Science.gov

Sample records for acute brain damage

  1. 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 ...

  2. Association between Peripheral Oxidative Stress and White Matter Damage in Acute Traumatic Brain Injury

    PubMed Central

    Lin, Wei-Ming; Chen, Meng-Hsiang; Wang, Hung-Chen; Lu, Cheng-Hsien; Chen, Pei-Chin; Chen, Hsiu-Ling; Tsai, Nai-Wen; Su, Yu-Jih; Li, Shau-Hsuan; Kung, Chia-Te; Chiu, Tsui-Min; Weng, Hsu-Huei; Lin, Wei-Che

    2014-01-01

    The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI). However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS) concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA) and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM) damage and increased systemic oxidative stress in TBI which suggests common inflammatory processes that covary in both the peripheral and central reactions after TBI. PMID:24804213

  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. Acute exposure of uranyl nitrate causes lipid peroxidation and histopathological damage in brain and bone of Wistar rat.

    PubMed

    Ghosh, Somnath; Kumar, Amit; Pandey, Badri Narain; Mishra, Kaushala Prasad

    2007-01-01

    Although the kidneys are the main target organs for uranium (U) toxicity, recent studies have shown that U can cross the blood-brain barrier to accumulate in the brain. Uranyl nitrate (U-238)induced oxidative damage was investigated in brain and bone of Wistar rats after intraperitoneal injection of uranyl nitrate at acute doses either nephrotoxic (576 microg of U/kg body weight) or subnephrotoxic (144 microg U/kg body weight). The health effects of U administration at 576 microg of U/kg body weight were seen in terms of decrease in food intake and no gain in body weight compared to respective controls. These alterations were correlated with increased lipid peroxidation as measured by thiobarbituric acid reactive substances in rat brain and bone. However, at lower dosage of U (144 microg U/kg body weight), no significant lipid peroxidation was observed in brain and bone. Histological examination of U-treated (576 microg of U/kg body weight) rat brain tissues showed marked and diffuse cystic degeneration and a similar pattern in histological alterations was observed in kidneys in treated animals; whereas no significant histological change was observed in rat brains and kidney treated with a lower dose of U (144 microg U/kg body weight). It is concluded that administration of U at an acute nephrotoxic dose caused oxidative stress in brain and bone manifested as lipid peroxidation and histopathological damage.

  5. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

    PubMed Central

    Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni

    2008-01-01

    Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131

  6. Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke

    PubMed Central

    2011-01-01

    Background Neuroserpin has shown neuroprotective effects in animal models of cerebral ischemia and has been associated with functional outcome after ischemic stroke. Our aim was to study whether neuroserpin serum levels could be associated to biomarkers of excitotoxicity, inflammation and blood brain barrier disruption. Methods We prospectively included 129 patients with ischemic stroke (58.1% male; mean age, 72.4 ± 9.6 years) not treated with tPA within 12 hours (h) of symptoms onset (mean time, 4.7 ± 2.1 h). Poor functional outcome at 3 months was considered as a modified Rankin scale score >2. Serum levels of neuroserpin, Interleukin 6 (IL-6), Intercellular adhesion molecule-1 (ICAM-1), active Matrix metalloproteinase 9 (MMP-9), and cellular fibronectin (cFn) (determined by ELISA) and glutamate (determined by HPLC) were measured on admission, 24 and 72 h. The main variable was considered the decrease of neuroserpin levels within the first 24 h. ROC analysis was used to select the best predictive value for neuroserpin to predict poor functional outcome due to a lack of linearity. Results The decrease of neuroserpin levels within the first 24 h was negatively correlated with serum levels at 24 hours of glutamate (r = -0.642), IL-6 (r = -0.678), ICAM-1 (r = -0.345), MMP-9 (r = -0.554) and cFn (r = -0.703) (all P < 0.0001). In the multivariate analysis, serum levels of glutamate (OR, 1.04; CI95%, 1.01-1.06, p = 0.001); IL-6 (OR, 1.4; CI95%, 1.1-1.7, p = 0.001); and cFn (OR, 1.3; CI95%, 1.1-1.6, p = 0.002) were independently associated with a decrease of neuroserpin levels <70 ng/mL at 24 h after adjusting for confounding factors. Conclusions These findings suggest that neuroprotective properties of neuroserpin may be related to the inhibition of excitotoxicity, inflammation, as well as blood brain barrier disruption that occur after acute ischemic stroke. PMID:21569344

  7. 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

  8. 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.

  9. Acute brain trauma.

    PubMed

    Martin, G T

    2016-01-01

    In the 20th century, the complications of head injuries were controlled but not eliminated. The wars of the 21st century turned attention to blast, the instant of impact and the primary injury of concussion. Computer calculations have established that in the first 5 milliseconds after the impact, four independent injuries on the brain are inflicted: 1) impact and its shockwave, 2) deceleration, 3) rotation and 4) skull deformity with vibration (or resonance). The recovery, pathology and symptoms after acute brain trauma have always been something of a puzzle. The variability of these four modes of injury, along with a variable reserve of neurones, explains some of this problem.

  10. Chronic Neuropsychological Sequelae of Cholinesterase Inhibitors in the Absence of Structural Brain Damage: Two Cases of Acute Poisoning

    PubMed Central

    Roldán-Tapia, Lola; Leyva, Antonia; Laynez, Francisco; Santed, Fernando Sánchez

    2005-01-01

    Here we describe two cases of carbamate poisoning. Patients AMF and PVM were accidentally poisoned by cholinesterase inhibitors. The medical diagnosis in both cases was overcholinergic syndrome, as demonstrated by exposure to cholinesterase inhibitors. The widespread use of cholinesterase inhibitors, especially as pesticides, produces a great number of human poisoning events annually. The main known neurotoxic effect of these substances is cholinesterase inhibition, which causes cholinergic overstimulation. Once AMF and PVM had recovered from acute intoxication, they were subjected to extensive neuropsychological evaluation 3 and 12 months after the poisoning event. These assessments point to a cognitive deficit in attention, memory, perceptual, and motor domains 3 months after intoxication. One year later these sequelae remained, even though the brain magnetic resonance imaging (MRI) and computed tomography (CT) scans were interpreted as being within normal limits. We present these cases as examples of neuropsychological profiles of long-term sequelae related to acute poisoning by cholinesterase inhibitor pesticides and show the usefulness of neuropsychological assessment in detecting central nervous system dysfunction in the absence of biochemical or structural markers. PMID:15929901

  11. 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

  12. Not just the brain: methamphetamine disrupts blood-spinal cord barrier and induces acute glial activation and structural damage of spinal cord cells.

    PubMed

    Kiyatkin, Eugene A; Sharma, Hari S

    2015-01-01

    Acute methamphetamine (METH) intoxication induces metabolic brain activation as well as multiple physiological and behavioral responses that could result in life-threatening health complications. Previously, we showed that METH (9 mg/kg) used in freely moving rats induces robust leakage of blood-brain barrier, acute glial activation, vasogenic edema, and structural abnormalities of brain cells. These changes were tightly correlated with drug-induced brain hyperthermia and were greatly potentiated when METH was used at warm ambient temperatures (29°C), inducing more robust and prolonged hyperthermia. Extending this line of research, here we show that METH also strongly increases the permeability of the blood-spinal cord barrier as evidenced by entry of Evans blue and albumin immunoreactivity in T9-12 segments of the spinal cord. Similar to the blood-brain barrier, leakage of bloodspinal cord barrier was associated with acute glial activation, alterations of ionic homeostasis, water tissue accumulation (edema), and structural abnormalities of spinal cord cells. Similar to that in the brain, all neurochemical alterations correlated tightly with drug-induced elevations in brain temperature and they were enhanced when the drug was used at 29°C and brain hyperthermia reached pathological levels (>40°C). We discuss common features and differences in neural responses between the brain and spinal cord, two inseparable parts of the central nervous system affected by METH exposure. PMID:25687701

  13. Not just the brain: methamphetamine disrupts blood-spinal cord barrier and induces acute glial activation and structural damage of spinal cord cells.

    PubMed

    Kiyatkin, Eugene A; Sharma, Hari S

    2015-01-01

    Acute methamphetamine (METH) intoxication induces metabolic brain activation as well as multiple physiological and behavioral responses that could result in life-threatening health complications. Previously, we showed that METH (9 mg/kg) used in freely moving rats induces robust leakage of blood-brain barrier, acute glial activation, vasogenic edema, and structural abnormalities of brain cells. These changes were tightly correlated with drug-induced brain hyperthermia and were greatly potentiated when METH was used at warm ambient temperatures (29°C), inducing more robust and prolonged hyperthermia. Extending this line of research, here we show that METH also strongly increases the permeability of the blood-spinal cord barrier as evidenced by entry of Evans blue and albumin immunoreactivity in T9-12 segments of the spinal cord. Similar to the blood-brain barrier, leakage of bloodspinal cord barrier was associated with acute glial activation, alterations of ionic homeostasis, water tissue accumulation (edema), and structural abnormalities of spinal cord cells. Similar to that in the brain, all neurochemical alterations correlated tightly with drug-induced elevations in brain temperature and they were enhanced when the drug was used at 29°C and brain hyperthermia reached pathological levels (>40°C). We discuss common features and differences in neural responses between the brain and spinal cord, two inseparable parts of the central nervous system affected by METH exposure.

  14. Neuronal damage in brain inflammation.

    PubMed

    Aktas, Orhan; Ullrich, Oliver; Infante-Duarte, Carmen; Nitsch, Robert; Zipp, Frauke

    2007-02-01

    In contrast to traditional textbook paradigms, recent studies indicate neuronal damage in classic neuroinflammatory diseases of the brain, such as multiple sclerosis or meningitis. In these cases, immune cells invade the central nervous system compartments, accompanied by a massive breakdown of the blood-brain barrier and typical changes of the cerebrospinal fluid. On the other hand, inflammation within the central nervous system is a common phenomenon even in classic noninflammatory brain diseases that are characterized by degeneration or trauma of neuronal structures, such as Alzheimer disease, Parkinson disease, or stroke. In these cases, inflammation is a frequent occurrence but displays different, more subtle, patterns compared with, for example, multiple sclerosis. Concepts for directly protecting neurons and axons in neuroinflammatory diseases may improve the outcome of the patients. In parallel, epidemiological and animal experimental evidences, as well as first clinical trials indicate the benefit of immunomodulatory therapies for classic noninflammatory brain diseases. We review the evidence for inflammatory neuronal damage and its clinical impact in the context of these diseases. PMID:17296833

  15. 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)

  16. Air pollution and brain damage.

    PubMed

    Calderón-Garcidueñas, Lilian; Azzarelli, Biagio; Acuna, Hilda; Garcia, Raquel; Gambling, Todd M; Osnaya, Norma; Monroy, Sylvia; DEL Tizapantzi, Maria Rosario; Carson, Johnny L; Villarreal-Calderon, Anna; Rewcastle, Barry

    2002-01-01

    Exposure to complex mixtures of air pollutants produces inflammation in the upper and lower respiratory tract. Because the nasal cavity is a common portal of entry, respiratory and olfactory epithelia are vulnerable targets for toxicological damage. This study has evaluated, by light and electron microscopy and immunohistochemical expression of nuclear factor-kappa beta (NF-kappaB) and inducible nitric oxide synthase (iNOS), the olfactory and respiratory nasal mucosae, olfactory bulb, and cortical and subcortical structures from 32 healthy mongrel canine residents in Southwest Metropolitan Mexico City (SWMMC), a highly polluted urban region. Findings were compared to those in 8 dogs from Tlaxcala, a less polluted, control city. In SWMMC dogs, expression of nuclear neuronal NF-kappaB and iNOS in cortical endothelial cells occurred at ages 2 and 4 weeks; subsequent damage included alterations of the blood-brain barrier (BBB), degenerating cortical neurons, apoptotic glial white matter cells, deposition of apolipoprotein E (apoE)-positive lipid droplets in smooth muscle cells and pericytes, nonneuritic plaques, and neurofibrillary tangles. Persistent pulmonary inflammation and deteriorating olfactory and respiratory barriers may play a role in the neuropathology observed in the brains of these highly exposed canines. Neurodegenerative disorders such as Alzheimer's may begin early in life with air pollutants playing a crucial role.

  17. Brain Damage in Deaf Vocational Rehabilitation Clients.

    ERIC Educational Resources Information Center

    Getz, Marc; Vernon, McCay

    1986-01-01

    Screening of 54 deaf vocational clients by the Bender-Gestalt and other tests indicated the likely presence of significantly more brain damage than among the hearing population with a particularly high correlation between low IQ and brain damage in the deaf population. (DB)

  18. 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

  19. 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

  20. Glibenclamide reduces secondary brain damage after experimental traumatic brain injury.

    PubMed

    Zweckberger, K; Hackenberg, K; Jung, C S; Hertle, D N; Kiening, K L; Unterberg, A W; Sakowitz, O W

    2014-07-11

    Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI. Anesthetized adult Sprague-Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15min after CCI injury and continuously via osmotic pumps throughout 7days. In an acute trial (180min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24h after CCI injury and contusion volumes were measured by MRI scanning technique at 8h, 24h, 72h, and 7d post injury. Throughout the entire time of observation neurological function was quantified using the "beam-walking" test. Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47%±0.37% (glibenclamide) vs. 80.83%±0.44% (control); p<0.05; n=14). Contusion sizes increased continuously within 72h following CCI injury, but glibenclamide-treated animals had significantly smaller volumes at any time-points, like 172.53±38.74mm(3) (glibenclamide) vs. 299.20±64.02mm(3) (control) (p<0.01; n=10; 24h) or 211.10±41.03mm(3) (glibenclamide) vs. 309.76±19.45mm(3) (control) (p<0.05; n=10; 72h), respectively. An effect on acute parameters, however, could not be detected, most likely because of the up-regulation of the channel within 3-6h after injury. Furthermore, there was no significant effect on motor function assessed by the beam-walking test throughout 7days. In accordance to these results and the available literature, glibenclamide seems to have promising potency in

  1. 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

  2. [Work after brain damage: unpredictability of outcomes].

    PubMed

    Bouchet-Nokri, Hélène; Afaska, Isabelle; Onnaïnty, Isabelle; Soriano, Véronique; Coste, Emmanuelle

    2013-09-01

    The Unit for Evaluation, Re-Education and Socio-Professional Orientation (UEROS) is a bridge between the hospital environment and professional life. It assists brain-damaged patients with their social and professional reintegration while taking into account their specific needs. PMID:24218924

  3. Neuroimaging in alcoholism: ethanol and brain damage.

    PubMed

    Mann, K; Agartz, I; Harper, C; Shoaf, S; Rawlings, R R; Momenan, R; Hommer, D W; Pfefferbaum, A; Sullivan, E V; Anton, R F; Drobes, D J; George, M S; Bares, R; Machulla, H J; Mundle, G; Reimold, M; Heinz, A

    2001-05-01

    This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The co-chairs were Karl Mann and Ingrid Agartz. The presentations were (1) Neuropathological changes in alcohol-related brain damage, by Clive Harper; (2) Regional brain volumes including the hippocampus and monoamine metabolites in alcohol dependence, by Ingrid Agartz, Susan Shoaf, Robert R, Rawlings, Reza Momenan, and Daniel W Hommer; (3) Diffusion tensor abnormalities in imaging of white matter alcoholism, by Adolf Pfefferbaum and Edith V. Sullivan; (4) Use of functional MRI to evaluate brain activity during alcohol cue exposure in alcoholics: Relationship to craving, by Raymond F. Anton, David J. Drobes, and Mark S. George; and (5) mu-Opiate receptor availability in alcoholism: First results from a positron emission tomography study, by Karl Mann, Roland Bares, Hans-Juergen Machulla, Goetz Mundle, Matthias Reimold, and Andreas Heinz.

  4. 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…

  5. Autophagy in acute brain injury: feast, famine, or folly?

    PubMed

    Smith, Craig M; Chen, Yaming; Sullivan, Mara L; Kochanek, Patrick M; Clark, Robert S B

    2011-07-01

    In the central nervous system, increased autophagy has now been reported after traumatic brain and spinal cord injury, cerebral ischemia, intracerebral hemorrhage, and seizures. This increase in autophagy could be physiologic, converting damaged or dysfunctional proteins, lipids, and/or organelles to their amino acid and fatty acid components for recycling. On the other hand, this increase in autophagy could be supraphysiologic, perhaps consuming and eliminating functional proteins, lipids, and/or organelles as well. Whether an increase in autophagy is beneficial (feast) or detrimental (famine) in brain likely depends on both the burden of intracellular substrate targeted for autophagy and the capacity of the cell's autophagic machinery. Of course, increased autophagy observed after brain injury could also simply be an epiphenomenon (folly). These divergent possibilities have clear ramifications for designing therapeutic strategies targeting autophagy after acute brain injury and are the subject of this review. This article is part of a Special Issue entitled "Autophagy and protein degradation in neurological diseases."

  6. Acquired agraphia caused by focal brain damage.

    PubMed

    Anderson, S W; Saver, J; Tranel, D; Damasio, H

    1993-03-01

    Motor and linguistic aspects of writing were evaluated in 31 subjects with focal damage in 1 of 3 regions of the left hemisphere: (1) dorsolateral frontal lobe sparing primary motor cortex (group FL), (2) parietal lobe (group PL), or (3) temporal lobe (group TL). A standard procedure was used to evaluate writing for grapheme formation, spatial arrangement, spelling, word selection, grammar, and perseveration. It was predicted that agraphia would be observed in all 3 groups, and that the most severe impairments would be associated with frontal lobe damage, particularly in aspects of writing dependent on sequencing (grapheme formation, spelling, and grammar). It was found that agraphia was common in all groups, particularly in the acute epoch, and that all groups showed considerable recovery of writing by the chronic epoch. Few differences were found between groups. However, the FL group was impaired on spelling and grammar relative to the PL group in the acute epoch and impaired on grammar relative to the TL group in the chronic epoch. The findings are consistent with the notion that writing relies on a distributed neuroanatomical network, which acts in concert to link fragments of visuomotor activity with component linguistic elements.

  7. 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.

  8. Zika Virus Can Damage Fetal Brain Late in Pregnancy: Study

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_161451.html Zika Virus Can Damage Fetal Brain Late in Pregnancy: ... 2016 WEDNESDAY, Oct. 12, 2016 (HealthDay News) -- The Zika virus may harm a baby's brain even if ...

  9. Vasoparalysis associated with brain damage in asphyxiated term infants

    SciTech Connect

    Pryds, O.; Greisen, G.; Lou, H.; Friis-Hansen, B. )

    1990-07-01

    The relationship of cerebral blood flow to acute changes in arterial carbon dioxide and mean arterial blood pressure (MABP) was determined during the first day of life in 19 severely asphyxiated term infants supported by mechanical ventilation. For comparison, 12 infants without perinatal asphyxia were also investigated. Global cerebral blood flow (CBF infinity) was determined by xenon 133 clearance two or three times within approximately 2 hours. During the cerebral blood flow measurement, the amplitude-integrated electroencephalogram and visual-evoked potential were recorded. Changes in arterial carbon dioxide pressure followed adjustments of the ventilator settings, whereas MABP fluctuated spontaneously. Arterial oxygen pressure and blood glucose concentration were in the normal range. Five of the asphyxiated infants had isoelectric electroencephalograms and died subsequently with severe brain damage. They had a high CBF infinity (mean 30.6 ml/100 gm/min) and abolished carbon dioxide and MABP reactivity. Lower CBF infinity (mean 14.7 ml/100 gm/min) and abolished MABP reactivity were found in another five asphyxiated infants with burst-suppression electroencephalograms in whom computed tomographic or clinical signs of brain lesions developed. The carbon dioxide reactivity was preserved in these infants. In the remaining nine asphyxiated infants without signs of central nervous system abnormality, carbon dioxide and MABP reactivity were preserved, as was also the case in the control group. We conclude that abolished autoregulation is associated with cerebral damage in asphyxiated infants and that the combination of isoelectric electroencephalograms and cerebral hyperperfusion is an early indicator of very severe brain damage.

  10. Extending the viability of acute brain slices

    PubMed Central

    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

  11. 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.

  12. BRAIN DAMAGE AND BEHAVIOR, A CLINICAL-EXPERIMENTAL STUDY.

    ERIC Educational Resources Information Center

    SCHULMAN, JEROME L.; AND OTHERS

    THIS MONOGRAPH RELATES RESULTS OF A STUDY WHICH WAS UNDERTAKEN TO ATTEMPT TO ANSWER THREE QUESTIONS--TO WHAT EXTENT DO EIGHT TECHNIQUES COMMONLY USED TO DIAGNOSE BRAIN DAMAGE CO-VARY, TO WHAT EXTENT DO THE VARIOUS BEHAVIORAL SYMPTOMS THAT OCCUR WITH BRAIN DAMAGE CO-VARY, AND TO WHAT EXTENT DO THE DIAGNOSTIC MEASURES, SINGLY OR IN GROUPS, PREDICT…

  13. 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)…

  14. Therapeutic hypothermia for acute brain injuries.

    PubMed

    Andresen, Max; Gazmuri, Jose Tomás; Marín, Arnaldo; Regueira, Tomas; Rovegno, Maximiliano

    2015-01-01

    Therapeutic hypothermia, recently termed target temperature management (TTM), is the cornerstone of neuroprotective strategy. Dating to the pioneer works of Fay, nearly 75 years of basic and clinical evidence support its therapeutic value. Although hypothermia decreases the metabolic rate to restore the supply and demand of O₂, it has other tissue-specific effects, such as decreasing excitotoxicity, limiting inflammation, preventing ATP depletion, reducing free radical production and also intracellular calcium overload to avoid apoptosis. Currently, mild hypothermia (33°C) has become a standard in post-resuscitative care and perinatal asphyxia. However, evidence indicates that hypothermia could be useful in neurologic injuries, such as stroke, subarachnoid hemorrhage and traumatic brain injury. In this review, we discuss the basic and clinical evidence supporting the use of TTM in critical care for acute brain injury that extends beyond care after cardiac arrest, such as for ischemic and hemorrhagic strokes, subarachnoid hemorrhage, and traumatic brain injury. We review the historical perspectives of TTM, provide an overview of the techniques and protocols and the pathophysiologic consequences of hypothermia. In addition, we include our experience of managing patients with acute brain injuries treated using endovascular hypothermia. PMID:26043908

  15. Therapeutic hypothermia for acute brain injuries.

    PubMed

    Andresen, Max; Gazmuri, Jose Tomás; Marín, Arnaldo; Regueira, Tomas; Rovegno, Maximiliano

    2015-06-05

    Therapeutic hypothermia, recently termed target temperature management (TTM), is the cornerstone of neuroprotective strategy. Dating to the pioneer works of Fay, nearly 75 years of basic and clinical evidence support its therapeutic value. Although hypothermia decreases the metabolic rate to restore the supply and demand of O₂, it has other tissue-specific effects, such as decreasing excitotoxicity, limiting inflammation, preventing ATP depletion, reducing free radical production and also intracellular calcium overload to avoid apoptosis. Currently, mild hypothermia (33°C) has become a standard in post-resuscitative care and perinatal asphyxia. However, evidence indicates that hypothermia could be useful in neurologic injuries, such as stroke, subarachnoid hemorrhage and traumatic brain injury. In this review, we discuss the basic and clinical evidence supporting the use of TTM in critical care for acute brain injury that extends beyond care after cardiac arrest, such as for ischemic and hemorrhagic strokes, subarachnoid hemorrhage, and traumatic brain injury. We review the historical perspectives of TTM, provide an overview of the techniques and protocols and the pathophysiologic consequences of hypothermia. In addition, we include our experience of managing patients with acute brain injuries treated using endovascular hypothermia.

  16. Cocaine induces DNA damage in distinct brain areas of female rats under different hormonal conditions.

    PubMed

    de Souza, Marilise F; Gonçales, Tierre A; Steinmetz, Aline; Moura, Dinara J; Saffi, Jenifer; Gomez, Rosane; Barros, Helena M T

    2014-04-01

    We evaluated levels of neuronal DNA damage after acute or repeated cocaine treatment in different brain areas of female rats after ovariectomy or sham surgery. Rats in the control and acute groups were given saline i.p., whereas in the repeated group were given 15 mg/kg, i.p., cocaine for 8 days. After a 10 day washout period, the control group was given saline i.p., whereas rats in the acute and repeated groups were given a challenge dose of 15 mg/kg, i.p., cocaine. After behavioural assessment, rats were killed and the cerebellum, hippocampus, hypothalamus, prefrontal cortex and striatum were dissected for the Comet assay. Acute cocaine exposure induced DNA damage in all brain areas. This effect persisted after repeated administration, except in the hypothalamus, where repeated treatment did not cause increased DNA damage. Sexual hormones exhibited a neuroprotective effect, decreasing cocaine-induced DNA damage in cycling rats in all brain areas. PMID:24552452

  17. 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…

  18. 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

  19. 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

  20. 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

  1. [Differentiated treatment of acute diffuse brain injuries].

    PubMed

    Pedachenko, E G; Dziak, L A; Sirko, A G

    2012-01-01

    Diagnosis and treatment results of 57 patients with acute diffuse brain injury have been analyzed. Patients were divided into two groups: first study period 2000-2005; second study period 2006-2010. The main differences between the first and the second study periods were in health condition and brain functions monitoring parameters, therapy approaches and goals. Increasing of axial and lateral dislocation symptoms during progression from the first type of diffuse injury to the fourth one is related to intracranial hypertension (ICH) occurrence rate and significance it's significance. During the second study period, ICH was found in 25% patients with the second type of injury, 57% patients with the third type of injury, and 80%, with the fourth type of injury. Mean ICP in the group of patients with the second type of diffuse injury comprised 14.4 +/- 6.6 mmHg; with the third type of injury, 30 +/- 20.6 mmHg; with the fourth type of injuty, 37.6 +/- 14.1 mmHg. Introduction of differentiated approach to conservative or surgical treatment method application to acute diffuse brain injuries patients based on ICP monitoring data led to 13.8% reduction in mortality in the second study period compared with the first study period.

  2. PGF(2alpha) FP receptor contributes to brain damage following transient focal brain ischemia.

    PubMed

    Saleem, Sofiyan; Ahmad, Abdullah Shafique; Maruyama, Takayuki; Narumiya, Shuh; Doré, Sylvain

    2009-01-01

    Although some of the COX-2 metabolites and prostaglandins have been implicated in stroke and excitotoxicity, the role of prostaglandin F(2alpha) (PGF(2alpha)) and its FP receptor have not been elucidated in the pathogenesis of ischemic-reperfusion (I/R) brain injury. Here we investigated the FP receptor's contribution in a unilateral middle cerebral artery (MCA) occlusion model of focal cerebral ischemia in mice. The MCA in wild type (WT) and FP knockout (FP(-/-)) C57BL/6 male mice was transiently occluded with a monofilament for 90 min. After 96 h of reperfusion, the FP(-/-) mice had 25.3% less neurological deficit (P < 0.05) and 34.4% smaller infarct volumes (P < 0.05) than those of the WT mice. In a separate cohort, physiological parameters were monitored before, during, and after ischemia, and the results revealed no differences between the groups. Because excitotoxicity is an acute mediator of stroke outcome, the effect of acute NMDA-induced neurotoxicity was also tested. Forty-eight hours after unilateral intrastriatal NMDA injection, excitotoxic brain damage was 20.8% less extensive in the FP(-/-) mice (P < 0.05) than in the WT counterparts, further supporting the toxic contribution of the FP receptor in I/R injury. Additionally, we investigated the effect of post-treatment with the FP agonist latanoprost in mice subjected to MCA occlusion; such treatment resulted in an increase in neurological deficit and infarct size in WT mice (P < 0.05), though no effects were observed in the latanoprost-treated FP(-/-) mice. Together, the results suggest that the PGF(2alpha) FP receptor significantly enhances cerebral ischemic and excitotoxic brain injury and that these results are of importance when planning for potential development of therapeutic drugs to treat stroke and its acute and/or long term consequences.

