regenerating aspen (Populus tremuloides) and maple (Acer saccharum) trees at an open-air O{sub 3} pollution experiment near Rhinelander WI USA. This study is the first of its kind to examine the effects of acute O{sub 3} exposure on aspen and maple sprouts after the parent trees, which were grown under elevated O{sub 3} and/or CO{sub 2} for 12 years, were harvested. Acute O{sub 3} damage was not uniform within the crowns of aspen suckers; it was most severe in the mature, fully expanded photosynthesizing leaves. Young expanding leaves showed no visible signs of acute O{sub 3} damage contrary to expectations. Stomatal conductance played a primary role in the severity of acute O{sub 3} damage as it directly controlled O{sub 3} uptake. Maple sprouts, which had lower stomatal conductance, smaller stomatal aperture, higher stomatal density and larger leaf surface area, were tolerant of acute O{sub 3} exposure. Moreover, elevated CO{sub 2} did not ameliorate the adverse effects of acute O{sub 3} dose on aspen and maple sprouts, in contrast to its ability to counteract the effects of long-term chronic exposure to lower O{sub 3} levels.

  4. Parameters of diffusional kurtosis imaging for the diagnosis of acute cerebral infarction in different brain regions

    PubMed Central

    Guo, Yue-Lin; Li, Su-Juan; Zhang, Zhong-Ping; Shen, Zhi-Wei; Zhang, Gui-Shan; Yan, Gen; Wang, Yan-Ting; Rao, Hai-Bing; Zheng, Wen-Bin; Wu, Ren-Hua

    2016-01-01

    Diffusional kurtosis imaging (DKI) is a new type diffusion-weighted sequence which measures the non-Gaussianity of water diffusion. The present study aimed to investigate whether the parameters of DKI could distinguish between differences in water molecule diffusion in various brain regions under the conditions of acute infarction and to identify the optimal DKI parameter for locating ischemic lesions in each brain region. A total of 28 patients with acute ischemic stroke in different brain regions were recruited for the present study. The relative values of DKI parameters were selected as major assessment indices, and the homogeneity of background image and contrast of adjacent structures were used as minor assessment indices. According to the brain region involved in three DKI parametric maps, including mean kurtosis (MK), axial kurtosis (Ka) and radial kurtosis (Kr), 112 groups of regions of interest were outlined in the following regions: Corpus callosum (n=17); corona radiata (n=26); thalamus (n=21); subcortical white matter (n=24); and cerebral cortex (n=24). For ischemic lesions in the corpus callosum and corona radiata, significant increases in relative Ka were detected, as compared with the other parameters (P<0.05). For ischemic lesions in the thalamus, subcortical white matter and cerebral cortices, an increase in the three parameters was detected, however this difference was not significant. Minor assessment indices demonstrated that Ka lacked tissue contrast and the background of Kr was heterogeneous; thus, MK was the superior assessment parameter for ischemic lesions in these regions. In conclusion, Ka is better suited for the diagnosis of acute ischemic lesions in highly anisotropic brain regions, such as the corpus callosum and corona radiate. MK may be appropriate for the lesions in low anisotropic or isotropic brain regions, such as the thalamus, subcortical white matter and cerebral cortices.

  5. How Acute Total Sleep Loss Affects the Attending Brain: A Meta-Analysis of Neuroimaging Studies

    PubMed Central

    Ma, Ning; Dinges, David F.; Basner, Mathias; Rao, Hengyi

    2015-01-01

    Study Objectives: Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Design: Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. Methods: The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. Results: The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Conclusion: Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. Citation: Ma N, Dinges DF, Basner M, Rao H. How acute total

  6. Nutritional treatment for acute and chronic traumatic brain injury patients.

    PubMed

    Curtis, L; Epstein, P

    2014-09-01

    Proper nutrition is critical for recovery from traumatic brain injury (TBI). Prompt enteral feeding of moderate to severe TBI patients has been associated with significantly lower mortality and rates of infection. Probiotic supplementation has been associated with significantly lower rates of infection in TBI and other trauma patients. Human studies have suggested that supplementation with omega 3 fats, vitamin D, N-Acetylcysteine, branched chain amino acids, and zinc may be helpful for recovery from TBI. Animal TBI models have suggested that alpha-lipoic acid, magnesium, taurine, coenzyme Q10, and many phytonutrients (such as resveratrol) are also helpful. Unfortunately, recent human clinical trials with citicoline in TBI and stroke patients have produced disappointing results. Much more research is needed on multifaceted nutritional strategies to treat TBI patients in both the immediate post-injury phase and throughout the patients lifespan. PMID:24844176

  7. Arterial damages in acute elbow dislocations: which diagnostic tests are required?

    PubMed

    Lutter, Christoph; Pfefferkorn, Ronny; Schoeffl, Volker

    2016-01-01

    Blunt vessel injuries of peripheral arteries caused by a direct trauma are rare. Studies have described the frequency of arterial ruptures following closed elbow dislocations in 0.3-1.7% of all cases. However, arterial damage does not always necessarily appear as a complete rupture of the vessel with a loss of peripheral circulation and ischaemic symptoms; a relatively strong periarticular system of collaterals can maintain circulation. Furthermore, the traumatic dislocation can also cause intimal tears, arterial dissections and aneurysms or thrombosis. In all cases of vessel injury, including total disruption, a peripheral pulse might still be palpable. 3 weeks after an acute elbow dislocation, we have diagnosed a patient with a long-segment stenosis of the brachial artery and a thrombosis of the radial artery. Therefore, the close anatomic proximity to the neurovascular structures should always be considered in cases of elbow dislocations, even if peripheral pulses are traceable. PMID:27436035

  8. Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response

    PubMed Central

    Xing, Meichun; Wang, Xiaohui; Palmai-Pallag, Timea; Shen, Huahao; Helleday, Thomas; Hickson, Ian D.; Ying, Songmin

    2015-01-01

    The MUS81 protein belongs to a conserved family of DNA structure-specific nucleases that play important roles in DNA replication and repair. Inactivation of the Mus81 gene in mice has no major deleterious consequences for embryonic development, although cancer susceptibility has been reported. We have investigated the role of MUS81 in human cells by acutely depleting the protein using shRNAs. We found that MUS81 depletion from human fibroblasts leads to accumulation of ssDNA and a constitutive DNA damage response that ultimately activates cellular senescence. Moreover, we show that MUS81 is required for efficient replication fork progression during an unperturbed S-phase, and for recovery of productive replication following replication stalling. These results demonstrate essential roles for the MUS81 nuclease in maintenance of replication fork integrity. PMID:26415217

  9. Post-Traumatic Seizures Exacerbate Histopathological Damage after Fluid-Percussion Brain Injury

    PubMed Central

    Bao, Ying-hui; Bramlett, Helen M.; Atkins, Coleen M.; Truettner, Jessie S.; Lotocki, George; Alonso, Ofelia F.

    2011-01-01

    Abstract The purpose of this study was to investigate the effects of an induced period of post-traumatic epilepsy (PTE) on the histopathological damage caused by traumatic brain injury (TBI). Male Sprague Dawley rats were given a moderate parasagittal fluid-percussion brain injury (1.9–2.1 atm) or sham surgery. At 2 weeks after surgery, seizures were induced by administration of a GABAA receptor antagonist, pentylenetetrazole (PTZ, 30 mg/kg). Seizures were then assessed over a 1-h period using the Racine clinical rating scale. To evaluate whether TBI-induced pathology was exacerbated by the seizures, contusion volume and cortical and hippocampal CA3 neuronal cell loss were measured 3 days after seizures. Nearly all TBI rats showed clinical signs of PTE following the decrease in inhibitory activity. In contrast, clinically evident seizures were not observed in TBI rats given saline or sham-operated rats given PTZ. Contusions in TBI-PTZ-treated rats were significantly increased compared to the TBI-saline-treated group (p < 0.001). In addition, the TBI-PTZ rats showed less NeuN-immunoreactive cells within the ipsilateral parietal cerebral cortex (p < 0.05) and there was a trend for decreased hippocampal CA3 neurons in TBI-PTZ rats compared with TBI-saline or sham-operated rats. These results demonstrate that an induced period of post-traumatic seizures significantly exacerbates the structural damage caused by TBI. These findings emphasize the need to control seizures after TBI to limit even further damage to the injured brain. PMID:20836615

  10. Behavioural profiles of children and adolescents after pre- or perinatal unilateral brain damage.

    PubMed

    Trauner, D A; Nass, R; Ballantyne, A

    2001-05-01

    Recent case reports of individuals with early-onset damage to the prefrontal cortex have suggested that such early insults could result in severely impaired social behaviour in later childhood and adolescence. The investigators speculated that the acquisition of complex social conventions and moral rules had been impaired. In a large cohort of children, we sought to determine whether early focal brain insults might result in clinically significant behavioural or emotional problems. This study reports on 39 children with pre- or perinatal-onset unilateral brain damage (focal lesion) from cerebral infarction or intraparenchymal haemorrhage, using the Achenbach Child Behavior Checklist to assess the presence or absence of behavioural and emotional difficulties. Two-thirds of the subjects had left hemisphere (LH) lesions and one-third had right hemisphere (RH) lesions. Age range was 4.0-15.4 years at the time of questionnaire completion. Their results were compared with those of 54 control children. Analyses were conducted on focal lesion versus controls, RH versus LH lesion, frontal versus non-frontal lesion, and seizure versus non-seizure groups. When the effect of IQ was partialled out, there were no significant differences on the nine Behavior Problem scales, the Internalizing-Externalizing dichotomy or the Total Problem score for any of the group comparisons. Our subjects showed no evidence of clinically significant behavioural or emotional problems, even when the frontal lobe was involved. Individuals with more extensive and bilateral damage may be at higher risk of significant behavioural and emotional dysfunction than were those in our study population. In future studies of brain-behaviour relationships in developing children, all potential causes for any observed behavioural abnormalities, such as genetic and environmental factors and toxin exposure, must be considered before concluding that specific anatomical lesions are causally related to specific

  11. Congenital brain damage: cognitive development correlates with lesion and electroencephalographic features.

    PubMed

    Riva, Daria; Franceschetti, Silvana; Erbetta, Alessandra; Baranello, Giovanni; Esposito, Silvia; Bulgheroni, Sara

    2013-04-01

    The purpose of this study was to assess cognitive development in 26 children with congenital focal brain lesion and unilateral spastic cerebral palsy first diagnosed and followed up for rehabilitation at our institution. Mean intelligence quotients (IQs) were correlated not only to the different features of the cerebral lesions, but also to the different types of electroencephalographic abnormalities. We also examined individual scores. We found that about 70% of the children had values of Full-Scale, Verbal, and Performance IQs within the normal range. No differences were found between left and right injured children. Different Verbal IQ-Performance IQ profiles were observed. Larger lesions and some electroencephalographic features, mainly signal slowing/attenuation as signs of structural brain damage, were significantly associated with lower intellectual abilities. The role of other factors, including genetic and environmental background variability, as well as rehabilitative treatments, on cognitive sequelae in such patients was discussed. PMID:22752481

  12. GM1 monosialoganglioside pretreatment protects against soman-induced seizure-related brain damage.

    PubMed

    Ballough, G P; Cann, F J; Smith, C D; Forster, J S; Kling, C E; Filbert, M G

    1998-05-01

    The effects of GM1 monosialoganglioside pretreatment on brain damage resulting from soman-induced seizure activity were examined in this study. Male Sprague-Dawley rats were infused with GM1 via an osmotic minipump connected through a permanent cannula implanted intracerebroventricularly and challenged with soman (83 micrograms/kg, i.e., 1.25 x LD50) 4 d after initiation of GM1 infusion. Electrocorticographic recordings were monitored via indwelling cortical electrodes. Twenty-seven hours after soman administration, anesthetized rats were euthanized via transcardial perfusion with buffered paraformaldehyde. Brains were processed for hematoxylin and eosin (H&E), cresyl violet (CV), and acetylcholinesterase (AChE) histochemistry, and glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) immunohistochemistry. All soman-challenged rats not infused with GM1 (n = 14) developed status epilepticus (SE). PMID:9778643

  13. Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage

    PubMed Central

    Kim, Kyeong-A; Akram, Muhammad; Shin, Young-Jun; Kim, Eun-Sun; Yu, Seong Woon; Majid, Arshad; Bae, Ok-Nam

    2014-01-01

    Background and Purpose Despite the rapidly increasing global burden of ischemic stroke, no therapeutic options for neuroprotection against stroke currently exist. Recent studies have shown that autophagy plays a key role in ischemic neuronal death and treatments that target autophagy may represent a novel strategy in neuroprotection. We investigated whether autophagy is regulated by carnosine, an endogenous pleiotropic dipeptide which has robust neuroprotective activity against ischemic brain damage. Methods We examined the effect of carnosine on mitochondrial dysfunction and autophagic processes in rat focal ischemia and in neuronal cultures. Results Autophagic pathways such as reduction of phosphorylated mTOR/p70S6K and the conversion of LC3-I to LC3-II were enhanced in the ischemic brain. However, treatment with carnosine significantly attenuated autophagic signaling in the ischemic brain, with improvement of brain mitochondrial function and mitophagy signaling. The protective effect of carnosine against autophagy was also confirmed in primary cortical neurons. Conclusion Taken together, our data suggest that the neuroprotective effect of carnosine is at least partially mediated by mitochondrial protection, and attenuation of deleterious autophagic processes. Our findings shed new light on the mechanistic pathways that this exciting neuroprotective agent influences. PMID:24938837

  14. Genotoxic evaluation of Mikania laevigata extract on DNA damage caused by acute coal dust exposure.

    PubMed

    Freitas, Tiago P; Heuser, Vanina D; Tavares, Priscila; Leffa, Daniela D; da Silva, Gabriela A; Citadini-Zanette, Vanilde; Romão, Pedro R T; Pinho, Ricardo A; Streck, Emilio L; Andrade, Vanessa M

    2009-06-01

    In the present article, we report data on the possible antigenotoxic activity of Mikania laevigata extract (MLE) after acute intratracheal instillation of coal dust using the comet assay in peripheral blood, bone marrow, and liver cells and the micronucleus test in peripheral blood of Wistar rats. The animals were pretreated for 2 weeks with saline solution (groups 1 and 2) or MLE (100 mg/kg) (groups 3 and 4). On day 15, the animals were anesthetized with ketamine (80 mg/kg) and xylazine (20 mg/kg), and gross mineral coal dust (3 mg/0.3 mL saline) (groups 2 and 4) or saline solution (0.3 mL) (groups 1 and 3) was administered directly in the lung by intratracheal administration. Fifteen days after coal dust or saline instillation, the animals were sacrificed, and the femur, liver, and peripheral blood were removed. The results showed a general increase in the DNA damage values at 8 hours for all treatment groups, probably related to surgical procedures that had stressed the animals. Also, liver cells from rats treated with coal dust, pretreated or not with MLE, showed statistically higher comet assay values compared to the control group at 14 days after exposure. These results could be expected because the liver metabolizes a variety of organic compounds to more polar by-products. On the other hand, the micronucleus assay results did not show significant differences among groups. Therefore, our data do not support the antimutagenic activity of M. laevigata as a modulator of DNA damage after acute coal dust instillation. PMID:19627217

  15. Selective Cyclooxygenase-2 Inhibition Protects Against Myocardial Damage in Experimental Acute Ischemia

    PubMed Central

    Carnieto, Alberto; Dourado, Paulo Magno Martins; da Luz, Protásio Lemos; Chagas, Antonio Carlos Palandri

    2009-01-01

    BACKGROUND Acute myocardial infarction is associated with tissue inflammation. Early coronary reperfusion clearly improves the outcome but may help propagate the inflammatory response and enhance tissue damage. Cyclooxygenase-2 is an enzyme that catalyzes the initial step in the formation of inflammatory prostaglandins from arachidonic acid. Cyclooxygenase-2 levels are increased when ischemic cardiac events occur. The overall function of COX-2 in the inflammatory process generated by myocardial ischemic damage has not yet been elucidated. GOAL The objective of this study was to determine whether a selective cyclooxygenase-2 inhibitor (rofecoxib) could alter the evolution of acute myocardial infarction after reperfusion. METHODS AND RESULTS This study was performed with 48 mongrel dogs divided into two groups: controls and those treated with the drug. All animals were prepared for left anterior descending coronary artery occlusion. The dogs then underwent 180 minutes of coronary occlusion, followed by 30 minutes of reperfusion. Blood samples were collected from the venous sinus immediately before coronary occlusion and after 30 minutes of reperfusion for measurements of CPK-MB, CPK-MBm and troponin I. During the experiment we observed the mean blood pressure, heart rate and coronary flow. The coronary flow and heart rate did not change, but in the control group, there was blood pressure instability, in addition to maximal levels of CPK-MB post-infarction. The same results were observed for CPK-MBm and troponin I. CONCLUSION In a canine model of myocardial ischemia-reperfusion, selective inhibition of Cyclooxygenase-2 with rofecoxib was not associated with early detrimental effects on the hemodynamic profile or the gross extent of infarction; in fact, it may be beneficial by limiting cell necrosis. PMID:19330252

  16. Genotoxic Evaluation of Mikania laevigata Extract on DNA Damage Caused by Acute Coal Dust Exposure

    SciTech Connect

    Freitas, T.P.; Heuser, V.D.; Tavares, P.; Leffa, D.D.; da Silva, G.A.; Citadini-Zanette, V.; Romao, P.R.T.; Pinho, R.A.; Streck, E.L.; Andrade,V.M.

    2009-06-15

    We report data on the possible antigenotoxic activity of Mikania laevigata extract (MLE) after acute intratracheal instillation of coal dust using the comet assay in peripheral blood, bone marrow, and liver cells and the micronucleus test in peripheral blood of Wistar rats. The animals were pretreated for 2 weeks with saline solution (groups 1 and 2) or MLE (100 mg/kg) (groups 3 and 4). On day 15, the animals were anesthetized with ketamine (80 mg/kg) and xylazine (20 mg/kg), and gross mineral coal dust (3 mg/0.3 mL saline) (groups 2 and 4) or saline solution (0.3 mL) (groups 1 and 3) was administered directly in the lung by intratracheal administration. Fifteen days after coal dust or saline instillation, the animals were sacrificed, and the femur, liver, and peripheral blood were removed. The results showed a general increase in the DNA damage values at 8 hours for all treatment groups, probably related to surgical procedures that had stressed the animals. Also, liver cells from rats treated with coal dust, pretreated or not with MLE, showed statistically higher comet assay values compared to the control group at 14 days after exposure. These results could be expected because the liver metabolizes a variety of organic compounds to more polar by-products. On the other hand, the micronucleus assay results did not show significant differences among groups. Therefore, our data do not support the antimutagenic activity of M. laevigata as a modulator of DNA damage after acute coal dust instillation.

  17. Brain damage associated with apraxia of speech: evidence from case studies.

    PubMed

    Moser, Dana; Basilakos, Alexandra; Fillmore, Paul; Fridriksson, Julius

    2016-08-01

    The site of crucial damage that causes acquired apraxia of speech (AOS) has been debated in the literature. This study presents five in-depth cases that offer insight into the role of brain areas involved in AOS. Four of the examined participants had a primary impairment of AOS either with (n = 2) or without concomitant mild aphasia (n = 2). The fifth participant presented with a lesion relatively isolated to the left anterior insula (AIns-L), damage that is rarely reported in the literature, but without AOS. Taken together, these cases challenge the role of the AIns-L and implicate the left motor regions in AOS. PMID:27264534

  18. Volume regulatory loss of Na, Cl, and K from rat brain during acute hyponatremia

    SciTech Connect

    Melton, J.E.; Patlak, C.S.; Pettigrew, K.D.; Cserr, H.F.

    1987-04-01

    This study quantitatively evaluates the contribution of tissue Na, Cl, and K loss to brain volume regulation during acute dilutional hyponatremia (DH) and examines the mechanism of Na loss. DH was produced in pentobarbital sodium-anesthetized rats by intraperitoneal infusion of distilled water and brain water and electrolytes analyzed 30 min, 1 h, 3 h, 4 h, or 6 h later. The rate of Na and Cl loss was greatest during the first 30 min of DH. Net loss of Na and Cl was maximal after 3 h of DH. K loss was slower, achieving significance after 3 h. Electrolyte loss was sufficient to account for observed brain volume regulation after three or more hours of DH. Measurements of /sup 22/Na influx and efflux across the blood brain barrier showed that barrier permeability to Na is unchanged during DH. Analysis of results using a two-compartment model of plasma-brain exchange suggests that loss of brain Na during DH does not result solely from a shift of electrolyte across the blood-brain barrier to plasma, and thus provides indirect evidence for an additional pathway for Na loss, presumably via cerebrospinal fluid.

  19. Are preterm newborns who have relative hyperthyrotropinemia at increased risk of brain damage?

    PubMed Central

    Korzeniewski, Steven J.; Soto-Rivera, Carmen L.; Fichorova, Raina N.; Allred, Elizabeth; Kuban, Karl C. K.; O’Shea, T. Michael; Paneth, Nigel; Agus, Michael; Dammann, Olaf; Leviton, Alan

    2015-01-01

    Background We sought to disentangle the contributions of hyperthyrotropinemia (an indicator of thyroid dysfunction) (HTT) and intermittent or sustained systemic inflammation (ISSI) to structural and functional indicators of brain damage. Methods We measured the concentrations of TSH on day 14, and of 25 inflammation-related proteins in blood collected during the first 2 postnatal weeks from 786 infants born before the 28th week of gestation who were not considered to have hypothyroidism. We defined hyperthyrotropinemia (HTT) as a TSH concentration in the highest quartile for gestational age on postnatal day 14 and ISSI was defined as a concentration in the top quartile for gestational age of a specific inflammation-related protein on two separate days a week apart during the first two postnatal weeks. We first assessed the risk of brain damage indicators comparing 1) neonates who had HTT to those without (regardless of ISSI), and 2) neonates with HTT only, ISSI only, or HTT+ ISSI, to those who were exposed to neither HTT nor ISSI. HTT was defined as a TSH concentration in the highest quartile for gestational age on postnatal day 14. Results In univariable models that compared those with HTT to those without, HTT was not significantly associated with any indicator of brain damage. In models that compared HTT only, ISSI only, and HTT+ISSI, to those with neither, children with ISSI only or with HTT+ISSI were at significantly higher risk of ventriculomegaly [odds ratios (OR) ranged from 2–6], while those with HTT only were at significantly reduced risk of a hypoechoic lesion [ORs ranged from 0.2–0.4]. Children with HTT only had a higher risk of quadriparesis and those with ISSI alone had a higher risk of hemiparesis [ORs ranged from 1.6–2.4]. Elevated risk of a very low mental development score was associated with both ISSI only and with HTT+ISSI while a very low motor development score and microcephaly were associated with HTT+ISSI. Conclusions The association

  20. Damage to histaminergic tuberomammillary neurons and other hypothalamic neurons with traumatic brain injury.

    PubMed

    Valko, Philipp O; Gavrilov, Yury V; Yamamoto, Mihoko; Finn, Kristen; Reddy, Hasini; Haybaeck, Johannes; Weis, Serge; Scammell, Thomas E; Baumann, Christian R

    2015-01-01

    The need for increased sleep after traumatic brain injury is a common and disabling complaint, yet its etiology is unknown. Previous studies have demonstrated diffuse damage to various hypothalamic systems, but the integrity of the histaminergic tuberomammillary nucleus, a major arousal-promoting system located in the posterior hypothalamus, has never been examined in head trauma patients. Here, we demonstrate that severe head trauma is associated with a marked loss (41%) of histaminergic neurons. Reduced histamine signaling may contribute to increased sleep need, and therapies that enhance histaminergic tone may improve arousal after head trauma or other conditions. PMID:25363332

  1. Post-traumatic hypoxia exacerbates brain tissue damage: analysis of axonal injury and glial responses.

    PubMed

    Hellewell, Sarah C; Yan, Edwin B; Agyapomaa, Doreen A; Bye, Nicole; Morganti-Kossmann, M Cristina

    2010-11-01

    Traumatic brain injury (TBI) resulting in poor neurological outcome is predominantly associated with diffuse brain damage and secondary hypoxic insults. Post-traumatic hypoxia is known to exacerbate primary brain injury; however, the underlying pathological mechanisms require further elucidation. Using a rat model of diffuse traumatic axonal injury (TAI) followed by a post-traumatic hypoxic insult, we characterized axonal pathology, macrophage/microglia accumulation, and astrocyte responses over 14 days. Rats underwent TAI alone, TAI followed by 30 min of hypoxia (TAI + Hx), hypoxia alone, or sham-operation (n = 6/group). Systemic hypoxia was induced by ventilating rats with 12% oxygen in nitrogen, resulting in a ∼ 50% reduction in arterial blood oxygen saturation. Brains were assessed for axonal damage, macrophage/microglia accumulation, and astrocyte activation at 1, 7, and 14 days post-treatment. Immunohistochemistry with axonal damage markers (β-amyloid precursor protein [β-APP] and neurofilament) showed strong positive staining in TAI + Hx rats, which was most prominent in the corpus callosum (retraction bulbs 69.8 ± 18.67; swollen axons 14.2 ± 5.25), and brainstem (retraction bulbs 294 ± 118.3; swollen axons 50.3 ± 20.45) at 1 day post-injury. Extensive microglia/macrophage accumulation detected with the CD68 antibody was maximal at 14 days post-injury in the corpus callosum (macrophages 157.5 ± 55.48; microglia 72.71 ± 20.75), and coincided with regions of axonal damage. Astrocytosis assessed with glial fibrillary acidic protein (GFAP) antibody was also abundant in the corpus callosum and maximal at 14 days, with a trend toward an increase in TAI + Hx animals (18.99 ± 2.45 versus 13.56 ± 0.81; p = 0.0617). This study demonstrates for the first time that a hypoxic insult following TAI perpetuates axonal pathology and cellular inflammation, which may account for the poor neurological outcomes seen in TBI patients who experience post

  2. Candesartan and glycyrrhizin ameliorate ischemic brain damage through downregulation of the TLR signaling cascade.

    PubMed

    Barakat, Waleed; Safwet, Nancy; El-Maraghy, Nabila N; Zakaria, Mohamed N M

    2014-02-01

    Stroke is the second leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. The final outcome of stroke is determined not only by the volume of the ischemic core, but also by the extent of secondary brain damage inflicted to penumbral tissues by brain swelling, impaired microcirculation, and inflammation. The only drug approved for the treatment ischemic stroke is recombinant tissue plasminogen activator (rt-PA). The current study was designed to investigate the protective effects of candesartan (0.15 mg/kg, orally) and glycyrrhizin (30 mg/kg, orally) experimentally-induced ischemic brain damage in C57BL/6 mice (middle cerebral artery occlusion, MCAO) in comparison to the effects of a standard neuroprotective drug (cerebrolysin, 7.5 mg/kg, IP). All drugs were administered 30 min before and 24h after MCAO. Both candesartan and glycyrrhizin ameliorated the deleterious effects of MCAO as indicated by the improvement in the performance of the animals in behaviour tests, reduction in brain infarction, neuronal degeneration, and leukocyte infiltration. In addition, MCAO induced a significant upregulation in the different elements of the TLR pathway including TLR-2 and TLR-4, Myd88, TRIF and IRF-3 and the downstream effectors TNF-α, IL-1β, IL-6 and NF-kB. All these changes were significantly ameliorated by treatment with candesartan and glycyrrhizin. The results of the current study represent a new indication for both candesartan and glycyrrhizin in the management of ischemic stroke with effects comparable to those of the standard neuroprotective drug cerebrolysin. PMID:24378346

  3. Are Himalayan Sherpas better protected against brain damage associated with extreme altitude climbs?

    PubMed

    Garrido, E; Segura, R; Capdevila, A; Pujol, J; Javierre, C; Ventura, J L

    1996-01-01

    1. The potential risk of brain damage when low-landers attempt to climb the highest summits is a well-known fact. However, very little is known about what occurs to Himalayan natives, perfectly adapted to high altitude, when performing the same type of activity. 2. Taking into account their long-life climbing experience at extreme altitudes, we examined seven of the most recognized Sherpas with the aim of performing a comprehensive neurological evaluation based on medical history, physical examination and magnetic resonance brain imaging. We compared them with one group of 21 lowland elite climbers who had ascended to altitudes of over 8000 m, and another control group of 21 healthy individuals who had never been exposed to high altitude. 3. While all of the lowland climbers presented psychoneurological symptoms during or after the expeditions, and 13 of them (61%) showed magnetic resonance abnormalities (signs of mild cortical atrophy and/or periventricular high-intensity signal areas in the white matter), only one Sherpa (14%) showed similar changes in the scans, presenting neurological symptoms at extreme altitude. The neurological examination was normal in all three groups, and no neuroimaging abnormalities were detected in the control group. 4. The significant differences, in both clinical and neuroimaging terms, suggest that Sherpa highlanders have better brain protection when exposed to extreme altitude. Although the key to protection against cerebral hypoxia cannot be established, it is possible that an increase in the usually short period of acclimatization could minimize brain damage in those low-landers who attempt the highest summits without supplementary oxygen. PMID:8697710

  4. Synthesis of a Novel Photopolymerized Nanocomposite Hydrogel for Treatment of Acute Mechanical Damage to Cartilage

    PubMed Central

    Schlichting, Kathryn; Copeland-Johnson, Trishelle M.; Goodman, Matthew; Lipert, Robert J.; Prozorov, Tanya; Liu, Xunpei; McKinley, Todd O.; Lin, Zhiqun; Martin, James A.; Mallapragada, Surya K.

    2014-01-01

    Intraarticular fractures initiate a cascade of pathobiologic and pathomechanical events that culminate in posttraumatic osteoarthritis (PTOA). Hallmark features of PTOA include destruction of the cartilage matrix in combination with loss of chondrocytes and acute mechanical damage (AMD). Currently, treatment of intraarticular fractures essentially is completely focused on restoration of the macroanatomy of the joint. However, current treatment ignores AMD sustained by cartilage at the time of injury. We are exploring aggressive biomaterial-based interventions designed to treat the primary pathologic components of AMD. This study describes the development of a novel injectable copolymer solution that forms gels at physiological temperatures that can be photocrosslinked, and can form nanocomposite gels insitu through mineralization. The injectable copolymer solution will allow the material to fill cracks in the cartilage after trauma. The mechanical properties of the nanocomposite are similar to that of native cartilage, as measured by compressive and shear testing. It thereby has the potential to mechanically stabilize and restore local structural integrity to acutely injured cartilage. Additionally, the insitu mineralization ensures good adhesion at the interface between the biomaterial and cartilage, as measured through tensile and shear testing. Therefore, we have successfully developed a new injectable insitu forming nanocomposite with mechanical properties of similar magnitude to that of native cartilage, and which can bond well to native cartilage. This material has the potential to stabilize injured cartilage and prevent PTOA. PMID:21530694

  5. Astrocytes Promote Oligodendrogenesis after White Matter Damage via Brain-Derived Neurotrophic Factor

    PubMed Central

    Miyamoto, Nobukazu; Maki, Takakuni; Shindo, Akihiro; Liang, Anna C.; Maeda, Mitsuyo; Egawa, Naohiro; Itoh, Kanako; Lo, Evan K.; Lok, Josephine; Ihara, Masafumi

    2015-01-01

    Oligodendrocyte precursor cells (OPCs) in the adult brain contribute to white matter homeostasis. After white matter damage, OPCs compensate for oligodendrocyte loss by differentiating into mature oligodendrocytes. However, the underlying mechanisms remain to be fully defined. Here, we test the hypothesis that, during endogenous recovery from white matter ischemic injury, astrocytes support the maturation of OPCs by secreting brain-derived neurotrophic factor (BDNF). For in vitro experiments, cultured primary OPCs and astrocytes were prepared from postnatal day 2 rat cortex. When OPCs were subjected to chemical hypoxic stress by exposing them to sublethal CoCl2 for 7 d, in vitro OPC differentiation into oligodendrocytes was significantly suppressed. Conditioned medium from astrocytes (astro-medium) restored the process of OPC maturation even under the stressed conditions. When astro-medium was filtered with TrkB-Fc to remove BDNF, the BDNF-deficient astro-medium no longer supported OPC maturation. For in vivo experiments, we analyzed a transgenic mouse line (GFAPcre/BDNFwt/fl) in which BDNF expression is downregulated specifically in GFAP+ astrocytes. Both wild-type (GFAPwt/BDNFwt/fl mice) and transgenic mice were subjected to prolonged cerebral hypoperfusion by bilateral common carotid artery stenosis. As expected, compared with wild-type mice, the transgenic mice exhibited a lower number of newly generated oligodendrocytes and larger white matter damage. Together, these findings demonstrate that, during endogenous recovery from white matter damage, astrocytes may promote oligodendrogenesis by secreting BDNF. SIGNIFICANCE STATEMENT The repair of white matter after brain injury and neurodegeneration remains a tremendous hurdle for a wide spectrum of CNS disorders. One potentially important opportunity may reside in the response of residual oligodendrocyte precursor cells (OPCs). OPCs may serve as a back-up for generating mature oligodendrocytes in damaged white

  6. The economics of treating stroke as an acute brain attack

    PubMed Central

    Bogousslavsky, Julien; Paciaroni, Maurizio

    2009-01-01

    Currently, treatments for ischemic stroke focus on restoring or improving perfusion to the ischemic area using thrombolytics. The increased hospitalization costs related to thrombolysis are offset by a decrease in rehabilitation costs, for a net cost savings to the healthcare system. However, early treatment is essential. The benefit of thrombolysis is time-dependent but only a very small proportion of patients, 2%, are presently being treated with tPA. In the United States, if the proportion of all ischemic stroke patients that receive tPA were increased to 4, 6, 8, 10, 15, or 20%, the realized cost saving would be approximately $ 15, 22, 30, 37, 55, and 74 million, respectively. Being so, efforts should be made to educate the public and paramedics regarding early stroke signs. Furthermore, additional acute stroke therapy training programs need to be established for emergency departments. Finally, hospital systems need to be re-engineered to treat patients as quickly as possible in order to optimize thrombolytic benefit as well as maximize cost-effectiveness. PMID:19775424

  7. The economics of treating stroke as an acute brain attack.

    PubMed

    Bogousslavsky, Julien; Paciaroni, Maurizio

    2009-01-01

    Currently, treatments for ischemic stroke focus on restoring or improving perfusion to the ischemic area using thrombolytics. The increased hospitalization costs related to thrombolysis are offset by a decrease in rehabilitation costs, for a net cost savings to the healthcare system. However, early treatment is essential. The benefit of thrombolysis is time-dependent but only a very small proportion of patients, 2%, are presently being treated with tPA. In the United States, if the proportion of all ischemic stroke patients that receive tPA were increased to 4, 6, 8, 10, 15, or 20%, the realized cost saving would be approximately $ 15, 22, 30, 37, 55, and 74 million, respectively. Being so, efforts should be made to educate the public and paramedics regarding early stroke signs. Furthermore, additional acute stroke therapy training programs need to be established for emergency departments. Finally, hospital systems need to be re-engineered to treat patients as quickly as possible in order to optimize thrombolytic benefit as well as maximize cost-effectiveness. PMID:19775424

  8. A novel quantification of blood-brain barrier damage and histochemical typing after embolic stroke in rats.

    PubMed

    Michalski, Dominik; Grosche, Jens; Pelz, Johann; Schneider, Dietmar; Weise, Christopher; Bauer, Ute; Kacza, Johannes; Gärtner, Ulrich; Hobohm, Carsten; Härtig, Wolfgang

    2010-11-01

    Treatment strategies in acute ischemic stroke are still limited. Considering numerous translation failures, research is tending to a preferred use of human-like animal models, and a more-complex perspective of tissue salvaging involving endothelial, glial and neuronal components according to the neurovascular unit (NVU) concept. During ischemia, blood-brain barrier (BBB) alterations lead to brain edema and hemorrhagic transformation affecting NVU components. The present study aims on a novel quantification method of BBB damage and affected tissue following experimental cerebral ischemia, closely to the human condition. Wistar rats underwent embolic middle cerebral artery occlusion, followed by an intravenous application of fluorescein isothiocyanate (FITC)-tagged albumin (≈70kDa) and/or biotinylated rat IgG (≈150kDa) as BBB permeability markers. Both fluorescent agents revealed similar leakage and allow quantification of BBB permeability by fluorescence microscopy, and after immunohistochemical conversion into a permanent diaminobenzidine label at light-microscopical level. The following markers were identified for sufficient detection of NVU components: Rat endothelial cell antigen-1 (RECA) and laminin for vessels, Lycopersicon esculentum and Griffonia simplicifolia agglutinin for vessels and microglial subpopulations, ionized calcium binding adaptor molecule 1 (Iba1), CD68 and CD11b for macrophages, activated microglia, monocytes and neutrophils, S100β for astroglia, as well as NeuN and HuC/D for neurons. This is the first report confirming the usefulness of simultaneously applied FITC-albumin and biotinylated rat IgG as BBB permeability markers in experimental stroke, and, specifying antibodies and lectins for multiple fluorescence labeling of NVU components. Newly elaborated protocols might facilitate a more-complex outcome measurement in drug development for cerebral ischemia. PMID:20732314

  9. Excessive α-tocopherol exacerbates microglial activation and brain injury caused by acute ischemic stroke

    PubMed Central

    Khanna, Savita; Heigel, Mallory; Weist, Jessica; Gnyawali, Surya; Teplitsky, Seth; Roy, Sashwati; Sen, Chandan K.; Rink, Cameron

    2015-01-01

    The vitamin E family includes both tocopherols and tocotrienols, where α-tocopherol (αTOC) is the most bioavailable form. Clinical trials testing the therapeutic efficacy of high-dose αTOC against stroke have largely failed or reported negative outcomes when a “more is better” approach to supplementation (>400 IU/d) was used. This work addresses mechanisms by which supraphysiologic αTOC may contribute to stroke-induced brain injury. Ischemic stroke injury and the neuroinflammatory response were studied in tocopherol transfer protein-deficient mice maintained on a diet containing αTOC vitamin E at the equivalent human dose of 1680 IU/d. Ischemic stroke-induced brain injury was exacerbated in the presence of supraphysiologic brain αTOC levels. At 48 h after stroke, S100B and RAGE expression was increased in stroke-affected cortex of mice with elevated brain αTOC levels. Such increases were concomitant with aggravated microglial activation and neuroinflammatory signaling. A poststroke increase in markers of oxidative injury and neurodegeneration in the presence of elevated brain αTOC establish that at supraphysiologic levels, αTOC potentiates neuroinflammatory responses to acute ischemic stroke. Exacerbation of microglial activation by excessive αTOC likely depends on its unique cell signaling regulatory properties independent of antioxidant function. Against the background of clinical failure for high-dose αTOC, outcomes of this work identify risk for exacerbating stroke-induced brain injury as a result of supplementing diet with excessive levels of αTOC.—Khanna, S., Heigel,M., Weist, J., Gnyawali, S., Teplitsky, S., Roy, S., Sen, C. K., Rink, C. Excessive α-tocopherol exacerbates microglial activation and brain injury caused by acute ischemic stroke. PMID:25411436

  10. Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

    PubMed Central

    Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H.; Valcour, Victor

    2012-01-01

    Objective Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury. PMID:23229129

  11. Ca2+ toxicity and mitochondrial damage in acute pancreatitis: translational overview

    PubMed Central

    Maléth, József; Hegyi, Péter

    2016-01-01

    Acute pancreatitis (AP) is a leading cause of hospitalization among non-malignant gastrointestinal disorders. The mortality of severe AP can reach 30–50%, which is most probably owing to the lack of specific treatment. Therefore, AP is a major healthcare problem, which urges researchers to identify novel drug targets. Studies from the last decades highlighted that the toxic cellular Ca2+ overload and mitochondrial damage are key pathogenic steps in the disease development affecting both acinar and ductal cell functions. Moreover, recent observations showed that modifying the cellular Ca2+ signalling might be beneficial in AP. The inhibition of Ca2+ release from the endoplasmic reticulum or the activity of plasma membrane Ca2+ influx channels decreased the severity of AP in experimental models. Similarly, inhibition of mitochondrial permeability transition pore (MPTP) opening also seems to improve the outcome of AP in in vivo animal models. At the moment MPTP blockers are under detailed clinical investigation to test whether interventions in MPTP openings and/or Ca2+ homeostasis of the cells can be specific targets in prevention or treatment of cell damage in AP. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377719

  12. Ca2+ toxicity and mitochondrial damage in acute pancreatitis: translational overview.

    PubMed

    Maléth, József; Hegyi, Péter

    2016-08-01

    Acute pancreatitis (AP) is a leading cause of hospitalization among non-malignant gastrointestinal disorders. The mortality of severe AP can reach 30-50%, which is most probably owing to the lack of specific treatment. Therefore, AP is a major healthcare problem, which urges researchers to identify novel drug targets. Studies from the last decades highlighted that the toxic cellular Ca(2+) overload and mitochondrial damage are key pathogenic steps in the disease development affecting both acinar and ductal cell functions. Moreover, recent observations showed that modifying the cellular Ca(2+) signalling might be beneficial in AP. The inhibition of Ca(2+) release from the endoplasmic reticulum or the activity of plasma membrane Ca(2+) influx channels decreased the severity of AP in experimental models. Similarly, inhibition of mitochondrial permeability transition pore (MPTP) opening also seems to improve the outcome of AP in in vivo animal models. At the moment MPTP blockers are under detailed clinical investigation to test whether interventions in MPTP openings and/or Ca(2+) homeostasis of the cells can be specific targets in prevention or treatment of cell damage in AP.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377719

  13. Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

    PubMed Central

    Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

    2015-01-01

    The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

  14. Neurosensory Symptom Complexes after Acute Mild Traumatic Brain Injury

    PubMed Central

    Szczupak, Mikhaylo; Kiderman, Alexander; Crawford, James; Murphy, Sara; Marshall, Kathryn; Pelusso, Constanza

    2016-01-01

    Mild Traumatic Brain Injury (mTBI) is a prominent public health issue. To date, subjective symptom complaints primarily dictate diagnostic and treatment approaches. As such, the description and qualification of these symptoms in the mTBI patient population is of great value. This manuscript describes the symptoms of mTBI patients as compared to controls in a larger study designed to examine the use of vestibular testing to diagnose mTBI. Five symptom clusters were identified: Post-Traumatic Headache/Migraine, Nausea, Emotional/Affective, Fatigue/Malaise, and Dizziness/Mild Cognitive Impairment. Our analysis indicates that individuals with mTBI have headache, dizziness, and cognitive dysfunction far out of proportion to those without mTBI. In addition, sleep disorders and emotional issues were significantly more common amongst mTBI patients than non-injured individuals. A simple set of questions inquiring about dizziness, headache, and cognitive issues may provide diagnostic accuracy. The consideration of other symptoms may be critical for providing prognostic value and treatment for best short-term outcomes or prevention of long-term complications. PMID:26727256

  15. Evaluation of brain function in acute carbon monoxide poisoning with multimodality evoked potentials

    SciTech Connect

    He, Fengsheng; Liu, Xibao; Yang, Shi; Zhang, Shoulin ); Xu, Guanghua; Fang, Guangchai; Pan, Xiaowen )

    1993-02-01

    The median nerve somatosensory evoked potentials (SEP), pattern reversal visual evoked potentials (VEP), and brain stem auditory evoked potentials (BAEP) were studied in 109 healthy adults and in 88 patients with acute carbon monoxide (CO) poisoning. The upper limits for normal values of peak and interpeak latencies of multimodalities of evoked potentials in the reference group were established by a stepwise multiple regression analysis. SEP changes selectively affecting N32 and N60 were found in 78.8% of patients. There was prolonged PI00 latency of VEP in 58.2% of the cases examined. The prevalence of BAEP abnormalities in comatose patients (36%) was significantly higher than that (8.6%) in conscious patients. BAEP abnormalities were most frequently seen in comatose patients who had diminished brain stem reflexes (77.8%). It has been found that a consistent abnormality involving N2O and subsequent peaks in SEP, a remarkable prolongation of PI00 latency in VEP, or a prolongation of Ill-V interpeak latency in BAEP as well as the reoccurrence of evoked potential abnormalities after initial recovery all indicate unfavorable outcomes in patients with acute CO poisoning. The multimodality evoked potentials have proved to be sensitive indicators in the evaluation of brain dysfunction and in the prediction of prognosis of acute CO poisoning and the development of delayed encephalopathy. 16 refs., 4 figs., 6 tabs.

  16. Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

    PubMed

    Gonçalves, Cinara L; Rezin, Gislaine T; Ferreira, Gabriela K; Jeremias, Isabela C; Cardoso, Mariane R; Valvassori, Samira S; Munhoz, Bruna J P; Borges, Gabriela D; Bristot, Bruno N; Leffa, Daniela D; Andrade, Vanessa M; Quevedo, João; Streck, Emilio L

    2013-08-01

    Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage. PMID:23636618

  17. Acute protease supplementation effects on muscle damage and recovery across consecutive days of cycle racing.

    PubMed

    Shing, Cecilia M; Chong, Suzzen; Driller, Matthew W; Fell, James W

    2016-01-01

    Bromelain, a mixture of proteases obtained from pineapples, has been demonstrated to reduce exercise-induced muscle damage and inflammation, enhancing recovery. This investigation aimed to establish if markers of muscle damage and testosterone were influenced by acute bromelain supplementation in competitive cyclists taking part in a six-day cycle stage race. Fifteen highly trained cyclists [age: 22, [Formula: see text] = 1.2 years, height: 1.79, [Formula: see text] = 0.01 m, body mass: 68.69, [Formula: see text] = 1.97 kg] were supplemented with either bromelain (1000 mg·day(-1)) (n = 8) or a placebo (n = 7) across six days of competitive racing in a randomised, double-blind, placebo-controlled trial. Blood was collected from each cyclist on days one, three and six of racing and analysed for creatine kinase (CK), myoglobin, lactate dehydrogenase (LDH) and testosterone. CK activity (P < 0.001, d = 17.4-18.8), LDH activity (P < 0.004, d = 0.5-2.5) and myoglobin concentration (P < 0.007, d = 3.4-4.8) were elevated from pre-race on days three and six of racing in both groups. Testosterone concentrations were significantly lower on the final day of racing (P = 0.03, d = 1.3) and there was a trend for bromelain to maintain testosterone concentrations across the race period (P = 0.05, d = 1.04-1.70) when compared to placebo. Fatigue rating was lower in the bromelain group on day four of racing (P = 0.01). Consecutive days of competitive cycling were associated with increased markers of muscle damage and a reduction in circulating testosterone across the race period. Bromelain supplementation reduced subjective feelings of fatigue and was associated with a trend to maintain testosterone concentration. PMID:25604346

  18. Alterations in rat brain polyphosphoinositide metabolism due to acute ethanol administration.

    PubMed

    Chandrasekhar, R; Huang, H M; Sun, G Y

    1988-04-01

    The effects of acute ethanol administration on the polyphosphoinositide metabolism of rat brain cerebral cortex were examined. Intracerebral injections of [gamma-32P]ATP proved to be an effective in vivo method to prelabel brain phospholipids, especially the polyphosphoinositides. High acute doses of ethanol (8 or 6 g/kg b.wt.) administered by gavage significantly inhibited the breakdown of polyphosphoinositides as judged by an elevation in the concentration as well as the labeling of these compounds. Concomitantly, there was a significant reduction in the level of diacylglycerols. Low acute doses of ethanol (2 g/kg b.wt.) did not seem to have any effects on the basal levels or labeling of these compounds. The changes in polyphosphoinositide labeling due to ethanol intoxication were reverted to near control values when animals regained their righting reflex (approximately 4 hr). These studies demonstrate that, under normal conditions, polyphosphoinositides and diacylglycerols are maintained in a dynamic equilibrium and that acute doses of ethanol can suppress the signal transduction process and disturb this equilibrium. PMID:2834532

  19. Antimicrobial Peptides and Complement in Neonatal Hypoxia-Ischemia Induced Brain Damage

    PubMed Central

    Rocha-Ferreira, Eridan; Hristova, Mariya

    2015-01-01

    Hypoxic-ischemic encephalopathy (HIE) is a clinical condition in the neonate, resulting from oxygen deprivation around the time of birth. HIE affects 1–5/1000 live births worldwide and is associated with the development of neurological deficits, including cerebral palsy, epilepsy, and cognitive disabilities. Even though the brain is considered as an immune-privileged site, it has innate and adaptive immune response and can produce complement (C) components and antimicrobial peptides (AMPs). Dysregulation of cerebral expression of AMPs and C can exacerbate or ameliorate the inflammatory response within the brain. Brain ischemia triggers a prolonged inflammatory response affecting the progression of injury and secondary energy failure and involves both innate and adaptive immune systems, including immune-competent and non-competent cells. Following injury to the central nervous system (CNS), including neonatal hypoxia-ischemia (HI), resident microglia, and astroglia are the main cells providing immune defense to the brain in a stimulus-dependent manner. They can express and secrete pro-inflammatory cytokines and therefore trigger prolonged inflammation, resulting in neurodegeneration. Microglial cells express and release a wide range of inflammation-associated molecules including several components of the complement system. Complement activation following neonatal HI injury has been reported to contribute to neurodegeneration. Astrocytes can significantly affect the immune response of the CNS under pathological conditions through production and release of pro-inflammatory cytokines and immunomodulatory AMPs. Astrocytes express β-defensins, which can chemoattract and promote maturation of dendritic cells (DC), and can also limit inflammation by controlling the viability of these same DC. This review will focus on the balance of complement components and AMPs within the CNS following neonatal HI injury and the effect of that balance on the subsequent brain damage

  20. Attenuation of Oxidative Damage by Boerhaavia diffusa L. Against Different Neurotoxic Agents in Rat Brain Homogenate.

    PubMed

    Ayyappan, Prathapan; Palayyan, Salin Raj; Kozhiparambil Gopalan, Raghu

    2016-01-01

    Due to a high rate of oxidative metabolic activity in the brain, intense production of reactive oxygen metabolite occurs, and the subsequent generation of free radicals is implicated in the pathogenesis of traumatic brain injury, epilepsy, and ischemia as well as chronic neurodegenerative diseases. In the present study, protective effects of polyphenol rich ethanolic extract of Boerhaavia diffusa (BDE), a neuroprotective edible medicinal plant against oxidative stress induced by different neurotoxic agents, were evaluated. BDE was tested against quinolinic acid (QA), 3-nitropropionic acid (NPA), sodium nitroprusside (SNP), and Fe (II)/EDTA complex induced oxidative stress in rat brain homogenates. QA, NPA, SNP, and Fe (II)/EDTA treatment caused an increased level of thiobarbituric acid reactive substances (TBARS) in brain homogenates along with a decline in the activities of antioxidant enzymes. BDE treatment significantly decreased the production of TBARS (p < .05) and increased the activities of antioxidant enzymes like catalase and superoxide dismutase along with increased concentration of non-enzymatic antioxidant, reduced glutathione (GSH). Similarly, BDE caused a significant decrease in the lipid peroxidation (LPO) in the cerebral cortex. Inhibitory potential of BDE against deoxyribose degradation (IC50 value 38.91 ± 0.12 μg/ml) shows that BDE can protect hydroxyl radical induced DNA damage in the tissues. Therefore, B. diffusa had high antioxidant potential that could inhibit the oxidative stress induced by different neurotoxic agents in brain. Since many of the neurological disorders are associated with free radical injury, these data may imply that B. diffusa, functioning as an antioxidant agent, may be beneficial for reducing various neurodegenerative complications. PMID:26268727

  1. Proton relaxation in acute and subacute ischemic brain edema

    SciTech Connect

    Boisvert, D.P.; Handa, Y.; Allen, P.S. )

    1990-01-01

    The relation between regional ischemic brain edema and tissue proton relaxation rates (R1 = 1/T1; R2 = 1/T2) were studied in 16 macaque monkeys subjected to MCA occlusion. In vivo R2 measurements were obtained from multiple spin-echo (eight echoes) images taken at 2-, 3-, 4-, and 72-hr postischemia. In vitro R1 and R2 values were determined for corresponding regions after sacrifice at 4 hr (n = 8) or at 72-hr postischemia in seven surviving animals. The water content of the white and gray matter tissue samples was measured by the wet/dry method. Four animals (25%) showed ipsilateral regions of increased signal intensity as early as 2 hr after MCA occlusion. All seven animals imaged at 72 hr displayed such regions. Despite the absence of measured changes in tissue water content, significant decreases in R2, but not in R1, occurred at 4 hr. At this stage, R2 values correlated more closely than R1 with individual variations in water content. At 72 hr, marked decreases in both R1 and R2 were measured in ischemic deep gray matter and white matter. Cortical gray matter was unchanged. In edematous gray and white matter, both R1 and R2 correlated closely with tissue water content, but R2 was consistently 10 to 20 times more sensitive than R1. Biexponential R2 decay was observed at 4 and 72 hr, but only in the white matter region that became severely edematous at 72 hr.

  2. Increased blood-brain transfer in a rabbit model of acute liver failure

    SciTech Connect

    Horowitz, M.E.; Schafer, D.F.; Molnar, P.; Jones, E.A.; Blasberg, R.G.; Patlak, C.S.; Waggoner, J.; Fenstermacher, J.D.

    1983-05-01

    The blood-to-brain transfer of (/sup 14/C)alpha-aminoisobutyric acid was investigated by quantitative autoradiography in normal rabbits and rabbits with acute liver failure induced by the selective hepatotoxin galactosamine. The blood-to-brain transfer of alpha-aminoisobutyric acid was similar in control animals and animals 2 and 7 h after galactosamine injections, but was increased five- to tenfold in certain gray-matter areas of the brain in animals 11 and 18 h after galactosamine treatment. No detectable differences in white-matter uptake of (/sup 14/C)alpha-aminoisobutyric acid were found between the control and treated groups. The increase in alpha-aminoisobutyric acid transfer within the gray-matter areas suggested that a general or nonspecific increase in brain capillary permeability occurred in these areas. No clinical signs of early hepatic encephalopathy were observed in the treated rabbits, except for 1 animal from the 18-h postgalactosamine group. Thus, enhanced blood-brain transfer of alpha-aminoisobutyric acid preceded the development of overt hepatic encephalopathy. The distribution of radioactivity after the intravenous administration of (/sup 14/C)galactosamine showed that virtually none of the hepatotoxin localized in the brain, suggesting that the drug itself does not have a direct effect upon the blood-brain barrier or the brain. The increased uptake of alpha-aminoisobutyric acid at 11 and 18 h implies that the transfer of other solutes would also be enhanced, that central nervous system homeostasis would be compromised, and that the resulting changes in brain fluid composition could contribute to or cause hepatic encephalopathy.

  3. Exploring social cognition in patients with apathy following acquired brain damage

    PubMed Central

    2014-01-01

    Background Research on cognition in apathy has largely focused on executive functions. To the best of our knowledge, no studies have investigated the relationship between apathy symptoms and processes involved in social cognition. Apathy symptoms include attenuated emotional behaviour, low social engagement and social withdrawal, all of which may be linked to underlying socio-cognitive deficits. Methods We compared patients with brain damage who also had apathy symptoms against similar patients with brain damage but without apathy symptoms. Both patient groups were also compared against normal controls on key socio-cognitive measures involving moral reasoning, social awareness related to making judgements between normative and non-normative behaviour, Theory of Mind processing, and the perception of facial expressions of emotion. We also controlled for the likely effects of executive deficits and depressive symptoms on these comparisons. Results Our results indicated that patients with apathy were distinctively impaired in making moral reasoning decisions and in judging the social appropriateness of behaviour. Deficits in Theory of Mind and perception of facial expressions of emotion did not distinguish patients with apathy from those without apathy. Conclusion Our findings point to a possible socio-cognitive profile for apathy symptoms and provide initial insights into how socio-cognitive deficits in patients with apathy may affect social functioning. PMID:24450311

  4. [The clinical study of the first febrile convulsion in children with brain-damage].

    PubMed

    Asoh, M

    1997-05-01

    Forty-nine patients with cerebral palsy, mental retardation, or other congenital neurological disorders who had experienced febrile convulsions and had no previous nonfebrile seizures were presented. They were followed for 1.6 years to 15 years (mean: 6.8 years) after the initial febrile convulsion. The incidence of subsequent epilepsy (two or more afebrile seizures) was 39%, and 80% of them developed epilepsy within 2 years after the first febrile convulsion. The paroxysmal discharges on EEG recorded prior to or after the first febrile convulsion did not predict the occurrence of later epilepsy. Also under 3 years of age, EEG findings led to the same result. There was no definite evidence that administration of anticonvulsive drugs prevented later epilepsy. Pre-existing neurological abnormality was identified as a risk factor for epilepsy, and was an indication of persistent medication. There is no clear prophylactic procedure against long-lasting attacks. Accordingly, medical therapy can be started when epilepsy has developed. Patients with very severe brain damage who could not move except lying comprised only 6% of all cases, and 69% of the epilepsy patients were well controlled. They showed a good prognosis as compared with children with brain-damage in general with epilepsy. PMID:9146028

  5. Piano training in youths with hand motor impairments after damage to the developing brain

    PubMed Central

    Lampe, Renée; Thienel, Anna; Mitternacht, Jürgen; Blumenstein, Tobias; Turova, Varvara; Alves-Pinto, Ana

    2015-01-01

    Damage to the developing brain may lead to impairment of the hand motor function and negatively impact on patients’ quality of life. Development of manual dexterity and finger and hand motor function may be promoted by learning to play the piano. The latter brings together music with the intensive training of hand coordination and fine finger mobility. We investigated if learning to play the piano helped to improve hand motor skills in 18 youths with hand motor disorders resulting from damage during early brain development. Participants trained 35–40 minutes twice a week for 18 months with a professional piano teacher. With the use of a Musical Instrument Digital Interface piano, the uniformity of finger strokes could be objectively assessed from the timing of keystrokes. The analysis showed a significant improvement in the uniformity of keystrokes during the training. Furthermore, the youths showed strong motivation and engagement during the study. This is nevertheless an open study, and further studies remain needed to exclude effects of growth and concomitant therapies on the improvements observed and clarify which patients will more likely benefit from learning to play the piano. PMID:26345312

  6. Piano training in youths with hand motor impairments after damage to the developing brain.

    PubMed

    Lampe, Renée; Thienel, Anna; Mitternacht, Jürgen; Blumenstein, Tobias; Turova, Varvara; Alves-Pinto, Ana

    2015-01-01

    Damage to the developing brain may lead to impairment of the hand motor function and negatively impact on patients' quality of life. Development of manual dexterity and finger and hand motor function may be promoted by learning to play the piano. The latter brings together music with the intensive training of hand coordination and fine finger mobility. We investigated if learning to play the piano helped to improve hand motor skills in 18 youths with hand motor disorders resulting from damage during early brain development. Participants trained 35-40 minutes twice a week for 18 months with a professional piano teacher. With the use of a Musical Instrument Digital Interface piano, the uniformity of finger strokes could be objectively assessed from the timing of keystrokes. The analysis showed a significant improvement in the uniformity of keystrokes during the training. Furthermore, the youths showed strong motivation and engagement during the study. This is nevertheless an open study, and further studies remain needed to exclude effects of growth and concomitant therapies on the improvements observed and clarify which patients will more likely benefit from learning to play the piano. PMID:26345312

  7. Dimensions of Personality Disturbance After Focal Brain Damage: Investigation with the Iowa Scales of Personality Change

    PubMed Central

    Barrash, Joseph; Asp, Erik; Markon, Kristian; Manzel, Kenneth; Anderson, Steven W.; Tranel, Daniel

    2011-01-01

    This study employed a multi-step, rational-empirical approach to identify dimensions of personality disturbance in brain-damaged individuals: (1) Five dimensions were hypothesized based on empirical literature and conceptual grounds. (2) Principal components analysis was performed on the Iowa Scales of Personality Change to determine the pattern of covariance among 30 personality characteristics. (3) When discrepancies existed between principal components analysis results and conceptually-based dimensions, empirical findings and clinical considerations were weighed to determine assignment of ISPC scales to dimensions. (4) The fit of data to the refined dimensions was assessed by examination of intercorrelations. (5) Differential predictions concerning the relationship of dimensions to ventromedial prefrontal (vmPFC) damage were tested. This process resulted in specification of five dimensions: Disturbed Social Behavior, Executive/Decision-Making Deficits, Diminished Motivation/Hypo-emotionality, Irascibility, and Distress. In accord with predictions, the 28 participants with vmPFC lesions, compared to 96 participants with focal lesions elsewhere in the brain, had significantly more Disturbed Social Behavior and Executive/Decision-Making Deficits, and tended to have more Diminished Motivation/Hypo-emotionality. Irascibility was not significantly higher among the vmPFC group, and the groups had very similar levels of Distress. The findings indicate that conceptually distinctive dimensions with differential relationships to vmPFC can be derived from the Iowa Scales of Personality Change. PMID:21500116

  8. Dimensions of personality disturbance after focal brain damage: investigation with the Iowa Scales of Personality Change.