  3. Endotoxin-induced lung alveolar cell injury causes brain cell damage

    PubMed Central

    Rodríguez-González, Raquel; Ramos-Nuez, Ángela; Martín-Barrasa, José Luis; López-Aguilar, Josefina; Baluja, Aurora; Álvarez, Julián; Rocco, Patricia RM; Pelosi, Paolo

    2015-01-01

    Sepsis is the most common cause of acute respiratory distress syndrome, a severe lung inflammatory disorder with an elevated morbidity and mortality. Sepsis and acute respiratory distress syndrome involve the release of inflammatory mediators to the systemic circulation, propagating the cellular and molecular response and affecting distal organs, including the brain. Since it has been reported that sepsis and acute respiratory distress syndrome contribute to brain dysfunction, we investigated the brain-lung crosstalk using a combined experimental in vitro airway epithelial and brain cell injury model. Conditioned medium collected from an in vitro lipopolysaccharide-induced airway epithelial cell injury model using human A549 alveolar cells was subsequently added at increasing concentrations (no conditioned, 2%, 5%, 10%, 15%, 25%, and 50%) to a rat mixed brain cell culture containing both astrocytes and neurons. Samples from culture media and cells from mixed brain cultures were collected before treatment, and at 6 and 24 h for analysis. Conditioned medium at 15% significantly increased apoptosis in brain cell cultures 24 h after treatment, whereas 25% and 50% significantly increased both necrosis and apoptosis. Levels of brain damage markers S100 calcium binding protein B and neuron-specific enolase, interleukin-6, macrophage inflammatory protein-2, as well as matrix metalloproteinase-9 increased significantly after treating brain cells with ≥2% conditioned medium. Our findings demonstrated that human epithelial pulmonary cells stimulated with bacterial lipopolysaccharide release inflammatory mediators that are able to induce a translational clinically relevant and harmful response in brain cells. These results support a brain-lung crosstalk during sepsis and sepsis-induced acute respiratory distress syndrome. PMID:25135986

  4. 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)

  5. 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…

  6. 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.

  7. 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

  8. Mechanisms and prevention of secondary brain damage during intensive care.

    PubMed

    Dearden, N M

    1998-01-01

    The injured brain may be damaged by primary impact, secondary injury from secondary damage due to initiation of destructive inflammatory and biochemical cascades by the primary injury or secondary ischemic injury following secondary insults that initiate or augment these immunological and biochemical cascades. Cerebral ischemia will arise whenever delivery of oxygen and substrates to the brain fall below metabolic needs. Many factors lead to the development of secondary insults to the injured brain during initial resuscitation, transport, surgery, and subsequent intensive care. Continuous monitoring of cerebral oxygenation (jugular oximetry, brain tissue PO2) and cerebral blood flow velocity (transcranial Doppler ultrasonography) in patients with brain trauma reveals multiple episodes of transient hypoperfusion with an adverse relationship between incidence and outcome. Secondary brain insults arise through systemic or intracranial mechanisms that reduce cerebral blood flow from compromised CPP, vascular distortion or cerebrovascular narrowing or lower oxygen delivery from hypoxemia associated with airway obstruction, pulmonary pathology, or anemia. Secondary brain ischemia remains a common pathway to secondary brain damage in most critically ill neurosurgical patients. In the future prevention of secondary brain injury may well hinge on giving a cocktail of novel agents that modify destructive biochemical and inflammatory pathways, each having a potential therapeutic window possibly in a subgroup of patients. To date, phase 3 clinical trials of several agents including PEGSOD and tyrilizad mesylate have failed to show relevant efficacy after brain trauma or subarachnoid hemorrhage. The therapeutic role of calcium channel blockers in traumatic subarachnoid hemorrhage is currently under investigation following the results of subgroup metaanalysis. Several phase 3, NMDA receptor antagonist studies are underway in brain trauma with results expected soon. Although we

  9. Oxidative stress, DNA damage, and the telomeric complex as therapeutic targets in acute neurodegeneration

    PubMed Central

    Smith, Joshua A.; Park, Sookyoung; Krause, James S.; Banik, Naren L.

    2013-01-01

    Oxidative stress has been identified as an important contributor to neurodegeneration associated with acute CNS injuries and diseases such as spinal cord injury (SCI), traumatic brain injury (TBI), and ischemic stroke. In this review, we briefly detail the damaging effects of oxidative stress (lipid peroxidation, protein oxidation, etc.) with a particular emphasis on DNA damage. Evidence for DNA damage in acute CNS injuries is presented along with its downstream effects on neuronal viability. In particular, unchecked oxidative DNA damage initiates a series of signaling events (e.g. activation of p53 and PARP-1, cell cycle re-activation) which have been shown to promote neuronal loss following CNS injury. These findings suggest that preventing DNA damage might be an effective way to promote neuronal survival and enhance neurological recovery in these conditions. Finally, we identify the telomere and telomere-associated proteins (e.g. telomerase) as novel therapeutic targets in the treatment of neurodegeneration due to their ability to modulate the neuronal response to both oxidative stress and DNA damage. PMID:23422879

  10. 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.

  11. 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.

  12. Monochloroacetic acid toxicity in the mouse associated with blood-brain barrier damage

    SciTech Connect

    Berardi, M.R.

    1986-01-01

    Monochloroacetic acid (MCA) damages the blood-brain barrier (BBB) of mice when administered orally at lethal doses. Damage was characterized by the finding of RBC's in the brain parenchyma of mice exhibiting neurologic dysfunction after MCA treatment, and by the entry of (/sup 14/C)inulin and (/sup 3/H)dopamine into the brain following a lethal dose of MCA. Results of acute toxicity studies, pharmacological antidote studies, and toxicokinetics studies in mice and rats are also presented. Acute toxicity of MCA in rats and mice by several routes of administration was determined. Toxicity of molten MCA by the dermal route was characterized by a small amount of surface area exposure and short application time necessary to produce death in both species. Some mice surviving an acute lethal oral dose of MCA exhibited a rigid clasping of the front paws (myotonia) with impairment of walking. Oral administration of (/sup 14/C)MCA to both mice and rats was followed by a rapid elimination of radioactivity from non-cerebral tissues and rapid appearance in the urine. As the dose was increased from a trace dose to a toxic dose, the percent of the administrated dose which was found in the tissues, including brain regions, was greatly increased. Two hours after oral administration of an LD80 of MCA to mice, and coinciding with the onset of toxic signs, entry of (/sup 14/C)inulin into brain regions was significantly increased compared to controls. Both MCA lethality and front paw dysfunction in mice appear to be associated with damage to the BBB.

  13. 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

  14. 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.

  15. Reduplicative paramnesia in patients with focal brain damage.

    PubMed

    Murai, T; Toichi, M; Sengoku, A; Miyoshi, K; Morimune, S

    1997-07-01

    Reduplicative paramnesia (RP) has drawn attention as a distinct behavioral syndrome caused by focal brain damage. To elucidate the pathogenesis of RP, we assessed its prevalence among patients with focal brain damage and followed those patients with typical RP. Seventy-seven patients with focal brain damage (47 with left hemispheric, 21 with right hemispheric, and 9 with bilateral damage) were assessed for the presence of RP using a questionnaire intended to elucidate this condition. Two patients showed typical RP for place, and four patients showed atypical RP (three for place and one for person); altogether, these six patients constituted 7.8% of the sample. In three patients, the lesions were situated in the right hemisphere; in two, the lesions were bilateral (right dominant); and in one, the lesions were in the left hemisphere, indicating the relative importance of right hemispheric damage and a possible contributory role of additional left hemispheric damage in RP. The case studies of patients with typical RP suggest the heterogeneity of the underlying cognitive factors in RP.

  16. Acute liver damage and anorexia nervosa: a case report.

    PubMed

    Bridet, Lionel; Martin, Juan Jose Beitia; Nuno, Jose Luis Cabriada

    2014-04-01

    Anorexia nervosa is an eating disorder predominantly affecting young women and characterized by an intense fear of gaining weight and becoming fat. Liver injury with mild elevation of hepatic enzymes is a frequent complication, and steatosis of the liver is thought to be the major underlying pathology. However, acute hepatic failure with transaminase levels over 1000 u/L is a very rare complication, and the precise mechanism of the liver injury is still unclear. We report a case of a 35-year-old woman with a history of anorexia nervosa who developed acute liver damage with deep coma in relation to profound hypoglycemia. The treatment was hydration, correction of electrolyte and fluid imbalance, and gradual nutritional support to prevent refeeding syndrome. Our patient's consciousness was significantly improved with the recovery of liver function and normalization of transaminase levels. Although the mechanism of pathogenesis is largely unknown, we discuss the two principal hypotheses: starvation-induced autophagy and acute hypoperfusion.

  17. 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

  18. 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.

  19. 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

  20. "Neuropeptides in the brain defense against distant organ damage".

    PubMed

    Hamasaki, Mike Yoshio; Barbeiro, Hermes Vieira; Barbeiro, Denise Frediani; Cunha, Débora Maria Gomes; Koike, Marcia Kiyomi; Machado, Marcel Cerqueira César; Pinheiro da Silva, Fabiano

    2016-01-15

    Delirium, or acute confusional state, is a common manifestation in diseases that originate outside the central nervous system, affecting 30-40% of elderly hospitalized patients and up to 80% of the critically ill, even though it remains unclear if severe systemic inflammation is able or not to induce cellular disturbances and immune activation in the brain. Neuropeptides are pleotropic molecules heterogeneously distributed throughout the brain and possess a wide spectrum of functions, including regulation of the inflammatory response, so we hypothesized that they would be the major alarm system in the brain before overt microglia activation. In order to investigate this hypothesis, we induced acute pancreatitis in 8-10week old rats and collected brain tissue, 12 and 24h following pancreatic injury, to measure neuropeptide and cytokine tissue levels. We found significantly higher levels of β-endorphin, orexin and oxytocin in the brain of rats submitted to pancreatic injury, when compared to healthy controls. Interestingly, these differences were not associated with increased local cytokine levels, putting in evidence that neuropeptide release occurred independently of microglia activation and may be a pivotal alarm system to initiate neurologic reactions to distant inflammatory non-infectious aggression.

  1. Single-cell resolution mapping of neuronal damage in acute focal cerebral ischemia using thallium autometallography.

    PubMed

    Stöber, Franziska; Baldauf, Kathrin; Ziabreva, Iryna; Harhausen, Denise; Zille, Marietta; Neubert, Jenni; Reymann, Klaus G; Scheich, Henning; Dirnagl, Ulrich; Schröder, Ulrich H; Wunder, Andreas; Goldschmidt, Jürgen

    2014-01-01

    Neuronal damage shortly after onset or after brief episodes of cerebral ischemia has remained difficult to assess with clinical and preclinical imaging techniques as well as with microscopical methods. We here show, in rodent models of middle cerebral artery occlusion (MCAO), that neuronal damage in acute focal cerebral ischemia can be mapped with single-cell resolution using thallium autometallography (TlAMG), a histochemical technique for the detection of the K(+)-probe thallium (Tl(+)) in the brain. We intravenously injected rats and mice with thallium diethyldithiocarbamate (TlDDC), a lipophilic chelate complex that releases Tl(+) after crossing the blood-brain barrier. We found, within the territories of the affected arteries, areas of markedly reduced neuronal Tl(+) uptake in all animals at all time points studied ranging from 15 minutes to 24 hours after MCAO. In large lesions at early time points, areas with neuronal and astrocytic Tl(+) uptake below thresholds of detection were surrounded by putative penumbral zones with preserved but diminished Tl(+) uptake. At 24 hours, the areas of reduced Tl(+)uptake matched with areas delineated by established markers of neuronal damage. The results suggest the use of (201)TlDDC for preclinical and clinical single-photon emission computed tomography (SPECT) imaging of hyperacute alterations in brain K(+) metabolism and prediction of tissue viability in cerebral ischemia.

  2. [Neuroendocrine dysfunction and brain damage. A consensus statement].

    PubMed

    Leal-Cerro, Alfonso; Rincón, María Dolores; Domingo, Manel Puig

    2009-01-01

    This consensus statement aims to enhance awareness of the incidence and risks of hypopituitarism in patients with traumatic brain injury (TBI) and/or brain hemorrhages among physicians treating patients with brain damage. The importance of this problem is related not only to the frequency of TBI but also to its prevalence in younger populations. The consequences of TBI are characterized by a series of symptoms that depend on the type of sequels related to neuroendocrine dysfunction. The signs and symptoms of hypopituitarism are often confused with those of other sequels of TBI. Consequently, patients with posttraumatic hypopituitarism may receive suboptimal rehabilitation unless the underlying hormone deficiency is identified and treated. This consensus is based on the recommendation supported by expert opinion that patients with a TBI and/or brain hemorrhage should undergo endocrine evaluation in order to assess pituitary function and, if deficiency is detected, should receive hormone replacement therapy.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. Avermectin induced inflammation damage in king pigeon brain.

    PubMed

    Chen, Li-Jie; Sun, Bao-Hong; Qu, Jian Ping; Xu, Shiwen; Li, Shu

    2013-11-01

    To determine the effect of Avermectin (AVM) on inflammation damage in king pigeon brain, eighty two-month-old American king pigeons were randomly divided into four groups, and were fed with either commercial diet or AVM-supplemented diet containing 20 mg kg(-1)diet, 40 mg kg(-1)diet, and 60 mg kg(-1)diet AVM for 30, 60 and 90 d, respectively. Then, the expression level of inflammatory factors (iNOS, PTGEs, NF-κB), histological damage, and ultra-structural damage were examined. It showed that AVM caused higher expressions (P<0.05) of iNOS, PTGEs, NF-κB with disorganized histological and ultra-structural structures in cerebrum, cerebellum, and optic lobe. Meanwhile, inflammatory and histopathological damage were induced by AVM in king pigeon brains. In addition, the main targeted organelle in nervous system was mitochondria, which indicated that mitochondria may be relevant to the process of inflammation induced by AVM. To our best knowledge, this is the first report to study the toxic effect of AVM on inflammatory damage in king pigeon. Thus, the information presented in this study is believed to be helpful in supplementing data for further AVM toxicity study.

  8. [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.

  9. Ethyl Pyruvate Protects against Blood-Brain Barrier Damage and Improves Long-Term Neurological Outcomes in a Rat Model of Traumatic Brain Injury

    PubMed Central

    Shi, Hong; Wang, Hailian; Pu, Hongjian; Shi, Yejie; Zhang, Jia; Zhang, Wenting; Wang, Guohua; Hu, Xiaoming; Leak, Rehana K.; Chen, Jun; Gao, Yanqin

    2015-01-01

    Aims Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced long-term brain damage. Ethyl pyruvate (EP) has shown neuroprotection in several models of acute brain injury. The present study therefore investigated the potential beneficial effect of EP on long-term outcomes after TBI and the underlying mechanisms. Methods Male adult rats were subjected to unilateral controlled cortical impact injury. EP was injected intraperitoneally 15 min after TBI and again at 12, 24, 36, 48, and 60 h after TBI. Neurological deficits, blood-brain barrier (BBB) integrity and neuroinflammation were assessed. Results EP improved sensorimotor and cognitive functions and ameliorated brain tissue damage up to 28 d post-TBI. BBB breach and brain edema were attenuated by EP at 48 h after TBI. EP suppressed matrix metalloproteinase (MMP)-9 production from peripheral neutrophils and reduced the number of MMP-9-overproducing neutrophils in the spleen, and therefore mitigated MMP-9-mediated BBB breakdown. Moreover, EP exerted potent anti-inflammatory effects in cultured microglia and inhibited the elevation of inflammatory mediators in the brain after TBI. Conclusion EP confers long-term neuroprotection against TBI, possibly through breaking the vicious cycle among MMP-9-mediated BBB disruption, neuroinflammation and long-lasting brain damage. PMID:25533312

  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. Epileptic Encephalopathy in Children with Risk Factors for Brain Damage

    PubMed Central

    Ricardo-Garcell, Josefina; Harmony, Thalía; Porras-Kattz, Eneida; Colmenero-Batallán, Miguel J.; Barrera-Reséndiz, Jesús E.; Fernández-Bouzas, Antonio; Cruz-Rivero, Erika

    2012-01-01

    In the study of 887 new born infants with prenatal and perinatal risk factors for brain damage, 11 children with West syndrome that progressed into Lennox-Gastaut syndrome and another 4 children with Lennox-Gastaut syndrome that had not been preceded by West syndrome were found. In this study we present the main findings of these 15 subjects. In all infants multifactor antecedents were detected. The most frequent risk factors were prematurity and severe asphyxia; however placenta disorders, sepsis, and hyperbilirubinemia were also frequent. In all infants MRI direct or secondary features of periventricular leukomalacia were observed. Followup of all infants showed moderate to severe neurodevelopmental delay as well as cerebral palsy. It is concluded that prenatal and perinatal risk factors for brain damage are very important antecedents that should be taken into account to follow up those infants from an early age in order to detect and treat as early as possible an epileptic encephalopathy. PMID:22957240

  12. Beneficial Effect of Erythropoietin Short Peptide on Acute Traumatic Brain Injury.

    PubMed

    Wang, Bo; Kang, Mitchell; Marchese, Michelle; Rodriguez, Esther; Lu, Wei; Li, Xintong; Maeda, Yasuhiro; Dowling, Peter

    2016-04-01

    There is currently no effective medical treatment for traumatic brain injury (TBI). Beyond the immediate physical damage caused by the initial impact, additional damage evolves due to the inflammatory response that follows brain injury. Here we show that therapy with JM4, a low molecular weight 19-amino acid nonhematopoietic erythropoietin (EPO) peptidyl fragment, containing amino acids 28-46 derived from the first loop of EPO, markedly reduces acute brain injury. Mice underwent controlled cortical injury and received either whole molecule EPO, JM4, or sham-treatment with phosphate-buffered saline. Animals treated with JM4 peptide exhibited a large decrease in number of dead neural cells and a marked reduction in lesion size at both 3 and 8 days postinjury. Therapy with JM4 also led to improved functional recovery and we observed a treatment window for JM4 peptide that remained open for at least 9 h postinjury. The full-length EPO molecule was divided into a series of 6 contiguous peptide segments; the JM4-containing segment and the adjoining downstream region contained the bulk of the death attenuating effects seen with intact EPO molecule following TBI. These findings indicate that the JM4 molecule substantially blocks cell death and brain injury following acute brain trauma and, as such, presents an excellent opportunity to explore the therapeutic potential of a small-peptide EPO derivative in the medical treatment of TBI. PMID:26715414

  13. Gender differences in alcohol-induced neurotoxicity and brain damage.

    PubMed

    Alfonso-Loeches, Silvia; Pascual, María; Guerri, Consuelo

    2013-09-01

    Considerable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1β, TNF-α), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse.

  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. 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

  16. Resveratrol Protects the Brain of Obese Mice from Oxidative Damage

    PubMed Central

    Rege, Shraddha D.; Kumar, Sruthi; Wilson, David N.; Tamura, Leslie; Geetha, Thangiah; Mathews, Suresh T.; Huggins, Kevin W.; Broderick, Tom L.; Babu, Jeganathan Ramesh

    2013-01-01

    Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a polyphenolic phytoalexin that exerts cardioprotective, neuroprotective, and antioxidant effects. Recently it has been shown that obesity is associated with an increase in cerebral oxidative stress levels, which may enhance neurodegeneration. The present study evaluates the neuroprotective action of resveratrol in brain of obese (ob/ob) mice. Resveratrol was administered orally at the dose of 25 mg kg−1 body weight daily for three weeks to lean and obese mice. Resveratrol had no effect on body weight or blood glucose levels in obese mice. Lipid peroxides were significantly increased in brain of obese mice. The enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and nonenzymatic antioxidants tocopherol, ascorbic acid, and glutathione were decreased in obese mice brain. Administration of resveratrol decreased lipid peroxide levels and upregulated the antioxidant activities in obese mice brain. Our findings indicate a neuroprotective effect of resveratrol by preventing oxidative damage in brain tissue of obese mice. PMID:24163719

  17. 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.

  18. 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

  19. 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

  20. Hydrogen-rich water attenuates brain damage and inflammation after traumatic brain injury in rats.

    PubMed

    Tian, Runfa; Hou, Zonggang; Hao, Shuyu; Wu, Weichuan; Mao, Xiang; Tao, Xiaogang; Lu, Te; Liu, Baiyun

    2016-04-15

    Inflammation and oxidative stress are the two major causes of apoptosis after traumatic brain injury (TBI). Most previous studies of the neuroprotective effects of hydrogen-rich water on TBI primarily focused on antioxidant effects. The present study investigated whether hydrogen-rich water (HRW) could attenuate brain damage and inflammation after traumatic brain injury in rats. A TBI model was induced using a controlled cortical impact injury. HRW or distilled water was injected intraperitoneally daily following surgery. We measured survival rate, brain edema, blood-brain barrier (BBB) breakdown and neurological dysfunction in all animals. Changes in inflammatory cytokines, inflammatory cells and Cho/Cr metabolites in brain tissues were also detected. Our results demonstrated that TBI-challenged rats exhibited significant brain injuries that were characterized by decreased survival rate and increased BBB permeability, brain edema, and neurological dysfunction, while HRW treatment ameliorated the consequences of TBI. HRW treatment also decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β and HMGB1), inflammatory cell number (Iba1) and inflammatory metabolites (Cho) and increased the levels of an anti-inflammatory cytokine (IL-10) in the brain tissues of TBI-challenged rats. In conclusion, HRW could exert a neuroprotective effect against TBI and attenuate inflammation, which suggests HRW as an effective therapeutic strategy for TBI patients. PMID:26826009

  1. 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.

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

    PubMed

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

    2014-10-01

    Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron levels 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 h (lateral ventricle volume: 24.1 ± 3.0 vs. 9.9 ± 0.2 mm(3) in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm(3) in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI.

  4. 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

  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.

  6. Acute sun damage and photoprotective responses in whales.

    PubMed

    Martinez-Levasseur, Laura M; Gendron, Diane; Knell, Rob J; O'Toole, Edel A; Singh, Manuraj; Acevedo-Whitehouse, Karina

    2011-05-22

    Rising levels of ultraviolet radiation (UVR) secondary to ozone depletion are an issue of concern for public health. Skin cancers and intraepidermal dysplasia are increasingly observed in individuals that undergo chronic or excessive sun exposure. Such alterations of skin integrity and function are well established for humans and laboratory animals, but remain unexplored for mammalian wildlife. However, effects are unlikely to be negligible, particularly for species such as whales, whose anatomical or life-history traits force them to experience continuous sun exposure. We conducted photographic and histological surveys of three seasonally sympatric whale species to investigate sunburn and photoprotection. We find that lesions commonly associated with acute severe sun damage in humans are widespread and that individuals with fewer melanocytes have more lesions and less apoptotic cells. This suggests that the pathways used to limit and resolve UVR-induced damage in humans are shared by whales and that darker pigmentation is advantageous to them. Furthermore, lesions increased significantly in time, as would be expected under increasing UV irradiance. Apoptosis and melanocyte proliferation mirror this trend, suggesting that whales are capable of quick photoprotective responses. We conclude that the thinning ozone layer may pose a risk to the health of whales and other vulnerable wildlife.

  7. 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

  8. 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.

  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.

  10. 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.

  11. Stimulation of functional vision in children with perinatal brain damage.

    PubMed

    Alimović, Sonja; Mejaski-Bosnjak, Vlatka

    2011-01-01

    Cerebral visual impairment (CVI) is one of the most common causes of bilateral visual loss, which frequently occurs due to perinatal brain injury. Vision in early life has great impact on acquisition of basic comprehensions which are fundamental for further development. Therefore, early detection of visual problems and early intervention is necessary. The aim of the present study is to determine specific visual functioning of children with perinatal brain damage and the influence of visual stimulation on development of functional vision at early age of life. We initially assessed 30 children with perinatal brain damage up to 3 years of age, who were reffered to our pediatric low vision cabinet in "Little house" from child neurologists, ophthalmologists Type and degree of visual impairment was determined according to functional vision assessment of each child. On the bases of those assessments different kind of visual stimulations were carried out with children who have been identified to have a certain visual impairment. Through visual stimulation program some of the children were stimulated with light stimulus, some with different materials under the ultraviolet (UV) light, and some with bright color and high contrast materials. Children were also involved in program of early stimulation of overall sensory motor development. Goals and methods of therapy were determined individually, based on observation of child's possibilities and need. After one year of program, reassessment was done. Results for visual functions and functional vision were compared to evaluate the improvement of the vision development. These results have shown that there was significant improvement in functional vision, especially in visual attention and visual communication.

  12. Imaging Evaluation of Acute Traumatic Brain Injury.

    PubMed

    Mutch, Christopher A; Talbott, Jason F; Gean, Alisa

    2016-10-01

    Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Imaging plays an important role in the evaluation, diagnosis, and triage of patients with TBI. Recent studies suggest that it also helps predict patient outcomes. TBI consists of multiple pathoanatomic entities. This article reviews the current state of TBI imaging including its indications, benefits and limitations of the modalities, imaging protocols, and imaging findings for each of these pathoanatomic entities. Also briefly surveyed are advanced imaging techniques, which include several promising areas of TBI research. PMID:27637393

  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'.

  14. 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

  15. 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

  16. 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

  17. 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...

  18. Point localisation in patients with unilateral brain damage.

    PubMed Central

    Tartaglione, A; Benton, A L; Cocito, L; Bino, G; Favale, E

    1981-01-01

    The ability to reproduce the position of points in a plane was examined by a copying test in a control group and in unilaterally brain damaged patients. The procedure was designed to minimise the influence of visual field defects and of spatial hemi-inattention on performance. Accuracy of of localisation and direction of errors were studied in each half of the plane. Analysis showed a greater impairment of localisation ability in the patients with right hemisphere disease; however, the performance of both hemispheric groups was characterised by a reduction of accuracy in half of the plane contralateral to the side of the lesion. Both hemispheric groups showed an abnormal direction of errors in the left half of the plane, but the two groups presented a different pattern of errors. PMID:7310411

  19. 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.

  20. The effects of acute ethanol exposure and ageing on rat brain glutathione metabolism.

    PubMed

    Sommavilla, Michela; Sánchez-Villarejo, M Victoria; Almansa, Inmaculada; Sánchez-Vallejo, Violeta; Barcia, Jorge M; Romero, Francisco Javier; Miranda, María

    2012-09-01

    Binge alcohol consumption in adolescents is increasing, and it has been proposed that immature brain deals poorly with oxidative stress. The aim of our work was to study the effect of an acute dose of ethanol on glutathione (GSH) metabolism in frontal cortex, hippocampus and striatum of juvenile and adult rats. We have observed no change in levels of glutathione produced by acute alcohol in the three brain areas studied of juvenile and adult rats. Only in the frontal cortex the ratio of GSH/GSSG was increased in the ethanol-treated adult rats. GSH levels in the hippocampus and striatum were significantly higher in adult animals compared to young ones. Higher glutathione peroxidase (GPx) activity in adult rats was observed in frontal cortex and in striatum. Our data show an increased GSH concentration and GPx activity in different cerebral regions of the adult rat, compared to the young ones, suggesting that age-related variations of total antioxidant defences in brain may predispose young brain structures to ethanol-induced, oxidative stress-mediated tissue damage.

  1. [Arterial and venous brain reactivity in the acute period of brain concussion].

    PubMed

    Dicheskul, M L; Kulikov, V P

    2009-01-01

    Arterial and venous brain reactivity has been studied in 38 patients in the acute period of brain concussion (BC) and 32 healthy volunteers using transcranial color duplex scanning of brain vessels. The assessment of arterial inflow was conducted for the medial brain artery (MBA) and that of venous outflow - for the basal vein (BV) of Rosenthal. Hyperkinetic and orthostatic probes were used for assessment of cerebrovascular reactivity. BC was not accompanied by marked changes of cerebral resting hemodynamic parameters. The increase of peak blood flow velocity in MBA in the acute period which is characteristic of the brain hyperinfusion was found in 20% of patients and that in BA compensating the disturbed outflow along the surface brain system - in 25% of patients. In normalcy, the brain venous reactivity to hypercapnia was higher than arterial one and that to orthostasis corresponded to the intensity of arterial changes. The lack of quantitative differences in the reaction of arterial and venous blood flow to hypercapnia and the predominance of venous reactivity value in orthostasis in patients with BC suggest the disturbance of venous tone regulation in these patients.