    PubMed

    Barrash, Joseph; Asp, Erik; Markon, Kristian; Manzel, Kenneth; Anderson, Steven W; Tranel, Daniel

    2011-10-01

    This study employed a multistep, rational-empirical approach to identify dimensions of personality disturbance in brain-damaged individuals: (a) Five dimensions were hypothesized based on empirical literature and conceptual grounds; (b) principal components analysis was performed on the Iowa Scales of Personality Change (ISPC) to determine the pattern of covariance among 30 personality characteristics; (c) when discrepancies existed between principal components analysis results and conceptually based dimensions, empirical findings and clinical considerations were weighed to determine assignment of ISPC scales to dimensions; (d) the fit of data to the refined dimensions was assessed by examination of intercorrelations; (e) differential predictions concerning the relationship of dimensions to ventromedial prefrontal cortex (vmPFC) damage were tested. This process resulted in the specification of five dimensions: Disturbed Social Behavior, Executive/Decision-Making Deficits, Diminished Motivation/Hypo-Emotionality, Irascibility, and Distress. In accord with predictions, the 28 participants with vmPFC lesions, compared to 96 participants with focal lesions elsewhere in the brain, had significantly more Disturbed Social Behavior and Executive/Decision-Making Deficits and tended to have more Diminished Motivation/Hypo-Emotionality. Irascibility was not significantly higher among the vmPFC group, and the groups had very similar levels of Distress. The findings indicate that conceptually distinctive dimensions with differential relationships to vmPFC can be derived from the Iowa Scales of Personality Change. PMID:21500116

  9. The problem of aphasia in the assessment of consciousness in brain-damaged patients.

    PubMed

    Majerus, Steve; Bruno, Marie-Aurélie; Schnakers, Caroline; Giacino, Joseph T; Laureys, Steven

    2009-01-01

    The assessment of the level and content of consciousness in brain-damaged patients relies to a large extent on behavioral assessment techniques. The limited behavioral repertoire displayed by vegetative and minimally conscious states requires the use of highly sensitive and reliable behavioral assessment methods, allowing the detection of subtle changes in behavior and associated level of consciousness. This situation is further complicated when patients with such disorders of consciousness have underlying deficits in the domain of communication functions, such as aphasia. The present paper examines the consequences of receptive and/or productive aphasia on the already limited behavioral repertoire presented in these patients and discusses a number of behavioral and neuroimaging assessment procedures designed to: (1) detect the presence of aphasia in patients with disorders of consciousness, and (2) reliably assess the level of consciousness of brain-damaged patients while taking into account the existence of receptive and/or expressive language deficits. The combined use of behavioral and neuroimaging assessment techniques appears to be particularly promising for disentangling impaired consciousness and aphasia. PMID:19818894

  10. A Case of Acute Motor Axonal Neuropathy Mimicking Brain Death and Review of the Literature

    PubMed Central

    Ravikumar, Sandhya; Poysophon, Poysophon; Poblete, Roy; Kim-Tenser, May

    2016-01-01

    We describe a case report of fulminant Guillain–Barré syndrome (GBS) mimicking brain death. A previously healthy 60-year-old male was admitted to the neurointensive care unit after developing rapidly progressive weakness and respiratory failure. On presentation, the patient was found to have absent brainstem and spinal cord reflexes resembling that of brain death. Acute motor axonal neuropathy, a subtype of GBS, was diagnosed by cerebrospinal fluid and nerve conduction velocity testing. An electroencephalogram showed that the patient had normal, appropriately reactive brain function. Transcranial Doppler (TCD) ultrasound showed appropriate blood flow to the brain. GBS rarely presents with weakness so severe as to mimic brain death. This article provides a review of similar literature. This case demonstrates the importance of performing a proper brain death examination, which includes evaluation for irreversible cerebral injury, exclusion of any confounding conditions, and performance of tests such as electroencephalography and TCDs when uncertainty exists about the reliability of the clinical exam. PMID:27199887

  11. Acute brain metabolic effects of cocaine in rhesus monkeys with a history of cocaine use.

    PubMed

    Henry, Porche' Kirkland; Murnane, Kevin S; Votaw, John R; Howell, Leonard L

    2010-12-01

    Cocaine addiction involves an escalation in drug intake which alters many brain functions. The present study documented cocaine-induced changes in brain metabolic activity as a function of cocaine self-administration history. Experimentally naive rhesus monkeys (N = 6) were given increasing access to cocaine under a fixed-ratio schedule of intravenous (i.v.) drug self-administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used to measure acute intramuscular (i.m.) cocaine-induced changes in brain metabolism in the cocaine-naïve state, following 60 sessions under limited-access conditions (1 h/day), following 60 sessions under extended-access conditions (4 h/day), and following 4 weeks of drug withdrawal. In the cocaine-naïve state, cocaine-induced increases in brain metabolism were restricted to the prefrontal cortex. As cocaine exposure increased from limited to extended access, metabolic effects expanded throughout the frontal cortex and were induced within the striatum. Conversely, cocaine-induced activation was far less robust following withdrawal. The results highlight a progressive expansion of the metabolic effects of cocaine to include previously unaffected dopamine innervated brain regions as a consequence of cocaine self-administration history. The identification of brain regions progressively influenced by drug exposure may be highly relevant toward efforts to develop treatments for cocaine addiction. PMID:20680706

  12. Iron porphyrinate Fe(TPPS) reduces brain cell damage in rats intrastriatally lesioned by quinolinate.

    PubMed

    González-Cortés, Carolina; Salinas-Lara, Citlaltepetl; Gómez-López, Marcos Artemio; Tena-Suck, Martha Lilia; Pérez-De La Cruz, Verónica; Rembao-Bojórquez, Daniel; Pedraza-Chaverrí, José; Gómez-Ruiz, Celedonio; Galván-Arzate, Sonia; Ali, Syed F; Santamaría, Abel

    2008-01-01

    It has been recently demonstrated that the reactive nitrogen species (RNS) peroxynitrite (ONOO(-)) is involved in the neurotoxic pattern produced by quinolinic acid in the rat brain [V. Pérez-De La Cruz, C. González-Cortés, S. Galván-Arzate, O.N. Medina-Campos, F. Pérez-Severiano, S.F. Ali, J. Pedraza-Chaverrí, A. Santamaría, Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III), Neuroscience 135 (2005) 463-474.]. The aim of this work was to investigate whether ONOO(-) can also be responsible for morphological alterations and inflammatory events in the same paradigm. For this purpose, we evaluated the effect of a pre-treatment with the iron porphyrinate Fe(TPPS), a well-known ONOO(-) decomposition catalyst (10 mg/kg, i.p., 120 min before lesion), on the quinolinate-induced striatal cell damage and immunoreactivities to glial-fibrilar acidic protein (GFAP), interleukin 6 (IL-6) and inducible nitric oxide synthase (iNOS), one and seven days after the intrastriatal infusion of quinolinate (240 nmol/microl) to rats. The striatal tissue from animals lesioned by quinolinate showed a significant degree of damage and enhanced immunoreactivities to GFAP, IL-6 and iNOS, both at 1 and 7 days post-lesion. Pre-treatment of rats with Fe(TPPS) significantly attenuated or prevented all these markers at both post-lesion times tested, except for GFAP immunoreactivity at 7 days post-lesion and iNOS immunoreactivity at 1 day post-lesion. Altogether, our results suggest that ONOO(-) is actively participating in triggering inflammatory events and morphological alterations in the toxic model produced by quinolinate, since the use of agents affecting its formation, such as Fe(TPPS), are effective experimental tools to reduce the brain lesions associated to excitotoxic and oxidative damage. PMID:18579343

  13. Nanosize Titanium Dioxide Stimulates Reactive Oxygen Species in Brain Microglia and Damages Neurons in Vitro

    PubMed Central

    Long, Thomas C.; Tajuba, Julianne; Sama, Preethi; Saleh, Navid; Swartz, Carol; Parker, Joel; Hester, Susan; Lowry, Gregory V.; Veronesi, Bellina

    2007-01-01

    Background Titanium dioxide is a widely used nanomaterial whose photo-reactivity suggests that it could damage biological targets (e.g., brain) through oxidative stress (OS). Objectives Brain cultures of immortalized mouse microglia (BV2), rat dopaminergic (DA) neurons (N27), and primary cultures of embryonic rat striatum, were exposed to Degussa P25, a commercially available TiO2 nanomaterial. Physical properties of P25 were measured under conditions that paralleled biological measures. Findings P25 rapidly aggregated in physiological buffer (800–1,900 nm; 25°C) and exposure media (~ 330 nm; 37°C), and maintained a negative zeta potential in both buffer (–12.2 ± 1.6 mV) and media (–9.1 ± 1.2 mV). BV2 microglia exposed to P25 (2.5–120 ppm) responded with an immediate and prolonged release of reactive oxygen species (ROS). Hoechst nuclear stain was reduced after 24-hr (≥100 ppm) and 48-hr (≥2.5 ppm) exposure. Microarray analysis on P25-exposed BV2 microglia indicated up-regulation of inflammatory, apoptotic, and cell cycling pathways and down-regulation of energy metabolism. P25 (2.5–120 ppm) stimulated increases of intracellular ATP and caspase 3/7 activity in isolated N27 neurons (24–48 hr) but did not produce cytotoxicity after 72-hr exposure. Primary cultures of rat striatum exposed to P25 (5 ppm) showed a reduction of immunohistochemically stained neurons and microscopic evidence of neuronal apoptosis after 6-hr exposure. These findings indicate that P25 stimulates ROS in BV2 microglia and is nontoxic to isolated N27 neurons. However, P25 rapidly damages neurons at low concentrations in complex brain cultures, plausibly though microglial generated ROS. PMID:18007996

  14. Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients

    PubMed Central

    Vanhaudenhuyse, Audrey; Noirhomme, Quentin; Tshibanda, Luaba J.-F.; Bruno, Marie-Aurelie; Boveroux, Pierre; Schnakers, Caroline; Soddu, Andrea; Perlbarg, Vincent; Ledoux, Didier; Brichant, Jean-François; Moonen, Gustave; Maquet, Pierre; Greicius, Michael D.

    2010-01-01

    The ‘default network’ is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than during attention-demanding tasks. Recent studies have shown that it is possible to reliably identify this network in the absence of any task, by resting state functional magnetic resonance imaging connectivity analyses in healthy volunteers. However, the functional significance of these spontaneous brain activity fluctuations remains unclear. The aim of this study was to test if the integrity of this resting-state connectivity pattern in the default network would differ in different pathological alterations of consciousness. Fourteen non-communicative brain-damaged patients and 14 healthy controls participated in the study. Connectivity was investigated using probabilistic independent component analysis, and an automated template-matching component selection approach. Connectivity in all default network areas was found to be negatively correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative then coma patients. Furthermore, precuneus connectivity was found to be significantly stronger in minimally conscious patients as compared with unconscious patients. Locked-in syndrome patient’s default network connectivity was not significantly different from controls. Our results show that default network connectivity is decreased in severely brain-damaged patients, in proportion to their degree of consciousness impairment. Future prospective studies in a larger patient population are needed in order to evaluate the prognostic value of the presented methodology. PMID:20034928

  15. Deficiency in the inner mitochondrial membrane peptidase 2-like (Immp21) gene increases ischemic brain damage and impairs mitochondrial function

    PubMed Central

    Ma, Yi; Mehta, Suresh L.; Lu, Baisong; Andy Li, P.

    2011-01-01

    Mitochondrial dysfunction plays an important role in mediating ischemic brain damage. Immp2l is an inner mitochondrial membrane peptidase that processes mitochondrial proteins cytochrome c1 (Cyc1). Homozygous mutation of Immp2l (Immp2lTg(Tyr)979Ove or Immp2l−/−) elevates mitochondrial membrane potential, increases superoxide (•O2−) production in the brain and impairs fertility. The objectives of this study are to explore the effects of heterozygous mutation of lmmp2l (Immp2l+/−) on ischemic outcome and to determine the influence of Immp2l deficiency on brain mitochondria after stroke. Male Immp2l+/− and wild-type (WT) mice were subjected to 1-h focal cerebral ischemia. Their brains were harvested after 5 and 24-h of reperfusion. The results showed that infarct volume and DNA oxidative damage significantly increased in the Immp2l+/− mice. There were no obvious cerebral vasculature abnormalities between the two types of mice viewed by Indian ink perfusion. The increased damage in Immp2l+/− mice was associated with early increase in •O2− production. Mitochondrial respiratory rate, total mitochondrial respiratory capacity and mitochondrial respiratory complex activities were decreased at 5-h of recirculation in Immp2l+/− mice compared to WT mice. Our results suggest that lmmp2l deficiency increases ischemic brain damage by enhancing •O2− production and damaging mitochondrial functional performance. PMID:21824519

  16. Objective instrumental memory and performance tests for evaluation of patients with brain damage: a search for a behavioral diagnostic tool.

    PubMed

    Harness, B Z; Bental, E; Carmon, A

    1976-03-01

    Cognition and performance of patients with localized and diffuse brain damage was evaluated through the application of objective perceptual testing. A series of visual perceptual and verbal tests, memory tests, as well as reaction time tasks were administered to the patients by logic programming equipment. In order to avoid a bias due to communicative disorders, all responses were motor, and achievement was scored in terms of correct identification and latencies of response. Previously established norms based on a large sample of non-brain-damaged hospitalized patients served to standardize the performance of the brain-damaged patient since preliminary results showed that age and educational level constitute an important variable affecting performance of the control group. The achievement of brain-damaged patients, corrected for these factors, was impaired significantly in all tests with respect to both recognition and speed of performance. Lateralized effects of brain damage were not significantly demonstrated. However, when the performance was analyzed with respect to the locus of visual input, it was found that patients with right hemispheric lesions showed impairment mainly on perception of figurative material, and that this deficit was more apparent in the left visual field. Conversely, patients with left hemispheric lesions tended to show impairment on perception of visually presented verbal material when the input was delivered to the right visual field. PMID:931718

  17. Selective deficit of second language: a case study of a brain-damaged Arabic-Hebrew bilingual patient

    PubMed Central

    Ibrahim, Raphiq

    2009-01-01

    Background An understanding of how two languages are represented in the human brain is best obtained from studies of bilingual patients who have sustained brain damage. The primary goal of the present study was to determine whether one or both languages of an Arabic-Hebrew bilingual individual are disrupted following brain damage. I present a case study of a bilingual patient, proficient in Arabic and Hebrew, who had sustained brain damage as a result of an intracranial hemorrhage related to herpes encephalitis. Methods The patient's performance on several linguistic tasks carried out in the first language (Arabic) and in the second language (Hebrew) was assessed, and his performance in the two languages was compared. Results The patient displayed somewhat different symptomatologies in the two languages. The results revealed dissociation between the two languages in terms of both the types and the magnitude of errors, pointing to aphasic symptoms in both languages, with Hebrew being the more impaired. Further analysis disclosed that this dissociation was apparently caused not by damage to his semantic system, but rather by damage at the lexical level. Conclusion The results suggest that the principles governing the organization of lexical representations in the brain are not similar for the two languages. PMID:19284632

  18. [Characteristics of brain tissue damage in kaolin-induced infantile rat hydrocephalus].

    PubMed

    Okuyama, T; Hashi, K; Okada, T; Sasaki, S

    1986-01-01

    Experimental hydrocephalus was induced by an intracisternal injection of 4% or 40% kaolin suspension in 2 days old Wistar rats. They were examined histologically and microangiographically 2 weeks after the injection of kaolin. Hydrocephalic rats were classified into 2 groups, severe hydrocephalic group A and mild hydrocephalic group B. In group A, a marked enlargement of the entire ventricular system with a thinning of the cerebral mantle was observed. On the other hand, the dilatation of the fourth ventricle was more pronounced compared with the other ventricles in group B. In group A, a spongy appearance of brain tissue was observed in the periventricular white matter accompanied with an intracerebral cavity. In these edematous areas, the lack of carbon black perfusion was apparent indicating an occurrence of microcirculatory disturbances. These microcirculatory disturbances and mechanical compression to the cerebral parenchyma may produce defective brain tissue (intracerebral cavity formation). The ependymal cell walls and subependymal glial cell layers were well preserved in spite of the damaged periventricular white matter. In group A, kaolin was present in the fourth ventricle and Sylvian aqueduct. Subependymal gliosis containing macrophages and newly produced blood vessels were observed in the region between the periventricular brain tissue and kaolin granules. These findings indicate that kaolin may produce changes in the ependymal cell and cerebral parenchyma as well as fibrosis and meningitis in the subarachnoid space. PMID:3964487

  19. Blockade of intracellular actions of calcium may protect against ischaemic damage to the gerbil brain.

    PubMed Central

    Asano, T.; Ikegaki, I.; Satoh, S.; Mochizuki, D.; Hidaka, H.; Suzuki, Y.; Shibuya, M.; Sugita, K.

    1991-01-01

    1. The brain cytoprotective effects of a putative calcium-associated protein kinase inhibitor, HA1077, as well as a calcium entry blocker nicardipine were evaluated in models of cerebral ischaemia in Mongolian gerbils. Morphological changes characterizing delayed neuronal death of selectively vulnerable CA1 pyramidal neurones in the hippocampus of the Mongolian gerbil brain occurred 7 days after transient bilateral occlusion of the common carotid arteries. 2. A single injection of HA1077 (1 and 3 mg kg-1, i.p.) 5 min after the occlusion led to a dose-dependent protection of the CA1 neurones. Repeated administrations of HA1077 (1 and 3 mg kg-1, i.p., twice daily for 7 days post-ischaemia) revealed an increase in the number of normal cells, compared to findings with a single administration. 3. In contrast to HA1077, nicardipine (0.3 and 1 mg kg-1, i.p.) did not reduce neuronal degeneration. 4. HA1077 did not interact with the ion channel within which MK-801 binds, as determined by receptor binding. 5. The calcium ionophore, A23187, caused a tonic contraction in canine cerebral arterial strips. HA1077, but not nicardipine, relaxed the A23187-induced contraction, concentration-dependently. 6. These results suggest that blockade of the intracellular actions of calcium may provide protection against ischaemic damage in the brain. Images Figure 1 PMID:1912980

  20. Maladaptive change of body representation in the brain after damage to central or peripheral nervous system.

    PubMed

    Oouchida, Yutaka; Sudo, Tamami; Inamura, Tetsunari; Tanaka, Naofumi; Ohki, Yukari; Izumi, Shin-Ichi

    2016-03-01

    Our brain has great flexibility to cope with various changes in the environment. Use-dependent plasticity, a kind of functional plasticity, plays the most important role in this ability to cope. For example, the functional recovery of paretic limb motor movement during post-stroke rehabilitation depends mainly on how much it is used. Patients with hemiparesis, however, tend to gradually disuse the paretic limb because of its motor impairment. Decreased use of the paretic hand then leads to further functional decline brought by use-dependent plasticity. To break this negative loop, body representation, which is the conscious and unconscious information regarding body state stored in the brain, is key for using the paretic limb because it plays an important role in selecting an effector while a motor program is generated. In an attempt to understand body representation in the brain, we reviewed animal and human literature mainly on the alterations of the sensory maps in the primary somatosensory cortex corresponding to the changes in limb usage caused by peripheral or central nervous system damage. PMID:26748075

  1. Low-Power 2-MHz Pulsed-Wave Transcranial Ultrasound Reduces Ischemic Brain Damage in Rats.

    PubMed

    Alexandrov, Andrei V; Barlinn, Kristian; Strong, Roger; Alexandrov, Anne W; Aronowski, Jaroslaw

    2011-09-01

    It is largely unknown whether prolonged insonation with ultrasound impacts the ischemic brain tissue by itself. Our goal was to evaluate safety and the effect of high-frequency ultrasound on infarct volume in rats. Thirty-two Long-Evans rats with permanent middle cerebral and carotid artery occlusions received either 2-MHz ultrasound at two levels of insonation power (128 or 10 mW) or no ultrasound (controls). We measured cerebral hemorrhage, indirect and direct infarct volume as well as edema volume at 24 h. No cerebral hemorrhages were detected in all animals. Exposure to low-power (10 mW) ultrasound resulted in a significantly decreased indirect infarct volume (p = 0.0039), direct infarct volume (p = 0.0031), and brain edema volume (p = 0.01) compared with controls. High-power (128 mW) ultrasound had no significant effects. An additional experiment with India ink showed a greater intravascular penetration of dye into ischemic tissues exposed to low-power ultrasound. Insonation with high-frequency, low-power ultrasound reduces ischemic brain damage in rat. Its effect on edema reduction and possible promotion of microcirculation could be used to facilitate drug and nutrient delivery to ischemic areas. PMID:24323655

  2. Overexpression of Thioredoxin in Transgenic Mice Attenuates Focal Ischemic Brain Damage

    NASA Astrophysics Data System (ADS)

    Takagi, Yasushi; Mitsui, Akira; Nishiyama, Akira; Nozaki, Kazuhiko; Sono, Hiroshi; Gon, Yasuhiro; Hashimoto, Nobuo; Yodoi, Junji

    1999-03-01

    Thioredoxin (TRX) plays important biological roles both in intra- and extracellular compartments, including in regulation of various intracellular molecules via thiol redox control. We produced TRX overexpressing mice and confirmed that there were no anatomical and physiological differences between wild-type (WT) mice and TRX transgenic (Tg) mice. In the present study we subjected mice to focal brain ischemia to shed light on the role of TRX in brain ischemic injury. At 24 hr after middle cerebral artery occlusion, infarct areas and volume were significantly smaller in Tg mice than in WT mice. Moreover neurological deficit was ameliorated in Tg mice compared with WT mice. Protein carbonyl content, a marker of cellular protein oxidation, in Tg mice showed less increase than did that of WT mice after the ischemic insult. Furthermore, c-fos expression in Tg mice was stronger than in WT mice 1 hr after ischemia. Our results suggest that transgene expression of TRX decreased ischemic neuronal injury and that TRX and the redox state modified by TRX play a crucial role in brain damage during stroke.

  3. Pyrroloquinoline quinone protects mouse brain endothelial cells from high glucose-induced damage in vitro

    PubMed Central

    Wang, Zhong; Chen, Guo-qiang; Yu, Gui-ping; Liu, Chang-jian

    2014-01-01

    Aim: To investigate the effects of pyrroloquinoline quinone (PQQ), an oxidoreductase cofactor, on high glucose-induced mouse endothelial cell damage in vitro. Methods: Mouse brain microvascular endothelial bEND.3 cells were exposed to different glucose concentrations (5.56, 25 and 40 mmol/L) for 24 or 48 h. The cell viability was examined using MTT assay. Flow cytometry was used to analyze the apoptosis and ROS levels in the cells. MitoTracker Green staining was used to examine the mitochondria numbers in the cells. Western blot analysis was used to analyze the expression of HIF-1α and the proteins in JNK pathway. Results: Treatment of bEND.3 cells with high glucose significantly decreased the cell viability, while addition of PQQ (1 and 10 μmol/L) reversed the high glucose-induced cell damage in a concentration-dependent manner. Furthermore, PQQ (100 μmol/L) significantly suppressed the high glucose-induced apoptosis and ROS production in the cells. PQQ significantly reversed the high glucose-induced reduction in both the mitochondrial membrane potential and mitochondria number in the cells. The high glucose treatment significantly increased the expression of HIF-1α and JNK phosphorylation in the cells, and addition of PQQ led to a further increase of HIF-1α level and a decrease of JNK phosphorylation. Addition of JNK inhibitor SP600125 (10 μmol/L) also significantly suppressed high glucose-induced apoptosis and JNK phosphorylation in bEND.3 cells. Conclusion: PQQ protects mouse brain endothelial cells from high glucose damage in vitro by suppressing intracellular ROS and apoptosis via inhibiting JNK signaling pathway. PMID:25283505

  4. Omega-3 prevents behavior response and brain oxidative damage in the ketamine model of schizophrenia.

    PubMed

    Zugno, A I; Chipindo, H L; Volpato, A M; Budni, J; Steckert, A V; de Oliveira, M B; Heylmann, A S; da Rosa Silveira, F; Mastella, G A; Maravai, S G; Wessler, P G; Binatti, A R; Panizzutti, B; Schuck, P F; Quevedo, J; Gama, C S

    2014-02-14

    Supplementation with omega-3 has been identified as an adjunctive alternative for the treatment of psychiatric disorders, in order to minimize symptoms. Considering the lack of understanding concerning the pathophysiology of schizophrenia, the present study hypothesized that omega 3 prevents the onset of symptoms similar to schizophrenia in young Wistar rats submitted to ketamine treatment. Moreover, the role of oxidative stress in this model was assessed. Omega-3 (0.8g/kg) or vehicle was given by orogastric gavage once daily. Both treatments were performed during 21days, starting at the 30th day of life in young rats. After 14days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25mg/kg ip daily) was started and maintained until the last day of the experiment. We evaluated the pre-pulse inhibition of the startle reflex, activity of antioxidant systems and damage to proteins and lipids. Our results demonstrate that supplementation of omega-3 prevented: decreased inhibition of startle reflex, damage to lipids in the hippocampus and striatum and damage to proteins in the prefrontal cortex. Furthermore, these changes are associated with decreased GPx in brain tissues evaluated. Together, our results suggest the prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia. PMID:24316471

  5. Frontal lobe syndrome reassessed: comparison of patients with lateral or medial frontal brain damage.

    PubMed

    Paradiso, S; Chemerinski, E; Yazici, K M; Tartaro, A; Robinson, R G

    1999-11-01

    Examination of mood and behaviour changes after frontal damage may contribute to understanding the functional role of distinct prefrontal areas in depression and anxiety. Depression and anxiety disorders, symptoms, and behaviour were compared in eight patients with single lateral and eight patients with single medial frontal lesions matched for age, sex, race, education, socioeconomic status, side, and aetiology of lesion 2 weeks and 3 months after brain injury. DSM IV major depressive and generalised anxiety disorders were more frequent in patients with lateral compared with medial lesions at 2 weeks but not at 3 months. At 3 months, however, patients with lateral damage showed greater severity of depressive symptoms, and greater impairment in both activities of daily living and social functioning. At initial evaluation depressed mood and slowness were more frequent, whereas at 3 months slowness, lack of energy, and social unease were more frequent in the lateral than the medial group. Patients with lateral lesions showed greater reduction of emotion and motivation (apathy) during both examinations. Medial frontal injury may fail to produce emotional dysregulation or may inhibit experience of mood changes, anxiety, or apathy. Lateral prefrontal damage may disrupt mood regulation and drive while leaving intact the ability to experience (negative) emotions. PMID:10519877

  6. Microcavitation as a Neuronal Damage Mechanism in Blast Traumatic Brain Injury

    NASA Astrophysics Data System (ADS)

    Franck, Christian; Estrada, Jonathan

    2015-11-01

    Blast traumatic brain injury (bTBI) is a leading cause of injury in the armed forces. Diffuse axonal injury, the hallmark feature of blunt TBI, has been investigated in direct mechanical loading conditions. However, recent evidence suggests inertial cavitation as a possible bTBI mechanism, particularly in the case of exposure to blasts. Cavitation damage to free surfaces has been well-studied, but bubble interactions within confined 3D environments, in particular their stress and strain signatures are not well understood. The structural damage due to cavitation in living tissues - particularly at the cellular level - are incompletely understood, in part due to the rapid bubble formation and deformation strain rates of up to ~ 105-106 s-1. This project aims to characterize material damage in 2D and 3D cell culture environments by utilizing a novel high-speed red-blue diffraction assisted image correlation method at speeds of up to 106 frames per second. We gratefully acknowledge funding from the Office of Naval Research (POC: Dr. Tim Bentley).

  7. Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials

    PubMed Central

    Ma, Junpeng; Xu, Jianguo

    2015-01-01

    Objective To evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI). Methods PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP) were searched for randomized controlled trials (RCTs) comparing progesterone and placebo administrated in acute TBI patients. The primary outcome was mortality and the secondary outcomes were unfavorable outcomes and adverse events. A meta-analysis was conducted to evaluate the efficacy and safety of progesterone administrated in patients with acute TBI. Results A total of 6 studies met inclusion criteria, involving 2,476 patients. The risk of bias was considered to be low in 4 studies but high in the other 2 studies. The results of meta-analysis indicated progesterone did not reduce the mortality (RR = 0.83, 95% CI = 0.57–1.20) or unfavorable outcomes (RR = 0.89, 95% CI = 0.78–1.02) of acute TBI patients in comparison with placebo. Sensitivity analysis yielded consistent results. Progesterone was basically safe and well tolerated in TBI patients with the exception of increased risk of phlebitis or thrombophlebitis (RR = 3.03, 95% CI = 1.96–4.66). Conclusions Despite some modest bias, present evidence demonstrated that progesterone was well tolerated but did not reduce the mortality or unfavorable outcomes of adult patients with acute TBI. PMID:26473361

  8. Acute Methanol Poisoning: Prevalence and Predisposing Factors of Haemorrhagic and Non-Haemorrhagic Brain Lesions.

    PubMed

    Zakharov, Sergey; Kotikova, Katerina; Vaneckova, Manuela; Seidl, Zdenek; Nurieva, Olga; Navratil, Tomas; Caganova, Blazena; Pelclova, Daniela

    2016-08-01

    The purpose was to study the prevalence and predisposing factors of brain lesions in survivors of acute methanol poisoning. Clinical data on 106 patients with methanol poisoning were collected during the Czech mass poisoning outbreak. Of 83 survivors, in 46 (55%) patients, follow-up examinations including magnetic resonance imaging of brain (MR) were performed 3-8 and 24-28 months after discharge from the hospital. Of 46 patients with a median age of 49 (interquartile range, 35-57) years, 24 (52%) patients had a total of 40 abnormal brain findings with haemorrhagic lesions detected in 15 (33%) and non-haemorrhagic lesions found in 9 (19%) patients. The patients with haemorrhagic brain lesions were more acidemic (lower arterial blood pH, higher base deficit) and had higher glycaemia and lactacidaemia on admission than those without haemorrhages (all p < 0.05). Thirteen of 32 (41%) of patients with systemic anticoagulation and 2 of 14 (14%) of patients without it had haemorrhagic lesions (p = 0.080). Bleeding complications during the treatment occurred in 4 of 15 (27%) patients, and 5 of 15 (33%) patients had conditions predisposing to haemorrhage in the group with haemorrhagic lesions. In three cases with a series of computer tomography (CT)/MR performed during hospitalization, the necrotic lesions in the brain remained non-haemorrhagic during hospitalization and haemorrhagic lesions were detected on the follow-up MR examinations only. No association between brain haemorrhages and systemic anticoagulation during dialysis was found: brain haemorrhages might occur in severely poisoned patients treated without systemic anticoagulation, whereas treatment with high doses of heparin might not lead to brain haemorrhages. PMID:26806851

  9. Nafamostat mesilate protects against acute cerebral ischemia via blood-brain barrier protection.

    PubMed

    Wang, Jing; Li, Chenhui; Chen, Tao; Fang, Yinquan; Shi, Xinzhong; Pang, Tao; Zhang, Luyong; Liao, Hong

    2016-06-01

    Serine proteases, such as thrombin, are contributors to the disruption of the blood-brain barrier (BBB) and exacerbate brain damage during ischemic stroke, for which the current clinical therapy remains unsatisfactory. However, the effect of nafamostat mesilate (NM), a synthetic serine protease inhibitor, on BBB disruption following cerebral ischemia is unknown. Here, we investigated the in vivo effect of NM on BBB integrity in rats subjected to transient middle cerebral artery occlusion (MCAO) and explored the possible mechanism in an in vitro BBB model comprising rat brain microvascular endothelial cells and astrocytes after oxygen and glucose deprivation (OGD) in the presence of thrombin. The results showed that NM treatment remarkably attenuated transient MCAO-induced brain infarcts, brain oedema and motor dysfunction in addition to BBB disruption, which might be related to changes in tight junction protein expression and localization. Meanwhile, NM preserved BBB integrity and alleviated the changes in tight junction protein expression and localization and cytoskeleton rearrangement in rat brain microvascular endothelial cells via thrombin inhibition. Our findings suggest that NM treatment can preserve BBB integrity through the inhibition of thrombin, which might be correlated with the regulation of PKCα/RhoA/MLC2 pathway components. PMID:26861077

  10. Protective effect of Xingnaojia formulation on rats with brain and liver damage caused by chronic alcoholism

    PubMed Central

    LI, SHUANG; WANG, SU; GUO, ZHI-GANG; HUANG, NING; ZHAO, FAN-RONG; ZHU, MO-LI; MA, LI-JUAN; LIANG, JIN-YING; ZHANG, YU-LIN; HUANG, ZHONG-LIN; WAN, GUANG-RUI

    2015-01-01

    The aim of this study was to observe the effect of a formulation of traditional Chinese medicine extracts known as Xingnaojia (XNJ) on the liver function, learning ability and memory of rats with chronic alcoholism and to verify the mechanism by which it protects the brain and liver. A rat model of chronic alcoholism was used in the study. The spatial learning ability and memory of the rats were tested. The rats were then sacrificed and their brains and hepatic tissues were isolated. The activity of superoxide dismutase (SOD) and levels of glutamate (Glu), N-methyl D-aspartate receptor subtype 2B (NR2B), cyclin-dependent kinase 5 (CDK5) and cannabinoid receptor 1 (CB1) in the hippocampus were analyzed. The ultrastructure of the hepatic tissue was observed by electron microscopy. In addition, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum were tested and the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TCHOL) were analyzed. XNJ enhanced the learning and memory of rats with chronic alcoholism. Treatment with XNJ increased the activity of SOD, and decreased the expression levels of NR2B mRNA and NR2B, CB1 and CDK5 proteins in the brain tissues compared with those in the model rats. It also increased the activity of ALDH in the serum and liver, decreased the serum levels of LDL, TG and TCHOL and increased the serum level of HDL. These results indicate that XNJ exhibited a protective effect against brain and liver damage in rats with chronic alcoholism. PMID:26640531

  11. Prevention of neonatal oxygen-induced brain damage by reduction of intrinsic apoptosis

    PubMed Central

    Sifringer, M; Bendix, I; Börner, C; Endesfelder, S; von Haefen, C; Kalb, A; Holifanjaniaina, S; Prager, S; Schlager, G W; Keller, M; Jacotot, E; Felderhoff-Mueser, U

    2012-01-01

    Within the last decade, it became clear that oxygen contributes to the pathogenesis of neonatal brain damage, leading to neurocognitive impairment of prematurely born infants in later life. Recently, we have identified a critical role for receptor-mediated neuronal apoptosis in the immature rodent brain. However, the contribution of the intrinsic apoptotic pathway accompanied by activation of caspase-2 under hyperoxic conditions in the neonatal brain still remains elusive. Inhibition of caspases appears a promising strategy for neuroprotection. In order to assess the influence of specific caspases on the developing brain, we applied a recently developed pentapeptide-based group II caspase inhibitor (5-(2,6-difluoro-phenoxy)-3(R,S)-(2(S)-(2(S)-(3-methoxycarbonyl-2(S)-(3-methyl-2(S)-((quinoline-2-carbonyl)-amino)-butyrylamino)propionylamino)3-methylbutyrylamino)propionylamino)-4-oxo-pentanoic acid methyl ester; TRP601). Here, we report that elevated oxygen (hyperoxia) triggers a marked increase in active caspase-2 expression, resulting in an initiation of the intrinsic apoptotic pathway with upregulation of key proteins, namely, cytochrome c, apoptosis protease-activating factor-1, and the caspase-independent protein apoptosis-inducing factor, whereas BH3-interacting domain death agonist and the anti-apoptotic protein B-cell lymphoma-2 are downregulated. These results coincide with an upregulation of caspase-3 activity and marked neurodegeneration. However, single treatment with TRP601 at the beginning of hyperoxia reversed the detrimental effects in this model. Hyperoxia-mediated neurodegeneration is supported by intrinsic apoptosis, suggesting that the development of highly selective caspase inhibitors will represent a potential useful therapeutic strategy in prematurely born infants. PMID:22237207

  12. Intranasal delivery of obidoxime to the brain prevents mortality and CNS damage from organophosphate poisoning.

    PubMed

    Krishnan, Jishnu K S; Arun, Peethambaran; Appu, Abhilash P; Vijayakumar, Nivetha; Figueiredo, Taíza H; Braga, Maria F M; Baskota, Sudikshya; Olsen, Cara H; Farkas, Natalia; Dagata, John; Frey, William H; Moffett, John R; Namboodiri, Aryan M A

    2016-03-01

    Intranasal delivery is an emerging method for bypassing the blood brain barrier (BBB) and targeting therapeutics to the CNS. Oximes are used to counteract the effects of organophosphate poisoning, but they do not readily cross the BBB. Therefore, they cannot effectively counteract the central neuropathologies caused by cholinergic over-activation when administered peripherally. For these reasons we examined intranasal administration of oximes in an animal model of severe organophosphate poisoning to determine their effectiveness in reducing mortality and seizure-induced neuronal degeneration. Using the paraoxon model of organophosphate poisoning, we administered the standard treatment (intramuscular pralidoxime plus atropine sulphate) to all animals and then compared the effectiveness of intranasal application of obidoxime (OBD) to saline in the control groups. Intranasally administered OBD was effective in partially reducing paraoxon-induced acetylcholinesterase inhibition in the brain and substantially reduced seizure severity and duration. Further, intranasal OBD completely prevented mortality, which was 41% in the animals given standard treatment plus intranasal saline. Fluoro-Jade-B staining revealed extensive neuronal degeneration in the surviving saline-treated animals 24h after paraoxon administration, whereas no detectable degenerating neurons were observed in any of the animals given intranasal OBD 30min before or 5min after paraoxon administration. These findings demonstrate that intranasally administered oximes bypass the BBB more effectively than those administered peripherally and provide an effective method for protecting the brain from organophosphates. The addition of intranasally administered oximes to the current treatment regimen for organophosphate poisoning would improve efficacy, reducing both brain damage and mortality. PMID:26751814

  13. Simulated Microgravity and Low-Dose/Low-Dose-Rate Radiation Induces Oxidative Damage in the Mouse Brain.

    PubMed

    Mao, Xiao Wen; Nishiyama, Nina C; Pecaut, Michael J; Campbell-Beachler, Mary; Gifford, Peter; Haynes, Kristine E; Becronis, Caroline; Gridley, Daila S

    2016-06-01

    Microgravity and radiation are stressors unique to the spaceflight environment that can have an impact on the central nervous system (CNS). These stressors could potentially lead to significant health risks to astronauts, both acutely during the course of a mission or chronically, leading to long-term, post-mission decrements in quality of life. The CNS is sensitive to oxidative injury due to high concentrations of oxidizable, unsaturated lipids and low levels of antioxidant defenses. The purpose of this study was to evaluate oxidative damage in the brain cortex and hippocampus in a ground-based model for spaceflight, which includes prolonged unloading and low-dose radiation. Whole-body low-dose/low-dose-rate (LDR) gamma radiation using (57)Co plates (0.04 Gy at 0.01 cGy/h) was delivered to 6 months old, mature, female C57BL/6 mice (n = 4-6/group) to simulate the radiation component. Anti-orthostatic tail suspension was used to model the unloading, fluid shift and physiological stress aspects of the microgravity component. Mice were hindlimb suspended and/or irradiated for 21 days. Brains were isolated 7 days or 9 months after irradiation and hindlimb unloading (HLU) for characterization of oxidative stress markers and microvessel changes. The level of 4-hydroxynonenal (4-HNE) protein, an oxidative specific marker for lipid peroxidation, was significantly elevated in the cortex and hippocampus after LDR + HLU compared to controls (P < 0.05). The combination group also had the highest level of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression compared to controls (P < 0.05). There was a significant decrease in superoxide dismutase (SOD) expression in the animals that received HLU only or combined LDR + HLU compared to control (P < 0.05). In addition, 9 months after LDR and HLU exposure, microvessel densities were the lowest in the combination group, compared to age-matched controls in the cortex (P < 0.05). Our data provide the first evidence

  14. Blocking B7-1/CD28 Pathway Diminished Long-Range Brain Damage by Regulating the Immune and Inflammatory Responses in a Mouse Model of Intracerebral Hemorrhage.

    PubMed

    Ma, Lu; Shen, Xi; Gao, Yuan; Wu, Qiong; Ji, Mengmeng; Luo, Chengliang; Zhang, Mingyang; Wang, Tao; Chen, Xiping; Tao, Luyang

    2016-07-01

    Acute brain injuries can activate bidirectional crosstalk between the injured brain and the immune system. The immune system, particularly T lymphocytes and cytokines, has been implicated in the progression of brain injury after intracerebral hemorrhage (ICH). Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) binding cognate receptor provides a secondary signaling to T cell activation. The aim of our study was to explore the effects of anti-B7-1 antibody on the development and prognosis of cerebral hemorrhage and to investigate the possible underlying mechanism. Mice were inner canthus veniplex administered with anti-B7-1 antibody at 10 min and 24 h after ICH and sacrificed on the third day after ICH. Immune function was assessed via splenocyte proliferation assay and organism index, respectively. IFN-γ and IL-4 were detected by enzyme-linked immuno sorbent assay. The cerebral edema was evaluated via brain water content. The levels of autophagy and apoptosis related proteins were measured by western blotting analysis. In addition, functional outcome was studied with pole-climbing test and morris water maze. The mice were weighed on 0, 1, 3, 14 and 21 days after ICH. The treatment with anti-B7-1 antibody significantly lowered immune function, and reduced the latency of water maze on 18 and 20 days, the ratio of IFN-γ/IL-4 as well as body weight on day 3 after cerebral hemorrhage. Our study suggests that in the cerebral hemorrhage mice brain anti-B7-1 antibody may reduce long-range brain damage by reversing immune imbalance. PMID:26980009

  15. Acute high-altitude hypoxic brain injury: Identification of ten differential proteins.

    PubMed

    Li, Jianyu; Qi, Yuting; Liu, Hui; Cui, Ying; Zhang, Li; Gong, Haiying; Li, Yaxiao; Li, Lingzhi; Zhang, Yongliang

    2013-11-01

    Hypobaric hypoxia can cause severe brain damage and mitochondrial dysfunction, and is involved in hypoxic brain injury. However, little is currently known about the mechanisms responsible for mitochondrial dysfunction in hypobaric hypoxic brain damage. In this study, a rat model of hypobaric hypoxic brain injury was established to investigate the molecular mechanisms associated with mitochondrial dysfunction. As revealed by two-dimensional electrophoresis analysis, 16, 21, and 36 differential protein spots in cerebral mitochondria were observed at 6, 12, and 24 hours post-hypobaric hypoxia, respectively. Furthermore, ten protein spots selected from each hypobaric hypoxia subgroup were similarly regulated and were identified by mass spectrometry. These detected proteins included dihydropyrimidinase-related protein 2, creatine kinase B-type, isovaleryl-CoA dehydrogenase, elongation factor Ts, ATP synthase beta-subunit, 3-mercaptopyruvate sulfurtransferase, electron transfer flavoprotein alpha-subunit, Chain A of 2-enoyl-CoA hydratase, NADH dehydrogenase iron-sulfur protein 8 and tropomyosin beta chain. These ten proteins are all involved in the electron transport chain and the function of ATP synthase. Our findings indicate that hypobaric hypoxia can induce the differential expression of several cerebral mitochondrial proteins, which are involved in the regulation of mitochondrial energy production. PMID:25206614

  16. Detrimental role of pericyte Nox4 in the acute phase of brain ischemia.

    PubMed

    Nishimura, Ataru; Ago, Tetsuro; Kuroda, Junya; Arimura, Koichi; Tachibana, Masaki; Nakamura, Kuniyuki; Wakisaka, Yoshinobu; Sadoshima, Junichi; Iihara, Koji; Kitazono, Takanari

    2016-06-01

    Pericytes are mural cells abundantly present in cerebral microvessels and play important roles, including the formation and maintenance of the blood-brain barrier. Nox4 is a major source of reactive oxygen species in cardiovascular cells and modulate cellular functions, particularly under pathological conditions. In the present study, we found that the expression of Nox4 was markedly induced in microvascular cells, including pericytes, in peri-infarct areas after middle cerebral artery occlusion stroke models in mice. The upregulation of Nox4 was greater in a permanent middle cerebral artery occlusion model compared with an ischemia/reperfusion transient middle cerebral artery occlusion model. We performed permanent middle cerebral artery occlusion on mice with Nox4 overexpression in pericytes (Tg-Nox4). Infarct volume was significantly greater with enhanced reactive oxygen species production and blood-brain barrier breakdown in peri-infarct areas in Tg-Nox4, compared with littermate controls. In cultured brain pericytes, Nox4 was significantly upregulated by hypoxia and was promptly downregulated by reoxygenation. Phosphorylation of NFκB and production of matrix metalloproteinase 9 were significantly increased in both cultured pericytes overexpressing Nox4 and in peri-infarct areas in Tg-Nox4. Collectively, Nox4 is upregulated in pericytes in peri-infarct areas after acute brain ischemia and may enhance blood-brain barrier breakdown through activation of NFκB and matrix metalloproteinase 9, thereby causing enlargement of infarct volume. PMID:26661159

  17. Abnormal EEG Complexity and Functional Connectivity of Brain in Patients with Acute Thalamic Ischemic Stroke

    PubMed Central

    Liu, Shuang; Guo, Jie; Meng, Jiayuan; Wang, Zhijun; Yao, Yang; Yang, Jiajia; Qi, Hongzhi; Ming, Dong

    2016-01-01

    Ischemic thalamus stroke has become a serious cardiovascular and cerebral disease in recent years. To date the existing researches mostly concentrated on the power spectral density (PSD) in several frequency bands. In this paper, we investigated the nonlinear features of EEG and brain functional connectivity in patients with acute thalamic ischemic stroke and healthy subjects. Electroencephalography (EEG) in resting condition with eyes closed was recorded for 12 stroke patients and 11 healthy subjects as control group. Lempel-Ziv complexity (LZC), Sample Entropy (SampEn), and brain network using partial directed coherence (PDC) were calculated for feature extraction. Results showed that patients had increased mean LZC and SampEn than the controls, which implied the stroke group has higher EEG complexity. For the brain network, the stroke group displayed a trend of weaker cortical connectivity, which suggests a functional impairment of information transmission in cortical connections in stroke patients. These findings suggest that nonlinear analysis and brain network could provide essential information for better understanding the brain dysfunction in the stroke and assisting monitoring or prognostication of stroke evolution. PMID:27403202

  18. Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke

    PubMed Central

    Lakhan, Shaheen E.; Kirchgessner, Annette; Tepper, Deborah; Leonard, Aidan

    2013-01-01

    Ischemic stroke continues to be one of the most challenging diseases in translational neurology. Tissue plasminogen activator (tPA) remains the only approved treatment for acute ischemic stroke, but its use is limited to the first hours after stroke onset due to an increased risk of hemorrhagic transformation over time resulting in enhanced brain injury. In this review we discuss the role of matrix metalloproteinases (MMPs) in blood-brain barrier (BBB) disruption as a consequence of ischemic stroke. MMP-9 in particular appears to play an important role in tPA-associated hemorrhagic complications. Reactive oxygen species can enhance the effects of tPA on MMP activation through the loss of caveolin-1 (cav-1), a protein encoded in the cav-1 gene that serves as a critical determinant of BBB permeability. This review provides an overview of MMPs’ role in BBB breakdown during acute ischemic stroke. The possible role of MMPs in combination treatment of acute ischemic stroke is also examined. PMID:23565108

  19. Whole-Brain Computed Tomographic Perfusion Imaging in Acute Cerebral Venous Sinus Thrombosis

    PubMed Central

    Mokin, Maxim; Ciambella, Chelsey C.; Masud, Muhammad W.; Levy, Elad I.; Snyder, Kenneth V.; Siddiqui, Adnan H.

    2016-01-01

    Background Acute cerebral venous sinus thrombosis (VST) can be difficult to diagnose because of its diverse clinical presentation. The utility of perfusion imaging for diagnosing VST is not well understood. Summary We retrospectively reviewed cases of acute VST in patients who underwent whole-brain (320-detector-row) computed tomographic (CT) perfusion imaging in combination with craniocervical CT venography. Perfusion maps that were analyzed included cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time, and time to peak. Among the 10 patients with acute VST included in this study, 9 had perfusion abnormalities. All perfusion abnormalities were localized in areas adjacent to the occluded sinus and did not match typical anterior or posterior circulation arterial territories. Bilateral perfusion deficits were seen in 4 cases. In 2 cases, parenchymal hemorrhage was diagnosed on noncontrast CT imaging; in those cases, focal CBV and CBF were reduced. Key Messages Whole-brain CT perfusion imaging with 320-detector-row scanners can further assist in establishing the diagnosis of VST by detecting perfusion abnormalities corresponding to venous and not arterial territories. CT perfusion could assist in the differentiation between focal reversible changes, such as those caused by vasogenic edema, and irreversible changes due to infarction. PMID:27051406

  20. Acute and chronic watercress supplementation attenuates exercise-induced peripheral mononuclear cell DNA damage and lipid peroxidation.

    PubMed

    Fogarty, Mark C; Hughes, Ciara M; Burke, George; Brown, John C; Davison, Gareth W

    2013-01-28

    Pharmacological antioxidant vitamins have previously been investigated for a prophylactic effect against exercise-induced oxidative stress. However, large doses are often required and may lead to a state of pro-oxidation and oxidative damage. Watercress contains an array of nutritional compounds such as β-carotene and α-tocopherol which may increase protection against exercise-induced oxidative stress. The present randomised controlled investigation was designed to test the hypothesis that acute (consumption 2 h before exercise) and chronic (8 weeks consumption) watercress supplementation can attenuate exercise-induced oxidative stress. A total of ten apparently healthy male subjects (age 23 (SD 4) years, stature 179 (SD 10) cm and body mass 74 (SD 15) kg) were recruited to complete the 8-week chronic watercress intervention period (and then 8 weeks of control, with no ingestion) of the experiment before crossing over in order to compete the single-dose acute phase (with control, no ingestion). Blood samples were taken at baseline (pre-supplementation), at rest (pre-exercise) and following exercise. Each subject completed an incremental exercise test to volitional exhaustion following chronic and acute watercress supplementation or control. The main findings show an exercise-induced increase in DNA damage and lipid peroxidation over both acute and chronic control supplementation phases (P< 0.05 v. supplementation), while acute and chronic watercress attenuated DNA damage and lipid peroxidation and decreased H₂O₂ accumulation following exhaustive exercise (P< 0.05 v. control). A marked increase in the main lipid-soluble antioxidants (α-tocopherol, γ-tocopherol and xanthophyll) was observed following watercress supplementation (P< 0.05 v. control) in both experimental phases. These findings suggest that short- and long-term watercress ingestion has potential antioxidant effects against exercise-induced DNA damage and lipid peroxidation. PMID:22475430

  1. High-strain-rate brain injury model using submerged acute rat brain tissue slices.

    PubMed

    Sarntinoranont, Malisa; Lee, Sung J; Hong, Yu; King, Michael A; Subhash, Ghatu; Kwon, Jiwoon; Moore, David F

    2012-01-20

    Blast-induced traumatic brain injury (bTBI) has received increasing attention in recent years due to ongoing military operations in Iraq and Afghanistan. Sudden impacts or explosive blasts generate stress and pressure waves that propagate at high velocities and affect sensitive neurological tissues. The immediate soft tissue response to these stress waves is difficult to assess using current in vivo imaging technologies. However, these stress waves and resultant stretching and shearing of tissue within the nano- to microsecond time scale of blast and impact are likely to cause initial injury. To visualize the effects of stress wave loading, we have developed a new ex vivo model in which living tissue slices from rat brain, attached to a ballistic gelatin substrate, were subjected to high-strain-rate loads using a polymer split Hopkinson pressure bar (PSHPB) with real-time high-speed imaging. In this study, average peak fluid pressure within the test chamber reached a value of 1584±63.3 psi. Cavitation due to a trailing underpressure wave was also observed. Time-resolved images of tissue deformation were collected and large maximum eigenstrains (0.03-0.42), minimum eigenstrains (-0.33 to -0.03), maximum shear strains (0.09-0.45), and strain rates (8.4×10³/sec) were estimated using digital image correlation (DIC). Injury at 4 and 6 h was quantified using Fluoro-Jade C. Neuronal injury due to PSHPB testing was found to be significantly greater than injury associated with the tissue slice paradigm alone. While large pressures and strains were encountered for these tests, this system provides a controllable test environment to study injury to submerged brain slices over a range of strain rate, pressure, and strain loads. PMID:21970544

  2. Diffuse leukoencephalopathy and brain edema: unusual presentations of CNS relapse of acute myeloid leukemia.

    PubMed

    Schumann, Michael; Kiewe, Philipp; Hartlieb, Sissel; Neumann, Martin; Schilling, Andreas; Koch, Hans-Christian; Thiel, Eckhard; Korfel, Agnieszka

    2010-04-01

    An isolated CNS relapse is rarely seen in acute myeloid leukemia. However, it has a potentially fatal clinical outcome. We herein present the case of a 39-year-old man, who presented to our emergency room with horizontal diplopic images, vertigo, bilateral deafness, and progressing somnolence. Cerebral imaging revealed cerebral and cerebellar edema and a diffuse leukoencephalopathy. With the one-year-old history of an initially successfully treated FAB-M0 acute myeloid leukemia (AML) in mind, a lumbar puncture was carried out that showed a vast number of myeloid blasts in the morphologic analysis of the cerebrospinal fluid. In conjunction with normal findings in the peripheral blood-count with differential and the bone marrow examination a diagnosis of an isolated CNS relapse of the AML was made. Cytarabine chemotherapy was initiated and the symptoms resolved rapidly. To our surprise, cerebral imaging in the course of the treatment not only showed a resolution of the brain edema but also of the leukoencephalopathy, pointing to a direct infiltration of brain parenchyma by leukemic blasts. The case highlights the relevance of the CNS as a pharmacologic "sanctuary" for tumor cells in patients that on prior treatments have not received intrathecal chemotherapy or chemotherapeutics that cross the blood-brain barrier. PMID:18826442

  3. Acute effect of aspartame-induced oxidative stress in Wistar albino rat brain

    PubMed Central

    Ashok, Iyaswamy; Sheeladevi, Rathinasamy; Wankhar, Dapkupar

    2015-01-01

    Abstract The present study was carried out to investigate the acute effect of aspartame on oxidative stress in the Wistar albino rat brain. We sought to investigate whether acute administration of aspartame (75 mg/kg) could release methanol and induce oxidative stress in the rat brain 24 hours after administration. To mimic human methanol metabolism, methotrexate treated rats were used to study aspartame effects. Wistar strain male albino rats were administered with aspartame orally as a single dose and studied along with controls and methotrexate treated controls. Blood methanol and formate level were estimated after 24 hours and rats were sacrificed and free radical changes were observed in discrete regions by assessing the scavenging enzymes, reduce dglutathione (GSH), lipid peroxidation and protein thiol levels. There was a significant increase in lipid peroxidation levels, superoxide dismutase activity (SOD), glutathione peroxidase levels (GPx), and catalase activity (CAT) with a significant decrease in GSH and protein thiol. Aspartame exposure resulted in detectable methanol even after 24 hours. Methanol and its metabolites may be responsible for the generation of oxidative stress in brain regions. The observed alteration in aspartame fed animals may be due to its metabolite methanol and elevated formate. The elevated free radicals due to methanol induced oxidative stress. PMID:26445572

  4. [Asystolias in the acute phase of brain stroke. Report of a case].

    PubMed

    Belvis, R; Marti-Fàbregas, J; Franquet, E; Cocho, D; Valencia, C; Martí-Vilalta, J L

    2003-04-01

    Brain areas involved in heart autonomic control are not well characterized. Insulae have been proposed as control centers. A lesion in these areas may induce a cardiac autonomic dysfunction (arrhythmias, atrioventricular conduction abnormalities). Asystolia has not been previously reported. A 65-year-old man suffered an acute ischemia of the right middle cerebral artery (MCA) territory. NIHSS score was 19 points. Brain CT scan was normal. Transcranial Doppler (TCD) showed occlusion of the right MCA. Fibrinolysis was initiated 135 minutes after stroke onset with TCD monitoring. Twenty minutes later he suffered cardiac arrest with asystolia trace in the ECG monitor. Fibrinolysis was stopped during resuscitation. Four minutes later, he recovered with the same NIHSS score. Aggressive resuscitation maneuvers were not necessary. A repeated brain CT scan showed infarct signs in the whole MCA territory and a new TCD did not show any change. Serial blood analyses including cardiac nzymes were normal. The patient experienced four brief cardiac arrests in the next nine hours, so a temporary cardiac pacemaker was placed for four days. He was treated with aspirin and was discharged 14 days after admission. He has not experienced recurrences during a 6-month follow-up. We could not diagnose the etiology of the cardiac arrests. All the episodes occurred in the acute stroke stage and arrhythmia, atrioventricular block, myocardial ischemia or structural lesions were not found in the cardiac study. We propose that ischemia in the right insula induced sudden and transitory interruptions of the sympathetic cardiac tone. PMID:12677486

  5. Acute effect of aspartame-induced oxidative stress in Wistar albino rat brain.

    PubMed

    Ashok, Iyaswamy; Sheeladevi, Rathinasamy; Wankhar, Dapkupar

    2015-09-01

    The present study was carried out to investigate the acute effect of aspartame on oxidative stress in the Wistar albino rat brain. We sought to investigate whether acute administration of aspartame (75 mg/kg) could release methanol and induce oxidative stress in the rat brain 24 hours after administration. To mimic human methanol metabolism, methotrexate treated rats were used to study aspartame effects. Wistar strain male albino rats were administered with aspartame orally as a single dose and studied along with controls and methotrexate treated controls. Blood methanol and formate level were estimated after 24 hours and rats were sacrificed and free radical changes were observed in discrete regions by assessing the scavenging enzymes, reduce dglutathione (GSH), lipid peroxidation and protein thiol levels. There was a significant increase in lipid peroxidation levels, superoxide dismutase activity (SOD), glutathione peroxidase levels (GPx), and catalase activity (CAT) with a significant decrease in GSH and protein thiol. Aspartame exposure resulted in detectable methanol even after 24 hours. Methanol and its metabolites may be responsible for the generation of oxidative stress in brain regions. The observed alteration in aspartame fed animals may be due to its metabolite methanol and elevated formate. The elevated free radicals due to methanol induced oxidative stress. PMID:26445572

  6. Acute lithium administration selectively lowers tyrosine levels in serum and brain

    PubMed Central

    McFarlane, Hewlet G.; Steele, John; Vinion, Keenan; Bongiovanni, Rodolfo; Double, Manda; Jaskiw, George E.

    2016-01-01

    Lithium exerts anti-dopaminergic behavioral effects. We examined whether some of these might be mediated by changes in brain levels of tyrosine (TYR), the precursor to dopamine. Lithium chloride (LiCl2) 3.0 mEq/kg IP acutely lowered serum TYR and the ratio of serum TYR to other large neutral amino acids (LNAAs); it also selectively lowered striatum TYR levels as measured in tissue or in vivo. While LiCl2 3.0 mEq/kg IP also augmented haloperidol (0.19 mg/kg SC)-induced catalepsy, this lithium effect was not attenuated by administration of TYR 100 mg/kg IP. We conclude that lithium acutely and selectively lowers brain TYR by lowering serum levels of tyrosine relative to the LNAAs that compete with it for transport across the blood–brain barrier. However, the lowering of TYR does not appear to significantly contribute to the ability of lithium to potentiate haloperidol-mediated catalepsy. PMID:21962398

  7. Acute decrease in alkaline phosphatase after brain injury: A potential mechanism for tauopathy.

    PubMed

    Arun, Peethambaran; Oguntayo, Samuel; Albert, Stephen Van; Gist, Irene; Wang, Ying; Nambiar, Madhusoodana P; Long, Joseph B

    2015-11-16

    Dephosphorylation of phosphorylated Tau (pTau) protein, which is essential for the preservation of neuronal microtubule assemblies and for protection against trauma-induced tauopathy and chronic traumatic encephalopathy (CTE), is primarily achieved in brain by tissue non-specific alkaline phosphatase (TNAP). Paired helical filaments (PHFs) and Tau isolated from Alzheimer's disease (AD) patients' brains have been shown to form microtubule assemblies with tubulin only after treatment with TNAP or protein phosphatase-2A, 2B and -1, suggesting that Tau protein in the PHFs of neurons in AD brain is hyperphosphorylated, which prevents microtubule assembly. Using blast or weight drop models of traumatic brain injury (TBI) in rats, we observed pTau accumulation in the brain as early as 6h post-injury and further accumulation which varied regionally by 24h post-injury. The pTau accumulation was accompanied by reduced TNAP expression and activity in these brain regions and a significantly decreased plasma total alkaline phosphatase activity after the weight drop. These results reveal that both blast- and impact acceleration-induced head injuries cause an acute decrease in the level/activity of TNAP in the brain, which potentially contributes to trauma-induced accumulation of pTau and the resultant tauopathy. The regional changes in the level/activity of TNAP or accumulation of pTau after these injuries did not correlate with the accumulation of amyloid precursor protein, suggesting that the basic mechanism underlying tauopathy in TBI might be distinct from that associated with AD. PMID:26483321

  8. Regulation of brain water during acute glucose-induced hyperosmolality in ovine fetuses, lambs, and adults.

    PubMed

    Stonestreet, Barbara S; Petersson, Katherine H; Sadowska, Grazyna B; Patlak, Clifford S

    2004-02-01

    We tested the hypothesis that, during acute glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and that brain volume regulation is present in fetuses, premature and newborn lambs. Brain water responses to glucose-induced hyperosmolality were measured in the cerebral cortex, cerebellum, and medulla of fetuses at 60% of gestation, premature ventilated lambs at 90% of gestation, newborn lambs, and adult sheep. After exposure of the sheep to increases in osmolality with glucose plus NaCl, brain water and electrolytes were measured. The ideal osmometer is a system in which impermeable solutes do not enter or leave in response to an osmotic stress. In the absence of volume regulation, brain solute remains constant as osmolality changes. The osmotically active solute demonstrated direct linear correlations with plasma osmolality in the cerebral cortex of the fetuses at 60% of gestation (r = 0.72, n = 24, P = 0.0001), premature lambs (r = 0.58, n = 22, P = 0.005), newborn lambs (r = 0.57, n = 24, P = 0.004), and adult sheep (r = 0.70, n = 18, P = 0.001). Similar findings were observed in the cerebellum and medulla. Increases in the quantity of osmotically active solute over the range of plasma osmolalities indicate that volume regulation was present in the brain regions of the fetuses, premature lambs, newborn lambs, and adult sheep during glucose-induced hyperosmolality. We conclude that, during glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and exhibits volume regulation in fetuses at 60% of gestation, premature lambs, newborn lambs, and adult sheep. PMID:14578364

  9. Effect of acute and recurrent hypoglycemia on changes in brain glycogen concentration.

    PubMed

    Herzog, Raimund I; Chan, Owen; Yu, Sunkyung; Dziura, James; McNay, Ewan C; Sherwin, Robert S

    2008-04-01

    Our objective was to evaluate whether excessive brain glycogen deposition might follow episodes of acute hypoglycemia (AH) and thus play a role in the hypoglycemia-associated autonomic failure seen in diabetic patients receiving intensive insulin treatment. We determined brain glucose and glycogen recovery kinetics after AH and recurrent hypoglycemia (RH), an established animal model of counterregulatory failure. A single bout of insulin-induced AH or RH for 3 consecutive days was used to deplete brain glucose and glycogen stores in rats. After microwave fixation and glycogen extraction, regional recovery kinetics in the brain was determined using a biochemical assay. Both AH and RH treatments reduced glycogen levels in the cerebellum, cortex, and hypothalamus from control levels of 7.78 +/- 0.55, 5.4 +/- 0.38, and 4.45 +/- 0.37 micromol/g, respectively, to approximately 50% corresponding to a net glycogen utilization rate between 0.6 and 1.2 micromol/g.h. After hypoglycemia, glycogen levels returned to baseline within 6 h in both the AH and the RH group. However, recovery of brain glycogen tended to be faster in rats exposed to RH. This effect followed more rapid recovery of brain glucose levels in the RH group, despite similar blood glucose levels in both groups. There was no statistically significant increase above baseline glycogen levels in either group. In particular, brain glycogen was not increased 24 h after the last of recurrent episodes of hypoglycemia, when a significant counterregulatory defect could be documented during a hyperinsulinemic hypoglycemic clamp study. We conclude that glycogen supercompensation is not a major contributory factor to the pathogenesis of hypoglycemia-associated autonomic failure. PMID:18187548

  10. Nrf2-ARE Activator Carnosic Acid Decreases Mitochondrial Dysfunction, Oxidative Damage and Neuronal Cytoskeletal Degradation Following Traumatic Brain Injury in Mice

    PubMed Central

    Miller, Darren M.; Singh, Indrapal N.; Wang, Juan A.; Hall, Edward D.