  2. 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

  3. [Relationship between location of stress erosive gastritis and brain damage in resuscitated patients].

    PubMed

    Suzaki, Fumio; Suzuki, Ryoichi; Sugiyama, Mitsugi

    2002-03-01

    Patients after resuscitation from cardiopulmonary arrest often show stress erosive gastritis. This study investigated the relationship between the location of gastric mucosal injury and the degree of brain damage. Forty-five resuscitated patients with gastrointestinal bleeding complications were enrolled and were examined by esophagogastric fiberscope after 72 hours of hospitalization. Their brainstem and cerebral functions were evaluated brainstem auditory evoked potential (BAEP) and electrical encephalogram (EEG), respectively. Thirty patients showed complications with acute gastric lesions. Ten patients had gastric mucosal injury in the antrum and they all showed a good response for BAEP (I, III and V waves were positive). In contrast, patients without antral gastric mucosal lesions showed poor response for ABR (defect of III and V waves) and EGG (Hockerday Grade III or IV). These results indicate that fair brainstem function is necessary for stress erosive gastritis in gastric antrum.

  4. Biomarkers and acute brain injuries: interest and limits.

    PubMed

    Mrozek, Ségolène; Dumurgier, Julien; Citerio, Giuseppe; Mebazaa, Alexandre; Geeraerts, Thomas

    2014-04-24

    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.

  5. 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

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

    PubMed

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

    2014-01-01

    The New South Wales Tissue Resource Centre 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 damage (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) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539).

  7. Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).

    PubMed

    Mukhopadhyay, Sanjay; Parambil, Joseph G

    2012-10-01

    Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF).

  8. 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,…

  9. 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…

  10. 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

  11. Central diabetes insipidus in children with acute brain insult.

    PubMed

    Yang, Yun-Hsuan; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Wu, Chang-Teng; Wang, Huei-Shyong; Hung, Po-Cheng; Chou, Min-Liang; Hsieh, Meng-Ying; Lin, Kuang-Lin

    2011-12-01

    Central diabetes insipidus occurs in patients with overwhelming central nervous system injuries, and may be associated with brain death. The clinical picture of children with acquired central diabetes insipidus after acute brain insult is seldom reported. We retrospectively reviewed cases dating from January 2000-February 2008 at a tertiary pediatric intensive care unit. Fifty-four patients (28 girls, 26 boys), aged 3 months to 18 years, were enrolled. Etiologies included severe central nervous system infection (35.2%), hypoxic-ischemic events (31.5%), head injury (18.5%), and vascular lesions (14.8%). In 39 (72.2%) patients, diabetes insipidus was diagnosed during the first 2 days after acute central nervous system injury, and 40 (74.0%) developed maximum serum sodium concentrations of >160 mEq/L. In 16, sequential cerebral salt wasting syndrome developed after their initial diabetes insipidus presentation. Overall mortality at 2 months after admission was 77.8%. Our results demonstrate that patients who develop central diabetes insipidus after acute central nervous system injury manifest high mortality. Development of central diabetes insipidus within the first 2 days and a maximum plasma sodium >160 mEq/L were significant predictors of outcomes.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. Death rates reflect accumulating brain damage in arthropods

    PubMed Central

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

    2005-01-01

    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. 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.

  19. Hyponatremia in acute brain disease: the cerebral salt wasting syndrome.

    PubMed

    Betjes, Michiel G.H.

    2002-02-01

    Hyponatremia in acute brain disease is a common occurrence, especially after an aneurysmal subarachnoid hemorrhage. Originally, excessive natriuresis, called cerebral salt wasting, and later the syndrome of inappropriate antidiuretic hormone secretion (SIADH), were considered to be the causes of hyponatremia. In recent years, it has become clear that most of these patients are volume-depleted and have a negative sodium balance, consistent with the original description of cerebral salt wasting. Elevated plasma concentrations of atrial or brain natriuretic peptide have been identified as the putative natriuretic factor. Hyponatremia and volume depletion may aggravate neurological symptoms, and timely treatment with adequate replacement of water and NaCl is essential. The use of fludrocortisone to increase sodium reabsorption by the renal tubules may be an alternative approach.

  20. 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.

  1. [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

  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. Near-Infrared Optical Imaging Noninvasively Detects Acutely Damaged Muscle.

    PubMed

    Chrzanowski, Stephen M; Batra, Abhinandan; Lee-McMullen, Brittany; Vohra, Ravneet S; Forbes, Sean C; Jiang, Huabei; Vandenborne, Krista; Walter, Glenn A

    2016-10-01

    Muscle damage is currently assessed through methods such as muscle biopsy, serum biomarkers, functional testing, and imaging procedures, each with its own inherent limitations, and a pressing need for a safe, repeatable, inexpensive, and noninvasive modality to assess the state of muscle health remains. Our aim was to develop and assess near-infrared (NIR) optical imaging as a novel noninvasive method of detecting and quantifying muscle damage. An immobilization-reambulation model was used for inducing muscle damage and recovery in the lower hindlimbs in mice. Confirmation of muscle damage was obtained using in vivo indocyanine green-enhanced NIR optical imaging, magnetic resonance imaging, and ex vivo tissue analysis. The soleus of the immobilized-reambulated hindlimb was found to have a greater amount of muscle damage compared to that in the contralateral nonimmobilized limb, confirmed by in vivo indocyanine green-enhanced NIR optical imaging (3.86-fold increase in radiant efficiency), magnetic resonance imaging (1.41-fold increase in T2), and an ex vivo spectrophotometric assay of indocyanine green uptake (1.87-fold increase in normalized absorbance). Contrast-enhanced NIR optical imaging provides a sensitive, rapid, and noninvasive screening method that can be used for imaging and quantifying muscle damage and recovery in vivo. PMID:27565039

  4. Systemic autoimmunity in TAM triple knockout mice causes inflammatory brain damage and cell death.

    PubMed

    Li, Qiutang; Lu, Qingjun; Lu, Huayi; Tian, Shifu; Lu, Qingxian

    2013-01-01

    The Tyro3, Axl and Mertk (TAM) triply knockout (TKO) mice exhibit systemic autoimmune diseases, with characteristics of increased proinflammatory cytokine production, autoantibody deposition and autoreactive lymphocyte infiltration into a variety of tissues. Here we show that TKO mice produce high level of serum TNF-α and specific autoantibodies deposited onto brain blood vessels. The brain-blood barrier (BBB) in mutant brains exhibited increased permeability for Evans blue and fluorescent-dextran, suggesting a breakdown of the BBB in the mutant brains. Impaired BBB integrity facilitated autoreactive T cells infiltrating into all regions of the mutant brains. Brain autoimmune disorder caused accumulation of the ubiquitin-reactive aggregates in the mutant hippocampus, and early formation of autofluorescent lipofuscins in the neurons throughout the entire brains. Chronic neuroinflammation caused damage of the hippocampal mossy fibers and neuronal apoptotic death. This study shows that chronic systemic inflammation and autoimmune disorders in the TKO mice cause neuronal damage and death.

  5. Acute ischaemic brain lesions in intracerebral haemorrhage: multicentre cross-sectional magnetic resonance imaging study.

    PubMed

    Gregoire, Simone M; Charidimou, Andreas; Gadapa, Naveen; Dolan, Eamon; Antoun, Nagui; Peeters, Andre; Vandermeeren, Yves; Laloux, Patrice; Baron, Jean-Claude; Jäger, Hans R; Werring, David J

    2011-08-01

    Subclinical acute ischaemic lesions on brain magnetic resonance imaging have recently been described in spontaneous intracerebral haemorrhage, and may be important to understand pathophysiology and guide treatment. The underlying mechanisms are uncertain. We tested the hypothesis that ischaemic lesions are related to magnetic resonance imaging markers of the severity and type of small-vessel disease (hypertensive arteriopathy or cerebral amyloid angiopathy) in a multicentre, cross-sectional study. We studied consecutive patients with intracerebral haemorrhage from four specialist stroke centres, and age-matched stroke service referrals without intracerebral haemorrhage. Acute ischaemic lesions were assessed on magnetic resonance imaging (<3 months after intracerebral haemorrhage) using diffusion-weighted imaging. White matter changes and cerebral microbleeds were rated with validated scales. We investigated associations between diffusion-weighted imaging lesions, clinical and radiological characteristics. We included 114 patients with intracerebral haemorrhage (39 with clinically probable cerebral amyloid angiopathy) and 47 age-matched controls. The prevalence of diffusion-weighted imaging lesions was 9/39 (23%) in probable cerebral amyloid angiopathy-related intracerebral haemorrhage versus 6/75 (8%) in the remaining patients with intracerebral haemorrhage (P = 0.024); no diffusion-weighted imaging lesions were found in controls. Diffusion-weighted imaging lesions were mainly cortical and were associated with mean white matter change score (odds ratio 1.14 per unit increase, 95% confidence interval 1.02-1.28, P = 0.024) and the presence of strictly lobar cerebral microbleeds (odds ratio 3.85, 95% confidence interval 1.15-12.93, P = 0.029). Acute, subclinical ischaemic brain lesions are frequent but previously underestimated after intracerebral haemorrhage, and are three times more common in cerebral amyloid angiopathy-related intracerebral haemorrhage than in

  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. 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.

  8. 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.

  9. 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.

  10. 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…

  11. Dense arrays of micro-needles for recording and electrical stimulation of neural activity in acute brain slices

    NASA Astrophysics Data System (ADS)

    Gunning, D. E.; Beggs, J. M.; Dabrowski, W.; Hottowy, P.; Kenney, C. J.; Sher, A.; Litke, A. M.; Mathieson, K.

    2013-02-01

    Objective. This paper describes the design, microfabrication, electrical characterization and biological evaluation of a high-density micro-needle array. The array records from and electrically stimulates individual neurons simultaneously in acute slices of brain tissue. Approach. Acute slices, arguably the closest in-vitro model of the brain, have a damaged surface layer. Since electrophysiological recording methods rely heavily on electrode-cell proximity, this layer significantly attenuates the signal amplitude making the use of traditional planar electrodes unsuitable. To penetrate into the tissue, bypassing the tissue surface, and to record and stimulate neural activity in the healthy interior volume of the slice, an array of 61 micro-needles was fabricated. Main results. This device is shown to record extracellular action potentials from individual neurons in acute cortical slices with a signal to noise ratio of up to ˜15:1. Electrical stimulation of individual neurons is achieved with stimulation thresholds of 1.1-2.9 µA. Significance. The novelty of this system is the combination of close needle spacing (60 µm), needle heights of up to 250 µm and small (5-10 µm diameter) electrodes allowing the recording of single unit activity. The array is coupled to a custom-designed readout system forming a powerful electrophysiological tool that permits two-way electrode-cell communication with populations of neurons in acute brain slices.

  12. Organophosphate-induced brain damage: mechanisms, neuropsychiatric and neurological consequences, and potential therapeutic strategies.

    PubMed

    Chen, Yun

    2012-06-01

    Organophosphate (OP)-induced brain damage is defined as progressive damage to the brain, resulting from the cholinergic neuronal excitotoxicity and dysfunction induced by OP-induced irreversible AChE inhibition. This delayed secondary neuronal damage that occurs mainly in the cholinergic regions of the brain that contain dense accumulations of cholinergic neurons and the majority of cholinergic projection, might be largely responsible for persistent profound neuropsychiatric and neurological impairments (memory, cognitive, mental, emotional, motor and sensory deficits) in the victims of OP poisoning. Neuroprotective strategies for attenuating OP-induced brain damage should target different development stages of OP-induced brain damage, and may include but not limited to: (1) Antidote therapies with atropine and related efficient anticholinergic drugs; (2) Anti-excitotoxic therapies targeting attenuation of cerebral edema and inflammatory reaction, blockage of calcium influx, inhibition of apoptosis program, and the control of seizures; (3) Neuroprotective strategies using cytokines, antioxidants and NMDAR antagonists (a single drug or a combination of drugs) to slow down the process of secondary neuronal damage; and (4) Therapies targeting individual symptoms or clusters of chronic neuropsychiatric and neurological symptoms. These neuroprotective strategies may help limit or prevent secondary neuronal damage at the early stage of OP poisoning and attenuate the subsequent neuropsychiatric and neurological impairments, thus reducing the long-term disability caused by exposure to OPs. PMID:22498093

  13. Waiver of consent in studies of acute brain injury.

    PubMed

    Clifton, Guy L; Knudson, Paula; McDonald, Marilyn

    2002-10-01

    A multicenter trial of hypothermia in patients with acute brain injury, designed to accrue 140 patients per year and randomizing in less than 6 h from injury, enrolled 392 patients. The design was to achieve 33 degrees C within 8 h after injury. For the first 9 months of the trial, the only consent mechanism permitted by federal regulations was prospective, informed consent. In the subsequent 33 months, after a change in federal regulations, waiver of consent could be used when family could not be located. Waiver of consent was used in 62% of patients enrolled. In the first 9 months of the trial, accrual was 65 patients. In the subsequent 3 years, an average yearly accrual was 127 patients. In the first 9 months, time from injury to randomization was 4.5 +/- 1.2 h; time to achievement of target temperature was 11.7 +/- 2.6 h. In years when waiver of consent was permitted, randomization time was 4.1 +/- 1.1 h, and time to target temperature was 7.9 +/- 2.7 h. For all years of the study, waiver of consent was used for 53% of minorities, 47% of unskilled workers, 33% of nonminorities, and 29% of skilled or professional workers. Minorities were underrepresented by 30% in the first 9 months of the study. We conclude that it is impracticable and unjust to perform studies of acute brain injury without use of waiver of consent when the treatment window is less than 6 h. PMID:12427322

  14. 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.,…

  15. Differentiation of Brain Damage Among Low IQ Subjects with Three Projective Techniques

    ERIC Educational Resources Information Center

    Wagner, Edwin E.; And Others

    1978-01-01

    The Rorschach, Hand, and Bender-Gestalt tests discriminated slightly between low IQ subjects classified as brain damaged or not. Substantial discrimination was observed between the same subjects classified by intelligence level. Brain impairment may underlie most or all retardation. The efficacy of projective techniques for diagnosing organicity…

  16. Inferencing Processes after Right Hemisphere Brain Damage: Effects of Contextual Bias

    ERIC Educational Resources Information Center

    Blake, Margaret Lehman

    2009-01-01

    Purpose: Comprehension deficits associated with right hemisphere brain damage (RHD) have been attributed to an inability to use context, but there is little direct evidence to support the claim. This study evaluated the effect of varying contextual bias on predictive inferencing by adults with RHD. Method: Fourteen adults with no brain damage…

  17. 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,…

  18. Acute Gonadotroph and Somatotroph Hormonal Suppression after Traumatic Brain Injury

    PubMed Central

    Wagner, Justin; Dusick, Joshua R.; McArthur, David L.; Cohan, Pejman; Wang, Christina; Swerdloff, Ronald; Boscardin, W. John

    2010-01-01

    Abstract Hormonal dysfunction is a known consequence of moderate and severe traumatic brain injury (TBI). In this study we determined the incidence, time course, and clinical correlates of acute post-TBI gonadotroph and somatotroph dysfunction. Patients had daily measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, growth hormone, and insulin-like growth factor-1 (IGF-1) for up to 10 days post-injury. Values below the fifth percentile of a healthy cohort were considered abnormal, as were non-measurable growth hormone (GH) values. Outcome measures were frequency and time course of hormonal suppression, injury characteristics, and Glasgow Outcome Scale (GOS) score. The cohort consisted of 101 patients (82% males; mean age 35 years; Glasgow Coma Scale [GCS] score ≤8 in 87%). In men, 100% had at least one low testosterone value, and 93% of all values were low; in premenopausal women, 43% had at least one low estradiol value, and 39% of all values were low. Non-measurable GH levels occurred in 38% of patients, while low IGF-1 levels were observed in 77% of patients, but tended to normalize within 10 days. Multivariate analysis revealed associations of younger age with low FSH and low IGF-1, acute anemia with low IGF-1, and older age and higher body mass index (BMI) with low GH. Hormonal suppression was not predictive of GOS score. These results indicate that within 10 days of complicated mild, moderate, and severe TBI, testosterone suppression occurs in all men and estrogen suppression occurs in over 40% of women. Transient somatotroph suppression occurs in over 75% of patients. Although this acute neuroendocrine dysfunction may not be TBI-specific, low gonadal steroids, IGF-1, and GH may be important given their putative neuroprotective functions. PMID:20214417

  19. 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.

  20. 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.

  1. 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.

  2. 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

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

    PubMed

    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

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Computed tomography of the brain in children with minimal brain damage: a preliminary study of 46 children.

    PubMed

    Bergström, K; Bille, B

    1978-11-01

    Forty-six children aged 4 to 15 years with minimal brain damage (MBD) underwent computed cranial tomography (CT). The criteria used for a diagnosis of MDB was the presence of clinical features of a developmental disturbance of the central nervous system causing incoordination. CT revealed abnormalities in 15 cases (32.6%), consisting in cerebral atrophy, asymmetry or an anomaly.

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

    PubMed

    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

  13. 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

  14. Effect of lacosamide on structural damage and functional recovery after traumatic brain injury in rats.

    PubMed

    Pitkänen, A; Immonen, R; Ndode-Ekane, X; Gröhn, O; Stöhr, T; Nissinen, J

    2014-05-01

    In a subgroup of patients, traumatic brain injury (TBI) results in the occurrence of acute epileptic seizures or even status epilepticus, which are treated with antiepileptic drugs (AEDs). Recent experimental data, however, suggest that administration of AEDs at the early post-injury phase can compromise the recovery process. The present study was designed to assess the profile of a novel anticonvulsant, lacosamide (Vimpat) on post-TBI structural, motor and cognitive outcomes. Moderate TBI was induced by lateral fluid-percussion injury in adult rats. Treatment with 0.9% saline or lacosamide (30 mg/kg, i.p.) was started at 30 min post-injury and continued at 8h intervals for 3d (total daily dose 90 mg/kg/d). Rats were randomly assigned to 4 treatment groups: sham-operated controls treated with vehicle (Sham-Veh) or lacosamide (Sham-LCM) and injured animals treated with vehicle (TBI-Veh) or lacosamide (TBI-LCM). As functional outcomes we tested motor recovery with composite neuroscore and beam-walking at 2, 7, and 15 d post-injury. Cognitive recovery was tested with the Morris water-maze at 12-14 d post-TBI. To assess the structural outcome, animals underwent magnetic resonance imaging (MRI) at 2 d post-TBI. At 16d post-TBI, rats were perfused for histology to analyze cortical and hippocampal neurodegeneration and axonal damage. Our data show that at 2 d post-TBI, both the TBI-Veh and TBI-LCM groups were equally impaired in neuroscore. Thereafter, motor recovery occurred similarly during the first week. At 2 wk post-TBI, recovery of the TBI-LCM group lagged behind that in the TBI-VEH group (p<0.05). Performance in beam-walking did not differ between the TBI-Veh and TBI-LCM groups. Both TBI groups were similarly impaired in the Morris water-maze at 2 wk post-TBI. MRI and histology did not reveal any differences in the cortical or hippocampal damage between the TBI-Veh and TBI-LCM groups. Taken together, acute treatment with LCM had no protective effects on post

  15. Korean red ginseng ameliorates acute 3-nitropropionic acid-induced cochlear damage in mice.

    PubMed

    Tian, Chunjie; Kim, Young Ho; Kim, Young Chul; Park, Kyung Tae; Kim, Seung Won; Kim, Youn Ju; Lim, Hye Jin; Choung, Yun-Hoon

    2013-01-01

    3-Nitropropionic acid (3-NP), a mitochondrial toxin, has been reported to induce an acute cochlear damage. Korean red ginseng (KRG) is known to have protective effects from some types of hearing loss. This study aimed to observe the protective effect of KRG in an ototoxic animal model using 3-NP intratympanic injection. BALB/c mice were classified into 5 groups (n=15) and dose-dependent toxic effects after intratympanic injection with 3-NP (300-5000 mM) on the left ear were investigated to determine the appropriate toxicity level of 3-NP. For observation of the protective effects of KRG, 23 mice were grouped into 3-NP (500 mM, n=12) and KRG+3-NP groups (300 mg/kg KRG for 7 days before 500 mM 3-NP administration, n=11). Auditory brain response (ABR) and cochlear morphological evaluations were performed before and after drug administration. The ABR thresholds in the 800-5000 mM groups exceeded the maximum recording limit at 16 and 32 kHz 1 day after 3-NP administration. The ABR threshold in the 500 mM 3-NP+KRG group was significantly lower than that in the 500 mM 3-NP group from post 1 week to 1 month. The mean type II fibrocyte counts significantly differed between the control and 3-NP groups and between the 3-NP and 3-NP+KRG groups. Spiral ganglion cell degeneration in the 3-NP group was more severe than that in the 3-NP+KRG group. This animal model exhibited a dose-dependent hearing loss with histological changes. KRG administration ameliorated the deterioration of hearing by 3-NP. PMID:23164932

  16. SUSPECTED EARLY MINIMAL BRAIN DAMAGE AND SEVERE PSYCHOPATHOLOGY IN ADOLESCENCE.

    ERIC Educational Resources Information Center

    POLLACK, MAX

    A GROUP OF ADOLESCENT AND YOUNG ADULT HOSPITALIZED PSYCHIATRIC PATIENTS (10 MALES AND TWO FEMALES) PREVIOUSLY DIAGNOSED AS HAVING SCHIZOPHRENIC OR PERSONALITY DISORDERS WERE REDIAGNOSED AS HAVING CHRONIC BRAIN SYNDROME. DEVELOPMENTAL DEVIANCY, BEHAVIOR DISORDERS STARTING IN CHILDHOOD, AND PSYCHOLOGICAL TEST PERFORMANCES WERE COMPATIBLE WITH AN…

  17. Hyperbaric oxygen suppresses hypoxic-ischemic brain damage in newborn rats.

    PubMed

    Zhu, Min; Lu, Mengru; Li, Qing-Jie; Zhang, Zhuo; Wu, Zheng-Zheng; Li, Jie; Qian, Lai; Xu, Yun; Wang, Zhong-Yuan

    2015-01-01

    The optimal therapeutic time-window and protective mechanism of hyperbaric oxygen in hypoxic-ischemic brain damage remain unclear. This study aimed to determine the neuroprotective effects of hyperbaric oxygen. Following hypoxic-ischemic brain damage modeling in neonatal rats, hyperbaric oxygen was administered at 6, 24, 48, and 72 hours and 1 week after hypoxia, respectively, once daily for 1 week. Fourteen days after hypoxic-ischemic brain damage, cell density and apoptosis rate, number of Fas-L+, caspase-8+, and caspase-3+ neuronal cells, levels of nitric oxide, malondialdehyde, and superoxide dismutase in hippocampus were examined. Morris water maze test was conducted 28 days after insult. Significant improvements were found in cell density, rate of apoptosis, oxidative stress markers, FasL, and caspases in rats treated with hyperbaric oxygen within 72 hours compared to hypoxic-ischemic injury. Similarly, time-dependent behavioral amelioration was observed in pups treated with hyperbaric oxygen. Our findings suggest that hyperbaric oxygen protects against hypoxic-ischemic brain damage by inhibiting oxidative stress and FasL-induced apoptosis, and optimal therapeutic time window is within 72 hours after hypoxic-ischemic brain damage.

  18. Stimulation of brain muscarinic acetylcholine receptors acutely reverses radiogenic hypodipsia

    SciTech Connect

    Mickley, G.A.; Stevens, K.E.

    1986-03-01

    A sufficiently large dose of ionizing radiation produces changes in water consumption. However, the direction, durations, and physiological substrates of these alterations remain in question. Here we report a 5-d hypodipsia in rats exposed to 600 rads /sup 60/Co but a more transient, albeit larger, reduction in drinking after 1000 /sup 60/Co. Brain cholinergic neurons have been implicated as mediators of thirst. Therefore, we explored the role of hypothalamic muscarinic receptors in the production of radiation-induced hypodipsia. This was accomplished through the intrahypothalamic injection of carbachol (a muscarinic agonist) or atropine (a muscarinic antagonist) in irradiated rats. Intracranial carbachol produced acute reversal of radiogenic hypodipsia while atropine potentiated the hypodipsia. These post-irradiation drug-induced behaviors were similar to those observed after the same drug treatments before irradiation. Since cholinergic neuronal functions persist and are labile (can be pharmacologically stimulated and blocked) after irradiation, this suggests that other neuronal systems and/or neurochemicals may be more prominently involved in radiogenic hypodipsia.

  19. Effect of acute and chronic hypernatremia on myoinositol and sorbitol concentration in rat brain and kidney.

    PubMed

    Lohr, J W; McReynolds, J; Grimaldi, T; Acara, M

    1988-01-01

    In animal models of hypernatremia, increases in brain electrolyte content account for the entire increase in osmolality in acute but not chronic hypernatremia, suggesting that there is generation of additional intracellular solutes ("idiogenic osmoles") in chronic hypernatremic states. In the present study, the concentration of the polyols myoinositol and sorbitol and water content were determined in the brain and kidneys of rats made acutely (2 hours) and chronically (72 hours) hypernatremic by intraperitoneal injection of NaCl and water restriction. Both the brain and the kidney responded to chronic hypernatremia with increased levels of myoinositol. Sorbitol levels increased in the kidney in response to both acute and chronic hypernatremia. Water content dropped in acute hypernatremia, but remained unchanged during chronic hyperosmolar challenge. We conclude that the polyols, myoinositol and sorbitol, may play a significant role in cellular osmoregulation in brain and kidney during chronic hypernatremia in the rat.

  20. 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.

  1. 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

  2. Laterality of mental imagery generation and operation: tests with brain-damaged patients and normal adults.

    PubMed

    Hatta, T; Koike, M; Langman, P

    1994-08-01

    The relationships between hemispheric function and components of the imagery process were examined in patients with unilateral right and left brain damage and in intact adult subjects. In the image generation condition, subjects were required to mentally generate Katakana letters corresponding to Hiragana letters displayed on a CRT. The results for the intact adults suggested a left hemisphere superiority, but the unilaterally brain-damaged subjects showed no hemispheric difference in this task. In the imagery operation task (transformation or lateral translation), subjects were asked to find a genuine Kanji among distractors (pseudo-Kanji) that were constructed from two Kanji radicals (themselves real Kanji) that were either displayed in reverse order or shifted apart. The results for both intact adults and patients with unilateral brain damage suggest the superiority of the right hemisphere. PMID:7525640

  3. The Acute Inflammatory Response in Trauma / Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

    PubMed Central

    Namas, R; Ghuma, A; Hermus, L; Zamora, R; Okonkwo, DO; Billiar, TR; Vodovotz, Y

    2009-01-01

    Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI). Inflammation is a finely tuned, dynamic, highly-regulated process that is not inherently detrimental, but rather required for immune surveillance, optimal post-injury tissue repair, and regeneration. The inflammatory response is driven by cytokines and chemokines and is partially propagated by damaged tissue-derived products (Damage-associated Molecular Patterns; DAMP's). DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines. Various animal models of T/HS in mice, rats, pigs, dogs, and non-human primates have been utilized in an attempt to move from bench to bedside. Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS and TBI in the near future. PMID:21483522

  4. 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.

  5. 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.