    2014-01-01

    The importance of free radical-induced oxidative damage after traumatic brain injury (TBI) has been well documented. Despite multiple clinical trials with radical-scavenging antioxidants that are neuroprotective in TBI models, none is approved for acute TBI patients. As an alternative antioxidant target, Nrf2 is a transcription factor that activates expression of antioxidant and cytoprotective genes by binding to antioxidant response elements (ARE) within DNA. Previous research has shown that neuronal mitochondria are susceptible to oxidative damage post-TBI, and thus the current study investigates whether Nrf2-ARE activation protects mitochondrial function when activated post-TBI. It was hypothesized that administration of carnosic acid (CA) would reduce oxidative damage biomarkers in brain tissue and also preserve cortical mitochondrial respiratory function post-TBI. A mouse controlled cortical impact (CCI) model was employed with a 1.0mm cortical deformation injury. Administration of CA at 15 minutes post-TBI reduced cortical lipid peroxidation, protein nitration, and cytoskeletal breakdown markers in a dose-dependent manner at 48 hours post-injury. Moreover, CA preserved mitochondrial respiratory function compared to vehicle animals. This was accompanied by decreased oxidative damage to mitochondrial proteins, suggesting the mechanistic connection of the two effects. Lastly, delaying the initial administration of CA up to 8 hours post-TBI was still capable of reducing cytoskeletal breakdown, thereby demonstrating a clinically relevant therapeutic window for this approach. This study demonstrates that pharmacological Nrf2-ARE induction is capable of neuroprotective efficacy when administered after TBI. PMID:25432068

  11. Obatoclax Potentiates the Cytotoxic Effect of Cytarabine on Acute Myeloid Leukemia Cells by Enhancing DNA Damage

    PubMed Central

    Xie, Chengzhi; Edwards, Holly; Caldwell, J. Timothy; Wang, Guan; Taub, Jeffrey W.; Ge, Yubin

    2014-01-01

    Resistance to cytarabine and anthracycline-based chemotherapy is a major cause of treatment failure for acute myeloid leukemia (AML) patients. Overexpression of Bcl-2, Bcl-xL, and/or Mcl-1 has been associated with chemoresistance in AML cell lines and with poor clinical outcome of AML patients. Thus, inhibitors of anti-apoptotic Bcl-2 family proteins could be novel therapeutic agents. In this study, we investigated how clinically achievable concentrations of obatoclax, a pan-Bcl-2 inhibitor, potentiate the antileukemic activity of cytarabine in AML cells. MTT assays in AML cell lines and diagnostic blasts, as well as flow cytometry analyses in AML cell lines revealed synergistic antileukemic activity between cytarabine and obatoclax. Bax activation was detected in the combined, but not the individual, drug treatments. This was accompanied by significantly increased loss of mitochondrial membrane potential. Most importantly, in AML cells treated with the combination, enhanced early induction of DNA double-strand breaks (DSBs) preceded a decrease of Mcl-1 levels, nuclear translocation of Bcl-2, Bcl-xL, and Mcl-1, and apoptosis. These results indicate that obatoclax enhances cytarabine-induced apoptosis by enhancing DNA DSBs. This novel mechanism provides compelling evidence for the clinical use of BH3 mimetics in combination with DNA-damaging agents in AML and possibly a broader range of malignancies. PMID:25308513

  12. γ-Oryzanol protects against acute cadmium-induced oxidative damage in mice testes.

    PubMed

    Spiazzi, Cristiano C; Manfredini, Vanusa; Barcellos da Silva, Fabiana E; Flores, Erico M M; Izaguirry, Aryele P; Vargas, Laura M; Soares, Melina B; Santos, Francielli W

    2013-05-01

    Cadmium is a non-essential heavy metal that is present at low levels mainly in food and water and also in cigar smoke. The present study evaluated the testicular damage caused by acute cadmium exposure and verified the protective role of γ-oryzanol (ORY). Mice were administrated with a single dose of 2.5mg/kg of CdCl2, and then treated with ORY (50mM in canola oil, 5mL/kg). Testes were removed after 24h and tested for lipid peroxidation (TBARS), protein carbonylation, DNA breakage, ascorbic acid, cadmium and non-proteic thiols contents, and for the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and δ-aminolevulic acid dehydratase (δ-ALA-D). Cadmium presented a significant alteration in all parameters, except GPx and CAT activities. Therapy reduced in a slight degree cadmium concentration in testes (around 23%). ORY restored SOD and GST activities as well as TBARS production to the control levels. Furthermore, ORY partially recovered δ-ALA-D activity inhibited by cadmium. This study provides the first evidence on the therapeutic properties of ORY in protecting against cadmium-induced testicular toxicity. PMID:23395783

  13. Coming back to oneself: a case of anoxic brain damage from a phenomenological perspective.

    PubMed

    Fürst, Elisabeth L'orange

    2015-03-01

    Struck by a cardiac arrest that lasted 3/4 of an hour, a 53-year-old man suddenly collapsed one day at work. The result was a serious anoxic brain damage that developed into dementia. This essay presents the process of 'coming back to himself' while it questions what this concept might imply. The descriptions and analyses rest upon an ethnographic study of his life, at hospitals and then at home, assisted by his wife, who is also the author of this article. Theoretically, the analysis depends on Merleau-Ponty's phenomenology of perception and is also based on the therapeutic use of music in treating people with dementia championed by Oliver Sachs. It is argued that the field of medicine has much to learn from the anthropological method of long-term observation, as well as theories of embodiment that see the body as simultaneously being an object and a subject. PMID:25300711

  14. The semantic anatomical network: Evidence from healthy and brain-damaged patient populations.

    PubMed

    Fang, Yuxing; Han, Zaizhu; Zhong, Suyu; Gong, Gaolang; Song, Luping; Liu, Fangsong; Huang, Ruiwang; Du, Xiaoxia; Sun, Rong; Wang, Qiang; He, Yong; Bi, Yanchao

    2015-09-01

    Semantic processing is central to cognition and is supported by widely distributed gray matter (GM) regions and white matter (WM) tracts. The exact manner in which GM regions are anatomically connected to process semantics remains unknown. We mapped the semantic anatomical network (connectome) by conducting diffusion imaging tractography in 48 healthy participants across 90 GM "nodes," and correlating the integrity of each obtained WM edge and semantic performance across 80 brain-damaged patients. Fifty-three WM edges were obtained whose lower integrity associated with semantic deficits and together with their linked GM nodes constitute a semantic WM network. Graph analyses of this network revealed three structurally segregated modules that point to distinct semantic processing components and identified network hubs and connectors that are central in the communication across the subnetworks. Together, our results provide an anatomical framework of human semantic network, advancing the understanding of the structural substrates supporting semantic processing. PMID:26059098

  15. Biomarkers of Brain Damage and Postoperative Cognitive Disorders in Orthopedic Patients: An Update

    PubMed Central

    Tomaszewski, Dariusz

    2015-01-01

    The incidence of postoperative cognitive dysfunction (POCD) in orthopedic patients varies from 16% to 45%, although it can be as high as 72%. As a consequence, the hospitalization time of patients who developed POCD was longer, the outcome and quality of life were worsened, and prolonged medical and social assistance were necessary. In this review the short description of such biomarkers of brain damage as the S100B protein, NSE, GFAP, Tau protein, metalloproteinases, ubiquitin C terminal hydrolase, microtubule-associated protein, myelin basic protein, α-II spectrin breakdown products, and microRNA was made. The role of thromboembolic material in the development of cognitive decline was also discussed. Special attention was paid to optimization of surgical and anesthetic procedures in the prevention of postoperative cognitive decline. PMID:26417595

  16. Reappraisal generation after acquired brain damage: The role of laterality and cognitive control

    PubMed Central

    Salas, Christian E.; Gross, James J.; Turnbull, Oliver H.

    2014-01-01

    In the past decade, there has been growing interest in the neuroanatomical and neuropsychological bases of reappraisal. Findings suggest that reappraisal activates a set of areas in the left hemisphere (LH), which are commonly associated with language abilities and verbally mediated cognitive control. The main goal of this study was to investigate whether individuals with focal damage to the LH (n = 8) were more markedly impaired on a reappraisal generation task than individuals with right hemisphere lesions (RH, n = 8), and healthy controls (HC, n = 14). The reappraisal generation task consisted of a set of ten pictures from the IAPS, depicting negative events of different sorts. Participants were asked to quickly generate as many positive reinterpretations as possible for each picture. Two scores were derived from this task, namely difficulty and productivity. A second goal of this study was to explore which cognitive control processes were associated with performance on the reappraisal task. For this purpose, participants were assessed on several measures of cognitive control. Findings indicated that reappraisal difficulty – defined as the time taken to generate a first reappraisal – did not differ between LH and RH groups. However, differences were found between patients with brain injury (LH + RH) and HC, suggesting that brain damage in either hemisphere influences reappraisal difficulty. No differences in reappraisal productivity were found across groups, suggesting that neurological groups and HC are equally productive when time constraints are not considered. Finally, only two cognitive control processes inhibition and verbal fluency- were inversely associated with reappraisal difficulty. Implications for the neuroanatomical and neuropsychological bases of reappraisal generation are discussed, and implications for neuro-rehabilitation are considered. PMID:24711799

  17. Sleep in the Acute Phase of Severe Traumatic Brain Injury: A Snapshot of Polysomnography.

    PubMed

    Wiseman-Hakes, Catherine; Duclos, Catherine; Blais, Hélène; Dumont, Marie; Bernard, Francis; Desautels, Alex; Menon, David K; Gilbert, Danielle; Carrier, Julie; Gosselin, Nadia

    2016-09-01

    Background and Objectives The onset of pervasive sleep-wake disturbances associated with traumatic brain injury (TBI) is poorly understood. This study aimed to (a) determine the feasibility of using polysomnography in patients in the acute, hospitalized stage of severe TBI and (b) explore sleep quality and sleep architecture during this stage of recovery, compared to patients with other traumatic injuries. Methods A cross-sectional case-control design was used. We examined the sleep of 7 patients with severe TBI (17-47 years; 20.3 ± 15.0 days postinjury) and 6 patients with orthopedic and/or spinal cord injuries (OSCI; 19-58 years; 16.9 ± 4.9 days postinjury). One night of ambulatory polysomnography was performed at bedside. Results Compared to OSCI patients, TBI patients showed a significantly longer duration of nocturnal sleep and earlier nighttime sleep onset. Sleep efficiency was low and comparable in both groups. All sleep stages were observed in both groups with normal proportions according to age. Conclusion Patients in the acute stage of severe TBI exhibit increased sleep duration and earlier sleep onset, suggesting that the injured brain enhances sleep need and/or decreases the ability to maintain wakefulness. As poor sleep efficiency could compromise brain recovery, further studies should investigate whether strategies known to optimize sleep in healthy individuals are efficacious in acute TBI. While there are several inherent challenges, polysomnography is a useful means of examining sleep in the early stage of recovery in patients with severe TBI. PMID:26704256

  18. Corticosteroids in acute traumatic brain injury: systematic review of randomised controlled trials.

    PubMed Central

    Alderson, P.; Roberts, I.

    1997-01-01

    OBJECTIVE: To quantify the effectiveness and safety of corticosteroids in the treatment of acute traumatic brain injury. DESIGN: Systematic review of randomised controlled trials of corticosteroids in acute traumatic brain injury. Summary odds ratios were estimated as an inverse variance weighted average of the odds ratios for each study. SETTING: Randomised trials available by March 1996. SUBJECTS: The included trials with outcome data comprised 2073 randomised participants. RESULTS: The effect of corticosteroids on the risk of death was reported in 13 included trials. The pooled odds ratio for the 13 trials was 0.91 (95% confidence interval 0.74 to 1.12). Pooled absolute risk reduction was 1.8% (-2.5% to 5.7%). For the 10 trials that reported death or disability the pooled odds ratio was 0.90 (0.72 to 1.11). For infections of any type the pooled odds ratio was 0.92 (0.69 to 1.23) and for the seven trials reporting gastrointestinal bleeding it was 1.05 (0.44 to 2.52). With only those trials with the best quality of concealment of allocation, the pooled odds ratio estimates for death and death or disability became closer to unity. CONCLUSIONS: This systematic review of randomised controlled trials of corticosteroids in acute traumatic brain injury shows that there remains considerable uncertainty over their effects. Neither moderate benefits nor moderate harmful effects can be excluded. The widely practicable nature of the drugs and the importance of the health problem suggest that large simple trials are feasible and worth while to establish whether there are any benefits from use of corticosteroids in this setting. PMID:9224126

  19. Baifuzi reduces transient ischemic brain damage through an interaction with the STREX domain of BKCa channels

    PubMed Central

    Chi, S; Cai, W; Liu, P; Zhang, Z; Chen, X; Gao, L; Qi, J; Bi, L; Chen, L; Qi, Z

    2010-01-01

    Stroke is a long-term disability and one of the leading causes of death. However, no successful therapeutic intervention is available for the majority of stroke patients. In this study, we explored a traditional Chinese medicine Baifuzi (Typhonium giganteum Engl.). We show, at first, that the ethanol extract of Baifuzi exerts neuroprotective effects against brain damage induced by transient global or focal cerebral ischemia in rats and mice. Second, the extract activated large-conductance Ca2+-activated K+ channel (BKCa) channels, and BKCa channel blockade suppressed the neuroprotection of the extract, suggesting that the BKCa is the molecular target of Baifuzi. Third, Baifuzi cerebroside (Baifuzi-CB), purified from its ethanol extract, activated BKCa channels in a manner similar to that of the extract. Fourth, the stress axis hormone-regulated exon (STREX) domain of the BKCa channel directly interacted with Baifuzi-CB, and its deletion suppressed channel activation by Baifuzi-CB. These results indicate that Baifuzi-CB activated the BKCa channel through its direct interaction with the STREX domain of the channel and suggests that Baifuzi-CB merits exploration as a potential therapeutic agent for treating brain ischemia. PMID:21364615

  20. Correlation of behavior with brain damage after in utero exposure to toxic agents

    SciTech Connect

    Norton, S.; Kimler, B.F.

    1987-03-01

    Early postnatal behaviors involving sensorimotor integration were measured along with thickness of the sensorimotor cortex in rats irradiated with 1.0 Gy on gestational day 11 or 17. Body weight and morphology of anterior pituitary cells were recorded. Irradiation on day 17 was more effective in reducing cortical thickness and body weight and performance on behavioral tests and less effective in altering pituitary cells than irradiation on day 11. Prediction of behavioral effects, using cortical layers, body weight and pituitary morphology as predictors in stepwise multiple regression, was measured in both irradiated and control rats. Cortical Layer V more than I more than IV and VI as significant predictors of behavior. The best predictions accounted for about half of the variance in the data. When behavioral data were used to predict brain damage, the best predictor was negative geotaxis. Significant association of behavior with Layers V and VI was found. These experiments show the difficulties in correlating complex behaviors with specific brain areas and, at the same time, implicate especially Layer V of the sensorimotor cortex in these behaviors.

  1. The DNA damage response molecule MCPH1 in brain development and beyond.

    PubMed

    Liu, Xiaoqian; Zhou, Zhong-Wei; Wang, Zhao-Qi

    2016-07-01

    Microcephalin (MCPH1) is identified as being responsible for the neurodevelopmental disorder primary microcephaly type 1, which is characterized by a smaller-than-normal brain size and mental retardation. MCPH1 has originally been identified as an important regulator of telomere integrity and of cell cycle control. Genetic and cellular studies show that MCPH1 controls neurogenesis by coordinating the cell cycle and the centrosome cycle and thereby regulating the division mode of neuroprogenitors to prevent the exhaustion of the progenitor pool and thereby microcephaly. In addition to its role in neurogenesis, MCPH1 plays a role in gonad development. MCPH1 also functions as a tumor suppressor in several human cancers as well as in mouse models. Here, we review the role of MCPH1 in DNA damage response, cell cycle control, chromosome condensation and chromatin remodeling. We also summarize the studies on the biological functions of MCPH1 in brain size determination and in pathologies, including infertility and cancer. PMID:27197793

  2. Acute astrocyte activation in brain detected by MRI: new insights into T(1) hypointensity.

    PubMed

    Sibson, Nicola R; Lowe, John P; Blamire, Andrew M; Martin, Matthew J; Obrenovitch, Tiho P; Anthony, Daniel C

    2008-03-01

    Increases in the T(1) of brain tissue, which give rise to dark or hypointense areas on T(1)-weighted images using magnetic resonance imaging (MRI), are common to a number of neuropathologies including multiple sclerosis (MS) and ischaemia. However, the biologic significance of T(1) increases remains unclear. Using a multiparametric MRI approach and well-defined experimental models, we have experimentally induced increases in tissue T(1) to determine the underlying cellular basis of such changes. We have shown that a rapid acute increase in T(1) relaxation in the brain occurs in experimental models of both low-flow ischaemia induced by intrastriatal injection of endothelin-1 (ET-1), and excitotoxicity induced by intrastriatal injection of N-methyl-D-aspartate (NMDA). However, there appears to be no consistent correlation between increases in T(1) relaxation and changes in other MRI parameters (apparent diffusion coefficient, T(2) relaxation, or magnetisation transfer ratio of tissue water). Immunohistochemically, one common morphologic feature shared by the ET-1 and NMDA models is acute astrocyte activation, which was detectable within 2 h of intracerebral ET-1 injection. Pretreatment with an inhibitor of astrocyte activation, arundic acid, significantly reduced the spatial extent of the T(1) signal change induced by intrastriatal ET-1 injection. These findings suggest that an increase in T(1) relaxation may identify the acute development of reactive astrocytes within a central nervous system lesion. Early changes in T(1) may, therefore, provide insight into acute and reversible injury processes in neurologic patients, such as those observed before contrast enhancement in MS. PMID:17851455

  3. Brain white matter damage in aging and cognitive ability in youth and older age.

    PubMed

    Valdés Hernández, Maria Del C; Booth, Tom; Murray, Catherine; Gow, Alan J; Penke, Lars; Morris, Zoe; Maniega, Susana Muñoz; Royle, Natalie A; Aribisala, Benjamin S; Bastin, Mark E; Starr, John M; Deary, Ian J; Wardlaw, Joanna M

    2013-12-01

    Cerebral white matter hyperintensities (WMH) reflect accumulating white matter damage with aging and impair cognition. The role of childhood intelligence is rarely considered in associations between cognitive impairment and WMH. We studied community-dwelling older people all born in 1936, in whom IQ had been assessed at age 11 years. We assessed medical histories, current cognitive ability and quantified WMH on MR imaging. Among 634 participants, mean age 72.7 (SD 0.7), age 11 IQ was the strongest predictor of late life cognitive ability. After accounting for age 11 IQ, greater WMH load was significantly associated with lower late life general cognitive ability (β = -0.14, p < 0.01) and processing speed (β = -0.19, p < 0.001). WMH were also associated independently with lower age 11 IQ (β = -0.08, p < 0.05) and hypertension. In conclusion, having more WMH is significantly associated with lower cognitive ability, after accounting for prior ability, age 11IQ. Early-life IQ also influenced WMH in later life. Determining how lower IQ in youth leads to increasing brain damage with aging is important for future successful cognitive aging. PMID:23850341

  4. Brain damage in preterm newborns and maternal medication: The ELGAN Study

    PubMed Central

    Tyler, Crystal P; Paneth, Nigel; Allred, Elizabeth N; Hirtz, Deborah; Kuban, Karl; McElrath, Thomas; O’Shea, T Michael; Miller, Cindy; Leviton, Alan

    2012-01-01

    Objective To evaluate the association between maternal medication use during pregnancy and cerebral white matter damage and cerebral palsy (CP) among very preterm infants. Study Design This analysis of data from the ELGAN Study included 877 infants born <28 weeks gestation. Mothers were interviewed, charts reviewed, placentas were cultured and assessed histologically, and children evaluated at 24 months corrected age. A diagnostic algorithm classified neurologic findings as quadriparetic CP, diparetic CP, hemiparetic CP, or no CP. Results After adjustment for the potential confounding of disorders for which medications might have been indicated, the risk of quadraparetic CP remained elevated among the infants of mothers who consumed aspirin (OR=3.0, 95% CI 1.3,6.9) and non-steroidal anti-inflammatory medications (NSAIDs) (OR=2.4, 95% CI 1.04,5.8). The risk of diparetic CP was also associated with maternal consumption of an NSAID, but only if the consumption was not approved by a physician (OR=3.5, 95% CI 1.1,11.0) Conclusion The possibility that aspirin and NSAID use in pregnancy could lead to perinatal brain damage cannot be excluded. PMID:22939723

  5. Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions.

    PubMed

    Curtis, Daniel J; Sood, Aman; Phillips, Tom J; Leinster, Veronica H L; Nishiguchi, Akihiro; Coyle, Christopher; Lacharme-Lora, Lizeth; Beaumont, Oliver; Kemp, Helena; Goodall, Roberta; Cornes, Leila; Giugliano, Michele; Barone, Rocco A; Matsusaki, Michiya; Akashi, Mitsuru; Tanaka, Hiroyoshi Y; Kano, Mitsunobu; McGarvey, Jennifer; Halemani, Nagaraj D; Simon, Katja; Keehan, Robert; Ind, William; Masters, Tracey; Grant, Simon; Athwal, Sharan; Collett, Gavin; Tannetta, Dionne; Sargent, Ian L; Scull-Brown, Emma; Liu, Xun; Aquilina, Kristian; Cohen, Nicki; Lane, Jon D; Thoresen, Marianne; Hanley, Jon; Randall, Andrew; Case, C Patrick

    2014-11-01

    Some psychiatric diseases in children and young adults are thought to originate from adverse exposures during foetal life, including hypoxia and hypoxia/reoxygenation. The mechanism is not understood. Several authors have emphasised that the placenta is likely to play an important role as the key interface between mother and foetus. Here we have explored whether a first trimester human placenta or model barrier of primary human cytotrophoblasts might secrete factors, in response to hypoxia or hypoxia/reoxygenation, that could damage neurones. We find that the secretions in conditioned media caused an increase of [Ca(2+)]i and mitochondrial free radicals and a decrease of dendritic lengths, branching complexity, spine density and synaptic activity in dissociated neurones from embryonic rat cerebral cortex. There was altered staining of glutamate and GABA receptors. We identify glutamate as an active factor within the conditioned media and demonstrate a specific release of glutamate from the placenta/cytotrophoblast barriers invitro after hypoxia or hypoxia/reoxygenation. Injection of conditioned media into developing brains of P4 rats reduced the numerical density of parvalbumin-containing neurones in cortex, hippocampus and reticular nucleus, reduced immunostaining of glutamate receptors and altered cellular turnover. These results show that the placenta is able to release factors, in response to altered oxygen, that can damage developing neurones under experimental conditions. PMID:24818543

  6. Rewarding brain stimulation reverses the disruptive effect of amygdala damage on emotional learning.

    PubMed

    Kádár, Elisabet; Ramoneda, Marc; Aldavert-Vera, Laura; Huguet, Gemma; Morgado-Bernal, Ignacio; Segura-Torres, Pilar

    2014-11-01

    Intracranial self-stimulation (SS) in the lateral hypothalamus, a rewarding deep-brain stimulation, is able to improve acquisition and retention of implicit and explicit memory tasks in rats. SS treatment is also able to reverse cognitive deficits associated with aging or with experimental brain injuries and evaluated in a two-way active avoidance (2wAA) task. The main objective of the present study was to explore the potential of the SS treatment to reverse the complete learning and memory impairment caused by bilateral lesion in the lateral amygdala (LA). The effects of post-training SS, administered after each acquisition session, were evaluated on distributed 2wAA acquisition and 10-day retention in rats with electrolytic bilateral LA lesions. SS effect in acetylcholinestaresase (AchE) activity was evaluated by immunohistochemistry in LA-preserved and Central nuclei (Ce) of the amygdala of LA-damaged rats. Results showed that LA lesion over 40% completely impeded 2wAA acquisition and retention. Post-training SS in the LA-lesioned rats improved conditioning and retention compared with both the lesioned but non-SS treated and the non-lesioned control rats. SS treatment also seemed to induce a decrease in AchE activity in the LA-preserved area of the lesioned rats, but no effects were observed in the Ce. This empirical evidence supports the idea that self-administered rewarding stimulation is able to completely counteract the 2wAA acquisition and retention deficits induced by LA lesion. Cholinergic mechanisms in preserved LA and the contribution of other brain memory-related areas activated by SS could mediate the compensatory effect observed. PMID:25106737

  7. Establishment and identification of a hypoxia-ischemia brain damage model in neonatal rats

    PubMed Central

    YAO, DAN; ZHANG, WEIRAN; HE, XUE; WANG, JINHU; JIANG, KEWEN; ZHAO, ZHENGYAN

    2016-01-01

    The present study was designed to set up a reliable model of severe hypoxia-ischemia brain damage (HIBD) in neonatal rats and several methods were used to identify whether the model was successful. A total of 40 healthy 7-day-old Sprague-Dawley rats were randomly divided into 2 groups: The sham-surgery group (n=18) and the HIBD model group (n=22). The HIBD model was produced according to the traditional Rice method. The rats were anesthetized with ethyl ether. The left common carotid artery (CCA) was exposed, ligated and cut. Following this, the rats were exposed to hypoxia in a normobaric chamber filled with 8% oxygen and 92% nitrogen for 2 h. In the sham-surgery group, the left CCA was exposed but was not ligated, cut or exposed to hypoxia. The neurobehavioral changes of the rats were observed in the 24 h after HIBD. The brains were collected after 72 h to observe the pathological morphological changes of the brain tissue. The behavioral ability and neurobehavioral changes were studied in each group. The water maze test was used for evaluating the learning-memory ability when the rats were 28 days old. Compared with the sham-surgery group, all the HIBD model rats had a lag of motor development. The rats had evident changes in anatomy and Nissl staining, and cognitive impairment was shown through the result of the water maze. Therefore, the model of HIBD in neonatal rats is feasible and provides a reliable model for subsequent studies. PMID:27073628

  8. Laser-induced accurate frontal cortex damage: a new tool for brain study

    NASA Astrophysics Data System (ADS)

    Flores, Gonzalo; Khotiaintsev, Sergei N.; Sanchez-Huerta, Maria L.; Ibanes, Osvaldo; Hernandez, Adan; Silva, Adriana B.; Calderon, Rafael; Ayala, Griselda; Marroquin, Javier; Svirid, Vladimir; Khotiaintsev, Yuri V.

    1999-01-01

    New laser-based technique for anatomical-functional study of the medial prefrontal cortex (MPFC) of the brain of experimental animals (rats) is presented. The technique is based on making accurate well-controlled lesions to small MPFC and subsequent observing behavioral alterations in the lesioned animals relative to control ones. Laser produces smaller and more accurate lesions in comparison to those obtained by traditional methods, such as: mechanical action, chemical means, and electrical currents. For producing the brain lesions, a 10 W CO2 CW laser is employed for reasons of its sufficiently high power, which is combined with relatively low cost-per-Watt ratio. In our experience, such power rating is sufficient for making MPFC lesions. The laser radiation is applied in a form of pulse series via hollow circular metallic waveguide made of stainless steel. The waveguide is of inner diameter 1.3 mm and 95 mm long. The anesthetized animals are placed in stereotaxic instrument. Via perforations made in the skull bone, the MPFC is exposed to the laser radiation. Several weeks later (after animal recuperation), standard behavioral tests are performed. They reveal behavioral changes, which point to a damage of some small regions of the MPFC. These results correlate with the histological data, which reveal the existence of small and accurate MPFC lesions. The present technique has good prospects for use in anatomical- functional studies of brain by areas. In addition, this technique appears to have considerable promise as a treatment method for some pathologies, e.g. the Parkinson's disease.

  9. Accelerated recovery from acute brain injuries: clinical efficacy of neurotrophic treatment in stroke and traumatic brain injuries.