  6. 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

  7. Concreteness/abstractness of stimulus-words and semantic clustering in right brain-damaged patients.

    PubMed

    Villardita, C; Grioli, S; Quattropani, M C

    1988-12-01

    Fifteen right brain-damaged patients and 15 normal controls were tested for learning, delayed recall and semantic clustering abilities using two lists of two/three-syllable words. The first list consisted of 12 familiar, concrete, high-imageability nouns belonging to three semantic categories and the second of 12 abstract, low-imageability, familiar nouns also belonging to three semantic categories. The right brain-damaged patients proved to have a learning and semantic clustering deficit for concrete but not for abstract words. This was interpreted as evidence for a selective right hemisphere capability for processing concrete, high-imageability words.

  8. 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.

  9. Very Early Administration of Progesterone for Acute Traumatic Brain Injury

    PubMed Central

    Wright, David W.; Yeatts, Sharon D.; Silbergleit, Robert; Palesch, Yuko Y.; Hertzberg, Vicki S.; Frankel, Michael; Goldstein, Felicia C.; Caveney, Angela F.; Howlett-Smith, Harriet; Bengelink, Erin M.; Manley, Geoffrey T.; Merck, Lisa H.; Janis, L. Scott; Barsan, William G.

    2015-01-01

    BACKGROUND Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI. METHODS We conducted a double-blind, multicenter clinical trial in which patients with severe, moderate-to-severe, or moderate acute TBI (Glasgow Coma Scale score of 4 to 12, on a scale from 3 to 15, with lower scores indicating a lower level of consciousness) were randomly assigned to intravenous progesterone or placebo, with the study treatment initiated within 4 hours after injury and administered for a total of 96 hours. Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome, as determined with the use of the stratified dichotomy of the Extended Glasgow Outcome Scale score at 6 months after injury. Secondary outcomes included mortality and the Disability Rating Scale score. RESULTS A total of 882 of the planned sample of 1140 patients underwent randomization before the trial was stopped for futility with respect to the primary outcome. The study groups were similar with regard to baseline characteristics; the median age of the patients was 35 years, 73.7% were men, 15.2% were black, and the mean Injury Severity Score was 24.4 (on a scale from 0 to 75, with higher scores indicating greater severity). The most frequent mechanism of injury was a motor vehicle accident. There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome (relative benefit of progesterone, 0.95; 95% confidence interval [CI], 0.85 to 1.06; P = 0.35). Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group (relative risk, 3.03; CI, 1.96 to 4.66). There were no significant differences in the other prespecified safety outcomes. CONCLUSIONS This clinical trial did not show a

  10. Investigating Metacognition, Cognition, and Behavioral Deficits of College Students with Acute Traumatic Brain Injuries

    ERIC Educational Resources Information Center

    Martinez, Sarah; Davalos, Deana

    2016-01-01

    Objective: Executive dysfunction in college students who have had an acute traumatic brain injury (TBI) was investigated. The cognitive, behavioral, and metacognitive effects on college students who endorsed experiencing a brain injury were specifically explored. Participants: Participants were 121 college students who endorsed a mild TBI, and 121…

  11. 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.

  12. 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…

  13. Structural integrity of medial temporal lobes of patients with acute mild traumatic brain injury.

    PubMed

    Holli-Helenius, Kirsi; Luoto, Teemu M; Brander, Antti; Wäljas, Minna; Iverson, Grant L; Ohman, Juha

    2014-07-01

    Post-traumatic amnesia (PTA) is an acute characteristic of traumatic brain injury (TBI) and the duration of PTA is commonly used to estimate the severity of brain injury. In the context of mild traumatic brain injury (MTBI), PTA is an essential part of the routine clinical assessment. Macroscopic lesions in temporal lobes, especially hippocampal regions, are thought to be connected to memory loss. However, conventional neuroimaging has failed to reveal neuropathological correlates of PTA in MTBI. Texture analysis (TA) is an image analysis technique that quantifies the minor MRI signal changes among image pixels and, therefore, the variations in intensity patterns within the image. The objective of this work was to apply the TA technique to MR images of MTBI patients and control subjects, and to assess the microstructural damage in medial temporal lobes of patients with MTBI with definite PTA. TA was performed for fluid-attenuated inversion recovery (FLAIR) images of 50 MTBI patients and 50 age- and gender-matched controls in the regions of the amygdala, hippocampus, and thalamus. It was hypothesized that 1) there would be statistically significant differences in TA parameters between patients with MTBIs and controls, and 2) the duration of PTA would be related to TA parameters in patients with MTBI. No significant textural differences were observed between patients and controls in the regions of interest (p>0.01). No textural features were observed to correlate with the duration of PTA. Subgroup analyses were conducted on patients with PTA of>1 h, (n=33) and compared the four TA parameters to the age- and gender-matched controls (n=33). The findings were similar. This study did not reveal significant textural changes in medial temporal structures that could be related to the duration of PTA.

  14. Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain

    PubMed Central

    Rump, Travis J.; Muneer, P.M. Abdul; Szlachetka, Adam M.; Lamb, Allyson; Haorei, Catherine; Alikunju, Saleena; Xiong, Huangui; Keblesh, James; Liu, Jianuo; Zimmerman, Matthew C.; Jones, Jocelyn; Donohue, Terrence M.; Persidsky, Yuri; Haorah, James

    2011-01-01

    The studies presented here demonstrate the protective effect of acetyl-L-carnitine (ALC) against alcohol-induced oxidative neuroinflammation, neuronal degeneration, and impaired neurotransmission. Our findings reveal the cellular and biochemical mechanisms of alcohol-induced oxidative damage in various types of brain cells. Chronic ethanol administration to mice caused an increase in inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine adduct formation in frontal cortical neurons but not in astrocytes from brains of these animals. Interestingly, alcohol administration caused a rather selective activation of NADPH oxidase (NOX), which, in turn, enhanced levels of reactive oxygen species (ROS) and 4-hydroxynonenal, but these were predominantly localized in astrocytes and microglia. Oxidative damage in glial cells was accompanied by their pronounced activation (astrogliosis) and coincident neuronal loss, suggesting that inflammation in glial cells caused neuronal degeneration. Immunohistochemistry studies indicated that alcohol consumption induced different oxidative mediators in different brain cell types. Thus, nitric oxide was mostly detected in iNOS-expressing neurons, whereas ROS were predominantly generated in NOX-expressing glial cells after alcohol ingestion. Assessment of neuronal activity in ex vivo frontal cortical brain tissue slices from ethanol-fed mice showed a reduction in long-term potentiation synaptic transmission compared with slices from controls. Coadministration of ALC with alcohol showed a significant reduction in oxidative damage and neuronal loss and a restoration of synaptic neurotransmission in this brain region, suggesting that ALC protects brain cells from ethanol-induced oxidative injury. These findings suggest the potential clinical utility of ALC as a neuroprotective agent that prevents alcohol-induced brain damage and development of neurological disorders. PMID:20708681

  15. Acute stress differentially affects aromatase activity in specific brain nuclei of adult male and female quail.

    PubMed

    Dickens, Molly J; Cornil, Charlotte A; Balthazart, Jacques

    2011-11-01

    The rapid and temporary suppression of reproductive behavior is often assumed to be an important feature of the adaptive acute stress response. However, how this suppression operates at the mechanistic level is poorly understood. The enzyme aromatase converts testosterone to estradiol in the brain to activate reproductive behavior in male Japanese quail (Coturnix japonica). The discovery of rapid and reversible modification of aromatase activity (AA) provides a potential mechanism for fast, stress-induced changes in behavior. We investigated the effects of acute stress on AA in both sexes by measuring enzyme activity in all aromatase-expressing brain nuclei before, during, and after 30 min of acute restraint stress. We show here that acute stress rapidly alters AA in the male and female brain and that these changes are specific to the brain nuclei and sex of the individual. Specifically, acute stress rapidly (5 min) increased AA in the male medial preoptic nucleus, a region controlling male reproductive behavior; in females, a similar increase was also observed, but it appeared delayed (15 min) and had smaller amplitude. In the ventromedial and tuberal hypothalamus, regions associated with female reproductive behavior, stress induced a quick and sustained decrease in AA in females, but in males, only a slight increase (ventromedial) or no change (tuberal) in AA was observed. Effects of acute stress on brain estrogen production, therefore, represent one potential way through which stress affects reproduction.

  16. Evaluation of plasma von Willebrand factor as a biomarker for acute arterial damage in rats.

    PubMed

    Newsholme, S J; Thudium, D T; Gossett, K A; Watson, E S; Schwartz, L W

    2000-01-01

    Plasma von Willebrand factor (vWF) was evaluated as a potential biomarker of acute arterial damage in rats after a vasotoxic dose of the dopaminergic vasodilator, fenoldopam (FP). Male Sprague-Dawley rats were given FP or isotonic saline by subcutaneous injection, and plasma vWF was measured at 2, 6, and 24 hours after challenge. Mean plasma vWF values increased in FP-treated rats compared to controls at 2 hours (167 vs 122%; p < 0.05) and 6 hours postdose (172 vs 130%; p < 0.01) but were comparable to control values after 24 hours. Mesenteric arterial lesions were observed microscopically in all FP-treated rats 24 hours postdose but were not present in rats at 1, 2, 4, 6, or 8 hours after FP challenge. Further, plasma vWF concentrations increased in saline-treated rats after only the minimal perturbation of repeated venipuncture. These results indicate an early, minimal, and transient release of vWF that precedes the onset of morphologically evident vascular damage. The minimal increases in plasma vWF concentrations were of limited predictive value, may be more reflective of an acute-phase reactant response, and were not considered a reliable biomarker of acute FP-induced arterial damage in the rat.

  17. Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure.

    PubMed

    Mishra, D; Flora, S J S

    2008-05-01

    Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain - parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50A ppm sodium arsenite in drinking water) for 10A months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes.

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

    PubMed

    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

    2014-08-01

    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.

  19. 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.

  20. The role of bradykinin B1 and B2 receptors for secondary brain damage after traumatic brain injury in mice

    PubMed Central

    Trabold, Raimund; Erös, Christian; Zweckberger, Klaus; Relton, Jane; Beck, Heike; Nussberger, Juerg; Müller-Esterl, Werner; Bader, Michael; Whalley, Eric; Plesnila, Nikolaus

    2010-01-01

    Inflammatory mechanisms are known to contribute to the pathophysiology of traumatic brain injury (TBI). Since bradykinin is one of the first mediators activated during inflammation, we investigated the role of bradykinin and its receptors in posttraumatic secondary brain damage. We subjected wild-type (WT), B1-, and B2-receptor-knockout mice to controlled cortical impact (CCI) and analyzed tissue bradykinin as well as kinin receptor mRNA and protein expression up to 48 h thereafter. Brain edema, contusion volume, and functional outcome were assessed 24 h and 7 days after CCI. Tissue bradykinin was maximally increased 2 h after trauma (P<0.01 versus sham). Kinin B1 receptor mRNA was upregulated up to four-fold 24 h after CCI. Immunohistochemistry showed that B1 and B2 receptors were expressed in the brain and were significantly upregulated in the traumatic penumbra 1 to 24 h after CCI. B2R−/− mice had significantly less brain edema (−51% versus WT, 24 h; P<0.001), smaller contusion volumes (∼50% versus WT 24 h and 7 d after CCI; P<0.05), and better functional outcome 7 days after TBI as compared with WT mice (P<0.05). The present results show that bradykinin and its B2 receptors play a causal role for brain edema formation and cell death after TBI. PMID:19773800

  1. Computer-Assisted Video Instruction in Training Paraprofessionals to Teach Brain-Damaged Clients.

    ERIC Educational Resources Information Center

    Glang, Ann; And Others

    1990-01-01

    This study evaluated the effects of computer-assisted video instruction (CAVI) on three paraprofessionals' implementation of the firming strategy (which presents new material in alternation with previously learned material) with three severely brain-damaged young men. Results indicated CAVI effectiveness with proficient strategy implementation,…

  2. Perception of Lexical Stress by Brain-Damaged Individuals: Effects on Lexical-Semantic Activation

    ERIC Educational Resources Information Center

    Shah, Amee P.; Baum, Shari R.

    2006-01-01

    A semantic priming, lexical-decision study was conducted to examine the ability of left- and right-brain damaged individuals to perceive lexical-stress cues and map them onto lexical-semantic representations. Correctly and incorrectly stressed primes were paired with related and unrelated target words to tap implicit processing of lexical prosody.…

  3. 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.,…

  4. 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…

  5. 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…

  6. Case studies on remediating memory deficits in brain-damaged individuals.

    PubMed

    Glasgow, R E; Zeiss, R A; Barrera, M; Lewinsohn, P M

    1977-10-01

    Two case reports illustrate the application of mnemonic techniques for the remediation of memory problems common to brain-damaged patients. A clinical paradigm for such work that includes general and specific assessment; laboratory evaluation of intervention strategies, and finally in-vitro application is described.

  7. The effects of acute alcohol administration on the human brain: insights from neuroimaging.

    PubMed

    Bjork, James M; Gilman, Jodi M

    2014-09-01

    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. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'.

  8. 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

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

    PubMed

    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.

  10. MLKL inhibition attenuates hypoxia-ischemia induced neuronal damage in developing brain.

    PubMed

    Qu, Yi; Shi, Jing; Tang, Ying; Zhao, Fengyan; Li, Shiping; Meng, Junjie; Tang, Jun; Lin, Xuemei; Peng, Xiaodong; Mu, Dezhi

    2016-05-01

    Mixed lineage kinase domain-like protein (MLKL) is a critical molecule mediating cell necroptosis. However, its role in brain injury remains obscure. We first investigated the functions and mechanisms of MLKL in mediating neuronal damage in developing brain after hypoxia-ischemia. Neuronal necroptosis was induced by oxygen-glucose deprivation (OGD) plus caspase inhibitor zVAD treatment (OGD/zVAD). We found that two important necroptosis related proteins, receptor-interacting protein 1 and 3 (RIP1, RIP3) were upregulated. Furthermore, the interaction of RIP1-RIP3 with MLKL increased. Inhibition of MLKL through siRNA diminished RIP1-RIP3-MLKL interaction and attenuated neuronal death induced by OGD/zVAD. The translocation of oligomerized MLKL to the neuronal membrane leading to the injury of cellular membrane is the possible new mechanism of neuronal necroptosis. Animal experiment with neonatal rats further proved that MLKL inhibition attenuated brain damage induced by hypoxia-ischemia. These findings suggest that MLKL is a target to attenuate brain damage in developing brain.

  11. Nerve cell damage in mammalian brain after exposure to microwaves from GSM mobile phones.

    PubMed

    Salford, Leif G; Brun, Arne E; Eberhardt, Jacob L; Malmgren, Lars; Persson, Bertil R R

    2003-06-01

    The possible risks of radio-frequency electromagnetic fields for the human body is a growing concern for our society. We have previously shown that weak pulsed microwaves give rise to a significant leakage of albumin through the blood-brain barrier. In this study we investigated whether a pathologic leakage across the blood-brain barrier might be combined with damage to the neurons. Three groups each of eight rats were exposed for 2 hr to Global System for Mobile Communications (GSM) mobile phone electromagnetic fields of different strengths. We found highly significant (p< 0.002) evidence for neuronal damage in the cortex, hippocampus, and basal ganglia in the brains of exposed rats.

  12. 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

  13. 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

  14. 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

  15. DNA Double-Strand Break Repair Genes and Oxidative Damage in Brain Metastasis of Breast Cancer

    PubMed Central

    Evans, Lynda; Duchnowska, Renata; Reed, L. Tiffany; Palmieri, Diane; Qian, Yongzhen; Badve, Sunil; Sledge, George; Gril, Brunilde; Aladjem, Mirit I.; Fu, Haiqing; Flores, Natasha M.; Gökmen-Polar, Yesim; Biernat, Wojciech; Szutowicz-Zielińska, Ewa; Mandat, Tomasz; Trojanowski, Tomasz; Och, Waldemar; Czartoryska-Arlukowicz, Bogumiła; Jassem, Jacek; Mitchell, James B.

    2014-01-01

    Background Breast cancer frequently metastasizes to the brain, colonizing a neuro-inflammatory microenvironment. The molecular pathways facilitating this colonization remain poorly understood. Methods Expression profiling of 23 matched sets of human resected brain metastases and primary breast tumors by two-sided paired t test was performed to identify brain metastasis–specific genes. The implicated DNA repair genes BARD1 and RAD51 were modulated in human (MDA-MB-231-BR) and murine (4T1-BR) brain-tropic breast cancer cell lines by lentiviral transduction of cDNA or short hairpin RNA (shRNA) coding sequences. Their functional contribution to brain metastasis development was evaluated in mouse xenograft models (n = 10 mice per group). Results Human brain metastases overexpressed BARD1 and RAD51 compared with either matched primary tumors (1.74-fold, P < .001; 1.46-fold, P < .001, respectively) or unlinked systemic metastases (1.49-fold, P = .01; 1.44-fold, P = .008, respectively). Overexpression of either gene in MDA-MB-231-BR cells increased brain metastases by threefold to fourfold after intracardiac injections, but not lung metastases upon tail-vein injections. In 4T1-BR cells, shRNA-mediated RAD51 knockdown reduced brain metastases by 2.5-fold without affecting lung metastasis development. In vitro, BARD1- and RAD51-overexpressing cells showed reduced genomic instability but only exhibited growth and colonization phenotypes upon DNA damage induction. Reactive oxygen species were present in tumor cells and elevated in the metastatic neuro-inflammatory microenvironment and could provide an endogenous source of genotoxic stress. Tempol, a brain-permeable oxygen radical scavenger suppressed brain metastasis promotion induced by BARD1 and RAD51 overexpression. Conclusions BARD1 and RAD51 are frequently overexpressed in brain metastases from breast cancer and may constitute a mechanism to overcome reactive oxygen species–mediated genotoxic stress in the metastatic

  16. The potential of neural stem cells to repair stroke-induced brain damage.

    PubMed

    Liu, Yi Ping; Lang, Bradley T; Baskaya, Mustafa K; Dempsey, Robert J; Vemuganti, Raghu

    2009-05-01

    Acute injuries to CNS such as stroke induce neural progenitor proliferation in adult brain which might be an endogenous attempt to self-repair. This process is known to be altered by several exogenous and endogenous modulators including growth factors that could help to reinforce the post-stroke neurogenesis. Increasing the neurogenesis may be a future therapeutic option to decrease the cognitive and behavioral deficits following stroke. In addition, transplantation of various types of stem cells into the injured brain is currently thought to be an exciting option to replace the neurons lost in the post-ischemic brain. These include immortalized stem cell lines, neural progenitors prepared from embryonic and adult animals and mesenchymal stem cells. Using exogenous stem cells in addition to modulating endogenous neurogenesis, we may be able to repair the injured brain after a devastating stroke. This article reviewed the current literature of these two issues. PMID:19283395

  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. Suppression and Facilitation of Pragmatic Performance: Effects of Emotional Content on Discourse Following Right and Left Brain Damage.

    ERIC Educational Resources Information Center

    Bloom, Ronald L.; And Others

    1993-01-01

    This study examined the effect of emotional content on the verbal pragmatic aspects of discourse production in right-brain-damaged (RBD), left-brain-damaged (LBD), and normal control adults. In the nonemotional conditions, LBDs were particularly impaired in pragmatics, whereas in the emotional condition, RBDs demonstrated pragmatic deficits.…

  19. [Neuropathological and morphometrical investigations on the localization of the perinatal hypoxic brain damage (author's transl)].

    PubMed

    Goertchen, R

    1981-01-01

    The localization and extent of nerve cell damage caused by perinatal hypoxia has been examined in 83 cases. In 54% of the cases nerve cell damage was localized in the medulla oblongata, in 40% the thalamus and in one third the substantia grisea centralis was affected by nerve cell necroses. In contrast to the phylogenetically older structures of CNS, nerve cell lesions occurred in our material only in 30% in the cerebral cortex and in 18% of our observation the cerebellar cortex. The results show, that the brain stem is especially vulnerable to perinatal hypoxia, this is at variance with hitherto existing conceptions. In a fourth part of the material, nerve cell damage was found in the medulla spinalis, especially in the columna anterior, After prolonged hypoxia the neuron-glia index in the lamina tecti deviates by 0.0491 from that following peracute anoxia. This caused by loss of nerve cells in the brain stem due to perinatal continuous hypoxia.

  20. 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

  1. Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

    PubMed Central

    la Garza, Francisco Javier Guzmán-de; Ibarra-Hernández, Juan Manuel; Cordero-Pérez, Paula; Villegas-Quintero, Pablo; Villarreal-Ovalle, Claudia Ivette; Torres-González, Liliana; Oliva-Sosa, Norma Edith; Alarcón-Galván, Gabriela; Fernández-Garza, Nancy Esthela; Muñoz-Espinosa, Linda Elsa; Cámara-Lemarroy, Carlos Rodrigo; Carrillo-Arriaga, José Gerardo

    2013-01-01

    OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion. PMID:23917671

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. Erythrocyte membrane fluidity and indices of plasmatic oxidative damage after acute physical exercise in humans.

    PubMed

    Berzosa, C; Gómez-Trullén, E M; Piedrafita, E; Cebrián, I; Martínez-Ballarín, E; Miana-Mena, F J; Fuentes-Broto, L; García, J J

    2011-06-01

    Optimal levels of membrane fluidity are essential for numerous cell functions including cell growth, solute transport and signal transduction. Since exercise enhances free radical production, our aim was to evaluate in healthy male subjects the effects of an acute bout of maximal and submaximal exercise on the erythrocyte membrane fluidity and its possible relation to the oxidative damage overproduction due to exercise. Subjects (n = 34) performed three cycloergometric tests: a continuous progressive exercise, a strenuous exercise until exhaustion and an acute bout of exercise at an intensity corresponding to 70% of maximal work capacity for 30 min. Venous blood samples were collected before and immediately after these exercises. Erythrocyte membrane fluidity was assessed by fluorescence spectroscopy. Plasma malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations and carbonyl content of plasmatic proteins were used as an index of lipid and protein oxidation, respectively. Exercise produced a dramatic drop in the erythrocyte membrane fluidity as compared to resting time, but this was not accompanied by significant changes in the plasmatic MDA and 4-HDA concentrations. The highest erythrocyte membrane rigidity was detected immediately after strenuous exercise until exhaustion was performed. Protein carbonyl levels were higher after exhaustive exercises than at rest. Continuous progressive and strenuous exercises until exhaustion, but not submaximal workload, resulted in a significant enhanced accumulation of carbonylated proteins in the plasma. These findings are consistent with the idea that exercise exaggerates oxidative damage, which may contribute, at least partially, to explain the rigidity in the membrane of the erythrocytes due to acute exercise.

  10. Taurine release in mouse brain stem slices under cell-damaging conditions.

    PubMed

    Saransaari, P; Oja, S S

    2007-01-01

    Taurine has been thought to be essential for the development and survival of neural cells and to protect them under cell-damaging conditions. In the brain stem taurine regulates many vital functions, including cardiovascular control and arterial blood pressure. We have recently characterized the release of taurine in the adult and developing brain stem under normal conditions. Now we studied the properties of preloaded [3H]taurine release under various cell-damaging conditions (hypoxia, hypoglycemia, ischemia, the presence of metabolic poisons and free radicals) in slices prepared from the mouse brain stem from developing (7-day-old) and young adult (3-month-old) mice, using a superfusion system. Taurine release was greatly enhanced under these cell-damaging conditions, the only exception being the presence of free radicals in both age groups. The ischemia-induced release was characterized to consist of both Ca2+-dependent and -independent components. Moreover, the release was mediated by Na+-, Cl--dependent transporters operating outwards, particularly in the immature brain stem. Cl- channel antagonists reduced the release at both ages, indicating that a part of the release occurs through ion channels, and protein kinase C appeared to be involved. The release was also modulated by cyclic GMP second messenger systems, since inhibitors of soluble guanylyl cyclase and phosphodiesterases suppressed ischemic taurine release. The inhibition of phospholipases also reduced taurine release at both ages. This ischemia-induced taurine release could constitute an important mechanism against excitotoxicity, protecting the brain stem under cell-damaging conditions.

  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. Acute toxicity and superficial damage to goldfish from the ionic liquid 1-methyl-3-octylimidazolium bromide.

    PubMed

    Li, Xiao-Yu; Zeng, Shi-Hu; Zhang, Wei-Hong; Liu, Li; Ma, Shuai; Wang, Jian-Ji

    2013-04-01

    In the present study, goldfish toxicity and superficial damage from 1-methyl-3-octylimidazolium bromide ([C8 mim]Br) exposure were evaluated by an acute toxicity test. These results show that the 24-h 50% lethal concentration for [C8 mim]Br in goldfish is 244 mg L(-1) , and this indicates that [C8 mim]Br is a chemical with moderate or low toxicity to organisms. Scanning electronic microscope and histological observations revealed that acute exposure to [C8 mim]Br induced obvious superficial damage to the skin, gill filaments, and intestinal villi of the goldfish, and this suggests that the skin, gills, and intestines may be the first direct targets of the ionic liquid in this fish. Histological examination also indicated that [C8 mim]Br-exposure caused damage to the goldfish's hepatopancreas and kidney, consisting mainly of hepatic cords in a loose connection, hepatic cytoplasmic vacuolation, renal parenchyma vacuolization, and intumescence of the renal tubule. In addition, we found that [C8 mim]Br caused a significant increase in malondialdehyde (MDA) level in the hepatopancreases from these goldfish, and thus we suggest that the MDA level may be a biomarker of [C8 mim]Br-toxicity in goldfish.

  13. Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing blood-brain barrier damage.

    PubMed

    Jiang, Jun; Wang, Wei; Sun, Yong Jun; Hu, Mei; Li, Fei; Zhu, Dong Ya

    2007-04-30

    Curcumin, a member of the curcuminoid family of compounds, is a yellow colored phenolic pigment obtained from powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/reperfusion injury. However, little is known about its mechanism. Disruption of the blood-brain barrier occurs after stroke. Protection of the blood-brain barrier has become an important target of stroke interventions in experimental therapeutic. The objective of the present study was to determine whether curcumin prevents cerebral ischemia/reperfusion injury by protecting blood-brain barrier integrity. We report that a single injection of curcumin (1 and 2 mg/kg, i.v.) 30 min after focal cerebral ischemia/reperfusion in rats significantly diminished infarct volume, improved neurological deficit, decreased mortality, reduced the water content of the brain and the extravasation of Evans blue dye in ipsilateral hemisphere in a dose-dependent manner. In cultured astrocytes, curcumin significantly inhibited inducible nitric oxide synthase (iNOS) expression and NO(x) (Nitrites/nitrates contents) production induced by lipopolysaccharide (LPS)/tumor necrosis factor alpha (TNF(alpha)). Furthermore, curcumin prevented ONOO(-) donor SIN-1-induced cerebral capillaries endothelial cells damage. We concluded that curcumin ameliorates cerebral ischemia/reperfusion injury by preventing ONOO(-) mediated blood-brain barrier damage. PMID:17303117

  14. 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.

  15. Mesenchymal stem cells as a treatment for neonatal ischemic brain damage.

    PubMed

    van Velthoven, Cindy T J; Kavelaars, Annemieke; Heijnen, Cobi J

    2012-04-01

    Mesenchymal stem cell (MSC)-based therapies have been proven effective in experimental models of numerous disorders. Treatment of ischemic brain injury by transplantation of MSCs in neonatal animal models has been shown to be effective in reducing lesion volume and improving functional outcome. The beneficial effect of MSC transplantation to treat neonatal brain injury might be explained by the great plasticity of the neonatal brain. The neonatal brain is still in a developmentally active phase, leading to a better efficiency of MSC transplantation than that observed in experiments using adult models of stroke. Enhanced neurogenesis and axonal remodeling likely underlie the improved functional outcome following MSC treatment after neonatal hypoxic-ischemic (HI) brain injury. With respect to the mechanism of repair by MSCs, MSCs do not survive long term and replace damaged tissue themselves. We propose that MSCs react to the needs of the ischemic cerebral environment by secretion of several growth factors, cytokines, and other bioactive molecules to regulate damage and repair processes. Parenchymal cells react to the secretome of the MSCs and contribute to stimulate repair processes. These intrinsic adaptive properties of MSCs make them excellent candidates for a novel therapy to treat the devastating effects of HI encephalopathy in the human neonate. PMID:22430383

  16. Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment

    PubMed Central

    Irimia, Andrei; Goh, S.-Y. Matthew; Torgerson, Carinna M.; Stein, Nathan R.; Chambers, Micah C.; Vespa, Paul M.; Van Horn, John D.