    PubMed

    Bornstein, N; Poon, W S

    2012-04-01

    Stroke is one of the most devastating vascular diseases in the world as it is responsible for almost five million deaths per year. Almost 90% of all strokes are ischemic and mainly due to atherosclerosis, cardiac embolism and small-vessel disease. Intracerebral or subarachnoid hemorrhage can lead to hemorrhagic stroke, which usually has the poorest prognosis. Cerebrolysin is a peptide preparation which mimics the action of a neurotrophic factor, protecting stroke-injured neurons and promoting neuroplasticity and neurogenesis. Cerebrolysin has been widely studied as a therapeutic tool for both ischemic and hemorrhagic stroke, as well as traumatic brain injury. In ischemic stroke, Cerebrolysin given as an adjuvant therapy to antiplatelet and rheologically active medication resulted in accelerated improvement in global, neurological and motor functions, cognitive performance and activities of daily living. Cerebrolysin was also safe and well tolerated when administered in patients suffering from hemorrhagic stroke. Traumatic brain injury leads to transient or chronic impairments in physical, cognitive, emotional and behavioral functions. This is associated with deficits in the recognition of basic emotions, the capacity to interpret the mental states of others, and executive functioning. Pilot clinical studies with adjuvant Cerebrolysin in the acute and postacute phases of the injury have shown faster recovery, which translates into an earlier onset of rehabilitation and shortened hospitalization time. PMID:22514794

  10. The association of the kynurenine pathway of tryptophan metabolism with acute brain dysfunction during critical illness*

    PubMed Central

    Adams Wilson, Jessica R.; Morandi, Alessandro; Girard, Timothy D.; Thompson, Jennifer L.; Boomershine, Chad S.; Shintani, Ayumi K.; Ely, E. Wesley; Pandharipande, Pratik P.

    2013-01-01

    Objectives Plasma tryptophan levels are associated with delirium in critically ill patients. Although tryptophan has been linked to the pathogenesis of other neurocognitive diseases through metabolism to neurotoxins via the kynurenine pathway, a role for kynurenine pathway activity in intensive care unit brain dysfunction (delirium and coma) remains unknown. This study examined the association between kynurenine pathway activity as determined by plasma kynurenine concentrations and kynurenine/tryptophan ratios and presence or absence of acute brain dysfunction (defined as delirium/coma-free days) in intensive care unit patients. Design, Setting, and Patients This was a prospective cohort study that utilized patient data and blood samples from the Maximizing Efficacy of Targeted Sedation and Reducing Neurologic Dysfunction trial, which compared sedation with dexmedetomidine vs. lorazepam in mechanically ventilated patients. Measurements and Main Results Baseline plasma kynurenine and tryptophan concentrations were measured using high-performance liquid chromatography with or without tandem mass spectrometry. Delirium was assessed daily using the Confusion Assessment Method for the Intensive Care Unit. Linear regression examined associations between kynurenine pathway activity and delirium/coma-free days after adjusting for sedative exposure, age, and severity of illness. Among 84 patients studied, median age was 60 yrs and Acute Physiology and Chronic Health Evaluation II score was 28.5. Elevated plasma kynurenine and kynurenine/tryptophan ratio were both independently associated with significantly fewer delirium/coma-free days (i.e., fewer days without acute brain dysfunction). Specifically, patients with plasma kynurenine or kynurenine/tryptophan ratios at the 75th percentile of our population had an average of 1.8 (95% confidence interval 0.6–3.1) and 2.1 (95% confidence interval 1.0–3.2) fewer delirium/coma-free days than those patients with values at the 25

  11. Nanowire-Based Electrode for Acute In Vivo Neural Recordings in the Brain

    PubMed Central

    Suyatin, Dmitry B.; Wallman, Lars; Thelin, Jonas; Prinz, Christelle N.; Jörntell, Henrik; Samuelson, Lars; Montelius, Lars; Schouenborg, Jens

    2013-01-01

    We present an electrode, based on structurally controlled nanowires, as a first step towards developing a useful nanostructured device for neurophysiological measurements in vivo. The sensing part of the electrode is made of a metal film deposited on top of an array of epitaxially grown gallium phosphide nanowires. We achieved the first functional testing of the nanowire-based electrode by performing acute in vivo recordings in the rat cerebral cortex and withstanding multiple brain implantations. Due to the controllable geometry of the nanowires, this type of electrode can be used as a model system for further analysis of the functional properties of nanostructured neuronal interfaces in vivo. PMID:23431387

  12. Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition.

    PubMed

    Ogasawara, Daisuke; Deng, Hui; Viader, Andreu; Baggelaar, Marc P; Breman, Arjen; den Dulk, Hans; van den Nieuwendijk, Adriann M C H; Soethoudt, Marjolein; van der Wel, Tom; Zhou, Juan; Overkleeft, Herman S; Sanchez-Alavez, Manuel; Mo, Simone; Nguyen, William; Conti, Bruno; Liu, Xiaojie; Chen, Yao; Liu, Qing-Song; Cravatt, Benjamin F; van der Stelt, Mario

    2016-01-01

    Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a structurally related control probe and their use, in combination with chemical proteomics and lipidomics, to determine the impact of acute DAGL blockade on brain lipid networks in mice. Within 2 h, DAGL inhibition produced a striking reorganization of bioactive lipids, including elevations in DAGs and reductions in endocannabinoids and eicosanoids. We also found that DAGLα is a short half-life protein, and the inactivation of DAGLs disrupts cannabinoid receptor-dependent synaptic plasticity and impairs neuroinflammatory responses, including lipopolysaccharide-induced anapyrexia. These findings illuminate the highly interconnected and dynamic nature of lipid signaling pathways in the brain and the central role that DAGL enzymes play in regulating this network. PMID:26668358

  13. Nanobodies as modulators of inflammation: potential applications for acute brain injury

    PubMed Central

    Rissiek, Björn; Koch-Nolte, Friedrich; Magnus, Tim

    2014-01-01

    Nanobodies are single domain antibodies derived from llama heavy-chain only antibodies (HCAbs). They represent a new generation of biologicals with unique properties: nanobodies show excellent tissue distribution, high temperature and pH stability, are easy to produce recombinantly and can readily be converted into different formats such as Fc-fusion proteins or hetero-dimers. Moreover, nanobodies have the unique ability to bind molecular clefts, such as the active site of enzymes, thereby interfering with the function of the target protein. Over the last decade, numerous nanobodies have been developed against proteins involved in inflammation with the aim to modulate their immune functions. Here, we give an overview about recently developed nanobodies that target immunological pathways linked to neuroinflammation. Furthermore, we highlight strategies to modify nanobodies so that they can overcome the blood brain barrier and serve as highly specific therapeutics for acute inflammatory brain injury. PMID:25374510

  14. Impact of acute and chronic stress hormone on male albino rat brain

    PubMed Central

    Han, Li-Li; Chen, Ling; Dong, Zhi-Ling

    2015-01-01

    The present investigation aimed to evaluate the acute and chronic effect of stress (stress hormone) in male albino rat brain. Nor-epinephrine was used for the treatment and saline used for the control. Nor-epinephrine was dissolved in the saline and administered orally to the rats. Following nor-epinephrine administration, the brain was removed surgically at 6 h, 12 h and 45 days. Alanine tansaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) were significantly altered in the rats. Lipid peroxidation was measured as malondialdehyde (MDA), showed altered lipid peroxidation. Hematological markers such as packed cell volume (PCV), white blood cells (WBC), neutrophil, lymphocytes and hemoglobin were significantly altered compared to controls. Altered serum biochemical and hematological markers, lipid peroxidation and enzyme activities leads to adverse effect in the cellular metabolism and physiological activities of rats. PMID:26261571

  15. A creative alternative for providing constant observation on an acute-brain-injury unit.

    PubMed

    Bailey, Marci; Amato, Shelly; Mouhlas, Christopher

    2009-01-01

    A performance improvement project to explore creative alternatives to improve the efficiency of constant observation was performed on an acute-brain-injury rehabilitation unit. The goals of the project were to increase opportunities for therapeutic cognitive stimulation among patients, increase nursing satisfaction regarding efficient use of resources to deliver rehabilitative care, decrease constant-observation salary costs, and maintain fall and restraint rates within 10% of baseline. Implementing the project involved developing a new job description (rehabilitation patient companion) and creating a day room where patients receiving constant observation could go between therapies to receive therapeutic cognitive stimulation. The program benefited patients, staff and the hospital. This project illustrates how a creative alternative to constant observation proves beneficial on many levels and improves the delivery of rehabilitative care to patients with traumatic brain injury. PMID:19160919

  16. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment

    PubMed Central

    Li, Xianchao; Hou, Wensheng; Wu, Xiaoying; Jiang, Wei; Chen, Haiyan; Xiao, Nong; Zhou, Ping

    2014-01-01

    Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hypoxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efficiencies are relatively low. Red or near-infrared light from 600–1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migration and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2, an increasing number of green fluorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 × 106 bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2 for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental findings indicate that 660 nm red light emitting diode irradiation promotes the migration of bone marrow mesenchymal stem cells, thereby enhancing the contribution of cell transplantation in the treatment of hypoxic-ischemic brain damage. PMID:25206807

  17. Hepatoprotective Effect of Otostegia persica Boiss. Shoot Extract on Carbon Tetrachloride-Induced Acute Liver Damage in Rats

    PubMed Central

    Nasiri Bezenjani, Sedighe; Pouraboli, Iran; Malekpour Afshar, Reza; Mohammadi, Gholamabbas

    2012-01-01

    In this study, the hepatoprotective effect of the methanol extract of aerial parts (shoot) from Otostegia persica Boiss (Golder) was investigated against the carbon tetrachloride (CCl4)-induced acute hepatotoxicity in male rats. Liver damage was induced through the oral administration of 50% CCl4 in liquid paraffin (2.5 mL/Kg bw, per os) 60 min after the administration of the methanol extract of O. persica shoot (in 200, 300, 400 mg/Kg bw doses) and assessed using biochemical parameters (plasma and liver tissue malondialdehyde (MDA), transaminase enzyme levels in plasma [aspartate transaminase (AST), alanine aminotransferase (ALT)] and liver glutathione (GSH) levels). Results show that the methanol extract of O. persica shoot is active at 300 mg/Kg (per os) and it possess remarkable antioxidant and hepatoprotective activities. Additionally, histopathological studies verified the effectiveness of this dose of extract in acute liver damage prevention. PMID:24250558

  18. Gene expression changes in female zebrafish (Danio rerio) brain in response to acute exposure to methylmercury

    USGS Publications Warehouse

    Richter, Catherine A.; Garcia-Reyero, Natàlia; Martyniuk, Chris; Knoebl, Iris; Pope, Marie; Wright-Osment, Maureen K.; Denslow, Nancy D.; Tillitt, Donald E.

    2011-01-01

    Methylmercury (MeHg) is a potent neurotoxicant and endocrine disruptor that accumulates in aquatic systems. Previous studies have shown suppression of hormone levels in both male and female fish, suggesting effects on gonadotropin regulation in the brain. The gene expression profile in adult female zebrafish whole brain induced by acute (96 h) MeHg exposure was investigated. Fish were exposed by injection to 0 or 0.5(mu or u)g MeHg/g. Gene expression changes in the brain were examined using a 22,000-feature zebrafish microarray. At a significance level of pbrain. Future studies will compare the gene expression profile induced in response to MeHg with that induced by other toxicants and will investigate responsive genes as potential biomarkers of MeHg exposure.

  19. GENE EXPRESSION CHANGES IN FEMALE ZEBRAFISH (DANIO RERIO) BRAIN IN RESPONSE TO ACUTE EXPOSURE TO METHYLMERCURY

    PubMed Central

    Richter, Catherine A.; Garcia-Reyero, Natàlia; Martyniuk, Chris; Knoebl, Iris; Pope, Marie; Wright-Osment, Maureen K.; Denslow, Nancy D.; Tillitt, Donald E.

    2010-01-01

    Methylmercury (MeHg) is a potent neurotoxicant and endocrine disruptor that accumulates in aquatic systems. Previous studies have shown suppression of hormone levels in both male and female fish, suggesting effects on gonadotropin regulation in the brain. The gene expression profile in adult female zebrafish whole brain induced by acute (96 hr) MeHg exposure was investigated. Fish were exposed by injection to 0 or 0.5 μg MeHg/g. Gene expression changes in the brain were examined using a 22,000 feature zebrafish microarray. At a significance level of p<0.01, 79 genes were up-regulated and 76 genes were down-regulated in response to MeHg exposure. Individual genes exhibiting altered expression in response to MeHg exposure implicate effects on glutathione metabolism in the mechanism of MeHg neurotoxicity. Gene ontology (GO) terms significantly enriched among altered genes included protein folding, cell redox homeostasis, and steroid biosynthetic process. The most affected biological functions were related to the nervous system development and function, as well as lipid metabolism and molecular transport. These results support the involvement of oxidative stress and effects on protein structure in the mechanism of action of MeHg in the female brain. Future studies will compare the gene expression profile induced in response to MeHg with that induced by other toxicants and investigate responsive genes as potential biomarkers of MeHg exposure. PMID:21082716

  20. Amplitude of Low-Frequency Fluctuations in Multiple-Frequency Bands in Acute Mild Traumatic Brain Injury

    PubMed Central

    Zhan, Jie; Gao, Lei; Zhou, Fuqing; Bai, Lijun; Kuang, Hongmei; He, Laichang; Zeng, Xianjun; Gong, Honghan

    2016-01-01

    Functional disconnectivity during the resting state has been observed in mild traumatic brain injury (mTBI) patients during the acute stage. However, it remains largely unknown whether the abnormalities are related to specific frequency bands of the low-frequency oscillations (LFO). Here, we used the amplitude of low-frequency fluctuations (ALFF) to examine the amplitudes of LFO in different frequency bands (slow-5: 0.01–0.027 Hz; slow-4: 0.027–0.073 Hz; and typical: 0.01–0.08 Hz) in patients with acute mTBI. A total of 24 acute mTBI patients and 24 age-, sex-, and education-matched healthy controls participated in this study. In the typical band, acute mTBI patients showed lower standardized ALFF in the right middle frontal gyrus and higher standardized ALFF in the right lingual/fusiform gyrus and left middle occipital gyrus. Further analyses showed that the difference between groups was concentrated in a narrower (slow-4) frequency band. In the slow-5 band, mTBI patients only exhibited higher standardized ALFF in the occipital areas. No significant correlation between the mini-mental state examination score and the standardized ALFF value was found in any brain region in the three frequency bands. Finally, no significant interaction between frequency bands and groups was found in any brain region. We concluded that the abnormality of spontaneous brain activity in acute mTBI patients existed in the frontal lobe as well as in distributed brain regions associated with integrative, sensory, and emotional roles, and the abnormal spontaneous neuronal activity in different brain regions could be better detected by the slow-4 band. These findings might contribute to a better understanding of local neural psychopathology of acute mTBI. Future studies should take the frequency bands into account when measuring intrinsic brain activity of mTBI patients. PMID:26869907

  1. Brain white matter changes during treatment of a child for acute lymphoblastic leukemia.

    PubMed

    Maeda, Miho; Hayakawa, Jun; Ueda, Takahiro; Migita, Makoto; Asano, Takeshi; Fukunaga, Yoshitaka; Amano, Yasuo

    2005-10-01

    A 13-year old boy with acute lymphoblastic leukemia had bilateral paresis of the upper extremities and aphasia 1 week after high dose methotrexate and triple intrathecal therapy (methotrexate, cytarabin, hydrocortisone). The stroke-like neurological symptoms disappeared on the third day. T2-weighted magnetic resonance imaging showed hyperintensities of white matter on the second day. Despite resolution of the neurological symptoms, magnetic resonance images were still abnormal 3 years after the attack. Methotrexate has been considered to be responsible for ischemic damage to oligodendroglial cells, resulting in demyelination. The changes are occasionally prolonged without persistent neurologic symptoms. PMID:16247223

  2. Induction of oxidative and nitrosative damage leads to cerebrovascular inflammation in an animal model of mild traumatic brain injury induced by primary blast.

    PubMed

    Abdul-Muneer, P M; Schuetz, Heather; Wang, Fang; Skotak, Maciej; Jones, Joselyn; Gorantla, Santhi; Zimmerman, Matthew C; Chandra, Namas; Haorah, James

    2013-07-01

    We investigate the hypothesis that oxidative damage of the cerebral vascular barrier interface (the blood-brain barrier, BBB) causes the development of mild traumatic brain injury (TBI) during a primary blast-wave spectrum. The underlying biochemical and cellular mechanisms of this vascular layer-structure injury are examined in a novel animal model of shock tube. We first established that low-frequency (123kPa) single or repeated shock wave causes BBB/brain injury through biochemical activation by an acute mechanical force that occurs 6-24h after the exposure. This biochemical damage of the cerebral vasculature is initiated by the induction of the free radical-generating enzymes NADPH oxidase 1 and inducible nitric oxide synthase. Induction of these enzymes by shock-wave exposure paralleled the signatures of oxidative and nitrosative damage (4-HNE/3-NT) and reduction of the BBB tight-junction (TJ) proteins occludin, claudin-5, and zonula occluden 1 in the brain microvessels. In parallel with TJ protein disruption, the perivascular unit was significantly diminished by single or repeated shock-wave exposure coinciding with the kinetic profile. Loosening of the vasculature and perivascular unit was mediated by oxidative stress-induced activation of matrix metalloproteinases and fluid channel aquaporin-4, promoting vascular fluid cavitation/edema, enhanced leakiness of the BBB, and progression of neuroinflammation. The BBB leakiness and neuroinflammation were functionally demonstrated in an in vivo model by enhanced permeativity of Evans blue and sodium fluorescein low-molecular-weight tracers and the infiltration of immune cells across the BBB. The detection of brain cell proteins neuron-specific enolase and S100β in the blood samples validated the neuroastroglial injury in shock-wave TBI. Our hypothesis that cerebral vascular injury occurs before the development of neurological disorders in mild TBI was further confirmed by the activation of caspase-3 and cell

  3. Induction of Oxidative and Nitrosative damage leads to Cerebrovascular Inflammation in Animal Model of Mild Traumatic Brain Injury Induced by Primary Blast

    PubMed Central

    Abdul-Muneer, P. M.; Schuetz, Heather; Wang, Fang; Skotak, Maciej; Jones, Joselyn; Gorantla, Santhi; Zimmerman, Matthew C.; Chandra, Namas; Haorah, James

    2014-01-01

    We investigate the hypothesis that oxidative damage of the cerebral vascular barrier interface (the blood brain barrier, BBB) causes the development of mild traumatic brain injury (mTBI) during primary blast wave spectrum. The underlying biochemical and cellular mechanisms of this vascular layer-structure injury are examined in a novel animal model of shock tube. We first established that low frequency (123 kPa) single or repeated shock wave causes BBB/brain injury through biochemical activation by acute mechanical force that occurs at 6–24 hrs after the exposure. This biochemical damage of the cerebral vasculature is initiated by the induction of free radical generating enzymes NADPH oxidase (NOX1) and inducible nitric oxide synthase (iNOS). Induction of these enzymes by shock wave exposure correlated well with the signatures of oxidative and nitrosative damage (4HNE/3NT) and reduction of the BBB tight junction (TJ) proteins occludin, claudin-5 and zonula occluden 1 (ZO-1) in the brain microvessel. In parallel with TJ protein disruption, the perivascular unit was significantly diminished by single or repeated shock wave exposure coinciding with the kinetic profile. Loosening of the vasculature and perivascular unit was mediated by oxidative stress-induced activation of matrix metalloproteinases and fluid channel aquaporin-4, promoting vascular fluid cavitation/edema, enhanced leakiness of the BBB and progression of neuroinflammation. The BBB leakiness and neuroinflammation were functionally demonstrated in an in vivo model by enhanced permeability of Na-Fl/EB low molecular weight tracers and the infiltration of immune cells across the BBB. The detection of brain cell matters NSE/S100β in the blood samples validated the neuro-astroglial injury in shock wave TBI. Our hypothesis that cerebral vascular injury occurring prior to the development of neurological disorders in mild TBI was further confirmed by the activation of caspase-3 and cell apoptosis mostly around

  4. Comparison of the Bender Gestalt Test for Both Black and White Brain-Damaged Patients Using Two Scoring Systems

    ERIC Educational Resources Information Center

    Butler, Oliver T.; And Others

    1976-01-01

    This study tested for cultural bias in the Bender Visual Motor Gestalt Test. Subjects were 72 black and white patients diagnosed as either brain damaged or psychiatric. Bender protocols were scored by Pascal-Suttell and Hain systems. No race effect appeared except for the Pascal-Suttell system for which blacks scored significantly better. (Author)

  5. Cluster Analysis of Children and Adolescents with Brain Damage and Learning Disabilities Using Neuropsychological, Psychoeducational, and Sociobehavioral Variables.

    ERIC Educational Resources Information Center

    Williams, Dorothy L.; And Others

    1992-01-01

    The Conners Rating Scale was used to identify psychoeducational, neuropsychological, and sociobehavioral variables in attempting to define subtypes within a population of 95 children (mean age 10.6 years) with learning disabilities (LD) or documented brain damage. Results supported the sociobehavioral component in LD subtyping and parallels…

  6. COMMUNICATION TRAINING IN CHILDHOOD BRAIN DAMAGE, A MONOGRAPH IN THE BANNERSTONE DIVISION OF AMERICAN LECTURES IN SPEECH AND HEARING.

    ERIC Educational Resources Information Center

    MECHAM, MERLIN J.; AND OTHERS

    INTENDED AS A TEXT SOURCE BOOK, OR PRACTICAL REFERENCE, THE BOOK DISCUSSES SPEECH AND HEARING PROBLEMS, PSYCHOLOGICAL AND LINGUISTIC IMPLICATIONS, AND SPECIAL EDUCATION FOR CEREBRAL PALSIED AND BRAIN DAMAGED CHILDREN. NUMBER AND COMPLEXITY OF SPEECH AND HEARING PROBLEMS ARE EMPHASIZED, I.E., NEUROMUSCULAR INVOLVEMENT, ARTICULATION, RHYTHM, VOICE…

  7. Poor Hand-Pointing to Sounds in Right Brain-Damaged Patients: Not Just a Problem of Spatial-Hearing

    ERIC Educational Resources Information Center

    Pavani, Francesco; Farne, Alessandro; Ladavas, Elisabetta

    2005-01-01

    We asked 22 right brain-damaged (RBD) patients and 11 elderly healthy controls to perform hand-pointing movements to free-field unseen sounds, while modulating two non-auditory variables: the initial position of the responding hand (left, centre or right) and the presence or absence of task-irrelevant ambient vision. RBD patients suffering from…

  8. The influence of acute or chronic nicotine treatment on ethanol-induced gastric mucosal damage in rats.

    PubMed

    Cho, C H; Chen, B W; Hui, W M; Lam, S K

    1990-01-01

    The influences of acute or chronic nicotine pretreatment on ethanol-induced changes on gastric secretion, mucosal blood flow (GMBF), and glandular mucosal damage were studied in anesthetized rats. Ethanol administration decreased gastric acid secretion and GMBF, which were accompanied by a marked increase in gastric mucosal damage. Acute nicotine incubation 2 or 4 mg dose-dependently elevated both the titratable acid in the luminal solution and the gastric secretory volume; it also prevented the depressive action on GMBF and gastric mucosal damage in ethanol-treated animals. Chronic nicotine treatment for 10 days reduced the inhibitory action of ethanol on gastric acid secretion; the higher dose (25 micrograms/ml drinking water) potentiated the decrease of GMBF and the ulcerogenic property of ethanol. However, chronic treatment with the lower dose (5 micrograms/ml drinking water) had the opposite effects; it also markedly increased the gastric secretory volume. It is concluded that acute nicotine pretreatment elevates, whereas chronic nicotine pretreatment differentially affects GMBF. These effects could account for their protective or preventive actions on ethanol ulceration. The increase in nonacid gastric secretory volume by nicotine could partially explain its antiulcer effect. Furthermore, the acid secretory state of the stomach appears unrelated to the ulcerogenic property of ethanol. PMID:2295286

  9. The effects of acute alcohol consumption and eccentric muscle damage on neuromuscular function.

    PubMed

    Barnes, Matthew J; Mündel, Toby; Stannard, Stephen R

    2012-02-01

    Voluntary and electrically stimulated muscular performance was examined to identify the effects of acute alcohol consumption on neuromuscular function in the presence and absence of exercise-induced muscle damage (EIMD). After initial neuromuscular performance measures were made, 12 subjects completed a bout of eccentric exercise (EX) using the quadriceps muscles of 1 leg while the remaining 11 subjects did not exercise (NX). Subjects then consumed either an alcoholic beverage containing 1 g·kg(-1) body weight (ALC) or a nonalcoholic beverage (OJ). On another occasion the contralateral leg of both groups was tested and those in the EX group performed an equivalent bout of eccentric exercise after which the other beverage was consumed. Measurements of neuromuscular function were made pre-exercise and 36 and 60 h post-beverage consumption. Creatine kinase (CK) was measured pre-exercise and at 12, 36, and 60 h. Significantly greater (p < 0.01) decrements in maximal voluntary isometric contraction were observed with EX ALC at 36 and 60 h compared with EX OJ, and no change was seen in the NX group. Significant decreases in voluntary activation were observed at 36 h (p = 0.003) and 60 h (p = 0.01) with EX ALC only. Elevations in CK were observed at all posteccentric exercise time points (all p < 0.05) under both EX OJ and ALC. No change in electromyography or low-frequency fatigue was observed under either treatment in either group. These results suggest that decreased neural drive appears to contribute to alcohol's effect on the magnitude of EIMD-related decrements in voluntary force generation. PMID:22185621

  10. EphB1 Suppression in Acute Myelogenous Leukemia: Regulating the DNA Damage Control System

    PubMed Central

    Kampen, K.R.; Scherpen, F.J.G.; Garcia-Manero, G.; Yang, H.; Kaspers, G.J.L.; Cloos, J.; Zwaan, C.M.; van den Heuvel-Eibrink, M.M.; Kornblau, S.M.; De Bont, E.S.J.M.

    2016-01-01

    Loss of ephrin receptor (EphB1) expression may associate with aggressive cancer phenotypes; however, the mechanism of action remains unclear. To gain detailed insight into EphB1 function in acute myelogenous leukemia (AML), comprehensive analysis of EphB1 transcriptional regulation was conducted. In AML cells, EphB1 transcript was inversely correlated with EphB1 promoter methylation. The presence of EphB1 allowed EfnB1 ligand–mediated p53 DNA binding, leading to restoration of the DNA damage response (DDR) cascade by the activation of ATR, Chk1, p53, p21, p38, CDK1tyr15, and Bax, and downregulation of HSP27 and Bcl2. Comparatively, reintroduction of EphB1 expression in EphB1-methylated AML cells enhanced the same cascade of ATR, Chk1, p21, and CDK1tyr15, which consequently enforced programmed cell death. Interestingly, in pediatric AML samples, EphB1 peptide phosphorylation and mRNA expression were actively suppressed as compared with normal bone marrow, and a significant percentage of the primary AML specimens had EphB1 promoter hyper-methylation. Finally, EphB1 repression associated with a poor overall survival in pediatric AML. Combined, the contribution of EphB1 to the DDR system reveals a tumor-suppressor function for EphB1 in pediatric AML. Implications The tumor-suppressor function of EphB1 is clinically relevant across many malignancies, suggesting that EphB1 is an important regulator of common cancer cell trans forming pathways. PMID:25944917

  11. Effect of diallyl disulfide on acute gastric mucosal damage induced by alcohol in rats.

    PubMed

    Lee, I-C; Baek, H-S; Kim, S-H; Moon, C; Park, S-H; Kim, S-H; Shin, I-S; Park, S-C; Kim, J-C

    2015-03-01

    This study investigated the gastroprotective effects of diallyl disulfide (DADS), a secondary organosulfur compound derived from garlic (Allium sativum L.) on experimental model of ethanol (EtOH)-induced gastric ulcer in rats. The antiulcerogenic activity of DADS was evaluated by gross/histopathological inspection, pro-inflammatory cytokines, and lipid peroxidation with antioxidant enzyme activities in the stomach. DADS (100 mg/kg) was administered by oral gavage 2 h prior to EtOH treatment (5 ml/kg). The animals were killed 1 h after receiving EtOH treatment. Pretreatment with DADS attenuated EtOH-induced gastric mucosal injury, as evidenced by decreased severity of hemorrhagic lesions and gastric ulcer index upon visual inspection. DADS also prevented histopathological alterations and gastric apoptotic changes caused by EtOH. An increase in tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase was observed in the gastric tissues of EtOH-treated rats that coincided with increased serum TNF-α and interleukin 6 levels. In contrast, DADS effectively suppressed production of pro-inflammatory mediators induced by EtOH. Furthermore, DADS prevented the formation of gastric malondialdehyde and the depletion of reduced glutathione content and restored antioxidant enzyme activities, such as catalase, glutathione peroxidase, and glutathione reductase in the gastric tissues of EtOH-treated rats. These results indicate that DADS prevents gastric mucosal damage induced by acute EtOH administration in rats and that the protective effects of DADS may be due to its potent antioxidant and anti-inflammatory activities. PMID:24972622

  12. The Effect of Paracetamol on Core Body Temperature in Acute Traumatic Brain Injury: A Randomised, Controlled Clinical Trial

    PubMed Central

    Saxena, Manoj K.; Taylor, Colman; Billot, Laurent; Bompoint, Severine; Gowardman, John; Roberts, Jason A.; Lipman, Jeffery; Myburgh, John

    2015-01-01

    Background Strategies to prevent pyrexia in patients with acute neurological injury may reduce secondary neuronal damage. The aim of this study was to determine the safety and efficacy of the routine administration of 6 grams/day of intravenous paracetamol in reducing body temperature following severe traumatic brain injury, compared to placebo. Methods A multicentre, randomised, blind, placebo-controlled clinical trial in adult patients with traumatic brain injury (TBI). Patients were randomised to receive an intravenous infusion of either 1g of paracetamol or 0.9% sodium chloride (saline) every 4 hours for 72 hours. The primary outcome was the mean difference in core temperature during the study intervention period. Results Forty-one patients were included in this study: 21 were allocated to paracetamol and 20 to saline. The median (interquartile range) number of doses of study drug was 18 (17–18) in the paracetamol group and 18 (16–18) in the saline group (P = 0.85). From randomisation until 4 hours after the last dose of study treatment, there were 2798 temperature measurements (median 73 [67–76] per patient). The mean ± standard deviation temperature was 37.4±0.5°C in the paracetamol group and 37.7±0.4°C in the saline group (absolute difference -0.3°C; 95% confidence interval -0.6 to 0.0; P = 0.09). There were no significant differences in the use of physical cooling, or episodes of hypotension or hepatic abnormalities, between the two groups. Conclusion The routine administration of 6g/day of intravenous paracetamol did not significantly reduce core body temperature in patients with TBI. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000444280 PMID:26678710

  13. Association of acute adverse effects with high local SAR induced in the brain from prolonged RF head and neck hyperthermia

    NASA Astrophysics Data System (ADS)

    Adibzadeh, F.; Verhaart, R. F.; Verduijn, G. M.; Fortunati, V.; Rijnen, Z.; Franckena, M.; van Rhoon, G. C.; Paulides, M. M.

    2015-02-01

    To provide an adequate level of protection for humans from exposure to radio-frequency (RF) electromagnetic fields (EMF) and to assure that any adverse health effects are avoided. The basic restrictions in terms of the specific energy absorption rate (SAR) were prescribed by IEEE and ICNIRP. An example of a therapeutic application of non-ionizing EMF is hyperthermia (HT), in which intense RF energy is focused at a target region. Deep HT in the head and neck (H&N) region involves inducing energy at 434 MHz for 60 min on target. Still, stray exposure of the brain is considerable, but to date only very limited side-effects were observed. The objective of this study is to investigate the stringency of the current basic restrictions by relating the induced EM dose in the brain of patients treated with deep head and neck (H&N) HT to the scored acute health effects. We performed a simulation study to calculate the induced peak 10 g spatial-averaged SAR (psSAR10g) in the brains of 16 selected H&N patients who received the highest SAR exposure in the brain, i.e. who had the minimum brain-target distance and received high forwarded power during treatment. The results show that the maximum induced SAR in the brain of the patients can exceed the current basic restrictions (IEEE and ICNIRP) on psSAR10g for occupational environments by 14 times. Even considering the high local SAR in the brain, evaluation of acute effects by the common toxicity criteria (CTC) scores revealed no indication of a serious acute neurological effect. In addition, this study provides pioneering quantitative human data on the association between maximum brain SAR level and acute adverse effects when brains are exposed to prolonged RF EMF.

  14. Prognostic Value of Brain and Acute Leukemia Cytoplasmic Gene Expression in Egyptian Children with Acute Myeloid Leukemia

    PubMed Central

    Hagag, Adel A.; El-Lateef, Amal Ezzat Abd

    2015-01-01

    Background Acute myeloid leukemia (AML) accounts for 25%–35% of acute leukemia in children. BAALC gene (Brain and Acute Leukemia Cytoplasmic gene) is a recently identified gene on chromosome 8q22.3 that has prognostic significance in AML. The aim of this work was to study the impact of BAALC gene expression on prognosis of AML in Egyptian children. Patients and methods This study was conducted on 40 Egyptian children with newly diagnosed AML who were subjected to full history taking, clinical examination and laboratory investigations including: complete blood count, LDH, bone marrow aspiration, cytochemistry, immunophenotyping and assessment of BAALC Gene by real time PCR in bone marrow aspirate mononuclear cells before the start of chemotherapy. Results Positive BAALC gene expression was found in 24 cases (60%) and negative expression in 16 cases (40%). Positive BAALC gene expression group includes 14 males and 10 females with mean age at presentation of 8.35±2.63 while negative BAALC gene expression includes 10 males and 6 females with mean age at presentation of 7.74±3.23 with no statistically significant differences between patients with positive and negative BAALC gene expression regarding age, sex and clinical presentations at time of diagnosis including pallor, purpura, splenomegaly, hepatomegaly and lymphadenopathy and laboratory investigations including WBCs and platelets counts, hemoglobin and LDH levels, and peripheral blood and bone marrow blast cell counts. There was significant association between positive BAALC gene expression and M1 and M2 compared with negative BAALC gene expression which is significantly associated with M4. There were statistically significant differences in disease outcome between positive and negative BAALC gene expression groups with higher rate of relapse and death and lower rate of complete remission and disease free survival in positive BAALC gene expression group compared with negative BAALC gene expression group. (p

  15. Detection of chronic brain damage by diffusion-weighted imaging with multiple b values in patients with type 2 diabetes.

    PubMed

    Liu, Tieli; Han, Yunpeng; Tang, Lemei; Wu, Jianlin; Miao, Yanwei; Gao, Bingbing; Shang, Jin

    2016-08-01

    The aim of the study was to evaluate the performance of parameters obtained from diffusion-weighted imaging (DWI) with multiple b values in the detection of chronic brain damage in patients with type 2 diabetes.We enrolled 30 patients with or without abnormalities on brain magnetic resonance imaging (lacunar infarction, leukoaraiosis, and/or brain atrophy) and 15 nondiabetic controls; obtained DWI parameters that included apparent diffusion coefficient (ADC), fast ADC (ADCfast), slow ADC (ADCslow), fraction of fast ADC (f), distributed diffusion coefficient (DDC), and stretched exponential (α); and performed receiver operating characteristic (ROC) analysis to evaluate the performance of parameters for the detection of chronic brain damage.The parameters ADC, ADCslow, f, and DDC were increased, whereas parameters ADCfast and α were decreased in type 2 diabetes patients compared with controls without diabetes. The centrum semiovale showed the most significant change in the evaluated parameters, and the changes in parameters ADCslow, f, and DDC were greater than the changes in other parameters. There was no significance between parameters of the biexponential model (ADCfast, ADCslow, f) and parameters of the stretched model (DDC, α), but parameters of both these models were superior to the parameter of monoexponential model (ADC). Moreover, ROC analysis showed that ADCslow of the centrum semiovale supplied by the anterior cerebral artery had the highest performance for detection of chronic brain damage (area under the ROC curve of 0.987, 93.3% sensitivity, and 100% specificity).Our study shows that DWI with multiple b values can quantitatively access chronic brain damage and may be used for detection and monitoring in type 2 diabetes patients. PMID:27583912

  16. Detection of chronic brain damage by diffusion-weighted imaging with multiple b values in patients with type 2 diabetes

    PubMed Central

    Liu, Tieli; Han, Yunpeng; Tang, Lemei; Wu, Jianlin; Miao, Yanwei; Gao, Bingbing; Shang, Jin

    2016-01-01

    Abstract The aim of the study was to evaluate the performance of parameters obtained from diffusion-weighted imaging (DWI) with multiple b values in the detection of chronic brain damage in patients with type 2 diabetes. We enrolled 30 patients with or without abnormalities on brain magnetic resonance imaging (lacunar infarction, leukoaraiosis, and/or brain atrophy) and 15 nondiabetic controls; obtained DWI parameters that included apparent diffusion coefficient (ADC), fast ADC (ADCfast), slow ADC (ADCslow), fraction of fast ADC (f), distributed diffusion coefficient (DDC), and stretched exponential (α); and performed receiver operating characteristic (ROC) analysis to evaluate the performance of parameters for the detection of chronic brain damage. The parameters ADC, ADCslow, f, and DDC were increased, whereas parameters ADCfast and α were decreased in type 2 diabetes patients compared with controls without diabetes. The centrum semiovale showed the most significant change in the evaluated parameters, and the changes in parameters ADCslow, f, and DDC were greater than the changes in other parameters. There was no significance between parameters of the biexponential model (ADCfast, ADCslow, f) and parameters of the stretched model (DDC, α), but parameters of both these models were superior to the parameter of monoexponential model (ADC). Moreover, ROC analysis showed that ADCslow of the centrum semiovale supplied by the anterior cerebral artery had the highest performance for detection of chronic brain damage (area under the ROC curve of 0.987, 93.3% sensitivity, and 100% specificity). Our study shows that DWI with multiple b values can quantitatively access chronic brain damage and may be used for detection and monitoring in type 2 diabetes patients. PMID:27583912

  17. Diversity of endurance training effects on antioxidant defenses and oxidative damage in different brain regions of adolescent male rats.

    PubMed

    Chalimoniuk, M; Jagsz, S; Sadowska-Krepa, E; Chrapusta, S J; Klapcinska, B; Langfort, J

    2015-08-01

    Studies on the effect of physical activity on brain oxidative stress, performed mostly in adult rats, have shown that moderate aerobic activity increases resistance to oxidative stress and reduces cellular damage. These effects can greatly differ between various brain regions. The postnatal period of the highest brain sensitivity to various stimuli is adolescence. We hypothesized that endurance training will modify brain antioxidant barrier differently in various regions, depending on their role in locomotion. Therefore, we studied the effect of moderate intensity endurance training on the activities of selected antioxidant enzymes (superoxide dismutase, gluthathione peroxidase and catalase and the contents of thiobarbituric acid-reactive substances (the key index of lipid peroxidation) and glutathione in several brain regions with dissimilar relationship to locomotion, as well as in circulating blood. Additionally, we investigated the effect of the training on nitric oxide synthase activity that may be a major player in exercise-related oxidative stress in brain regions that are directly involved in the locomotion control and execution (the striatum, midbrain and cerebellum). The training significantly enhanced nitric oxide synthase activity only in the latter three regions. Surprisingly, it elevated the activities of all studied antioxidant enzymes (excepting gluthathione peroxidase) in the neocortex, while no appreciable change in these activities was found in either the cerebellum (except for elevated catalase activity), or the striatum, or the midbrain. The training also elevated total glutathione content (a key protector of brain proteins under the conditions of enhanced nitric oxide production) in the cerebellum and striatum, but not in the other regions. The observed brain changes greatly differed from those in circulating blood and did not prevent the training-related increases in oxidative damage as evidenced by elevations in cerebellar and striatal

  18. Experimental carbon dioxide laser brain lesions and intracranial dynamics. Part 2. Effect on brain water content and its response to acute therapy

    SciTech Connect

    Tiznado, E.G.; James, H.E.; Moore, S.

    1985-04-01

    Experimental brain lesions were created over the left parietooccipital cortex of the albino rabbit through the intact dura mater with high radiating carbon dioxide laser energy. The brain water content was studied 2, 6, and 24 hours after the insult. Another two groups of animals received acute therapy with either dexamethasone (1 mg/kg) or furosemide (1 mg/kg). In all groups, Evans blue extravasation uniformly extended from the impact crater into the surrounding white matter. The brain water content in the gray matter was elevated from the control value by 2 hours after impact and remained elevated at 6 and 24 hours. The white matter brain water content did not increase until 6 hours after impact and remained elevated in the 24-hour group. After dexamethasone treatment, there was a significant decrease of water in the gray matter, but not in the white matter. With furosemide therapy, there was no reduction of gray or white matter brain water.

  19. Acute renal failure potentiates methylmalonate-induced oxidative stress in brain and kidney of rats.

    PubMed

    Schuck, P F; Alves, L; Pettenuzzo, L F; Felisberto, F; Rodrigues, L B; Freitas, B W; Petronilho, F; Dal-Pizzol, F; Streck, E L; Ferreira, G C

    2013-03-01

    Tissue methylmalonic acid (MMA) accumulation is the biochemical hallmark of methylmalonic acidemia. The disease is clinically characterized by progressive neurological deterioration and kidney failure, whose pathophysiology is still unclear. In the present work we investigated the effects of acute MMA administration on various parameters of oxidative stress in cerebral cortex and kidney of young rats, as well as the influence of acute renal failure on MMA-elicited effects on these parameters. Acute renal failure was induced by gentamicin, an aminoglycoside antibiotic whose utilization over prolonged periods causes nephrotoxicity. The administration of gentamicin alone increased carbonyl content and inhibited superoxide dismutase (SOD) activity in cerebral cortex, as well as increased thiobarbituric acid-reactive substances (TBA-RS) and sulfhydryl levels and diminished glutathione peroxidase activity in kidney. On the other hand, MMA administration increased TBA-RS levels in cerebral cortex and decreased SOD activity in kidney. Furthermore, the simultaneous administration of MMA and gentamicin to the rats provoked an augment in TBA-RS levels and superoxide generation in cerebral cortex and in TBA-RS, carbonyl and sulfhydryl levels in kidney, while diminished SOD activity in both studied tissues. Finally, nitrate/nitrite content, reduced glutathione levels, 2',7'-dihydrodichlorofluorescein oxidation and catalase activity were not affected by this animal treatment in either tissue. In conclusion, our present data are in line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on oxidative stress parameters in brain and peripheral tissues. PMID:23297832

  20. Elevated Endogenous Erythropoietin Concentrations Are Associated with Increased Risk of Brain Damage in Extremely Preterm Neonates

    PubMed Central

    Korzeniewski, Steven J.; Allred, Elizabeth; Logan, J. Wells; Fichorova, Raina N.; Engelke, Stephen; Kuban, Karl C. K.; O’Shea, T. Michael; Paneth, Nigel; Holm, Mari; Dammann, Olaf; Leviton, Alan

    2015-01-01

    Background We sought to determine, in very preterm infants, whether elevated perinatal erythropoietin (EPO) concentrations are associated with increased risks of indicators of brain damage, and whether this risk differs by the co-occurrence or absence of intermittent or sustained systemic inflammation (ISSI). Methods Protein concentrations were measured in blood collected from 786 infants born before the 28th week of gestation. EPO was measured on postnatal day 14, and 25 inflammation-related proteins were measured weekly during the first 2 postnatal weeks. We defined ISSI as a concentration in the top quartile of each of 25 inflammation-related proteins on two separate days a week apart. Hypererythropoietinemia (hyperEPO) was defined as the highest quartile for gestational age on postnatal day 14. Using logistic regression and multinomial logistic regression models, we compared risks of brain damage among neonates with hyperEPO only, ISSI only, and hyperEPO+ISSI, to those who had neither hyperEPO nor ISSI, adjusting for gestational age. Results Newborns with hyperEPO, regardless of ISSI, were more than twice as likely as those without to have very low (< 55) Mental (OR 2.3; 95% CI 1.5-3.5) and/or Psychomotor (OR 2.4; 95% CI 1.6-3.7) Development Indices (MDI, PDI), and microcephaly at age two years (OR 2.4; 95%CI 1.5-3.8). Newborns with both hyperEPO and ISSI had significantly increased risks of ventriculomegaly, hemiparetic cerebral palsy, microcephaly, and MDI and PDI < 55 (ORs ranged from 2.2-6.3), but not hypoechoic lesions or other forms of cerebral palsy, relative to newborns with neither hyperEPO nor ISSI. Conclusion hyperEPO, regardless of ISSI, is associated with elevated risks of very low MDI and PDI, and microcephaly, but not with any form of cerebral palsy. Children with both hyperEPO and ISSI are at higher risk than others of very low MDI and PDI, ventriculomegaly, hemiparetic cerebral palsy, and microcephaly. PMID:25793991

  1. Beneficial effects of TCP on soman intoxication in guinea pigs: seizures, brain damage and learning behaviour.

    PubMed

    de Groot, D M; Bierman, E P; Bruijnzeel, P L; Carpentier, P; Kulig, B M; Lallement, G; Melchers, B P; Philippens, I H; van Huygevoort, A H

    2001-12-01

    involvement of NMDA receptors in the maintenance of soman-induced seizures and the development of brain damage. They underline the current hypothesis that cholinergic mechanisms are responsible for eliciting seizure activity after soman and that, most likely, the subsequent recruitment of other excitatory neurotransmitters and loss of inhibitory control are responsible for the maintenance of seizures and the development of subsequent brain damage. PMID:11920922

  2. Pomegranate from Oman Alleviates the Brain Oxidative Damage in Transgenic Mouse Model of Alzheimer's disease

    PubMed Central

    Subash, Selvaraju; Essa, Musthafa Mohamed; Al-Asmi, Abdullah; Al-Adawi, Samir; Vaishnav, Ragini; Braidy, Nady; Manivasagam, Thamilarasan; Guillemin, Gilles J.

    2014-01-01

    Oxidative stress may play a key role in Alzheimer's disease (AD) neuropathology. Pomegranates (石榴 Shí Liú) contain very high levels of antioxidant polyphenolic substances, as compared to other fruits and vegetables. Polyphenols have been shown to be neuroprotective in different model systems. Here, the effects of the antioxidant-rich pomegranate fruit grown in Oman on brain oxidative stress status were tested in the AD transgenic mouse. The 4-month-old mice with double Swedish APP mutation (APPsw/Tg2576) were purchased from Taconic Farm, NY, USA. Four-month-old Tg2576 mice were fed with 4% pomegranate or control diet for 15 months and then assessed for the influence of diet on oxidative stress. Significant increase in oxidative stress was found in terms of enhanced levels of lipid peroxidation (LPO) and protein carbonyls. Concomitantly, decrease in the activities of antioxidant enzymes was observed in Tg2576 mice treated with control diet. Supplementation with 4% pomegranate attenuated oxidative damage, as evidenced by decreased LPO and protein carbonyl levels and restoration in the activities of the antioxidant enzymes [superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione (GSH), and Glutathione S transferase (GST)]. The activities of membrane-bound enzymes [Na+ K+-ATPase and acetylcholinesterase (AChE)] were altered in the brain regions of Tg2576 mouse treated with control diet, and 4% pomegranate supplementation was able to restore the activities of enzymes to comparable values observed in controls. The results suggest that the therapeutic potential of 4% pomegranate in the treatment of AD might be associated with counteracting the oxidative stress by the presence of active phytochemicals in it. PMID:25379464

  3. Implicit and Explicit Routes to Recognize the Own Body: Evidence from Brain Damaged Patients

    PubMed Central

    Candini, Michela; Farinelli, Marina; Ferri, Francesca; Avanzi, Stefano; Cevolani, Daniela; Gallese, Vittorio; Northoff, Georg; Frassinetti, Francesca

    2016-01-01

    Much research suggested that recognizing our own body-parts and attributing a body-part to our physical self-likely involve distinct processes. Accordingly, facilitation for self-body-parts was found when an implicit, but not an explicit, self-recognition was required. Here, we assess whether implicit and explicit bodily self-recognition is mediated by different cerebral networks and can be selectively impaired after brain lesion. To this aim, right- (RBD) and left- (LBD) brain damaged patients and age-matched controls were presented with rotated pictures of either self- or other-people hands. In the Implicit task participants were submitted to hand laterality judgments. In the Explicit task they had to judge whether the hand belonged, or not, to them. In the Implicit task, controls and LBD patients, but not RBD patients, showed an advantage for self-body stimuli. In the Explicit task a disadvantage emerged for self-compared to others' body stimuli in controls as well as in patients. Moreover, when we directly compared the performance of patients and controls, we found RBD, but not LBD, patients to be impaired in both the implicit and explicit recognition of self-body-part stimuli. Conversely, no differences were found for others' body-part stimuli. Crucially, 40% RBD patients showed a selective deficit for implicit processing of self-body-part stimuli, whereas 27% of them showed a selective deficit in the explicit recognition of their own body. Additionally, we provide anatomical evidence revealing the neural basis of this dissociation. Based on both behavioral and anatomical data, we suggest that different areas of the right hemisphere underpin implicit and explicit self-body knowledge.

  4. Acute Minocycline Treatment Mitigates the Symptoms of Mild Blast-Induced Traumatic Brain Injury

    PubMed Central

    Kovesdi, Erzsebet; Kamnaksh, Alaa; Wingo, Daniel; Ahmed, Farid; Grunberg, Neil E.; Long, Joseph B.; Kasper, Christine E.; Agoston, Denes V.

    2012-01-01

    Mild traumatic brain injury (mTBI) represents a significant challenge for the civilian and military health care systems due to its high prevalence and overall complexity. Our earlier works showed evidence of neuroinflammation, a late onset of neurobehavioral changes, and lasting memory impairment in a rat model of mild blast-induced TBI (mbTBI). The aim of our present study was to determine whether acute treatment with the non-steroidal anti-inflammatory drug minocycline (Minocin®) can mitigate the neurobehavioral abnormalities associated with mbTBI, Furthermore, we aimed to assess the effects of the treatment on select inflammatory, vascular, neuronal, and glial markers in sera and in brain regions associated with anxiety and memory (amygdala, prefrontal cortex, ventral, and dorsal hippocampus) following the termination (51 days post-injury) of the experiment. Four hours after a single exposure to mild blast overpressure or sham conditions, we treated animals with a daily dose of minocycline (50 mg/kg) or physiological saline (vehicle) for four consecutive days. At 8 and 45 days post-injury, we tested animals for locomotion, anxiety, and spatial memory. Injured animals exhibited significantly impaired memory and increased anxiety especially at the later testing time point. Conversely, injured and minocycline treated rats’ performance was practically identical to control (sham) animals in the open field, elevated plus maze, and Barnes maze. Protein analyses of sera and brain regions showed significantly elevated levels of all of the measured biomarkers (except VEGF) in injured and untreated rats. Importantly, minocycline treatment normalized serum and tissue levels of the majority of the selected inflammatory, vascular, neuronal, and glial markers. In summary, acute minocycline treatment appears to prevent the development of neurobehavioral abnormalities likely through mitigating the molecular pathologies of the injury in an experimental model of mb

  5. Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury

    PubMed Central

    Tu, Yue; Miao, Xiao-mei; Yi, Tai-long; Chen, Xu-yi; Sun, Hong-tao; Cheng, Shi-xiang; Zhang, Sai

    2016-01-01

    Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and blood-brain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points (20 μL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury. PMID:27482221

  6. The perception of peripersonal space in right and left brain damage hemiplegic patients

    PubMed Central

    Bartolo, Angela; Carlier, Mauraine; Hassaini, Sabrina; Martin, Yves; Coello, Yann

    2014-01-01

    Peripersonal space, as opposed to extrapersonal space, is the space that contains reachable objects and in which multisensory and sensorimotor integration is enhanced. Thus, the perception of peripersonal space requires combining information on the spatial properties of the environment with information on the current capacity to act. In support of this, recent studies have provided converging evidences that perceiving objects in peripersonal space activates a neural network overlapping with that subtending voluntary motor action and motor imagery. Other studies have also underlined the dominant role of the right hemisphere (RH) in motor planning and of the left hemisphere (LH) in on-line motor guiding, respectively. In the present study, we investigated the effect of a right or left hemiplegia in the perception of peripersonal space. 16 hemiplegic patients with brain damage to the left (LH) or right (RH) hemisphere and eight matched healthy controls performed a color discrimination, a motor imagery and a reachability judgment task. Analyses of response times and accuracy revealed no variation among the three groups in the color discrimination task, suggesting the absence of any specific perceptual or decisional deficits in the patient groups. In contrast, the patient groups revealed longer response times in the motor imagery task when performed in reference to the hemiplegic arm (RH and LH) or to the healthy arm (RH). Moreover, RH group showed longer response times in the reachability judgment task, but only for stimuli located at the boundary of peripersonal space, which was furthermore significantly reduced in size. Considered together, these results confirm the crucial role of the motor system in motor imagery task and the perception of peripersonal space. They also revealed that RH damage has a more detrimental effect on reachability estimates, suggesting that motor planning processes contribute specifically to the perception of peripersonal space. PMID

  7. Investigation of cavitation as a possible damage mechanism in blast-induced traumatic brain injury.

    PubMed

    Goeller, Jacques; Wardlaw, Andrew; Treichler, Derrick; O'Bruba, Joseph; Weiss, Greg

    2012-07-01

    Cavitation was investigated as a possible damage mechanism for war-related traumatic brain injury (TBI) due to an improvised explosive device (IED) blast. When a frontal blast wave encounters the head, a shock wave is transmitted through the skull, cerebrospinal fluid (CSF), and tissue, causing negative pressure at the contrecoup that may result in cavitation. Numerical simulations and shock tube experiments were conducted to determine the possibility of cranial cavitation from realistic IED non-impact blast loading. Simplified surrogate models of the head consisted of a transparent polycarbonate ellipsoid. The first series of tests in the 18-inch-diameter shock tube were conducted on an ellipsoid filled with degassed water to simulate CSF and tissue. In the second series, Sylgard gel, surrounded by a layer of degassed water, was used to represent the tissue and CSF, respectively. Simulated blast overpressure in the shock tube tests ranged from a nominal 10-25 pounds per square inch gauge (psig; 69-170 kPa). Pressure in the simulated CSF was determined by Kulite thin line pressure sensors at the coup, center, and contrecoup positions. Using video taken at 10,000 frames/sec, we verified the presence of cavitation bubbles at the contrecoup in both ellipsoid models. In all tests, cavitation at the contrecoup was observed to coincide temporally with periods of negative pressure. Collapse of the cavitation bubbles caused by the surrounding pressure and elastic rebound of the skull resulted in significant pressure spikes in the simulated CSF. Numerical simulations using the DYSMAS hydrocode to predict onset of cavitation and pressure spikes during cavity collapse were in good agreement with the tests. The numerical simulations and experiments indicate that skull deformation is a significant factor causing cavitation. These results suggest that cavitation may be a damage mechanism contributing to TBI that requires future study. PMID:22489674

  8. Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage

    PubMed Central

    Roll, Lars; Faissner, Andreas

    2014-01-01

    The limited regeneration capacity of the adult central nervous system (CNS) requires strategies to improve recovery of patients. In this context, the interaction of endogenous as well as transplanted stem cells with their environment is crucial. An understanding of the molecular mechanisms could help to improve regeneration by targeted manipulation. In the course of reactive gliosis, astrocytes upregulate Glial fibrillary acidic protein (GFAP) and start, in many cases, to proliferate. Beside GFAP, subpopulations of these astroglial cells coexpress neural progenitor markers like Nestin. Although cells express these markers, the proportion of cells that eventually give rise to neurons is limited in many cases in vivo compared to the situation in vitro. In the first section, we present the characteristics of endogenous progenitor-like cells and discuss the differences in their neurogenic potential in vitro and in vivo. As the environment plays an important role for survival, proliferation, migration, and other processes, the second section of the review describes changes in the extracellular matrix (ECM), a complex network that contains numerous signaling molecules. It appears that signals in the damaged CNS lead to an activation and de-differentiation of astrocytes, but do not effectively promote neuronal differentiation of these cells. Factors that influence stem cells during development are upregulated in the damaged brain as part of an environment resembling a stem cell niche. We give a general description of the ECM composition, with focus on stem cell-associated factors like the glycoprotein Tenascin-C (TN-C). Stem cell transplantation is considered as potential treatment strategy. Interaction of transplanted stem cells with the host environment is critical for the outcome of stem cell-based therapies. Possible mechanisms involving the ECM by which transplanted stem cells might improve recovery are discussed in the last section. PMID:25191223

  9. Effects of brain IKKβ gene silencing by small interfering RNA on P-glycoprotein expression and brain damage in the rat kainic acid-induced seizure model.

    PubMed

    Yu, Nian; Liu, Hao; Zhang, Yan-Fang; Su, Ling-Ying; Liu, Xin-Hong; Li, Le-Chao; Hao, Jin-Bo; Huang, Xian-Jing; Di, Qing

    2014-01-01

    Multidrug resistance mediated by over-expression of P-glycoprotein (P-gp) in brain is an important mechanism accounting for the drug-therapy failure in epilepsy. Over-expression of P-gp in epilepsy rat brain may be regulated by inflammation and nuclear factor-kappa B (NF-κB) activation. Inhibitory κ B kinase subunit β (IKKβ) is an up-stream molecular controlling NF-κB activation. With the small interfering RNA (siRNA) technique and kainic acid (KA)-induced rat epileptic seizure model, the present study was aimed to further evaluate the role of NF-κB inhibition, via blocking IKKβ gene transcription, in the epileptic brain P-gp over-expression, seizure susceptibility, and post-seizure brain damage. siRNA targeting IKKβ was administered to rats via intracerebroventricular injection before seizure induction by KA microinjection; scrambled siRNA was used as control. Brain mRNA and protein levels of IKKβ and P-gp were detected by RT-PCR and immunohistochemistry. NF-κB activity was measured by electrophoretic mobility shift assay. Latency to grade III or V seizure onset was recorded, brain damage was evaluated by neuronal cell counting and epileptiform activity was monitored by electroencephalography. IKKβ siRNA pre-treatment inhibited NF-κB activation and abolished P-gp over-expression in KA-induced epileptic rat brain, accompanied by decreased seizure susceptibility. These findings suggested that epileptogenic-induced P-gp over-expression could be regulated by IKKβ through the NF-κB pathway. PMID:24040792

  10. Mouse models of human PIK3CA-related brain overgrowth have acutely treatable epilepsy

    PubMed Central

    Roy, Achira; Skibo, Jonathan; Kalume, Franck; Ni, Jing; Rankin, Sherri; Lu, Yiling; Dobyns, William B; Mills, Gordon B; Zhao, Jean J; Baker, Suzanne J; Millen, Kathleen J

    2015-01-01

    Mutations in the catalytic subunit of phosphoinositide 3-kinase (PIK3CA) and other PI3K-AKT pathway components have been associated with cancer and a wide spectrum of brain and body overgrowth. In the brain, the phenotypic spectrum of PIK3CA-related segmental overgrowth includes bilateral dysplastic megalencephaly, hemimegalencephaly and focal cortical dysplasia, the most common cause of intractable pediatric epilepsy. We generated mouse models expressing the most common activating Pik3ca mutations (H1047R and E545K) in developing neural progenitors. These accurately recapitulate all the key human pathological features including brain enlargement, cortical malformation, hydrocephalus and epilepsy, with phenotypic severity dependent on the mutant allele and its time of activation. Underlying mechanisms include increased proliferation, cell size and altered white matter. Notably, we demonstrate that acute 1 hr-suppression of PI3K signaling despite the ongoing presence of dysplasia has dramatic anti-epileptic benefit. Thus PI3K inhibitors offer a promising new avenue for effective anti-epileptic therapy for intractable pediatric epilepsy patients. DOI: http://dx.doi.org/10.7554/eLife.12703.001 PMID:26633882

  11. Ultrasonography in acute interstitial laser irradiation of the pig brain: preliminary results.

    PubMed

    Menovsky, T; Beek, J F; Phoa, S S; Brouwer, P A; Klein, M G; Verlaan, C W; van Acker, R E; van Gemert, M J

    1995-01-01

    In this preliminary study, the use of real-time ultrasonography to visualize the effects of acute interstitial Nd:YAG laser irradiation was investigated in the normal pig brain. In six pigs, a craniotomy was performed. In the frontal or temporal lobe, a thermal laser lesion was made using a 600-micron-diameter optical fiber at powers of 1 W, 2 W, and 4 W with exposure times of 5 min and 10 min. Ten to thirty minutes after laser irradiation, the pigs were sacrificed. Ultrasound imaging was performed before, during, and after laser irradiation. During laser irradiation, a clear hyperechogenic area was observed around the fiber tip. The onset of the changes and the extent of the lesion were dependent on the power and exposure time. Histologic examination showed thermal lesions consisting of coagulation necrosis and edema. The size of the lesions correlated well with size on ultrasound imaging. The maximal lesion dimension was 12 mm in diameter (4 W for 5 min). In conclusion, within the limitations of this experimental setup, it is feasible to visualize interstitial laser-induced lesions in the brain by ultrasonography. This method is safe and simple and may be helpful in future applications of interstitial thermotherapy in brain tissue. PMID:9079450

  12. Role of CCR5 and its ligands in the control of vascular inflammation and leukocyte recruitment required for acute excitotoxic seizure induction and neural damage

    PubMed Central

    Louboutin, Jean-Pierre; Chekmasova, Alena; Marusich, Elena; Agrawal, Lokesh; Strayer, David S.