    2013-01-01

    Objective To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Methods Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. Results We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Conclusion Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. PMID:24011495

  17. 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.

  18. 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

  19. 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

  20. Metabolic fingerprinting to understand therapeutic effects and mechanisms of silybin on acute liver damage in rat

    PubMed Central

    Liang, Qun; Wang, Cong; Li, Binbing; Zhang, Ai-hua

    2015-01-01

    Background: Metabolic fingerprinting is a rapid and noninvasive analysis, representing a powerful approach for the characterization of phenotypes and the distinction of specific metabolic states due to environmental alterations. It has become a valuable analytical approach for the characterization of phenotypes and is the rapidly evolving field of the comprehensive measurement of ideally all endogenous metabolites in bio-samples. Silybin has displayed bright prospects in the prevention and therapy of liver injury, and we had conducted a preliminary exploration on the molecular mechanism of the hepatoprotective effects of silybin. Because the knowledge on the metabolic responses of an acute liver damage rat to the silybin is still scarce, metabolic fingerprinting can provide relevant information on the intrinsic metabolic adjustments. Materials and Methods: Here, the physiological and metabolic changes in the acute liver damage rat were investigated by performing a metabolic analysis. The phenotypic response was assessed by liquid chromatography/mass spectrometry (LC/MS) combined with pattern recognition approaches such as principal components analysis and partial least squares projection to supervised latent structures and discriminant analysis. Multivariate analysis of the data showed trends in scores plots that were related to the concentration of the silybin. Results: Results indicate 10 ions (7 upregulated and 3 downregulated) as differentiating metabolites. Key observations include perturbations of metabolic pathways linked to glutathione metabolism, tryptophan metabolism, cysteine and methionine metabolism, etc., Overall, this investigation illustrates the power of the LC/MS combined with the pattern recognition methods that can engender new insights into silybin affecting on metabolism pathways of an acute liver damage rat. Conclusion: The present study demonstrates that the combination of metabolic fingerprinting with appropriate chemometric analysis is a

  1. 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

  2. [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

  3. 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.

  4. 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.

  5. Infiltrating monocytes promote brain inflammation and exacerbate neuronal damage after status epilepticus.

    PubMed

    Varvel, Nicholas H; Neher, Jonas J; Bosch, Andrea; Wang, Wenyi; Ransohoff, Richard M; Miller, Richard J; Dingledine, Raymond

    2016-09-20

    The generalized seizures of status epilepticus (SE) trigger a series of molecular and cellular events that produce cognitive deficits and can culminate in the development of epilepsy. Known early events include opening of the blood-brain barrier (BBB) and astrocytosis accompanied by activation of brain microglia. Whereas circulating monocytes do not infiltrate the healthy CNS, monocytes can enter the brain in response to injury and contribute to the immune response. We examined the cellular components of innate immune inflammation in the days following SE by discriminating microglia vs. brain-infiltrating monocytes. Chemokine receptor 2 (CCR2(+)) monocytes invade the hippocampus between 1 and 3 d after SE. In contrast, only an occasional CD3(+) T lymphocyte was encountered 3 d after SE. The initial cellular sources of the chemokine CCL2, a ligand for CCR2, included perivascular macrophages and microglia. The induction of the proinflammatory cytokine IL-1β was greater in FACS-isolated microglia than in brain-invading monocytes. However, Ccr2 knockout mice displayed greatly reduced monocyte recruitment into brain and reduced levels of the proinflammatory cytokine IL-1β in hippocampus after SE, which was explained by higher expression of the cytokine in circulating and brain monocytes in wild-type mice. Importantly, preventing monocyte recruitment accelerated weight regain, reduced BBB degradation, and attenuated neuronal damage. Our findings identify brain-infiltrating monocytes as a myeloid-cell subclass that contributes to neuroinflammation and morbidity after SE. Inhibiting brain invasion of CCR2(+) monocytes could represent a viable method for alleviating the deleterious consequences of SE.

  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.

  7. 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

  8. Direct acute tubular damage contributes to Shigatoxin-mediated kidney failure.

    PubMed

    Porubsky, Stefan; Federico, Giuseppina; Müthing, Johannes; Jennemann, Richard; Gretz, Norbert; Büttner, Stefan; Obermüller, Nicholas; Jung, Oliver; Hauser, Ingeborg A; Gröne, Elisabeth; Geiger, Helmut; Gröne, Hermann-Josef; Betz, Christoph

    2014-09-01

    The pathogenesis and therapy of Shigatoxin 2 (Stx2)-mediated kidney failure remain controversial. Our aim was to test whether, during an infection with Stx2-producing E. coli (STEC), Stx2 exerts direct effects on renal tubular epithelium and thereby possibly contributes to acute renal failure. Mice represent a suitable model because they, like humans, express the Stx2-receptor Gb3 in the tubular epithelium but, in contrast to humans, not in glomerular endothelia, and are thus free of glomerular thrombotic microangiopathy (TMA). In wild-type mice, Stx2 caused acute tubular dysfunction with consequent electrolyte disturbance, which was most likely the cause of death. Tubule-specific depletion of Gb3 protected the mice from acute renal failure. In vitro, Stx2 induced secretion of proinflammatory cytokines and apoptosis in human tubular epithelial cells, thus implicating a direct effect of Stx2 on the tubular epithelium. To correlate these results to human disease, kidney biopsies and outcome were analysed in patients with Stx2-associated kidney failure (n = 11, aged 22-44 years). The majority of kidney biopsies showed different stages of an ongoing TMA; however, no glomerular complement activation could be demonstrated. All biopsies, including those without TMA, showed severe acute tubular damage. Due to these findings, patients were treated with supportive therapy without complement-inhibiting antibodies (eculizumab) or immunoadsorption. Despite the severity of the initial disease [creatinine 6.34 (1.31-17.60) mg/dl, lactate dehydrogenase 1944 (753-2792) U/l, platelets 33 (19-124)/nl and haemoglobin 6.2 (5.2-7.8) g/dl; median (range)], all patients were discharged after 33 (range 19-43) days with no neurological symptoms and no dialysis requirement [creatinine 1.39 (range 0.84-2.86) mg/dl]. The creatinine decreased further to 0.90 (range 0.66-1.27) mg/dl after 24 months. Based on these data, one may surmise that acute tubular damage represents a separate

  9. Chronic hypertension aggravates heat stress-induced brain damage: possible neuroprotection by cerebrolysin.

    PubMed

    Muresanu, Dafin Fior; Zimmermann-Meinzingen, Sibilla; Sharma, Hari Shanker

    2010-01-01

    Whole body hyperthermia (WBH) aggravates brain edema formation and cell damage in chronic hypertensive rats compared with normotensive animals. In this investigation, we examined the influence of cerebrolysin on WBH-induced edema formation and brain pathology in hypertensive and normotensive rats. Rats subjected to 4 h WBH at 38 degrees C in a biological oxygen demand (BOD) incubator showed breakdown of the blood-brain barrier (BBB), reduced cerebral blood flow (CBF), edema formation and cell injuries in several parts of the brain. These effects were further aggravated in chronic hypertensive rats (two-kidney one clip model (2K1C), for 4 weeks) subjected to WBH. Pretreatment with cerebrolysin (5 mL/kg, 24 h and 30 min before heat stress) markedly attenuated the BBB dysfunction and brain pathology in normal animals. However, in hypertensive animals, a high dose of cerebrolysin (10 mL/kg, 24 h and 30 min before heat stress) was needed to attenuate WBH-induced BBB dysfunction and brain pathology. These observations indicate that heat stress could affect differently in normal and hypertensive conditions. Furthermore, our results suggest that patients suffering from various chronic cardiovascular diseases may respond differently to hyperthermia and to neuroprotective drugs, e.g., cerebrolysin not reported earlier.

  10. 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

  11. Tertiary mechanisms of brain damage: a new hope for treatment of cerebral palsy?

    PubMed

    Fleiss, Bobbi; Gressens, Pierre

    2012-06-01

    Cerebral palsy is caused by injury or developmental disturbances to the immature brain and leads to substantial motor, cognitive, and learning deficits. In addition to developmental disruption associated with the initial insult to the immature brain, injury processes can persist for many months or years. We suggest that these tertiary mechanisms of damage might include persistent inflammation and epigenetic changes. We propose that these processes are implicit in prevention of endogenous repair and regeneration and predispose patients to development of future cognitive dysfunction and sensitisation to further injury. We suggest that treatment of tertiary mechanisms of damage might be possible by various means, including preventing the repressive effects of microglia and astrocyte over-activation, recapitulating developmentally permissive epigenetic conditions, and using cell therapies to stimulate repair and regeneration Recognition of tertiary mechanisms of damage might be the first step in a complex translational task to tailor safe and effective therapies that can be used to treat the already developmentally disrupted brain long after an insult.

  12. 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

  13. 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

  14. The challenge of mild traumatic brain injury: role of biochemical markers in diagnosis of brain damage.

    PubMed

    Mondello, Stefania; Schmid, Kara; Berger, Rachel P; Kobeissy, Firas; Italiano, Domenico; Jeromin, Andreas; Hayes, Ronal L; Tortella, Frank C; Buki, Andras

    2014-05-01

    During the past decade there has been an increasing recognition of the incidence of mild traumatic brain injury (mTBI) and a better understanding of the subtle neurological and cognitive deficits that may result from it. A substantial, albeit suboptimal, effort has been made to define diagnostic criteria for mTBI and improve diagnostic accuracy. Thus, biomarkers that can accurately and objectively detect brain injury after mTBI and, ideally, aid in clinical management are needed. In this review, we discuss the current research on serum biomarkers for mTBI including their rationale and diagnostic performances. Sensitive and specific biomarkers reflecting brain injury can provide important information regarding TBI pathophysiology and serve as candidate markers for predicting abnormal computed tomography findings and/or the development of residual deficits in patients who sustain an mTBI. We also outline the roles of biomarkers in settings of specific interest including pediatric TBI, sports concussions and military injuries, and provide perspectives on the validation of such markers for use in the clinic. Finally, emerging proteomics-based strategies for identifying novel markers will be discussed.

  15. Acute functional reactivation of the language network during awake intraoperative brain mapping.

    PubMed

    Spena, Giannantonio; Costi, Emanuele; Panciani, Pier Paolo; Roca, Elena; Migliorati, Karol; Fontanella, Marco Maria

    2015-01-01

    Acute brain plasticity during resection of central lesions has been recently described. In the cases reported, perilesional latent networks, useful to preserve the neurological functions, were detected in asymptomatic patients. In this paper, we presented a case of acute functional reactivation (AFR) of the language network in a symptomatic patient. Tumor resection allowed to acutely restore the neurological deficit. Intraoperative direct cortical stimulation (DCS) and functional neuroimaging showed new epicentres of activation of the language network after tumor excision. DCS in awake surgery is mandatory to reveal AFR needful to improve the extent of resection preserving the quality of life.

  16. [Clinical-diagnostic features of the acute period of brain concussion in military personnel].

    PubMed

    Tkachov, A V

    2008-01-01

    The comparative analysis of a complex examination of 78 patients aged 16-45 years in acute period of closed craniocereberal trauma (CCRCT) has been carried out. Physical examination was done on the first 10th and 30th day of the treatment. The author used specially developed multiple-aspect scales and questionnaires for objectification of patient complaints, magnetic resonance tomography, brain electroencephalography. A complex clinical and neuropsychological examination revealed that all cases of brain concussion were accompanied by various signs of asthenic disorders and in 81% of cases--by cognitive disorders. Patients in the acute period of brain concussion had significantly low indicators of cerebral neurodynamics in comparison with healthy individuals. It was shown by increase in signs of irritation, changes of bioelectric activity of the brain that was expressed by considerable blurriness of regional disjunctions and fading of an alpha rhythm. Specific changes of brain tissue in acute period of brain concussion were not registered when CT or MRT were used.

  17. 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.

  18. 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

  19. Interaction of nutrition and binge ethanol treatment on brain damage and withdrawal.

    PubMed

    Crews, F T; Braun, C J; Ali, R; Knapp, D J

    2001-01-01

    To determine if nutrition plays a role in ethanol withdrawal and alcohol-induced brain damage, the effects of a 4-day ethanol binge treatment using ethanol in a nutritionally complete liquid diet compared to ethanol mixed with water were studied. The nutritionally complete diet group (ETOH-diet) received a complete diet of sugars, proteins and fats with vitamins and minerals with approximately 53% of calories from ethanol while the nutritionally deprived group (ETOH-H2O) received 100% of calories from ethanol. No difference in withdrawal behavior was found between the ETOH-diet and ETOH-H2O groups during the 72-hour period studied. In addition, no difference was seen for serum levels of magnesium and zinc taken at last dose or following 72 h of withdrawal. Serum alanine aminotransferase (ALT) and ammonia were increased in both groups with ETOH-diet showing a greater increase in ALT than ETOH-H2O. Both groups showed damage in the olfactory bulb, perirhinal, agranular insular, piriform and lateral entorhinal cortical areas as well as hippocampal dentate gyrus and CA-3. Interestingly, the ETOH-diet group displayed more damage at last dose in the posterior dentate and CA-3 of hippocampus than did the ETOH-H2O group. This study suggests that nutritional components and total caloric intake do not effect behavior during ethanol withdrawal and that a nutritionally complete diet may increase ethanol-induced brain damage.

  20. The role and clinical significance of DNA damage response and repair pathways in primary brain tumors

    PubMed Central

    2013-01-01

    Primary brain tumors, in particular, glioblastoma multiforme (GBM), continue to have dismal survivability despite advances in treating other neoplasms. The goal of new anti-glioma therapy development is to increase their therapeutic ratios by enhancing tumor control and/or decreasing the severity and incidence of side effects. Because radiotherapy and most chemotherapy agents rely on DNA damage, the cell’s DNA damage repair and response (DRR) pathways may hold the key to new therapeutic strategies. DNA double-strand breaks (DSBs) generated by ionizing radiation and chemotherapeutic agents are the most lethal form of damage, and are repaired via either homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways. Understanding and exploitation of the differences in the use of these repair pathways between tumor and normal brain cells will allow for an increase in tumor cell killing and decreased normal tissue damage. A literature review and discussion on new strategies which can improve the anti-glioma therapeutic ratio by differentially targeting HR and NHEJ function in tumor and normal neuronal tissues is the focus of this article. PMID:23388100

  1. 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

  2. Distinct time courses of secondary brain damage in the hippocampus following brain concussion and contusion in rats.

    PubMed

    Nakajima, Yuko; Horiuchi, Yutaka; Kamata, Hiroshi; Yukawa, Masayoshi; Kuwabara, Masato; Tsubokawa, Takashi

    2010-07-01

    Secondary brain damage (SBD) is caused by apoptosis after traumatic brain injury that is classified into concussion and contusion. Brain concussion is temporary unconsciousness or confusion caused by a blow on the head without pathological changes, and contusion is a brain injury with hemorrhage and broad extravasations. In this study, we investigated the time-dependent changes of apoptosis in hippocampus after brain concussion and contusion using rat models. We generated the concussion by dropping a plumb on the dura from a height of 3.5 cm and the contusion by cauterizing the cerebral cortex. SBD was evaluated in the hippocampus by histopathological analyses and measuring caspase-3 activity that induces apoptotic neuronal cell death. The frequency of abnormal neuronal cells with vacuolation or nuclear condensation, or those with DNA fragmentation was remarkably increased at 1 hr after concussion (about 30% for each abnormality) from the pre-injury level (0%) and reached the highest level (about 50% for each) by 48 hrs, whereas the frequency of abnormal neuronal cells was increased at 1 hr after contusion (about 10%) and reached the highest level (about 40%) by 48 hrs. In parallel, caspase-3 activity was increased sevenfold in the hippocampus at 1 hr after concussion and returned to the pre-injury level by 48 hrs, whereas after contusion, caspase-3 activity was continuously increased to the highest level at 48 hrs (fivefold). Thus, anti-apoptotic-cell-death treatment to prevent SBD must be performed by 1 hr after concussion and at latest by 48 hrs after contusion.

  3. 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

  4. Factors that limit brain volume changes in response to acute and sustained hyper- and hyponatremia

    PubMed Central

    Holliday, Malcolm A.; Kalayci, M. N.; Harrah, Jean

    1968-01-01

    Rats were made acutely hyper- or hyponatremic by infusion of hypertonic saline or water, respectively. Other rats were maintained in these states from 1 to 7 days to observe the effects of time. Brain tissue water, Na, Cl, and K were compared with serum Na and Cl concentration (NaE and ClE). The following observations are noted: Brain Cl content varies directly with ClE and brain Na content in the Cl space (Nae) varies directly with NaE, indicating little or no restraint on the inward or outward movement of Na or Cl from the Cl space of brain. The intracellular volume of brain fluid (Vi) derived as the difference between total water and Cl space, decreases with hypernatremia and increases with hyponatremia. The changes in Vi in the acute studies are not accompanied by any change in brain K content, or calculated intracellular Na content, and are approximately 0.6 the changes predicted from osmotic behavior of cells, which apply four assumptions: (a) NaE is proportional to osmolality; (b) brain osmolality remains equal to plasma osmolality; (c) Vi is osmotically active; and (d) there is no net gain or loss of solute from Vi. The validity of these assumptions is considered. When changes in osmolality are sustained, Vi is much closer to control values than when in the acute phase. K content increases in hypernatremia and decreases in hyponatremia. The changes in K content can account for some of the adjustment in Vi observed over the extended period of hyper- or hyponatremia. The regression of (Na + K)/v upon NaE describes a slope less than 1.0 and an intercept of (Na + K)/v equal to 40% of the control (Na + K)/v. These characteristics are interpreted to mean that significant quantities of Na and K in brain are osmotically inactive. The brain protects itself from acute volume changes in response to change in NaE by the freedom for Na and Cl to move from the Cl space, by Vi not changing acutely to the degree predicted from osmotic properties of cells in general, and by

  5. 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…

  6. Reversible acute bilateral blindness resulting from a frontal brain tumor: a case report.

    PubMed

    Hayashi, Koji; Nakada, Mitsutoshi; Miyashita, Katsuyoshi; Hayashi, Yutaka; Hamada, Jun-ichiro

    2014-12-01

    We experienced an unusual case of a 15-year-old girl who suffered acute bilateral blindness caused by a frontal lobe tumour. She underwent emergent operation, after which her vision recovered. This case emphasizes that a brain mass can cause sudden onset blindness and an emergency intervention might save the patient's sight.

  7. Line and word bisection in right-brain-damaged patients with left spatial neglect.

    PubMed

    Veronelli, Laura; Vallar, Giuseppe; Marinelli, Chiara V; Primativo, Silvia; Arduino, Lisa S

    2014-01-01

    Right-brain-damaged patients with left unilateral spatial neglect typically set the mid-point of horizontal lines to the right of the objective center. By contrast, healthy participants exhibit a reversed bias (pseudoneglect). The same effect has been described also when bisecting orthographic strings. In particular, for this latter kind of stimulus, some recent studies have shown that visuo-perceptual characteristics, like stimulus length, may contribute to both the magnitude and the direction bias of the bisection performance (Arduino et al. in Neuropsychologia 48:2140-2146, 2010). Furthermore, word stress was shown to modulate reading performances in both healthy participants, and patients with left spatial neglect and neglect dyslexia (Cubelli and Beschin in Brain Lang 95:319-326, 2005; Rusconi et al. in Neuropsychology 18:135-140, 2004). In Experiment I, 22 right-brain-damaged patients (11 with left visuo-spatial neglect) and 11 matched neurologically unimpaired control participants were asked to set the subjective mid-point of word letter strings, and of lines of comparable length. Most patients exhibited an overall disproportionate rightward bias, sensitive to stimulus length, and similar for words and lines. Importantly, in individual patients, biases differed according to stimulus type (words vs. lines), indicating that at least partly different mechanisms may be involved. In Experiment II, the putative effects on the bisection bias of ortho-phonological information (i.e., word stress endings), arising from the non-neglected right hand side of the stimulus were investigated. The orthographic cue induced a rightward shift of the perceived mid-point in both patients and controls, with short words stressed on the antepenultimate final sequence inducing a smaller rightward deviation with respect to short words stressed on the penultimate final sequence. In conclusion, partly different mechanisms, including both visuo-spatial and lexical factors, may support

  8. 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

  9. 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

  10. Treatment with nicardipine protects brain in an animal model of hypertension-induced damage.

    PubMed

    Amenta, Francesco; Tomassoni, Daniele

    2004-05-01

    Control of blood pressure protects from the development of cerebrovascular lesions and vascular dementia (VaD). This study has assessed the influence of treatment with the dihydropyridine-type Ca2+ antagonist nicardipine on brain microanatomical changes in spontaneously hypertensive rats (SHR). SHR were treated from 16th to 26th week of age with hypotensive (3 mg/Kg/day) or non-hypotensive (0.1 mg/Kg/day) doses of nicardipine, with the non-dihydropyridine-type vasodilator hydralazine (10 mg/kg/day) or with vehicle (control group). Untreated age-matched Wistar Kyoto (WKY) rats were used as a normotensive reference group. Brain volume, number of neurons, glial fibrillary-acidic protein (GFAP)-immunoreactive astrocytes and neurofilament 200 KDa (NFP)-immunoreactivity (IR) were assessed in frontal and occipital cortex, hippocampus and striatum. A decrease of volume and number of nerve cells and a loss of NFP-IR was found in the frontal and occipital cortex and in the CA1 subfield of hippocampus and in the striatum of SHR. Treatment with nicardipine countered microanatomical changes occurring in SHR, whereas hydralazine displayed a less pronounced effect. Comparatively, the non-hypotensive dose of nicardipine was less active than the hypotensive one. The observation that equihypotensive doses of nicardipine or hydralazine did not protect brain in the same way from hypertensive brain damage suggests that lowering blood pressure is per se not enough for affording neuroprotection. The demonstration of neuroprotective effect of nicardipine suggests an use of the compound in situations in which hypertension is accompanied by the risk of brain damage.

  11. 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.

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

    PubMed

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

    2015-09-01

    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.

  13. Acute neuroprotective effects of extremely low-frequency electromagnetic fields after traumatic brain injury in rats.

    PubMed

    Yang, Yang; Li, Ling; Wang, Yan-Gang; Fei, Zhou; Zhong, Jun; Wei, Li-Zhou; Long, Qian-Fa; Liu, Wei-Ping

    2012-05-10

    Traumatic brain injury commonly has a result of a short window of opportunity between the period of initial brain injury and secondary brain injury, which provides protective strategies and can reduce damages of brain due to secondary brain injury. Previous studies have reported neuroprotective effects of extremely low-frequency electromagnetic fields. However, the effects of extremely low-frequency electromagnetic fields on neural damage after traumatic brain injury have not been reported yet. The present study aims to investigate effects of extremely low-frequency electromagnetic fields on neuroprotection after traumatic brain injury. Male Sprague-Dawley rats were used for the model of lateral fluid percussion injury, which were placed in non-electromagnetic fields and 15 Hz (Hertz) electromagnetic fields with intensities of 1 G (Gauss), 3 G and 5 G. At various time points (ranging from 0.5 to 30 h) after lateral fluid percussion injury, rats were treated with kainic acid (administered by intraperitoneal injection) to induce apoptosis in hippocampal cells. The results were as follows: (1) the expression of hypoxia-inducible factor-1α was dramatically decreased during the neuroprotective time window. (2) The kainic acid-induced apoptosis in the hippocampus was significantly decreased in rats exposed to electromagnetic fields. (3) Electromagnetic fields exposure shortened the escape time in water maze test. (4) Electromagnetic fields exposure accelerated the recovery of the blood-brain barrier after brain injury. These findings revealed that extremely low-frequency electromagnetic fields significantly prolong the window of opportunity for brain protection and enhance the intensity of neuroprotection after traumatic brain injury.

  14. 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

  15. 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.

  16. 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.

  17. Can neuropsychological testing produce unequivocal evidence of brain damage? II. Testing for right vs. left differences.

    PubMed

    Reitan, Ralph M; Wolfson, Deborah

    2008-01-01

    Sensation and perception, as well as motor functions, have played an important role in the history of psychology. Although tests of these abilities are sometimes included in neuropsychological assessments, comparisons of intraindividual performances on the two sides of the body (as a basis for drawing conclusions and comparisons about the functional status of the two cerebral hemispheres) are in many instances neglected or considered only casually. This study, utilizing several motor and sensory-perceptual tests, compared intraindividual differences on the two sides of the body in a group of controls and a group of persons with brain damage. The results indicated that the sensory-perceptual tests were particularly effective in differentiating the groups. More than 60% of the group with brain damage had greater differences on the two sides of the body than did any of the controls. These findings suggest that a substantial proportion of persons with cerebral disease or damage may be subject to unequivocal identification using sensory-perceptual tests that take only about 20 minutes to administer. These tests may serve a valuable role as an adjunct to comprehensive neuropsychological evaluation and should be further evaluated in this respect.

  18. The neural correlates of abstract and concrete words: evidence from brain-damaged patients.

    PubMed

    Papagno, Costanza; Martello, Giorgia; Mattavelli, Giulia

    2013-08-07

    Neuropsychological and activation studies on the neural correlates of abstract and concrete words have produced contrasting results. The present study explores the anatomical substrates of abstract/concrete words in 22 brain-damaged patients with a single vascular lesion either in the right or left hemisphere. One hundred and twenty (60 concrete and 60 abstract) noun triplets were used for a semantic similarity judgment task. We found a significant interaction in word type × group since left temporal brain-damaged patients performed significantly better with concrete than abstract words. Lesion mapping of patients with predominant temporal damage showed that the left superior and middle temporal gyri and the insula were the areas of major overlapping, while the anterior portion of the left temporal lobe was generally spared. Errors on abstract words mainly concerned (although at a non-significant level) semantically associate targets, while in the case of concrete words, coordinate targets were significantly more impaired than associate ones. Our results suggest that the left superior and middle temporal gyri and the insula are crucial regions in processing abstract words. They also confirm the hypothesis of a semantic similarity vs. associative organization of concrete and abstract concepts.

  19. 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

  20. 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

  1. 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

  2. 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

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

    PubMed

    Darbah, Joseph N T; Jones, Wendy S; Burton, Andrew J; Nagy, John; Kubiske, Mark E

    2011-09-01

    We studied the effect of high ozone (O(3)) concentration (110-490 nmol mol(-1)) on regenerating aspen (Populus tremuloides) and maple (Acer saccharum) trees at an open-air O(3) pollution experiment near Rhinelander WI USA. This study is the first of its kind to examine the effects of acute O(3) exposure on aspen and maple sprouts after the parent trees, which were grown under elevated O(3) and/or CO(2) for 12 years, were harvested. Acute O(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(3) damage contrary to expectations. Stomatal conductance played a primary role in the severity of acute O(3) damage as it directly controlled O(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(3) exposure. Moreover, elevated CO(2) did not ameliorate the adverse effects of acute O(3) dose on aspen and maple sprouts, in contrast to its ability to counteract the effects of long-term chronic exposure to lower O(3) levels.

  4. 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.

  5. 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

  6. Exposure of rats to ozone: evidence of damage to heart and brain

    SciTech Connect

    Rahman, I.; Massaro, G.D.; Massaro, D. )

    1992-01-01

    Ozone is a strong oxidizing agent, and in many locations it is a major atmospheric pollutant. It is phytotoxic and an important cause of lung dysfunction in humans. Recently, a significant association has been established between total atmospheric oxidants, of which ozone is one, and daily cardiovascular mortality rates. In this article, we show that exposure of rats to ozone for 5 days, in a concentration found in major urban centers, results in an increased concentration of thiobarbituric acid-reactive material (an indicator of lipid peroxidation) in heart and brain tissue as well as elevated activity of catalase and glutathione peroxidase (enzymic scavengers of peroxides) in these tissues. We examined the heart anatomically and found evidence of extracellular and intracellular edema. These findings indicate that the heart and brain are damaged by a concentration of ozone present in major urban centers; they may have important implications for chronic illness and degenerative processes in humans.

  7. Syzigium cumini seed extracts reduce tissue damage in diabetic rat brain.

    PubMed

    Stanely Mainzen Prince, P; Kamalakkannan, N; Menon, Venugopal P

    2003-02-01

    Syzigium cumini commonly known as Jamun, is widely used in different parts of India for the treatment of diabetes mellitus. Oral administration of an aqueous Jamun seed extract (JSEt) for 6 weeks caused a significant decrease in lipids, thiobarbituric acid reactive substances (TBARS) and an increase in catalase and superoxide dismutase in the brain of alloxan induced diabetic rats. Oral administration of an alcoholic JSEt for 6 weeks brought back all the parameters to near normal. The effect of alcoholic JSEt (100 mg/kg) was better than aqueous JSEt (5 g/kg). The effect of both these extracts was better than glibenclamide (600 microg/kg). Thus, our study shows that S. cumini seed extracts reduce tissue damage in diabetic rat brain. PMID:12648817

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

    PubMed

    Lutter, Christoph; Pfefferkorn, Ronny; Schoeffl, Volker

    2016-07-19

    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.

  9. Preventive effect of safranal against oxidative damage in aged male rat brain

    PubMed Central

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Samini, Fariborz

    2014-01-01

    An imbalance between production of reactive oxygen species (ROS) and its elimination by antioxidant defense system in the body has been implicated for causes of aging and neurodegenerative diseases. This study was design to assess the changes in activities of antioxidant enzymes (superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase), lipid peroxidation and reduced glutathione (GSH) levels in the brain of 2, 10 and 20 month old rats, and to determine the effect of safranal on the status of selected oxidative stress indices in the 10 and 20 month old rats. The aged rats (10 and 20 months) were given intraperitoneal injections of safranal (0.5 mg/kg day) daily for one month. The results of this study demonstrated that aging caused significant increase in the level of lipid peroxidation as well decrease in the GSH level and activities of SOD and GST in the brain of aging rats. The results of this study showed that safranal ameliorated the increased lipid peroxidation level as well as decreased GSH content of the brain of 10 and 20 month old rats. In addition, safranal treatment to the 20 month old rats, which restored the SOD and GST activities. In conclusion, safranal can be effective to protect susceptible aged brain from oxidative damage by increasing antioxidant defenses. PMID:25312506

  10. Plumbagin alters telomere dynamics, induces DNA damage and cell death in human brain tumour cells.

    PubMed

    Khaw, Aik Kia; Sameni, Safoura; Venkatesan, Shriram; Kalthur, Guruprasad; Hande, M Prakash

    2015-11-01

    Natural plant products may possess much potential in palliative therapy and supportive strategies of current cancer treatments with lesser cytotoxicity to normal cells compared to conventional chemotherapy. In the current study, anti-cancer properties of plumbagin, a plant-derived naphthoquinone, on brain cancer cells were determined. Plumbagin treatment resulted in the induction of DNA damage, cell cycle arrest and apoptosis, followed by suppression of the colony forming ability of the brain tumour cells. These effects were substantiated by upregulation of PTEN, TNFRSF1A and downregulation of E2F1 genes, along with a drop in MDM2, cyclin B1, survivin and BCL2 protein expression. Plumbagin induced elevated levels of caspase-3/7 activity as well. For the first time, we show here that plumbagin inhibits telomerase in brain tumour cells and results in telomere shortening following chronic long-term treatment. This observation implies considerable cytotoxicity of plumbagin towards cancer cells with higher telomerase activity. Collectively, our findings suggest plumbagin as a potential chemotherapeutic phytochemical in brain tumour treatment modalities.

  11. 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

  12. 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.

  13. Rehabilitation for cognitive-communication disorders in right hemisphere brain damage.

    PubMed

    Tompkins, Connie A

    2012-01-01

    Although the left hemisphere of the brain has long been linked with language, the right cerebral hemisphere also contributes importantly to cognitive operations that underlie language processing and communicative performance. Adults with right hemisphere damage (RHD) typically do not have aphasia, but they often have communication disorders that may have a substantial impact on their social functioning. After a brief summary of communicative and cognitive characteristics of RHD in adults and of extant theoretical accounts of common communicative difficulties, this article discusses rehabilitation issues, approaches, evidence, and needs.

  14. 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

  15. Tool use in left brain damage and Alzheimer's disease: What about function and manipulation knowledge?

    PubMed

    Jarry, Christophe; Osiurak, François; Besnard, Jérémy; Baumard, Josselin; Lesourd, Mathieu; Croisile, Bernard; Etcharry-Bouyx, Frédérique; Chauviré, Valérie; Le Gall, Didier

    2016-03-01

    Tool use disorders are usually associated with difficulties in retrieving function and manipulation knowledge. Here, we investigate tool use (Real Tool Use, RTU), function (Functional Association, FA) and manipulation knowledge (Gesture Recognition, GR) in 17 left-brain-damaged (LBD) patients and 14 AD patients (Alzheimer disease). LBD group exhibited predicted deficit on RTU but not on FA and GR while AD patients showed deficits on GR and FA with preserved tool use skills. These findings question the role played by function and manipulation knowledge in actual tool use. PMID:26765078

  16. Evidence of nitrosative damage in the brain white matter of patients with multiple sclerosis.

    PubMed

    Bizzozero, Oscar A; DeJesus, Gisela; Bixler, Heather A; Pastuszyn, Andrzej

    2005-01-01

    Nitric oxide (NO) has been implicated in the pathophysiology of both experimental autoimmune encephalomyelitis and multiple sclerosis (MS). NO-mediated protein damage in MS appears to be confined to large plaques where 3-nitrotyrosine has been detected. To determine whether nitrosative damage takes place beyond visible MS plaques, the occurrence of various NO-triggered protein modifications in normal-appearing white matter (NAWM) of eight MS brains was assessed and compared to that in white matter (WM) of four control brains. As determined by amino acid analysis and western blotting, no evidence of tyrosine nitration was found in the MS samples studied, suggesting that they did not contain appreciable amounts of plaque-derived material. The amino acid composition of total myelin proteins and proteolipid protein (PLP) was also unaltered in the diseased tissue, as was the fatty acid composition of PLP. In addition, we detected no changes in the number of protein free thiols suggesting that oxidation do not occur to any appreciable extent. However, the levels of nitrite in MS-NAWM were higher than those in control WM, while in the MS-gray matter (GM) the concentration of this ion was unaltered. Furthermore, five of the MS samples analyzed, and the same as those with high levels of glial fibrilary acidic protein, showed increased amounts of protein nitrosothiols as determined by the "biotin switch" method. S-nitrosation of GM proteins was again normal. There was no indication of N-nitrosation of tryptophan and N-terminal amino groups in both control and MS tissue. Overall, the data suggests that WM, but not GM, from MS brains is subjected to considerable nitrosative stress. This is the first report to present direct evidence of increased protein S-nitrosation and nitrite content in the brain parenchyma of MS patients.

  17. 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.

  18. 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.

  19. Characterization of empathy deficits following prefrontal brain damage: the role of the right ventromedial prefrontal cortex.

    PubMed

    Shamay-Tsoory, S G; Tomer, R; Berger, B D; Aharon-Peretz, J

    2003-04-01

    Impaired empathic response has been described in patients following brain injury, suggesting that empathy may be a fundamental aspect of the social behavior disturbed by brain damage. However, the neuroanatomical basis of impaired empathy has not been studied in detail. The empathic response of patients with localized lesions in the prefrontal cortex (n = 25) was compared to responses of patients with posterior (n = 17) and healthy control subjects (n = 19). To examine the cognitive processes that underlie the empathic ability, the relationships between empathy scores and the performance on tasks that assess processes of cognitive flexibility, affect recognition, and theory of mind (TOM) were also examined. Patients with prefrontal lesions, particularly when their damage included the ventromedial prefrontal cortex, were significantly impaired in empathy as compared to patients with posterior lesions and healthy controls. However, among patients with posterior lesions, those with damage to the right hemisphere were impaired, whereas those with left posterior lesions displayed empathy levels similar to healthy controls. Seven of nine patients with the most profound empathy deficit had a right ventromedial lesion. A differential pattern regarding the relationships between empathy and cognitive performance was also found: Whereas among patients with dorsolateral prefrontal damage empathy was related to cognitive flexibility but not to TOM and affect recognition, empathy scores in patients with ventromedial lesions were related to TOM but not to cognitive flexibility. Our findings suggest that prefrontal structures play an important part in a network mediating the empathic response and specifically that the right ventromedial cortex has a unique role in integrating cognition and affect to produce the empathic response. PMID:12729486

  20. Vision restoration after brain and retina damage: the "residual vision activation theory".

    PubMed

    Sabel, Bernhard A; Henrich-Noack, Petra; Fedorov, Anton; Gall, Carolin

    2011-01-01

    Vision loss after retinal or cerebral visual injury (CVI) was long considered to be irreversible. However, there is considerable potential for vision restoration and recovery even in adulthood. Here, we propose the "residual vision activation theory" of how visual functions can be reactivated and restored. CVI is usually not complete, but some structures are typically spared by the damage. They include (i) areas of partial damage at the visual field border, (ii) "islands" of surviving tissue inside the blind field, (iii) extrastriate pathways unaffected by the damage, and (iv) downstream, higher-level neuronal networks. However, residual structures have a triple handicap to be fully functional: (i) fewer neurons, (ii) lack of sufficient attentional resources because of the dominant intact hemisphere caused by excitation/inhibition dysbalance, and (iii) disturbance in their temporal processing. Because of this resulting activation loss, residual structures are unable to contribute much to everyday vision, and their "non-use" further impairs synaptic strength. However, residual structures can be reactivated by engaging them in repetitive stimulation by different means: (i) visual experience, (ii) visual training, or (iii) noninvasive electrical brain current stimulation. These methods lead to strengthening of synaptic transmission and synchronization of partially damaged structures (within-systems plasticity) and downstream neuronal networks (network plasticity). Just as in normal perceptual learning, synaptic plasticity can improve vision and lead to vision restoration. This can be induced at any time after the lesion, at all ages and in all types of visual field impairments after retinal or brain damage (stroke, neurotrauma, glaucoma, amblyopia, age-related macular degeneration). If and to what extent vision restoration can be achieved is a function of the amount of residual tissue and its activation state. However, sustained improvements require repetitive

  1. Vision restoration after brain and retina damage: the "residual vision activation theory".

    PubMed

    Sabel, Bernhard A; Henrich-Noack, Petra; Fedorov, Anton; Gall, Carolin

    2011-01-01

    Vision loss after retinal or cerebral visual injury (CVI) was long considered to be irreversible. However, there is considerable potential for vision restoration and recovery even in adulthood. Here, we propose the "residual vision activation theory" of how visual functions can be reactivated and restored. CVI is usually not complete, but some structures are typically spared by the damage. They include (i) areas of partial damage at the visual field border, (ii) "islands" of surviving tissue inside the blind field, (iii) extrastriate pathways unaffected by the damage, and (iv) downstream, higher-level neuronal networks. However, residual structures have a triple handicap to be fully functional: (i) fewer neurons, (ii) lack of sufficient attentional resources because of the dominant intact hemisphere caused by excitation/inhibition dysbalance, and (iii) disturbance in their temporal processing. Because of this resulting activation loss, residual structures are unable to contribute much to everyday vision, and their "non-use" further impairs synaptic strength. However, residual structures can be reactivated by engaging them in repetitive stimulation by different means: (i) visual experience, (ii) visual training, or (iii) noninvasive electrical brain current stimulation. These methods lead to strengthening of synaptic transmission and synchronization of partially damaged structures (within-systems plasticity) and downstream neuronal networks (network plasticity). Just as in normal perceptual learning, synaptic plasticity can improve vision and lead to vision restoration. This can be induced at any time after the lesion, at all ages and in all types of visual field impairments after retinal or brain damage (stroke, neurotrauma, glaucoma, amblyopia, age-related macular degeneration). If and to what extent vision restoration can be achieved is a function of the amount of residual tissue and its activation state. However, sustained improvements require repetitive

  2. Two-photon excitation STED microscopy in two colors in acute brain slices.

    PubMed

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

    2013-02-19

    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.

  3. Cerebral white matter injury and damage to myelin sheath following whole-brain ischemia.

    PubMed

    Chen, Yingzhu; Yi, Qiong; Liu, Gang; Shen, Xue; Xuan, Lihui; Tian, Ye

    2013-02-01

    Myelin sheath, either in white matter or in other regions of brain, is vulnerable to ischemia. The specific events involved in the progression of ischemia in white matter have not yet been elucidated. The aim of this study was to determine histopathological alterations in cerebral white matter and levels of myelin basic protein (MBP) in ischemia-injured brain tissue during the acute and subacute phases of central nervous injury following whole-brain ischemia. The whole cerebral ischemia model (four-vessel occlusion (4-VO)) was established in adult Sprague-Dawley rats and MBP gene expression and protein levels in the brain tissue were measured using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) at 2 days, 4 days, 7 days, 14 days, and 28 days following ischemia. Demyelination was determined by Luxol fast blue myelin staining, routine histopathological staining, and electron microscopy in injured brain tissue. Results showed that edema, vascular dilation, focal necrosis, demyelination, adjacent reactive gliosis and inflammation occurred 7 days after ischemia in HE staining and recovered to control levels at 28 days. The absence of Luxol fast blue staining and vacuolation was clearly visible at 7 days, 14 days, and 28 days. Semiquantitative analysis showed that the transparency of myelin had decreased significantly by 7 days, 14 days, and 28 days. Demyelination and ultrastructual changes were detected 7 days after ischemia. The relative levels of MBP mRNA decreased 2 days after ischemia and this trend continued throughout the remaining four points in time. The MBP levels measured using ELISA also decreased significantly at 2 days and 4 days, but they recovered by 7 days and returned to control levels by 14 days. These results suggest that the impact of ischemia on cerebral white matter is time-sensitive and that different effects may follow different courses over time.

  4. The differential effects of acute right- vs. left-sided vestibular failure on brain metabolism.

    PubMed

    Becker-Bense, Sandra; Dieterich, Marianne; Buchholz, Hans-Georg; Bartenstein, Peter; Schreckenberger, Mathias; Brandt, Thomas

    2014-07-01

    The human vestibular system is represented in the brain bilaterally, but it has functional asymmetries, i.e., a dominance of ipsilateral pathways and of the right hemisphere in right-handers. To determine if acute right- or left-sided unilateral vestibular neuritis (VN) is associated with differential patterns of brain metabolism in areas representing the vestibular network and the visual-vestibular interaction, patients with acute VN (right n = 9; left n = 13) underwent resting state (18)F-FDG PET once in the acute phase and once 3 months later after central vestibular compensation. The contrast acute vs. chronic phase showed signal differences in contralateral vestibular areas and the inverse contrast in visual cortex areas, both more pronounced in VN right. In VN left additional regions were found in the cerebellar hemispheres and vermis bilaterally, accentuated in severe cases. In general, signal changes appeared more pronounced in patients with more severe vestibular deficits. Acute phase PET data of patients compared to that of age-matched healthy controls disclosed similarities to these patterns, thus permitting the interpretation that the signal changes in vestibular temporo-parietal areas reflect signal increases, and in visual areas, signal decreases. These data imply that brain activity in the acute phase of right- and left-sided VN exhibits different compensatory patterns, i.e., the dominant ascending input is shifted from the ipsilateral to the contralateral pathways, presumably due to the missing ipsilateral vestibular input. The visual-vestibular interaction patterns were preserved, but were of different prominence in each hemisphere and more pronounced in patients with right-sided failure and more severe vestibular deficits.

  5. 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.

  6. 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

  7. Blood-brain barrier dysfunction in acute lead encephalopathy: a reappraisal.

    PubMed

    Bouldin, T W; Mushak, P; O'Tuama, L A; Krigman, M R

    1975-12-01

    Acute lead encephalopathy was induced in adult guinea pigs by administering daily oral doses of lead carbonate. During the development of the encephalopathy, the structural and functional integrity of the blood-brain barrier was evaluated with electron microscopy and tracer probes. Blood, cerebral gray matter, liver, and kidney were analyzed for lead, calcium, and magnesium content. The animals regularly developed an encephalopathy after four doses of lead. There were no discernible pathomorphologic alterations in the cerebral capillaries or perivascular glial sheaths. Furthermore, no evidence of blood-brain barrier dysfunction was demonstrated with Evans blue-albumin complex or horseradish peroxidase. Blood-brain barrier permeability to radiolead was not increased in the intoxicated animals. During the development of the encephalopathy there was a progressive rise in the lead concentration in all tissues. Concurrently, there was a significant rise in brain calcium. These results suggest that the encephalopathic effects of lead may be mediated directly at the neuronal level.

  8. Acute DNA damage activates the tumour suppressor p53 to promote radiation-induced lymphoma

    PubMed Central

    Lee, Chang-Lung; Castle, Katherine D.; Moding, Everett J.; Blum, Jordan M.; Williams, Nerissa; Luo, Lixia; Ma, Yan; Borst, Luke B.; Kim, Yongbaek; Kirsch, David G.

    2015-01-01

    Genotoxic cancer therapies, such as chemoradiation, cause haematological toxicity primarily by activating the tumour suppressor p53. While inhibiting p53-mediated cell death during cancer therapy ameliorates haematologic toxicity, whether it also impacts carcinogenesis remains unclear. Here we utilize a mouse model of inducible p53 short hairpin RNA (shRNA) to show that temporarily blocking p53 during total-body irradiation (TBI) not only ameliorates acute toxicity, but also improves long-term survival by preventing lymphoma development. Using KrasLA1 mice, we show that TBI promotes the expansion of a rare population of thymocytes that express oncogenic KrasG12D. However, blocking p53 during TBI significantly suppresses the expansion of KrasG12D-expressing thymocytes. Mechanistically, bone marrow transplant experiments demonstrate that TBI activates p53 to decrease the ability of bone marrow cells to suppress lymphoma development through a non-cell-autonomous mechanism. Together, our results demonstrate that the p53 response to acute DNA damage promotes the development of radiation-induced lymphoma. PMID:26399548

  9. Indian research on acute organic brain syndrome: Delirium

    PubMed Central

    Pinto, Charles

    2010-01-01

    Delirium, though quite often referred to psychiatrists for management, does not find many takers for analysis, research and publications. Acute in onset, multiplicity of etiology and manifestations, high risk of mortality delirium is very rewarding in proper management and outcome. Delirium has a limited agenda on teaching programs, research protocols and therapeutic strategies. There is a dearth of Indian studies both in international and national scientific literature. This annotation is based on a Medline search for “delirium India” on Pubmed, which resulted in 54 articles. A search in Indian Journal of Psychiatry for “delirium” resulted in 38 published articles, “delirium tremens” showed up only five articles. The articles are primarily from the Indian Journal of Psychiatry with cross reference to articles on Pubmed or Google search on Indian studies and a few international studies PMID:21836671

  10. 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

  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. Acute skin sun damage in children and its consequences in adults.

    PubMed

    Pustisek, Nives; Sikanić-Dugić, Nives; Hirsl-Hećej, Vlasta; Domljan, Mislav Luka

    2010-04-01

    Children spend more time outdoors than adults and there is compelling evidence that childhood is a particularly vulnerable time for the photocarcinogenic effects of the sun. The negative effects of solar radiation are accumulated during the entire lifetime; however 80% of total lifetime sun exposure is taking place before the age of 18 years. Child skin is more sensitive than adult skin because natural defense mechanisms are not fully developed. A short exposure to midday sun will result in sunburns. Epidemiologic studies show a higher incidence of malignant melanoma in persons with a history of sunburns during childhood and adolescence. Sun exposure among infants and pre-school children is largely dependent on the discretion of adult care providers. Sun protective habits of mothers may predict the level of sun exposure in children. It is very important to transfer the knowledge and positive habits of proper sun protection to children. The purpose of sun-safety behavior is not to avoid outdoor activities, but rather to protect the skin from detrimental sun effects. Proper sun protection of children includes protection from excessive sun exposure, sunburns and other forms of skin damage caused by sun, which may lead to the future development of skin cancers. This paper reviews acute skin reactivity to sun in childhood and adolescence that causes damage in skin structure and function and produces undesirable chronic changes in adults.

  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. 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

  15. 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. PMID:27446298

  16. Catalase-independent early-gene expression in rat brain following acute ethanol exposure.

    PubMed

    Canales, Juan J

    2004-07-30

    Early-gene expression evoked by acute ethanol treatment was studied in rat brain by quantitative immunocytochemistry, with reference to ethanol metabolism by the enzyme catalase. Colocalization with mu-opioid receptor (MOR) sites was also examined. Ethanol challenges [1, 2.5, and 4 g/kg intraperitoneally (i.p.)] evoked dose-dependent increases in c-Fos expression in several brain regions, but overlap with MOR-rich sites was only partial. Strong inhibition of brain catalase activity (ca. 60%) with 3-amino-1,2,4-triazole (AT, 1 g/kg i.p.) did not alter ethanol-induced c-Fos nor Krox-24 expression in any of the brain regions analyzed. This evidence demonstrates that catalase-mediated metabolism is not a requisite for c-Fos nor Krox-24 induction in rat brain following acute ethanol treatment, and suggests that ethanol is by itself capable of eliciting strong neuronal and circuit-level adaptations in the nervous system.

  17. Pattern of Brain Injury in the Acute Setting of Human Septic Shock

    PubMed Central

    2013-01-01

    Background Sepsis-associated brain dysfunction has been linked to white matter lesions (leukoencephalopathy) and ischemic stroke. Our objective was to assess the prevalence of brain lesions in septic shock patients requiring magnetic resonance imaging (MRI) for an acute neurologic change. Method Seventy-one septic shock patients were included in a prospective observational study. Patients underwent daily neurological examination. Brain MRI was obtained in patients who developed focal neurological deficit, seizure, coma, or delirium. Electroencephalogy was performed in case of coma, delirium, or seizure. Leukoencephalopathy was graded and considered present when white matter lesions were either confluent or diffuse. Patient outcome was evaluated at 6 months with the Glasgow Outcome Scale (GOS). Results We included 71 patients with median age of 65 years (56 to 76) and SAPS II at admission of 49 (38 to 60). MRI was indicated on focal neurological sign in 13 (18%), seizure in 7 (10%), coma in 33 (46%), and delirium in 35 (49%). MRI was normal in 37 patients (52%) and showed cerebral infarcts in 21 (29%), leukoencephalopathy in 15 (21%), and mixed lesions in 6 (8%). EEG malignant pattern was more frequent in patients with ischemic stroke or leukoencephalopathy. Ischemic stroke was independently associated with disseminated intravascular coagulation (DIC), focal neurologic signs, increased mortality, and worse GOS at 6 months. Conclusions Brain MRI in septic shock patients who developed acute brain dysfunction can reveal leukoencephalopathy and ischemic stroke, which is associated with DIC and increased mortality. PMID:24047502

  18. Gastroprotective Effects of PMK-S005 against Ethanol-Induced Acute Gastric Damage in Rats

    PubMed Central

    Choi, Yoon Jeong; Kim, Nayoung; Lee, Ju Yup; Nam, Ryoung Hee; Seo, Ji Hyung; Lee, Seonmin; Kim, Hee Jin; Choi, Yoon Jin; Lee, Hye Seung; Lee, Dong Ho

    2016-01-01

    Background/Aims This study aimed to examine the gastroprotective effects of PMK-S005, which is a synthetic S-allyl-l-cysteine (SAC; a sulfur-containing amino acid), against acute ethanol-induced gastric damage in rats. Methods Sprague-Dawley rats were divided into six groups, including a nonethanol group, groups treated with absolute ethanol 1 hour after pretreatment with various doses of PMK-S005 (1, 5, and 10 mg/kg) or rebamipide (50 mg/kg), and an absolute ethanol-only group. Ethanol-induced gross ulcer and mucus levels were measured. Myeloperoxidase, tumor necrosis factor α, interleukin 1β, PGE2, LTB4, cPLA2, COX-1, and COX-2 levels were estimated by enzyme-linked immunosorbent assay or Western blot analysis. Furthermore, the protein expression levels of antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO-1), GCLC, and GCLM, were assessed. Results PMK-S005 significantly attenuated the ethanol-induced gastric damage; it reduced mucosal inflammatory cytokine production and increased mucus levels. The expression levels of cPLA2, COX-1, and COX-2 were decreased by PMK-S005. PMK-S005 did not affect PGE2 synthesis, but LTB4 production was significantly suppressed. In addition, long-term administration of PMK-S005 significantly increased the expression of HO-1, NQO-1, GCLC, and GCLM. Conclusions These results strongly suggest that PMK-S005 prevents gastric mucosal damage and that these gastroprotective activities are due to anti-inflammatory effects and enhancement of the gastric defense system, including antioxidant enzymes. PMID:26347516

  19. 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

  20. 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

  1. The oxidative damage and inflammation caused by pesticides are reverted by lipoic acid in rat brain.

    PubMed

    Astiz, Mariana; de Alaniz, María J T; Marra, Carlos Alberto

    2012-12-01

    We have previously demonstrated that the administration of low doses of dimethoate, glyphosate and zineb to rats (i.p. 1/250 LD50, three times a week for 5weeks) provokes severe oxidative stress (OS) in specific brain regions: substantia nigra, cortex and hippocampus. These effects were also observed in plasma. Lipoic acid (LA) is considered an "ideal antioxidant" due to its ability to scavenge reactive species, reset antioxidant levels and cross the blood-brain barrier. To investigate its protective effect we administered LA (i.p. 25, 50 and 100mg/kg) simultaneously with the pesticide mixture (PM) for 5weeks. After suppression of PM administration, we evaluated the restorative effect of LA for a further 5weeks. LA prevented OS and the production of nitrites+nitrates [NOx] caused by PM in a dose-dependent manner. The PM-induced decrease in reduced glutathione and α-tocopherol levels in all brain regions was completely restored by LA at both high doses. PM administration also caused an increase in prostaglandins E(2) and F(2α) in brain that was reduced by LA in a dose-dependent fashion. Taking into account the relationship between OS, inflammation and apoptosis, we measured caspase and calpain activity. Only milli- and micro-calpain isoforms were increased in the PM-treated group and LA reduced the activities to basal levels. We also demonstrated that interrupting PM administration is not enough to restore the levels of all the parameters measured and that LA is necessary to achieve basal status. In our experimental model LA displayed a protective role against pesticide-induced damage, suggesting that LA administration is a promising therapeutic strategy to cope with disorders suspected to be caused by OS generators, especially in brain.

  2. 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.

  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 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.

  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. Behavior outcome after ischemic and hemorrhagic stroke, with similar brain damage, in rats.