    2011-01-01

    Chemokines may play a role in leukocyte migration across the blood-brain barrier (BBB) during neuroinflammation and other neuropathological processes, such as epilepsy. We investigated the role of the chemokine receptor CCR5 in seizures. We used a rat model based on intraperitoneal kainic acid (KA) administration. Four months before KA injection, adult rats were given femoral intramarrow inoculations of SV (RNAiR5-RevM10.AU1), which carries an interfering RNA (RNAi) against CCR5, plus a marker epitope (AU1), or its monofunctional RNAi-carrying homologue, SV(RNAiR5). This treatment lowered expression of CCR5 in circulating cells. In control rats, seizures induced elevated expression of CCR5 ligands MIP-1α and RANTES in the microvasculature, increased BBB leakage and CCR5+ cells, as well as neuronal loss, inflammation, and gliosis in the hippocampi. Animals given either the bifunctional or the monofunctional vector were largely protected from KA-induced seizures, neuroinflammation, BBB damage, and neuron loss. Brain CCR5 mRNA was reduced. Rats receiving RNAiR5-bearing vectors showed far greater repair responses: increased neuronal proliferation, and decreased production of MIP-1α and RANTES. Controls received unrelated SV(BUGT) vectors. Decrease in CCR5 in circulating cells strongly protected from excitotoxin-induced seizures, BBB leakage, CNS injury, and inflammation, and facilitated neurogenic repair.—Louboutin, J.-P., Chekmasova, A., Marusich, E., Agrawal, L., Strayer, D. S. Role of CCR5 and its ligands in the control of vascular inflammation and leukocyte recruitment required for acute excitotoxic seizure induction and neural damage. PMID:20940264

  13. Response Patterns in Brain Damaged Children and Teaching Styles. Final Report.

    ERIC Educational Resources Information Center

    Diller, Leonard; And Others

    A study involving 45 physically handicapped brain injured children (including Ss diagnosed with cerebral palsy, spina bifida, and other types of brain injury) and 10 physically handicapped non-brain injured children ranging in age from 2-8 years was conducted to determine if there is something distinctive about a brain injured child which suggests…

  14. Serum neurogranin measurement as a biomarker of acute traumatic brain injury

    PubMed Central

    Yang, Jun; Korley, Frederick K.; Dai, Min; Everett, Allen D.

    2015-01-01

    Objectives Neurogranin (NRGN) is a small neuronal protein that plays an important role in synaptic signaling by regulating calmodulin (CaM) availability. In this study, we developed an ELISA to measure NRGN quantitatively in serum samples from a cohort of acute traumatic brain injury (TBI) patients and a non-TBI control cohort, and explored the potential value of NRGN as a circulating biomarker for TBI. Design and methods Recombinant His-NRGN protein was used to develop mouse monoclonal capture and rabbit polyclonal detection antibodies, and they were used to develop a sandwich ELISA. After validation, we used this ELISA to measure serum samples from a cohort of typical adult acute TBI patients (N = 76 TBI cases) and non-TBI control patients (N = 150 controls). Results The NRGN ELISA lower limit of detection was 0.055 ng/mL, lower limit of quantification was 0.2 ng/mL, and interassay CVs were ≤ 10.7%. The average recovery was 99.9% (range from 97.2–102%). Serum NRGN concentrations in TBI cases were significantly higher than in controls (median values were 0.18 ng/mL vs. 0.02 ng/mL, p < 0.0001), but did not discriminate TBI cases with intracranial hemorrhage (p = 0.09). Conclusions We have developed a highly sensitive and reproducible ELISA for measuring circulating NRGN in blood samples. Serum NRGN concentrations in acute TBI patients were significantly higher than in controls, indicating that NRGN could have utility as a circulating biomarker for acute TBI. This report provides evidence to support larger and controlled TBI clinical studies for NRGN validation and prediction of outcomes. PMID:26025774

  15. The 2100MHz radiofrequency radiation of a 3G-mobile phone and the DNA oxidative damage in brain.

    PubMed

    Sahin, Duygu; Ozgur, Elcin; Guler, Goknur; Tomruk, Arın; Unlu, Ilhan; Sepici-Dinçel, Aylin; Seyhan, Nesrin

    2016-09-01

    We aimed to evaluate the effect of 2100MHz radiofrequency radiation emitted by a generator, simulating a 3G-mobile phone on the brain of rats during 10 and 40 days of exposure. The female rats were randomly divided into four groups. Group I; exposed to 3G modulated 2100MHz RFR signal for 6h/day, 5 consecutive days/wk for 2 weeks, group II; control 10 days, were kept in an inactive exposure set-up for 6h/day, 5 consecutive days/wk for 2 weeks, group III; exposed to 3G modulated 2100MHz RFR signal for 6h/day, 5 consecutive days/wk for 8 weeks and group IV; control 40 days, were kept in an inactive exposure set-up for 6h/day, 5 consecutive days/wk for 8 weeks. After the genomic DNA content of brain was extracted, oxidative DNA damage (8-hydroxy-2'deoxyguanosine, pg/mL) and malondialdehyde (MDA, nmoL/g tissue) levels were determined. Our main finding was the increased oxidative DNA damage to brain after 10 days of exposure with the decreased oxidative DNA damage following 40 days of exposure compared to their control groups. Besides decreased lipid peroxidation end product, MDA, was observed after 40 days of exposure. The measured decreased quantities of damage during the 40 days of exposure could be the means of adapted and increased DNA repair mechanisms. PMID:26775761

  16. A deficit perceiving slow motion after brain damage and a parallel deficit induced by crowding.

    PubMed

    Ma, Zheng; McCloskey, Michael; Flombaum, Jonathan I

    2015-10-01

    Motion perception is known to involve at least 2 kinds of mechanisms-lower level signal detectors and higher level algorithms for comparing object positions over time. When stimulus motion is modal (continuously visible), it is generally assumed that processing via lower level mechanisms is sufficient to make accurate motion judgments. We investigated the possibility that higher level mechanisms may also be involved in the processing of slow motion, even when it is smooth and continuous. This possibility was suggested by results from a brain-damaged patient, JKI, who showed left visual field deficits in both the explicit representation of object position and judgments concerning the direction of slow, but not fast, smooth motion. We investigated the possibility further by using crowding to induce a behaviorally similar motion-perception deficit in healthy observers. Crowding, which is known to impair object-position representation, impaired direction judgments for slow, but not for faster, smooth motion. The results suggest an everyday role for higher level mechanisms in the perception of slow motion, and they reinforce the taxonomy of motion perception in terms of underlying processing mechanisms as opposed to stimulus properties. PMID:26121499

  17. Flunarizine, a calcium entry blocker, ameliorates ischemic brain damage in the rat.

    PubMed

    Deshpande, J K; Wieloch, T

    1986-02-01

    The effects of flunarizine, a calcium entry blocker, were evaluated in a long-term survival model of ischemia in rats. One group of animals received the drug orally at 24 and 4 h prior to the insult (40 mg X kg-1 X dose-1). Another group was given flunarizine following the insult, intravenously at 5 min (0.1 mg X kg-1), and orally at 8 and 24 h (40 mg X kg-1 X dose-1). A third group received the solvent for the oral suspension on the same schedule as the pretreated group. Six animals from each group were subjected to 9 min ischemia and recovery of 7 days, at which time the brains were harvested for histologic study. In another six animals from each group, cortical metabolites and fatty acids were determined during early recirculation. Local cerebral blood flow was measured at 60 min recirculation in a third set of animals. Flunarizine significantly improved histological outcome (fewer irreversibly damaged cells) in both treatment groups. This amelioration was not related to improvement of cerebral blood flow during the period of delayed hypoperfusion, nor the postischemic levels of high-energy phosphates or free fatty acids. PMID:3946808

  18. Neuroprotective effects of a glutathione depletor in rat post-ischemic reperfusion brain damage.

    PubMed

    Giacomo, Claudia Di; Santangelo, Rosa; Sorrenti, Valeria; Volti, Giovanni L; Acquaviva, Rosaria

    2015-01-01

    The induction of heme oxygenase (HO), the rate-limiting enzyme in heme degradation, occurs as an adaptative response to oxidative stress and is consequent to decrease in cellular glutathione levels. Our previous studies demonstrated significant increase in survival rates of rats treated with glutathione depletors and submitted to transient cerebral ischemia. The aim of the present research was to test the effects of L-Buthionine sulfoximine (BSO), a glutathione depletor, during cerebral post-ischemic reperfusion. Cerebral ischemia was induced by bilateral clamping of common carotid arteries for 20 min. Each sample was used for glutathione ad lipid peroxidation level dosage and for evaluating the expression of heme oxygenase both after a single subcutaneous administration of BSO and without treatment. In the same experimental conditions, endothelial, inducible and neuronal Nitric Oxide Synthase (eNOS, iNOS and nNOS) and Dimethylarginine Dimethyl amine Hydrolases (DDAH-1 and DDAH-2) were also evaluated. Results obtained in the present study suggested that HO-1 over-expression may be implicated in the protective effect of BSO in post-ischemic reperfusion brain damage, although the involvement of other important stress mediators cannot be ruled out. PMID:25613502

  19. Partially flexible MEMS neural probe composed of polyimide and sucrose gel for reducing brain damage during and after implantation

    NASA Astrophysics Data System (ADS)

    Jeon, Myounggun; Cho, Jeiwon; Kim, Yun Kyung; Jung, Dahee; Yoon, Eui-Sung; Shin, Sehyun; Cho, Il-Joo

    2014-02-01

    This paper presents a flexible microelectromechanical systems (MEMS) neural probe that minimizes neuron damage and immune response, suitable for chronic recording applications. MEMS neural probes with various features such as high electrode densities have been actively investigated for neuron stimulation and recording to study brain functions. However, successful recording of neural signals in chronic application using rigid silicon probes still remains challenging because of cell death and macrophages accumulated around the electrodes over time from continuous brain movement. Thus, in this paper, we propose a new flexible MEMS neural probe that consists of two segments: a polyimide-based, flexible segment for connection and a rigid segment composed of thin silicon for insertion. While the flexible connection segment is designed to reduce the long-term chronic neuron damage, the thin insertion segment is designed to minimize the brain damage during the insertion process. The proposed flexible neural probe was successfully fabricated using the MEMS process on a silicon on insulator wafer. For a successful insertion, a biodegradable sucrose gel is coated on the flexible segment to temporarily increase the probe stiffness to prevent buckling. After the insertion, the sucrose gel dissolves inside the brain exposing the polyimide probe. By performing an insertion test, we confirm that the flexible probe has enough stiffness. In addition, by monitoring immune responses and brain histology, we successfully demonstrate that the proposed flexible neural probe incurs fivefold less neural damage than that incurred by a conventional silicon neural probe. Therefore, the presented flexible neural probe is a promising candidate for recording stable neural signals for long-time chronic applications.

  20. Acute and chronic complications of laser angioplasty: vascular wall damage and formation of aneurysms in the atherosclerotic rabbit.

    PubMed

    Lee, G; Ikeda, R M; Theis, J H; Chan, M C; Stobbe, D; Ogata, C; Kumagai, A; Mason, D T

    1984-01-15

    Acute and chronic vascular responses to laser exposure in atherosclerotic rabbits were studied. In 7 rabbits fed an atherogenic diet for 3 to 5 months before the study to induce aortic atherosclerosis, a flexible quartz fiber, 400 micron core diameter, attached to an argon ion laser was passed anterogradely or retrogradely to the atherosclerotic ascending aorta. The laser was turned on using power intensities of 1 to 2 W for 3 seconds. After laser treatment, the aortas were studied acutely in 3 rabbits and chronically in 4 rabbits after recovery for 1 to 14 days. In 2 rabbits studied acutely, the argon laser produced a vaporized crater within the atherosclerotic plaque at the endothelial surface; however, in 1 there was also vascular damage extending deep into the medial layer. In addition, aortic aneurysm with muscular wall damage occurred in 2 of the 4 animals studied chronically. Thus, vascular complications may arise when catheter laser angioplasty is randomly applied without visualizing specific plaque targets or without using safe dose increments of power intensities and durations of exposure. This study suggests caution in the clinical use of intensive phototherapy to cardiovascular lesions and stresses the need for further understanding of laser vascular consequences before application of laser angioplasty in patients. PMID:6695725

  1. Acute care in stroke: the importance of early intervention to achieve better brain protection.

    PubMed

    Díez-Tejedor, E; Fuentes, B

    2004-01-01

    It is known that 'time is brain', and only early therapies in acute stroke have been effective, like thrombolysis within the first 3 h, and useful neuroprotective drugs are searched for that probably would be effective only with their very early administration. General care (respiratory and cardiac care, fluid and metabolic management, especially blood glucose and blood pressure control, early treatment of hyperthermia, and prevention and treatment of neurological and systemic complications) in acute stroke patients is essential and must already start in the prehospital setting and continue at the patient's arrival to hospital in the emergency room and in the stroke unit. A review of published studies analyzing the influence of general care on stroke outcome and the personal experience from observational studies was performed. Glucose levels >8 mmol/l have been found to be predictive of a poor prognosis after correcting for age, stroke severity, and stroke subtype. Although a clinical trial of glucose-insulin-potassium infusions is ongoing, increased plasma glucose levels should be treated. Moreover, insulin therapy in critically ill patients, including stroke patients, is safe and determines lower mortality and complication rates. Both high and low blood pressure levels have been related to a poor prognosis in acute stroke, although the target levels have not been defined yet in clinical trials. The body temperature has been shown to have a negative effect on stroke outcome, and its control and early treatment of hyperthermia are important. Hypoxemia also worsens the stroke prognosis, and oxygen therapy in case of <92% O(2) saturation is recommended. Besides, blood pressure stabilization avoiding falls of the diastolic pressure and the lowering of glycemia and temperature have been related to a better prognosis in stroke units patients, and homeostasis maintenance is associated with a better outcome. General care has become an emergent and first-line brain

  2. Effects of chronic and acute stimulants on brain functional connectivity hubs.

    PubMed

    Konova, Anna B; Moeller, Scott J; Tomasi, Dardo; Goldstein, Rita Z

    2015-12-01

    The spatial distribution and strength of information processing 'hubs' are essential features of the brain׳s network topology, and may thus be particularly susceptible to neuropsychiatric disease. Despite growing evidence that drug addiction alters functioning and connectivity of discrete brain regions, little is known about whether chronic drug use is associated with abnormalities in this network-level organization, and if such abnormalities could be targeted for intervention. We used functional connectivity density (FCD) mapping to evaluate how chronic and acute stimulants affect brain hubs (i.e., regions with many short-range or long-range functional connections). Nineteen individuals with cocaine use disorders (CUD) and 15 healthy controls completed resting-state fMRI scans following a randomly assigned dose of methylphenidate (MPH; 20mg) or placebo. Short-range and long-range FCD maps were computed for each participant and medication condition. CUD participants had increased short-range and long-range FCD in the ventromedial prefrontal cortex, posterior cingulate/precuneus, and putamen/amygdala, which in areas of the default mode network correlated with years of use. Across participants, MPH decreased short-range FCD in the thalamus/putamen, and decreased long-range FCD in the supplementary motor area and postcentral gyrus. Increased density of short-range and long-range functional connections to default mode hubs in CUD suggests an overrepresentation of these resource-expensive hubs. While the effects of MPH on FCD were only partly overlapping with those of CUD, MPH-induced reduction in the density of short-range connections to the putamen/thalamus, a network of core relevance to habit formation and addiction, suggests that some FCD abnormalities could be targeted for intervention. PMID:25721787

  3. Changes in brain oxidative metabolism induced by inhibitory avoidance learning and acute administration of amitriptyline.

    PubMed

    González-Pardo, Héctor; Conejo, Nélida M; Arias, Jorge L; Monleón, Santiago; Vinader-Caerols, Concepción; Parra, Andrés

    2008-05-01

    The effects of antidepressant drugs on memory have been somewhat ignored, having been considered a mere side effect of these compounds. However, the memory impairment caused by several antidepressants could be considered to form part of their therapeutic effects. Amitriptyline is currently one of the most prescribed tricyclic antidepressants, and exerts marked anticholinergic and antihistaminergic effects. In this study, we evaluated the effects of inhibitory avoidance (IA) learning and acute administration of amitriptyline on brain oxidative metabolism. Brain oxidative metabolism was measured in several limbic regions using cytochrome oxidase (CO) quantitative histochemistry. Amitriptyline produced a clear impairment in the IA task. In animals exposed only to the apparatus, amitriptyline decreased CO activity in nine brain regions, without affecting the remaining regions. In animals that underwent the IA training phase, amitriptyline reduced CO activity in only three of these nine regions. In animals treated with saline, IA acquisition increased CO activity in the medial prefrontal cortex, the prelimbic cortex, and the medial mammillary body, and diminished it in the medial septum and the nucleus basalis of Meynert with respect to animals exposed only to the IA apparatus. In animals treated with amitriptyline, IA acquisition did not modify CO activity in any of these regions, but increased it in the anteromedial nucleus of the thalamus, the diagonal band of Broca, and the dentate gyrus. The results reveal a pattern of changes in brain oxidative metabolism induced by IA training in saline-treated animals that was clearly absent in animals submitted to the same behavioural training but treated with amitriptyline. PMID:18313125

  4. Ultrastructural mitochondria changes in perihematomal brain and neuroprotective effects of Huperzine A after acute intracerebral hemorrhage

    PubMed Central

    Lu, Haiying; Jiang, Mei; Lu, Lei; Zheng, Guo; Dong, Qiang

    2015-01-01

    Aim The purpose of the study was to observe the ultrastructural changes of neuronal mitochondria in perihematomal brain tissue and assess the therapeutic potential of Huperzine A (HA, a mitochondrial protector) following intracerebral hemorrhage (ICH). Methods Brain hemorrhage was induced in adult Sprague Dawley rats by injecting autologous blood into the striatum and then removing the brains 3, 6, 12, 24, or 48 hours later to analyze mitochondrial ultrastructure in a blinded manner. Parallel groups of ICH rats were treated with HA or saline immediately after ICH. Perihematomal apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase-3 activation and cytochrome C translocation were tracked by immunoblots, and neurobehavioral test results were compared between the groups. Results Mitochondria in perihematomal neurons demonstrated dramatic changes including mitochondrial swelling, intracristal dilation, and decreased matrix density. HA treatment decreased mitochondrial injury and apoptosis, inhibited caspase-3 activation and cytochrome C translocation, and improved behavioral recovery. Conclusion These data show that ICH induces dramatic mitochondrial damage, and HA exhibits protective effects possibly through ameliorating mitochondrial injury and apoptosis. Collectively, these findings suggest a new direction for novel therapeutics. PMID:26508860

  5. Changes in the mitochondrial antioxidant systems in neurodegenerative diseases and acute brain disorders.

    PubMed

    Ruszkiewicz, Joanna; Albrecht, Jan

    2015-09-01

    Oxidative and nitrosative stress (ONS) contributes to the pathogenesis of most brain maladies, and the magnitude of ONS is related to the ability of cellular antioxidants to neutralize the accumulating reactive oxygen and nitrogen species (ROS/RNS). While the major ROS/RNS scavengers and regenerators of bio-oxidized molecules, superoxide dysmutases (SODs), glutathione (GSH), thioredoxin (Trx) and peroxiredoxin (Prx), are distributed in all cellular compartments. This review specifically focuses on the role of the systems operating in mitochondria. There is a growing consensus that the mitochondrial SOD isoform - SOD2 and GSH are critical for the cellular antioxidant defense. Variable changes of the expression or activities of one or more of the mitochondrial antioxidant systems have been documented in the brains derived from human patients and/or in animal models of neurodegenerative diseases (Alzheimer's disease, Parkinson's disease), cerebral ischemia, toxic brain cell damage associated with overexposure to mercury or excitotoxins, or hepatic encephalopathy. In many cases, ambiguity of the responses of the different antioxidant systems in one and the same disease needs to be more conclusively evaluated before the balance of the changes is viewed as beneficial or detrimental. Modulation of the mitochondrial antioxidant systems may in the future become a target of antioxidant therapy. PMID:25576182

  6. Acute Supramaximal Exercise Increases the Brain Oxygenation in Relation to Cognitive Workload.

    PubMed

    Bediz, Cem Seref; Oniz, Adile; Guducu, Cagdas; Ural Demirci, Enise; Ogut, Hilmi; Gunay, Erkan; Cetinkaya, Caner; Ozgoren, Murat

    2016-01-01

    Single bout of exercise can improve the performance on cognitive tasks. However, cognitive responses may be controversial due to different type, intensity, and duration of exercise. In addition, the mechanism of the effect of acute exercise on brain is still unclear. This study was aimed to investigate the effects of supramaximal exercise on cognitive tasks by means of brain oxygenation monitoring. The brain oxygenation of Prefrontal cortex (PFC) was measured on 35 healthy male volunteers via functional near infrared spectroscopy (fNIRS) system. Subjects performed 2-Back test before and after the supramaximal exercise wingate anerobic test (WAnT) lasting 30-s on cycle ergometer. The PFC oxygenation change evaluation revealed that PFC oxygenation rise during post-exercise 2-Back task was considerably higher than those in pre-exercise 2-Back task. In order to describe the relationship between oxygenation change and exercise performance, subjects were divided into two groups as high performers (HP) and low performers (LP) according to their peak power values (PP) obtained from the supramaximal test. The oxy-hemoglobin (oxy-Hb) values were compared between pre- and post-exercise conditions within subjects and also between subjects according to peak power. When performers were compared, in the HP group, the oxy-Hb values in post-exercise 2-Back test were significantly higher than those in pre-exercise 2-Back test. HP had significantly higher post-exercise oxy-Hb change (Δ) than those of LP. In addition, PP of the total group were significantly correlated with Δoxy-Hb.The key findings of the present study revealed that acute supramaximal exercise has an impact on the brain oxygenation during a cognitive task. Also, the higher the anerobic PP describes the larger the oxy-Hb response in post-exercise cognitive task. The current study also demonstrated a significant correlation between peak power (exercise load) and post-exercise hemodynamic responses (oxy-, deoxy- and

  7. Acute Supramaximal Exercise Increases the Brain Oxygenation in Relation to Cognitive Workload

    PubMed Central

    Bediz, Cem Seref; Oniz, Adile; Guducu, Cagdas; Ural Demirci, Enise; Ogut, Hilmi; Gunay, Erkan; Cetinkaya, Caner; Ozgoren, Murat

    2016-01-01

    Single bout of exercise can improve the performance on cognitive tasks. However, cognitive responses may be controversial due to different type, intensity, and duration of exercise. In addition, the mechanism of the effect of acute exercise on brain is still unclear. This study was aimed to investigate the effects of supramaximal exercise on cognitive tasks by means of brain oxygenation monitoring. The brain oxygenation of Prefrontal cortex (PFC) was measured on 35 healthy male volunteers via functional near infrared spectroscopy (fNIRS) system. Subjects performed 2-Back test before and after the supramaximal exercise wingate anerobic test (WAnT) lasting 30-s on cycle ergometer. The PFC oxygenation change evaluation revealed that PFC oxygenation rise during post-exercise 2-Back task was considerably higher than those in pre-exercise 2-Back task. In order to describe the relationship between oxygenation change and exercise performance, subjects were divided into two groups as high performers (HP) and low performers (LP) according to their peak power values (PP) obtained from the supramaximal test. The oxy-hemoglobin (oxy-Hb) values were compared between pre- and post-exercise conditions within subjects and also between subjects according to peak power. When performers were compared, in the HP group, the oxy-Hb values in post-exercise 2-Back test were significantly higher than those in pre-exercise 2-Back test. HP had significantly higher post-exercise oxy-Hb change (Δ) than those of LP. In addition, PP of the total group were significantly correlated with Δoxy-Hb.The key findings of the present study revealed that acute supramaximal exercise has an impact on the brain oxygenation during a cognitive task. Also, the higher the anerobic PP describes the larger the oxy-Hb response in post-exercise cognitive task. The current study also demonstrated a significant correlation between peak power (exercise load) and post-exercise hemodynamic responses (oxy-, deoxy- and

  8. Cognitive Improvement after Mild Traumatic Brain Injury Measured with Functional Neuroimaging during the Acute Period

    PubMed Central

    Wylie, Glenn R.; Freeman, Kalev; Thomas, Alex; Shpaner, Marina; OKeefe, Michael; Watts, Richard; Naylor, Magdalena R.

    2015-01-01

    Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject’s reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to

  9. Cognitive Improvement after Mild Traumatic Brain Injury Measured with Functional Neuroimaging during the Acute Period.

    PubMed

    Wylie, Glenn R; Freeman, Kalev; Thomas, Alex; Shpaner, Marina; OKeefe, Michael; Watts, Richard; Naylor, Magdalena R

    2015-01-01

    Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject's reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to

  10. Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice

    PubMed Central

    Doeppner, T R; Kaltwasser, B; Teli, M K; Bretschneider, E; Bähr, M; Hermann, D M

    2014-01-01

    Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests. Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared with transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood–brain barrier (BBB), reduction in microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity. Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment. PMID:25144721

  11. Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice.

    PubMed

    Doeppner, T R; Kaltwasser, B; Teli, M K; Bretschneider, E; Bähr, M; Hermann, D M

    2014-01-01

    Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests. Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared with transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood-brain barrier (BBB), reduction in microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity. Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment. PMID:25144721

  12. Verbal memory in brain damaged patients under different conditions of retrieval aids: a study of frontal, temporal, and diencephalic damaged subjects.

    PubMed

    Vogel, C C; Markowitsch, H J; Hempel, U; Hackenberg, P

    1987-04-01

    The performance of 36 patients, divided into six groups, and 13 control subjects was investigated in paired-associate learning. The patients had right or left prefrontal, right or left anterior lateral temporopolar or medial temporal lobe damage, or lesions restricted to diencephalic areas. As tasks, two lists of paired words had to be learned, with the first list presenting only the word pairs, and the second one embedding the word pairs in sentences of a highly imaginable content. Recall consisted of immediate or delayed (48 hrs) free recall of the first list (condition I), of immediate or delayed recall of the second list (with visual imagery as a learning aid; condition II), and of cued recall (in which the sentence form was presented with a blank space where the word to be recalled had been previously; condition III). Control subjects clearly performed best under all conditions, manifesting a ceiling effect for the second and third ones under immediate recall. Among the brain-damaged groups the diencephalic subjects were poorest and gained only little from the aids given for learning and recall. Of the four patients with medial temporal lobe damage, those two with bilateral lesions were nearly as bad as the diencephalic lesioned subjects. The other patients were markedly inferior to the control subjects, but gained considerably under conditions II and III. These statements hold for immediate and delayed recall, though for the delayed recall conditions all groups showed a reduction in performance which amounted to roughly half of the values they had had under immediate recall. It is concluded that increasing the possibilities for depth of information processing assists brain damaged (as well as normal) subjects in verbal learning, but that the advantage of aiding them at the moment of encoding and retrieval is highest for patients with restricted lesions and/or with lesions not invading the two regions most regularly implicated in long-term information

  13. Effect of progesterone intervention on the dynamic changes of AQP-4 in hypoxic-ischaemic brain damage

    PubMed Central

    Li, Xiaojuan; Bai, Ruiying; Zhang, Junhe; Wang, Xiaoyin

    2015-01-01

    To observe the effect of progesterone (PROG) on blood-brain barrier (BBB) permeability, brain tissue water content and dynamic changes of aquaporin-4 (AQP-4) in neonatal rats with hypoxic-ischaemic brain damage (HIBD). 72 neonatal Wistar rats, aged 7 days old, were randomly divided into control, hypoxic-ischaemic (6, 24 and 72 h, and 7 d subgroups) and drug groups (6, 24 and 72 h, and 7 d subgroups). The HIBD animal model was established. BBB was detected via an Evans blue tracer. Brain water content was determined by the dry/wet method. The AQP-4 expression in the cerebral cortex was observed through immunohistochemistry and Western blot. BBB permeability in the cerebral cortex of the neonatal rats, brain water content and AQP-4 expression in the hypoxia-ischaemia group were significantly higher than those of the control group after hypoxia for 6 h (P < 0.05), continued to rise within 24 h and then reached the peak at 72 h. BBB permeability in the cerebral cortex of the neonatal rats, brain water content and AQP-4 expression in the drug group were significantly lower than those of the hypoxia-ischaemia group after hypoxia for 6, 24 and 72 h (P < 0.05). Moreover, BBB permeability and BBB expression were positively correlated with the AQP-4 expression. In conclusion, PROG protects the brain of HIBD neonatal rats by alleviating the damage of BBB and cerebral oedema. The protective effect of PROG may be related to the down-regulation of AQP-4 expression in the cerebral cortex of neonatal rats. PMID:26770503

  14. Effect of progesterone intervention on the dynamic changes of AQP-4 in hypoxic-ischaemic brain damage.

    PubMed

    Li, Xiaojuan; Bai, Ruiying; Zhang, Junhe; Wang, Xiaoyin

    2015-01-01

    To observe the effect of progesterone (PROG) on blood-brain barrier (BBB) permeability, brain tissue water content and dynamic changes of aquaporin-4 (AQP-4) in neonatal rats with hypoxic-ischaemic brain damage (HIBD). 72 neonatal Wistar rats, aged 7 days old, were randomly divided into control, hypoxic-ischaemic (6, 24 and 72 h, and 7 d subgroups) and drug groups (6, 24 and 72 h, and 7 d subgroups). The HIBD animal model was established. BBB was detected via an Evans blue tracer. Brain water content was determined by the dry/wet method. The AQP-4 expression in the cerebral cortex was observed through immunohistochemistry and Western blot. BBB permeability in the cerebral cortex of the neonatal rats, brain water content and AQP-4 expression in the hypoxia-ischaemia group were significantly higher than those of the control group after hypoxia for 6 h (P < 0.05), continued to rise within 24 h and then reached the peak at 72 h. BBB permeability in the cerebral cortex of the neonatal rats, brain water content and AQP-4 expression in the drug group were significantly lower than those of the hypoxia-ischaemia group after hypoxia for 6, 24 and 72 h (P < 0.05). Moreover, BBB permeability and BBB expression were positively correlated with the AQP-4 expression. In conclusion, PROG protects the brain of HIBD neonatal rats by alleviating the damage of BBB and cerebral oedema. The protective effect of PROG may be related to the down-regulation of AQP-4 expression in the cerebral cortex of neonatal rats. PMID:26770503

  15. Brain sarcoma of meningeal origin after cranial irradiation in childhood acute lymphocytic leukemia. Case report

    SciTech Connect

    Tiberin, P.; Maor, E.; Zaizov, R.; Cohen, I.J.; Hirsch, M.; Yosefovich, T.; Ronen, J.; Goldstein, J.

    1984-10-01

    The authors report their experience with an unusual case of intracerebral sarcoma of meningeal cell origin in an 8 1/2-year-old girl. This tumor occurred 6 1/2 years after cranial irradiation at relatively low dosage (2200 rads) had been delivered to the head in the course of a multimodality treatment for acute lymphocytic leukemia. The tumor recurred approximately 10 months after the first surgical intervention. Macroscopic total excision of the recurrent growth followed by whole-brain irradiation (4500 rads) failed to eradicate it completely and local recurrence prompted reoperation 18 months later. This complication of treatment in long-term childhood leukemia survivors is briefly discussed, as well as the pathology of meningeal sarcomas.

  16. Low plasma levels of brain natriuretic peptide in severe acute heart failure: merely a case?

    PubMed

    Brentana, Loretta; Temporelli, Pier Luigi; Corrà, Ugo; Gattone, Marinella; Pistono, Massimo; Imparato, Alessandro; Gnemmi, Marco; Giannuzzi, Pantaleo

    2007-11-30

    Brain natriuretic peptide (BNP) is commonly