    PubMed

    Mestriner, Régis Gemerasca; Miguel, Patrícia Maidana; Bagatini, Pamela Brambilla; Saur, Lisiani; Boisserand, Lígia Simões Braga; Baptista, Pedro Porto Alegre; Xavier, Léder Leal; Netto, Carlos Alexandre

    2013-05-01

    Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile. We used 31 Wistar rats divided into the following groups: Sham (n=7), ischemic (IS) (n=12) or hemorrhagic (HS) (n=12). Brain ischemia or hemorrhage was induced by endotelin-1 (ET-1) and collagenase type IV-S (collagenase) microinjections, respectively. All groups were evaluated in the open field, cylinder and ladder walk behavioral tests at distinct time points as from baseline to 30 days post-surgery (30 PS). Histological and morphometric analyses were used to assess the volume of lost tissue and lesion length. Present results reveal that both forms of experimental stroke had a comparable long-term pattern of damage, since no differences were found in volume of tissue lost or lesion size 30 days after surgery. However, behavioral data showed that hemorrhagic rats were less impaired at skilled walking than ischemic ones at 15 and 30 days post-surgery. We suggest that experimentally comparable stroke design is useful because it reduces heterogeneity and facilitates the assessment of neurobiological differences related to stroke subtypes; and that spontaneous skilled walking recovery differs between experimental ischemic and hemorrhagic insults. PMID:23403282

  10. Assessment of hand after brain damage with the aim of functional surgery.

    PubMed

    Romain, M; Benaim, C; Allieu, Y; Pelissier, J; Chammas, M

    1999-01-01

    The semiology of the hand after brain damage is really rich. Its clinical evaluation remains quite difficult and must be integrated in the neuro-orthopedic and cognitive context. Deficiency, neuropsychological, analytic and functional status, must be assessed before any surgical decision aiming the improvement of prehension. Neuropsychological evaluation precise the hemispheric specialization: right hemisphere lesions conduct to unilateral spatial neglect while left hemispherical lesions determine language troubles and gesture impairment (apraxia). The analytical evaluation describes motor and sensitive function and assesses spasticity and pain. Concerning the functional assessment, the Enjalbert's score seems to be the most adapted to the upper limb. The assessment of hand deficiency and its origin is necessary to orientate the surgical decision and includes the Zancolli classification for the fingers and wrist and the House classification for the thumb. These classification used for cerebral palsy seems to be insufficient for all the different situations occurring after brain damage. A new classification is proposed based on 3 parameters: fingers extension, thumb abduction and supination. Surgical decision should be examined only after an adapted rehabilitation program.

  11. 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.

  12. 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.

  13. 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.

  14. Acute evaluation of conversational discourse skills in traumatic brain injury.

    PubMed

    LeBlanc, Joanne; de Guise, Elaine; Champoux, Marie-Claude; Couturier, Céline; Lamoureux, Julie; Marcoux, Judith; Maleki, Mohammed; Feyz, Mitra

    2014-12-01

    This study looked at performance on the conversational discourse checklist of the Protocole Montréal d'évaluation de la communication (D-MEC) in 195 adults with TBI of all severity hospitalized in a Level 1 Trauma Centre. To explore validity, results were compared to findings on tests of memory, mental flexibility, confrontation naming, semantic and letter category naming, verbal reasoning, and to scores on the Montreal Cognitive Assessment. The relationship to outcome as measured with the Disability Rating Scale (DRS), the Extended Glasgow Outcome Scale (GOS-E), length of stay, and discharge destinations was also determined. Patients with severe TBI performed significantly worse than mild and moderate groups (χ(2)(KW2df) = 24.435, p = .0001). The total D-MEC score correlated significantly with all cognitive and language measures (p < .05). It also had a significant moderate correlation with the DRS total score (r = -.6090, p < .0001) and the GOS-E score (r = .539, p < .0001), indicating that better performance on conversational discourse was associated with a lower disability rating and better global outcome. Finally, the total D-MEC score was significantly different between the discharge destination groups (F(3,90) = 20.19, p < .0001). Thus, early identification of conversational discourse impairment in acute care post-TBI was possible with the D-MEC and could allow for early intervention in speech-language pathology.

  15. Neuroprotective effect of suppression of astrocytic activation by arundic acid on brain injuries in rats with acute subdural hematomas.

    PubMed

    Wajima, Daisuke; Nakagawa, Ichiro; Nakase, Hiroyuki; Yonezawa, Taiji

    2013-06-26

    Acute subdural hematoma (ASDH) can cause massive ischemic cerebral blood flow (CBF) underneath the hematoma, but early surgical evacuation of the mass reduces mortality. The aim of this study was to evaluate whether arundic acid improves the secondary ischemic damage induced by ASDH. Our results confirmed that arundic acid decreases the expression of S100 protein produced by activated astrocytes around ischemic lesions due to cytotoxic edema after ASDH as well as reducing infarction volumes and numbers of apoptotic cells around the ischemic lesions. In this study, we also evaluate the relationship of brain edema and the expression of Aquaporin 4 (AQP4) in an ASDH model. The expression of AQP4 was decreased in the acute phase after ASDH. Cytotoxic edema, assumed to be the main cause of ASDH, could also cause ischemic lesions around the edema area. Arundic acid decreased the infarction volume and number of apoptotic cells via suppression of S100 protein expression in ischemic lesions without changing the expression of AQP4.

  16. 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

  17. 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

  18. 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

  19. Protective effect of resveratrol on fluoride induced alteration in protein and nucleic acid metabolism, DNA damage and biogenic amines in rat brain.

    PubMed

    Pal, Sudipta; Sarkar, Chaitali

    2014-09-01

    Fluoride, a well-established environmental carcinogen, has been found to cause various neurodegenerative diseases in human. Sub-acute exposure to fluoride at a dose of 20mg/kgb.w./day for 30 days caused significant alteration in pro-oxidant/anti-oxidant status of brain tissue as reflected by perturbation of reduced glutathione content, increased lipid peroxidation, protein carbonylation, nitric oxide and free hydroxyl radical production and decreased activities of antioxidant enzymes. Decreased proteolytic and transaminase enzymes' activities, protein and nucleic acid contents and associated DNA damage were observed in the brain of fluoride intoxicated rats. The neurotransmitters dopamine (DA), norepinephrine (NE) and serotonin level was also significantly altered after fluoride exposure. Protective effect of resveratrol on fluoride-induced metabolic and oxidative dysfunctions was evaluated. Resveratrol was found to inhibit changes in metabolic activities restoring antioxidant status, biogenic amine level and structural organization of the brain. Our findings indicated that resveratrol imparted antioxidative role in ameliorating fluoride-induced metabolic and oxidative stress in different regions of the brain.

  20. [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

  1. Coefficient of variation of R-R intervals in severe brain damage.

    PubMed

    Nezu, A; Kimura, S; Kobayashi, T; Osaka, H; Uehara, S

    1996-01-01

    The coefficient of variation of R-R intervals (CVRR) was studied in 18 children having severe brain damage with a mean +/- standard deviation (s.d.) age of 8.4 +/- 5.9 years, who were divided into ten patients complicated with respiratory insufficiency (RI group) and eight patients with severe athetotic cerebral palsy (SA group). CVRR was obtained in the resting supine position, and was compared with that in 22 neurologically normal controls. CVRR in the RI group (mean +/- S.D., 2.19 +/- 1.28%) was significantly lower than that in controls (5.56 +/- 1.53%), while CVRR in the SA group (11.30 +/- 3.91%) was significantly higher than that in controls (both P < 0.01, ANOVA). In particular, the four patients with brain death showed extremely low CVRR of 1.00-1.29%. Since CVRR was 4.09% in the patient aged 4 years with birth injury of the upper cervical spinal cord causing absence of spontaneous respiration, the extremely low CVRR in patients with brain death may be directly related to brainstem dysfunction. The cause of the high CVRR in the SA group was not determined. Thus, CVRR may be useful for quantitative evaluation of severe neurological disorder.

  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. 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.

  4. 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

  5. Acute sports-related traumatic brain injury and repetitive concussion.

    PubMed

    Guskiewicz, Kevin M; Broglio, Steven P

    2015-01-01

    Concussions are described as functional, not structural injuries, and therefore cannot be easily detected through standard diagnostic imaging. The vast differences between individual athletes makes identifying and evaluating sport-related concussion one of the most complex and perplexing injuries faced by medical personnel. The literature, as well as most consensus statements, supports the use of a multifaceted approach to concussion evaluation on the sideline of the athletic field. Using a standardized clinical examination that is supported by objective measures of concussion-related symptoms, cognitive function, and balance provides clinicians with the ability to track recovery in an objective manner. When used in combination, these tests allow for more informed diagnosis and treatment plan, which should involve a graduated return to play progression. Establishing a comprehensive emergency action plan that can guide the on-field management of a more serious and potentially catastrophic brain injury is also essential. This review will address these management issues, as well as the recent concerns about the risk of long-term neurologic conditions believed to be associated with repetitive concussion.

  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. 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

  8. Through metal binding, curcumin protects against lead- and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain.

    PubMed

    Daniel, Sheril; Limson, Janice L; Dairam, Amichand; Watkins, Gareth M; Daya, Santy

    2004-02-01

    Curcumin, the major constituent of turmeric is a known, naturally occurring antioxidant. The present study examined the ability of this compound to protect against lead-induced damage to hippocampal cells of male Wistar rats, as well as lipid peroxidation induced by lead and cadmium in rat brain homogenate. The thiobarbituric assay (TBA) was used to measure the extent of lipid peroxidation induced by lead and cadmium in rat brain homogenate. The results show that curcumin significantly protects against lipid peroxidation induced by both these toxic metals. Coronal brain sections of rats injected intraperitoneally with lead acetate (20 mg/kg) in the presence and absence of curcumin (30 mg/kg) were compared microscopically to determine the extent of lead-induced damage to the cells in the hippocampal CA1 and CA3 regions, and to establish the capacity of curcumin to prevent such damage. Lead-induced damage to the neurons was significantly curtailed in the rats injected with curcumin. Possible chelation of lead and cadmium by curcumin as its mechanism of neuroprotection against such heavy metal insult to the brain was investigated using electrochemical, ultraviolet spectrophotometric and infrared spectroscopic analyses. The results of the study show that there is an interaction between curcumin and both cadmium and lead, with the possible formation of a complex between the metal and this ligand. These results imply that curcumin could be used therapeutically to chelate these toxic metals, thus potentially reducing their neurotoxicity and tissue damage.

  9. DNA damage induced by phenylalanine and its analogue p-chlorophenylalanine in blood and brain of rats subjected to a model of hyperphenylalaninemia.

    PubMed

    Simon, Kellen R; Dos Santos, Rosane M; Scaini, Giselli; Leffa, Daniela D; Damiani, Adriani P; Furlanetto, Camila B; Machado, Jéssica L; Cararo, José H; Macan, Tamires P; Streck, Emilio L; Ferreira, Gustavo C; Andrade, Vanessa M; Schuck, Patrícia F

    2013-10-01

    Phenylketonuria (PKU) is a disease caused by a deficiency of phenylalanine hydroxylase (PAH), resulting in an accumulation of phenylalanine (Phe) in the brain tissue, cerebrospinal fluid, and other tissues of PKU patients. Considering that high levels of Phe are associated with neurological dysfunction and that the mechanisms underlying the neurotoxicity in PKU remain poorly understood, the main objective of this study was to investigate the in vivo and in vitro effects of Phe on DNA damage, as determined by the alkaline comet assay. The results showed that, compared to control group, the levels of DNA migration were significantly greater after acute administration of Phe, p-chlorophenylalanine (p-Cl-Phe, an inhibitor of PAH), or a combination thereof in cerebral cortex and blood, indicating DNA damage. These treatments also provoked increase of carbonyl content. Additionally, when Phe or p-Cl-Phe was present in the incubation medium, we observed an increase in the frequency and index of DNA damage in the cerebral cortex and blood, without affecting lactate dehydrogenase (LDH) release. Our in vitro and in vivo findings indicate that DNA damage occurs in the cerebral cortex and blood of rats receiving Phe, suggesting that this mechanism could be, at least in part, responsible for the neurological dysfunction in PKU patients.

  10. Oxidation-Reduction Potential as a Biomarker for Severity and Acute Outcome in Traumatic Brain Injury

    PubMed Central

    Levy, Stewart; Carrick, Matthew; Mains, Charles W.; Slone, Denetta S.

    2016-01-01

    There are few reliable markers for assessing traumatic brain injury (TBI). Elevated levels of oxidative stress have been observed in TBI patients. We hypothesized that oxidation-reduction potential (ORP) could be a potent biomarker in TBI. Two types of ORP were measured in patient plasma samples: the static state of oxidative stress (sORP) and capacity for induced oxidative stress (icORP). Differences in ORP values as a function of time after injury, severity, and hospital discharge were compared using ANOVAs with significance at p ≤ 0.05. Logit regression analyses were used to predict acute outcome comparing ORP, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), and Glasgow Coma Scale (GCS). Antioxidant capacity (icORP) on day 4 was prognostic for acute outcomes (p < 0.05). An odds ratio of 4.08 was associated with poor acute outcome when icORP > 7.25 μC. IcORP was a better predictor than ISS, AIS, or GCS scores. sORP increased in those with the highest ISS values (p < 0.05). Based on these findings ORP is useful biomarker for severity and acute outcome in TBI patients. Changes in ORP values on day 4 after injury were the most prognostic, suggesting that patients' response to brain injury over time is a factor that determines outcome.

  11. Chronic and acute alcohol administration induced neurochemical changes in the brain: comparison of distinct zebrafish populations.

    PubMed

    Chatterjee, Diptendu; Shams, Soaleha; Gerlai, Robert

    2014-04-01

    The zebrafish is increasingly utilized in the analysis of the effects of ethanol (alcohol) on brain function and behavior. We have shown significant population-dependent alcohol-induced changes in zebrafish behavior and have started to analyze alterations in dopaminergic and serotoninergic responses. Here, we analyze the effects of alcohol on levels of selected neurochemicals using a 2 × 3 (chronic × acute) between-subject alcohol exposure paradigm randomized for two zebrafish populations, AB and SF. Each fish first received the particular chronic treatment (0 or 0.5 vol/vol% alcohol) and subsequently the acute exposure (0, 0.5 or 1.0% alcohol). We report changes in levels of dopamine, DOPAC, serotonin, 5HIAA, glutamate, GABA, aspartate, glycine and taurine as quantified from whole brain extracts using HPLC. We also analyze monoamine oxidase and tyrosine hydroxylase enzymatic activity. The results demonstrate that compared to SF, AB is more responsive to both acute alcohol exposure and acute alcohol withdrawal at the level of neurochemistry, a finding that correlates well with prior behavioral observations and one which suggests the involvement of genes in the observed alcohol effects. We discuss correlations between the current results and prior behavioral findings, and stress the importance of characterization of zebrafish strains for future behavior genetic and psychopharmacology studies.

  12. Oxidation-Reduction Potential as a Biomarker for Severity and Acute Outcome in Traumatic Brain Injury.

    PubMed

    Bjugstad, Kimberly B; Rael, Leonard T; Levy, Stewart; Carrick, Matthew; Mains, Charles W; Slone, Denetta S; Bar-Or, David

    2016-01-01

    There are few reliable markers for assessing traumatic brain injury (TBI). Elevated levels of oxidative stress have been observed in TBI patients. We hypothesized that oxidation-reduction potential (ORP) could be a potent biomarker in TBI. Two types of ORP were measured in patient plasma samples: the static state of oxidative stress (sORP) and capacity for induced oxidative stress (icORP). Differences in ORP values as a function of time after injury, severity, and hospital discharge were compared using ANOVAs with significance at p ≤ 0.05. Logit regression analyses were used to predict acute outcome comparing ORP, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), and Glasgow Coma Scale (GCS). Antioxidant capacity (icORP) on day 4 was prognostic for acute outcomes (p < 0.05). An odds ratio of 4.08 was associated with poor acute outcome when icORP > 7.25 μC. IcORP was a better predictor than ISS, AIS, or GCS scores. sORP increased in those with the highest ISS values (p < 0.05). Based on these findings ORP is useful biomarker for severity and acute outcome in TBI patients. Changes in ORP values on day 4 after injury were the most prognostic, suggesting that patients' response to brain injury over time is a factor that determines outcome. PMID:27642494

  13. Oxidation-Reduction Potential as a Biomarker for Severity and Acute Outcome in Traumatic Brain Injury

    PubMed Central

    Levy, Stewart; Carrick, Matthew; Mains, Charles W.; Slone, Denetta S.

    2016-01-01

    There are few reliable markers for assessing traumatic brain injury (TBI). Elevated levels of oxidative stress have been observed in TBI patients. We hypothesized that oxidation-reduction potential (ORP) could be a potent biomarker in TBI. Two types of ORP were measured in patient plasma samples: the static state of oxidative stress (sORP) and capacity for induced oxidative stress (icORP). Differences in ORP values as a function of time after injury, severity, and hospital discharge were compared using ANOVAs with significance at p ≤ 0.05. Logit regression analyses were used to predict acute outcome comparing ORP, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), and Glasgow Coma Scale (GCS). Antioxidant capacity (icORP) on day 4 was prognostic for acute outcomes (p < 0.05). An odds ratio of 4.08 was associated with poor acute outcome when icORP > 7.25 μC. IcORP was a better predictor than ISS, AIS, or GCS scores. sORP increased in those with the highest ISS values (p < 0.05). Based on these findings ORP is useful biomarker for severity and acute outcome in TBI patients. Changes in ORP values on day 4 after injury were the most prognostic, suggesting that patients' response to brain injury over time is a factor that determines outcome. PMID:27642494

  14. Oxidation-Reduction Potential as a Biomarker for Severity and Acute Outcome in Traumatic Brain Injury.

    PubMed

    Bjugstad, Kimberly B; Rael, Leonard T; Levy, Stewart; Carrick, Matthew; Mains, Charles W; Slone, Denetta S; Bar-Or, David

    2016-01-01

    There are few reliable markers for assessing traumatic brain injury (TBI). Elevated levels of oxidative stress have been observed in TBI patients. We hypothesized that oxidation-reduction potential (ORP) could be a potent biomarker in TBI. Two types of ORP were measured in patient plasma samples: the static state of oxidative stress (sORP) and capacity for induced oxidative stress (icORP). Differences in ORP values as a function of time after injury, severity, and hospital discharge were compared using ANOVAs with significance at p ≤ 0.05. Logit regression analyses were used to predict acute outcome comparing ORP, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), and Glasgow Coma Scale (GCS). Antioxidant capacity (icORP) on day 4 was prognostic for acute outcomes (p < 0.05). An odds ratio of 4.08 was associated with poor acute outcome when icORP > 7.25 μC. IcORP was a better predictor than ISS, AIS, or GCS scores. sORP increased in those with the highest ISS values (p < 0.05). Based on these findings ORP is useful biomarker for severity and acute outcome in TBI patients. Changes in ORP values on day 4 after injury were the most prognostic, suggesting that patients' response to brain injury over time is a factor that determines outcome.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. Simvastatin reduces VEGF and NO levels in acute stages of experimental traumatic brain injury.

    PubMed

    Yüksel, Hatice; Yavuz, Özlem; Iş, Merih; Çomunoğlu, Nil; Üzüm, Gülay; Akyüz, Feyzullah; Yıldırım, Hayriye Ak

    2013-11-01

    This study was undertaken to evaluate the effect of simvastatin, a cholesterol-lowering agent, on vascular endothelial growth factors (VEGFs), nitric oxide (NO) levels and neuroprotection, in rats with experimentally induced traumatic brain injury (TBI). Forty Wistar albino rats were categorized into four groups: sham operated (S), trauma (T), trauma + vehicle (T + V) and trauma + simvastatin (T + S). The T, T + V and T + S groups were subjected to TBI. The T + V group was administered vehicle [ethanol:saline (1/2)] and the T + S group was administered 1 mg/kg of simvastatin 3 h after the injury insult. Blood and brain tissue specimens were obtained 24 h after the trauma to measure VEGFs and NO levels and perform histopathological examinations. The histopathological injury scores of brain tissues were significantly higher in the T group, and simvastatin significantly prevented brain injury in the T + S group. In the T group, significant increases of VEGF levels in serum and brain tissues were noted, which were prevented with simvastatin treatment in the T + S group. The markedly high levels of NO in brain tissues of the T group were decreased by simvastatin treatment in the T + S group. It can be concluded that, as evidenced by histopathological findings, simvastatin treatment improves neuropathology in acute stages of TBI.

  20. 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.

  1. 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

  2. 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

  3. A novel fluorinated stilbene exerts hepatoprotective properties in CCl(4)-induced acute liver damage.

    PubMed

    Rivera, Horacio; Morales-Ríos, Martha S; Bautista, Wendy; Shibayama, Mineko; Tsutsumi, Víctor; Muriel, Pablo; Pérez-Álvarez, Víctor

    2011-10-01

    There has been a recently increase in the development of novel stilbene-based compounds with in vitro anti-inflamatory properties. For this study, we synthesized and evaluated the anti-inflammatory properties of 2 fluorinated stilbenes on carbon tetrachloride (CCl₄)-induced acute liver damage. To achieve this, CCl₄ (4 g·kg(-1), per os) was administered to male Wistar rats, followed by either 2-fluoro-4'-methoxystilbene (FME) or 2,3-difluoro-4'-methoxystilbene (DFME) (10 mg·kg(-1), per os). We found that although both of the latter compounds prevented cholestatic damage (γ-glutamyl transpeptidase activity), only DFME showed partial but consistent results in the prevention of necrosis, as assessed by both alanine aminotransferase activity and histological analysis. Since inflammatory responses are mediated by cytokines, mainly tumour necrosis factor α (TNF-α), we used the Western blot technique to determine the action of FME and DFME on the expression level of this cytokine. The observed increase in the level of TNF-α caused by CCl₄ administration was only prevented by treatment with DFME, in agreement with our biochemical findings. This result was confirmed by measuring interleukin-6 (IL-6) levels, since the expression of this protein depends on the level of TNF-α. In this case, DFME completely blocked the CCl₄-induced increase of IL-6. Our results suggest that DFME possesses greater anti-inflammatory properties in vivo than FME. DFME constitutes a possible therapeutic agent for liver disease and could serve as a template for structure optimization.

  4. 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

  5. Low intensity microwave radiation induced oxidative stress, inflammatory response and DNA damage in rat brain.

    PubMed

    Megha, Kanu; Deshmukh, Pravin Suryakantrao; Banerjee, Basu Dev; Tripathi, Ashok Kumar; Ahmed, Rafat; Abegaonkar, Mahesh Pandurang

    2015-12-01

    Over the past decade people have been constantly exposed to microwave radiation mainly from wireless communication devices used in day to day life. Therefore, the concerns over potential adverse effects of microwave radiation on human health are increasing. Until now no study has been proposed to investigate the underlying causes of genotoxic effects induced by low intensity microwave exposure. Thus, the present study was undertaken to determine the influence of low intensity microwave radiation on oxidative stress, inflammatory response and DNA damage in rat brain. The study was carried out on 24 male Fischer 344 rats, randomly divided into four groups (n=6 in each group): group I consisted of sham exposed (control) rats, group II-IV consisted of rats exposed to microwave radiation at frequencies 900, 1800 and 2450 MHz, specific absorption rates (SARs) 0.59, 0.58 and 0.66 mW/kg, respectively in gigahertz transverse electromagnetic (GTEM) cell for 60 days (2h/day, 5 days/week). Rats were sacrificed and decapitated to isolate hippocampus at the end of the exposure duration. Low intensity microwave exposure resulted in a frequency dependent significant increase in oxidative stress markers viz. malondialdehyde (MDA), protein carbonyl (PCO) and catalase (CAT) in microwave exposed groups in comparison to sham exposed group (p<0.05). Whereas, levels of reduced glutathione (GSH) and superoxide dismutase (SOD) were found significantly decreased in microwave exposed groups (p<0.05). A significant increase in levels of pro-inflammatory cytokines (IL-2, IL-6, TNF-α, and IFN-γ) was observed in microwave exposed animal (p<0.05). Furthermore, significant DNA damage was also observed in microwave exposed groups as compared to their corresponding values in sham exposed group (p<0.05). In conclusion, the present study suggests that low intensity microwave radiation induces oxidative stress, inflammatory response and DNA damage in brain by exerting a frequency dependent effect

  6. An anticomplement agent that homes to the damaged brain and promotes recovery after traumatic brain injury in mice

    PubMed Central

    Ruseva, Marieta M.; Ramaglia, Valeria; Morgan, B. Paul; Harris, Claire L.

    2015-01-01

    Activation of complement is a key determinant of neuropathology and disability after traumatic brain injury (TBI), and inhibition is neuroprotective. However, systemic complement is essential to fight infections, a critical complication of TBI. We describe a targeted complement inhibitor, comprising complement receptor of the Ig superfamily (CRIg) fused with complement regulator CD59a, designed to inhibit membrane attack complex (MAC) assembly at sites of C3b/iC3b deposition. CRIg and CD59a were linked via the IgG2a hinge, yielding CD59-2a-CRIg dimer with increased iC3b/C3b binding avidity and MAC inhibitory activity. CD59-2a-CRIg inhibited MAC formation and prevented complement-mediated lysis in vitro. CD59-2a-CRIg dimer bound C3b-coated surfaces with submicromolar affinity (KD). In experimental TBI, CD59-2a-CRIg administered posttrauma homed to sites of injury and significantly reduced MAC deposition, microglial accumulation, mitochondrial stress, and axonal damage and enhanced neurologic recovery compared with placebo controls. CD59-2a-CRIg inhibited MAC-induced inflammasome activation and IL-1β production in microglia. Given the important anti-infection roles of complement opsonization, site-targeted inhibition of MAC should be considered to promote recovery postneurotrauma. PMID:26578778

  7. IL-1alpha induces angiogenesis in brain endothelial cells in vitro: implications for brain angiogenesis after acute injury.

    PubMed

    Salmeron, Kathleen; Aihara, Takuma; Redondo-Castro, Elena; Pinteaux, Emmanuel; Bix, Gregory

    2016-02-01

    Inflammation is a major contributor to neuronal injury and is associated with poor outcome after acute brain injury such as stroke. The pro-inflammatory cytokine interleukin (IL)-1 is a critical regulator of cerebrovascular inflammation after ischemic injury, mainly through action of both of its isoforms, IL-1α and IL-1β, at the brain endothelium. In contrast, the differential action of these ligands on endothelial activation and post-stroke angiogenesis is largely unknown. Here, we demonstrate that IL-1α is chronically elevated in the brain after experimental stroke suggesting that it is present during post-stroke angiogenic periods. Furthermore, we demonstrate that IL-1α is a potent mediator of endothelial activation and inducer of angiogenic markers in endothelial cells in vitro. Using brain endothelial cell lines, we found that IL-1α was significantly more potent than IL-1β at inducing endothelial cell activation, as measured by expression of the pro-angiogenic chemokine CXCL-1. IL-1α also induced strong expression of the angiogenic mediator IL-6 in a concentration-dependent manner. Furthermore, IL-1α induced significant proliferation and migration of endothelial cells, and promoted formation of tube-like structures that are established key hallmarks of angiogenesis in vitro. Finally, all of those responses were blocked by the IL-1 receptor antagonist (IL-1RA). In conclusion, our data highlights a potential new role for IL-1 in brain repair mechanisms and identifies IL-1α as a potential new therapy to promote post-stroke angiogenesis. Inflammation is a major contributor to neuronal injury and is associated with poor outcome after neurotrauma. We demonstrate that cytokine IL-1α is chronically elevated in the brain after experimental stroke suggesting that it is present chronically post-stroke. We demonstrate that IL-1α is a potent mediator of endothelial activation and inducer of angiogenic markers in endothelial cells. Our data highlights a new

  8. 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.

  9. Spirulina or dandelion-enriched diet of mothers alleviates lead-induced damages in brain and cerebellum of newborn rats.

    PubMed

    Gargouri, Manel; Ghorbel-Koubaa, Fatma; Bonenfant-Magné, Michèle; Magné, Christian; Dauvergne, Xavier; Ksouri, Riadh; Krichen, Yousef; Abdelly, Chedly; El Feki, Abdelfattah

    2012-07-01

    This study was aimed at evaluating the toxic effects of a prenatal exposure to lead acetate on brain tissues of newborn rats, and potent protective effects of spirulina (Arthropira platensis) or dandelion (Taraxacum officinalis) added to rat diet. Female rats were given a normal diet (control) or a diet enriched with spirulina or dandelion. Additionally, lead acetate was administered to one half of these rats through drinking water from the 5th day of gestation, to day 14 postpartum. Lead toxicity was assessed by measuring blood lead levels, brain weight, tissue damage, as well as protein content, lipid peroxidation and activities of antioxidant enzymes in brain tissues of neonates. Lead poisoning of mothers caused lead deposition in the brain and cerebellum of newborns and cerebellum tissue damages. Moreover, a significant decrease in weight and protein content of these tissues was found. Oxidative stress and changes in antioxidant enzyme activities in brain tissues were also recorded. Conversely, no such damages or biochemical changes were found in neonates from plant fed lead-poisoned mothers. These results strongly suggest that beneficial effects of spirulina- or dandelion-added diet on lead-intoxicated rats proceeded through the reduction of the lead-induced oxidative stress and related damages.

  10. Aquaporin-4 Deletion in Mice Reduces Encephalopathy and Brain Edema in Experimental Acute Liver Failure

    PubMed Central

    Rama Rao, Kakulavarapu V.; Verkman, A. S.; Curtis, Kevin M.; Norenberg, Michael D.

    2014-01-01

    Brain edema and associated astrocyte swelling leading to increased intracranial pressure are hallmarks of acute liver failure (ALF). Elevated blood and brain levels of ammonia have been implicated in the development of brain edema in ALF. Cultured astrocytes treated with ammonia have been shown to undergo cell swelling and such swelling was associated with an increase in the plasma membrane expression of aquaporin-4 (AQP4) protein. Further, silencing the AQP4 gene in cultured astrocytes was shown to prevent the ammonia-induced cell swelling. Here, we examined the evolution of brain edema in AQP4-null mice and their wild type counterparts (WT-mice) in different models of ALF induced by thioacetamide (TAA) or acetaminophen (APAP). Induction of ALF with TAA or APAP significantly increased brain water content in WT mice (by 1.6 ± 0.3 and 2.3 ± 0.4 %, respectively). AQP4 protein was significantly increased in brain plasma membranes of WT mice with ALF induced by either TAA or APAP. In contrast to WT-mice, brain water content did not increase in AQP4-null mice. Additionally, AQP4-null mice treated with either TAA or APAP showed a remarkably lesser degree of neurological deficits as compared to WT mice; the latter displayed an inability to maintain proper gait, and demonstrated a markedly reduced exploratory behavior, with the mice remaining in one corner of the cage with its head tilted downwards. These results support a central role of AQP4 in the brain edema associated with ALF. PMID:24321433

  11. Sulfonylurea Receptor 1 Contributes to the Astrocyte Swelling and Brain Edema in Acute Liver Failure

    PubMed Central

    Jayakumar, A.R.; Valdes, V.; Tong, X.Y.; Shamaladevi, N.; Gonzalez, W.; Norenberg, M.D.

    2014-01-01

    Astrocyte swelling (cytotoxic brain edema) is the major neurological complication of acute liver failure (ALF), a condition in which ammonia has been strongly implicated in its etiology. Ion channels and transporters are known to be involved in cell volume regulation and a disturbance in these systems may result in cell swelling. One ion channel known to contribute to astrocyte swelling/brain edema in other neurological disorders is the ATP-dependent, non-selective cation channel (NCCa-ATP channel). We therefore examined its potential role in the astrocyte swelling/brain edema associated with ALF. Cultured astrocytes treated with 5 mM ammonia showed a 3-fold increase in the sulfonylurea receptor type 1 (SUR1) protein expression, a marker of NCCa-ATP channel activity. Blocking SUR1 with glibenclamide significantly reduced the ammonia-induced cell swelling in cultured astrocytes. Additionally, overexpression of SUR1 in ammonia-treated cultured astrocytes was significantly reduced by co-treatment of cells with BAY 11-7082, an inhibitor of NF-κB, indicating the involvement of an NF-κB-mediated SUR1 upregulation in the mechanism of ammonia-induced astrocyte swelling. Brain SUR1 mRNA level was also found to be increased in the thioacetamide (TAA) rat model of ALF. Additionally, we found a significant increase in SUR1 protein expression in rat brain cortical astrocytes in TAA-treated rats. Treatment with glibenclamide significantly reduced the brain edema in this model of ALF. These findings strongly suggest the involvement of NCCa-ATP channel in the astrocyte swelling/brain edema in ALF, and that targeting this channel may represent a useful approach for the treatment of the brain edema associated with ALF. PMID:24443056

  12. Essential role of PD-L1 in regulatory T cell-afforded protection against blood-brain barrier damage after stroke

    PubMed Central

    Li, Peiying; Mao, Leilei; Liu, Xiangrong; Gan, Yu; Zheng, Jing; Thomson, Angus W.; Gao, Yanqin; Chen, Jun; Hu, Xiaoming

    2014-01-01

    Background and Purpose Our recent research revealed that adoptively-transferred regulatory T cells (Tregs) reduced acute ischemic brain injury by inhibiting neutrophil-derived MMP-9 and protecting against blood-brain barrier (BBB) damage. The mechanisms underlying Treg interactions with neutrophils remain elusive. This study evaluates the contribution of program death 1-ligand 1 (PD-L1) to Treg-mediated neutrophil inhibition and neuroprotection after cerebral ischemia. Methods In vitro experiments were carried out using a transwell system or a coculture system allowing cell-to-cell contact. Focal cerebral ischemia was induced in mice for 60min. Tregs (2×106) isolated from donor animals (wild-type or PD-L1−/−) were intravenously injected into ischemic recipients 2 h post-MCAO. MMP-9 production, BBB permeability and brain infarct were assessed at 1 or 3 days post-MCAO. Results In vitro experiments reveal that Treg-mediated inhibition of neutrophil MMP-9 required direct cell-to-cell contact. The suppression of MMP-9 was abolished when Tregs were pretreated with PD-L1 neutralizing Abs or when neutrophils were pre-treated with PD-1 Abs. In vivo studies confirmed that intravenous administration of Tregs pre-treated with PD-L1 Abs or Tregs isolated from PD-L1-deficient mice failed to inhibit MMP-9 production by blood neutrophils 1 day after 60 min middle cerebral artery occlusion (MCAO). Furthermore, the BBB damage after MCAO was greatly ameliorated in PD-L1-competent Treg-treated mice, but not in PD-L1-compromised Treg-treated mice. Consequently, PD-L1 dysfunction abolished Treg-mediated brain protection and neurological improvements 3 days after MCAO. Conclusions PD-L1 plays an essential role in the neuroprotection afforded by Tregs against cerebral ischemia by mediating the suppressive effect of Tregs on neutrophil-derived MMP-9. PMID:24496394

  13. Methylprednisolone exacerbates acute critical illness-related corticosteroid insufficiency associated with traumatic brain injury in rats.

    PubMed

    Chen, Xin; Zhang, Bin; Chai, Yan; Dong, Bo; Lei, Ping; Jiang, Rongcai; Zhang, Jianning

    2011-03-25

    Emerging evidence demonstrates that severe illness could induce critical illness-related corticosteroid insufficiency (CIRCI) and cause poor prognosis. The purpose of this study was to test the hypothesis that methylprednisolone (MP), a synthetic glucocorticoid, promotes post-traumatic apoptosis in both the hypothalamus and pituitary, resulting in acute CIRCI and increased mortality in the acute phase of traumatic brain injury (TBI). We tested this hypothesis by measuring acute CIRCI in rats subjected to fluid percussion injury (FPI) and treated with MP (5-30mg/kg). The corticosteroid response to TBI was evaluated using the corticosterone increase index (CII), where values less than 2.5 were considered indicative of acute CIRCI. The CII of MP treated rats was comparable to that of saline treated control rats before injury but was significantly decreased in injured rats receiving high-dose MP on post-injury day 7. Similarly, the incidence of acute CIRCI was significantly higher in the high-dose MP group on post-injury day 7. Furthermore, the CII of rats that did not survive post-injury was significantly lower compared to that of survival and was indicative of acute CIRCI. We also examined apoptosis in the paraventricular nucleus (PVN) of the hypothalamus and the adenohypophysis of the pituitary, using a TUNEL assay and transmission electron microscopy (TEM). The number of TUNEL-positive cells was significantly higher in injured rats treated with high-dose MP. No TUNEL-positive cells were detected in the adenohypophysis across experimental groups at either 7 or 14days after TBI. However, autopsies performed on rats that did not survive post-injury revealed obvious apoptotic cells in the adenohypophysis. Moreover, TEM revealed morphological changes characteristic of apoptosis in both the PVN and adenohypophysis of high-dose MP treated rats. These data suggest that MP therapy for TBI could increase neuronal apoptosis in both the hypothalamus and pituitary and

  14. 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

  15. 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

  16. Alleged brain damage, diminished capacity, mens rea, and misuse of medical concepts.

    PubMed

    Perr, I N

    1991-05-01

    As focus on the insanity defense diminishes, defendants may place emphasis on a lack of knowing or purposeful behavior in order to negate a criminal charge. This use of a mens rea defense in accord with Model Penal Code principles is exemplified by the current New Jersey statute. Such a defense may result in a lesser charge or a finding of not guilty. In addition to reviewing applicable law, this report presents a sex offense case in which remote brain damage was invoked as a purported basis for incapacity to formulate the required intent; the study also raises the issue of the inappropriate or questionable use of medical principles, a practice that diminishes professional credibility in the courts and in the community.

  17. [The importance of the cortex and subcortical structures of the brain in the perception of acute and chronic pain].

    PubMed

    Reschetniak, V K; Kukushkin, M L; Gurko, N S

    2014-01-01

    This review presents the current data in the literature about the importance of the cortex and subcortical structures of the brain in the perception of acute and chronic pain. Discussed the importance of various areas of the brain in perception discriminative and affective components of pain. Discusses also gender differences in pain perception depending on the functional activity of brain cortex and antinociceptive subcortical structures. Analyzed the morphological changes of cortical and subcortical structures of the brain in chronic pain syndromes. It is proved that the decrease in the volume of gray and white matter of cerebral cortex and subcortical structures is a consequence and not the cause of chronic pain syndrome. Discusses the features activate and deactivate certain areas of the cortex of the brain in acute and chronic pain. Analyzed same features the activation of several brain structures in migraine and cluster headache.

  18. 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

  19. 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

  20. Reappraisal generation after acquired brain damage: The role of laterality and cognitive control.

    PubMed

    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.

  1. Mechanisms of acute uremic encephalopathy: early activation of Fos and Fra-2 gene products in different nuclei/areas of the rat brain.

    PubMed

    Heidland, August; Sebekova, Katarina; Klassen, André; Palkovits, Miklós

    2010-09-01

    High levels of various uremic toxins such as guanidino compounds and advanced glycation endproducts, as well as an excess of parathyroid hormones, are involved in the pathogenesis of acute uremic encephalopathy. Moreover, distant effects of the damaged kidney with enhanced production of inflammatory mediators are implicated. Data on the pump activity of an abnormal Na-K-ATPase and inhibition of the organic anion transporter system in the brain have been published previously. Recently, the effect of an experimentally induced acute renal failure (ARF) on the neuronal cell activation of Fos and Fra-2 in the rat brain was investigated by immunohistochemistry. ARF was induced by using the following 3 rat models: bilateral nephrectomy, bilateral ureter ligation, and uranyl acetate injection with corresponding controls. The Fos and the Fra-2 immunoreactive neurons of the brain were determined in a total of 120 brain areas over a period of 3 days post bilateral nephrectomy and bilateral ureter ligation and 12 days after uranyl acetate. An activation response was observed in 73 of 120 areas of the brain. The responses were classified into 4 groups: (1) biogenic amines (noradrenaline, adrenaline, histamine, and 5-hydroxytryptamine), (2) stress-sensitive forebrain areas, (3) neuronal cell groups involved in the regulation of water and electrolyte homeostasis, and (4) central autonomic cell groups. In the uranyl acetate-induced ARF, activation of Fos and Fra-2 immunoreactivity took place at the earliest time-point (3 hours) which persisted even after improvement of ARF. This suggests the involvement of the toxic effects of uranium as a result of its accumulation in the brain.

  2. 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.

  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.

  4. 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

  5. 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

  6. Lesion correlates of impairments in actual tool use following unilateral brain damage.

    PubMed

    Salazar-López, E; Schwaiger, B J; Hermsdörfer, J

    2016-04-01

    To understand how the brain controls actions involving tools, tests have been developed employing different paradigms such as pantomime, imitation and real tool use. The relevant areas have been localized in the premotor cortex, the middle temporal gyrus and the superior and inferior parietal lobe. This study employs Voxel Lesion Symptom Mapping to relate the functional impairment in actual tool use with extent and localization of the structural damage in the left (LBD, N=31) and right (RBD, N=19) hemisphere in chronic stroke patients. A series of 12 tools was presented to participants in a carousel. In addition, a non-tool condition tested the prescribed manipulation of a bar. The execution was scored according to an apraxic error scale based on the dimensions grasp, movement, direction and space. Results in the LBD group show that the ventro-dorsal stream constitutes the core of the defective network responsible for impaired tool use; it is composed of the inferior parietal lobe, the supramarginal and angular gyrus and the dorsal premotor cortex. In addition, involvement of regions in the temporal lobe, the rolandic operculum, the ventral premotor cortex and the middle occipital gyrus provide evidence of the role of the ventral stream in this task. Brain areas related to the use of the bar largely overlapped with this network. For patients with RBD data were less conclusive; however, a trend for the involvement of the temporal lobe in apraxic errors was manifested. Skilled bar manipulation depended on the same temporal area in these patients. Therefore, actual tool use depends on a well described left fronto-parietal-temporal network. RBD affects actual tool use, however the underlying neural processes may be more widely distributed and more heterogeneous. Goal directed manipulation of non-tool objects seems to involve very similar brain areas as tool use, suggesting that both types of manipulation share identical processes and neural representations. PMID

  7. 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

  8. 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

  9. Relationship between the repair of radiation-induced DNA damage and recovery from potentially lethal damage in 9L rat brain tumor cells. [Gamma radiation

    SciTech Connect

    vanAnkeren, S.C.; Wheeler, K.T.

    1984-03-01

    The kinetics of repair of radiation-induced DNA damage and recovery from radiation-induced potentially lethal damage (PLD) for fed plateau-phase 9L/Ro rat brain tumor cells were compared after single doses of gamma-radiation and after combined treatment with 3 micrograms of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)/ml given 16 hr prior to irradiation. DNA damage and repair were assayed using alkaline filter elution, while cell survival was assayed by colony formation. Repair of radiation-induced DNA damage and recovery from radiation-induced PLD followed statistically identical biphasic kinetics; the fast-phase half-times were 4.1 +/- 0.3 (S.D.) min and 4.0 +/- 0.8 min, while the slow-phase half-times were 59.7 +/- 11.2 min and 78.7 +/- 34.1 min, respectively. Treatment with BCNU prior to irradiation resulted in both additional DNA damage and increased cell kill. When DNA damage and cell survival after the combined treatment were corrected for the contribution from BCNU given alone, no inhibition of either repair of radiation-induced DNA damage or of recovery from radiation-induced PLD was observed. However, postirradiation hypertonic treatment inhibited both DNA repair and recovery from radiation-induced PLD. These correlations between the kinetics of the molecular and cellular repair processes support a role for repair of radiation-induced DNA damage in recovery from radiation-induced PLD. The lack of inhibition by BCNU of both repair of radiation-induced DNA damage and of recovery from radiation-induced PLD also demonstrates that these are not the mechanisms by which BCNU enhances radiation-induced cytotoxicity in 9L cells.

  10. 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

  11. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment.

    PubMed

    Li, Xianchao; Hou, Wensheng; Wu, Xiaoying; Jiang, Wei; Chen, Haiyan; Xiao, Nong; Zhou, Ping

    2014-02-01

    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/cm(2), 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 × 10(6) bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm(2) 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.

  12. 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

  13. Role of spleen-derived monocytes/macrophages in acute ischemic brain injury.

    PubMed

    Kim, Eunhee; Yang, Jiwon; Beltran, Cesar D; Cho, Sunghee

    2014-08-01

    Monocytes/macrophages (MMs), mononuclear phagocytes, have been implicated in stroke-induced inflammation and injury. However, the presence of pro-inflammatory Ly-6C(high) and antiinflammatory Ly-6C(low) monocyte subsets raises uncertainty regarding their role in stroke pathologic assessment. With recent identification of the spleen as an immediate reservoir of MMs, this current study addresses whether the spleen-derived MMs are required for stroke pathologic assessment. We observed that the spleen was contracted in poststroke animals and the contraction was accompanied by decreased number of Ly-6C(high) and Ly-6C(low) subsets in the spleen. The deployment of these subsets from the spleen temporally coincided with respective increases in the ischemic brain. Compared to mice with the spleen, mice receiving a splenectomy just before the stroke displayed less accumulation of Ly-6C(high) and Ly-6C(low) MMs in the brain. Despite the reduced accumulation of both subsets, infarct size and swelling were not reduced in the asplenic mice. The dissociative findings of infarct size and extent of MM infiltration in the postischemic brain indicate minimal involvement of spleen-derived total MMs in acute infarct development. Selective Ly-6C(high) or Ly-6C(low) MM targeting is suggested to address the contribution of the individual subset to acute stroke pathologic assessment.

  14. 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

  15. 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.

  16. [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

  17. Nature and distribution of brain lesions in rats intoxicated with 3-nitropropionic acid: a type of hypoxic (energy deficient) brain damage.

    PubMed

    Hamilton, B F; Gould, D H

    1987-01-01

    The clinical signs and morphological brain lesions associated with histotoxic hypoxia induced by subcutaneous injection of 3-nitropropionic acid (NPA) in rats are described, and compared to hypoxic brain damage from other causes including ischemia and hypoglycemia. The brains were perfusion-fixed with paraformaldehyde/glutaraldehyde fixative, and examined by light and electron microscopy. Intoxicated rats developed severe neurological disease characterized by somnolence, uncoordinated gait with stereotypical paddling movements, and ventral or lateral recumbency. Recumbent rats had a selective, bilaterally symmetrical pattern of severe morphological injury in the caudate-putamen, hippocampus, and thalamus. Recumbency was a consistent indicator of the development of morphological brain lesions. In contrast to reports describing rat models of ischemia and hypoglycemia, morphological injury was not seen in the cerebral and cerebellar cortices of NPA-intoxicated rats. Ultrastructurally, neuronal alterations ranged from chromatin clumping with increased cytoplasmic lucency to severe cellular shrinkage or swelling with marked mitochondrial swelling (high amplitude swelling). White matter alterations included axonal swelling and adaxonal splitting of myelin lamellae. Vascular changes included perivascular deposits of proteinaceous material presumably from leakage of serum proteins, variable electron lucency of endothelial cell cytoplasm, an apparent increase in pinocytotic vesicles, rare platelet thrombosis of capillaries, and rare intravascular blebs of luminal plasma membrane. As a model of brain damage following energy deficiency, NPA intoxication has the advantages of producing morphological brain injury in a highly predictable anatomical pattern, and at a time paralleling the onset of clinical recumbency.

  18. Swimming training attenuates oxidative damage and increases enzymatic but not non-enzymatic antioxidant defenses in the rat brain

    PubMed Central

    Nonato, L.F.; Rocha-Vieira, E.; Tossige-Gomes, R.; Soares, A.A.; Soares, B.A.; Freitas, D.A.; Oliveira, M.X.; Mendonça, V.A.; Lacerda, A.C.; Massensini, A.R.; Leite, H.R.

    2016-01-01

    Although it is well known that physical training ameliorates brain oxidative function after injuries by enhancing the levels of neurotrophic factors and oxidative status, there is little evidence addressing the influence of exercise training itself on brain oxidative damage and data is conflicting. This study investigated the effect of well-established swimming training protocol on lipid peroxidation and components of antioxidant system in the rat brain. Male Wistar rats were randomized into trained (5 days/week, 8 weeks, 30 min; n=8) and non-trained (n=7) groups. Forty-eight hours after the last session of exercise, animals were euthanized and the brain was collected for oxidative stress analysis. Swimming training decreased thiobarbituric acid reactive substances (TBARS) levels (P<0.05) and increased the activity of the antioxidant enzyme superoxide dismutase (SOD) (P<0.05) with no effect on brain non-enzymatic total antioxidant capacity, estimated by FRAP (ferric-reducing antioxidant power) assay (P>0.05). Moreover, the swimming training promoted metabolic adaptations, such as increased maximal workload capacity (P<0.05) and maintenance of body weight. In this context, the reduced TBARS content and increased SOD antioxidant activity induced by 8 weeks of swimming training are key factors in promoting brain resistance. In conclusion, swimming training attenuated oxidative damage and increased enzymatic antioxidant but not non-enzymatic status in the rat brain. PMID:27706439

  19. 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.

  20. Immediate S-100B and neuron-specific enolase plasma measurements for rapid evaluation of primary brain damage in alcohol-intoxicated, minor head-injured patients.

    PubMed

    Mussack, Thomas; Biberthaler, Peter; Kanz, Karl Georg; Heckl, Ute; Gruber, Rudolf; Linsenmaier, Ulrich; Mutschler, Wolf; Jochum, Marianne

    2002-11-01

    The neuroproteins S-100B and neuron-specific enolase (NSE) released into the circulation are suggested to be reliable markers for primary brain damage. However, safe identification of relevant post-traumatic complications after minor head injury (MHI) is often hampered by acute intoxication of the patients. The objective of this study was to determine the diagnostic validity of immediate plasma measurements of S-100B and NSE in comparison with neurological examinations and cerebral computed tomography (CCT) findings in alcohol-intoxicated MHI patients. One hundered thrity-nine MHI individuals were enrolled in this prospective study during Munich's Oktoberfest 2000. Plasma levels of S-100B and NSE as well as serum alcohol and glucose values were determined by fully automated assays immediately after admission. The results were compared with Glasgow Coma Scale score, a brief neurological examination, and the CCT findings. Without being influenced by alcohol, median S-100B levels of the CCT+ group were significantly increased compared with those of the CCT- group (P < 0.001). NSE, alcohol, and glucose levels showed no significant group differences. As calculated by the ROC analysis, a cutoff value of 0.21 ng/mL with an area under the curve of 0.864 clearly differentiates between CCT+ and CCT- patients at a sensitivity of 100%, a specificity of 50.0%, and a positive likelihood ratio of 2.0. Although acute alcohol intoxication did not confound plasma measurements of S-100B and NSE, only S-100B levels below the cutoff level of 0.21 ng/mL seem to indicate absence of primary brain damage. Thus, in addition to routine neurological examinations, S-100B measurements immediately after admission might help to reduce CCT scans in alcohol-intoxicated patients early after MHI.

  1. Relationship between Morphofunctional Changes in Open Traumatic Brain Injury and the Severity of Brain Damage in Rats.

    PubMed

    Shakova, F M; Barskov, I V; Gulyaev, M V; Prokhorenko, S V; Romanova, G A; Grechko, A V

    2016-07-01

    A correlation between the severity of morphofunctional disturbances and the volume of brain tissue injury determined by MRT was demonstrated on the model of open traumatic brain injury in rats. A relationship between the studied parameters (limb placing and beam walking tests and histological changes) and impact force (the height of load fell onto exposed brain surface) was revealed.

  2. Relationship between Morphofunctional Changes in Open Traumatic Brain Injury and the Severity of Brain Damage in Rats.

    PubMed

    Shakova, F M; Barskov, I V; Gulyaev, M V; Prokhorenko, S V; Romanova, G A; Grechko, A V

    2016-07-01

    A correlation between the severity of morphofunctional disturbances and the volume of brain tissue injury determined by MRT was demonstrated on the model of open traumatic brain injury in rats. A relationship between the studied parameters (limb placing and beam walking tests and histological changes) and impact force (the height of load fell onto exposed brain surface) was revealed. PMID:27496035

  3. 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…

  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. It's Either Brain Damage or No Father: The False Issue of Deficit Vs. Difference Models of Afro-American Behavior.

    ERIC Educational Resources Information Center

    Valentine, Charles A.

    The distorting notions of the deficit and different Afro-American subculture have led white psychologists and guidance counselors to diagnose incorrectly behavior aberrations in Black children. A case study of a Black child who was hastily diagnosed and institutionalized as brain damaged, retarded, and psychotic illustrates this point. A…

  6. 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…

  7. 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

  8. Trauma-induced coagulopathy: standard coagulation tests, biomarkers of coagulopathy, and endothelial damage in patients with traumatic brain injury.

    PubMed

    Genét, Gustav Folmer; Johansson, Pär Ingemar; Meyer, Martin Abild Stengaard; Sølbeck, Sacha; Sørensen, Anne Marie; Larsen, Claus Falck; Welling, Karen Lise; Windeløv, Nis Agerlin; Rasmussen, Lars S; Ostrowski, Sisse Rye

    2013-02-15

    It remains to be debated whether traumatic brain injury (TBI) induces a different coagulopathy than does non-TBI. This study investigated traditional coagulation tests, biomarkers of coagulopathy, and endothelial damage in trauma patients with and without TBI. Blood from 80 adult trauma patients was sampled (median of 68 min [IQR 48-88] post-injury) upon admission to our trauma center. Plasma/serum were retrospectively analyzed for biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), coagulation activation/inhibition and fibrinolysis (protein C, activated protein C, tissue factor pathway inhibitor, antithrombin, prothrombin fragment 1+2, thrombin/antithrombin complex, von Willebrand factor, factor XIII, d-dimer, tissue-type plasminogen activator, plasminogen activator inhibitor-1), immunology (interleukin [IL]6), endothelial cell/glycocalyx damage (soluble thrombomodulin, syndecan-1), and vasculogenesis (angiopoietin-1, -2). Patients were stratified according to: (1) isolated severe head/neck injuries (Abbreviated injury score [AIS]-head/neck ≥ 3, AIS-other<3) (isoTBI); (2) severe head/neck and extracranial injuries (AIS-head/neck ≥ 3, AIS-other>3) (sTBI+other); and (3) injuries without significant head/neck injuries (AIS-head/neck<3, including all AIS-other scores) (non-TBI). Twenty-three patients presented with isoTBI, 15 with sTBI+other and 42 with non-TBI. Acute coagulopathy of trauma shock, defined as activated partial thromboplastin time (APTT) and/or international normalized ratio (INR)>35 sec and>1.2, was found in 13%, 47%, and 5%, respectively (p=0.000). sTBI+other had significantly higher plasma levels of adrenaline, noradrenaline, annexin V, d-dimer, IL-6, syndecan-1, soluble thrombomodulin, and reduced protein C and factor XIII levels (all p<0.05). No significant biomarker differences were found between isoTBI and non-TBI patients. Injury severity scale (ISS) rather than the presence or absence of head/neck injuries

  9. Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury.

    PubMed

    de Bragança, Ana C; Volpini, Rildo A; Mehrotra, Purvi; Andrade, Lúcia; Basile, David P

    2016-07-01

    Reductions in renal microvasculature density and increased lymphocyte activity may play critical roles in the progression of chronic kidney disease (CKD) following acute kidney injury (AKI) induced by ischemia/reperfusion injury (IRI). Vitamin D deficiency is associated with tubulointerstitial damage and fibrosis progression following IRI-AKI We evaluated the effect of vitamin D deficiency in sustained IRI-AKI, hypothesizing that such deficiency contributes to the early reduction in renal capillary density or alters the lymphocyte response to IRI Wistar rats were fed vitamin D-free or standard diets for 35 days. On day 28, rats were randomized into four groups: control, vitamin D deficient (VDD), bilateral IRI, and VDD+IRI Indices of renal injury and recovery were evaluated for up to 7 days following the surgical procedures. VDD rats showed reduced capillary density (by cablin staining), even in the absence of renal I/R. In comparison with VDD and IRI rats, VDD+IRI rats manifested a significant exacerbation of capillary rarefaction as well as higher urinary volume, kidney weight/body weight ratio, tissue injury scores, fibroblast-specific protein-1, and alpha-smooth muscle actin. VDD+IRI rats also had higher numbers of infiltrating activated CD4(+) and CD8(+) cells staining for interferon gamma and interleukin-17, with a significant elevation in the Th17/T-regulatory cell ratio. These data suggest that vitamin D deficiency impairs renal repair responses to I/R injury, exacerbates changes in renal capillary density, as well as promoting fibrosis and inflammation, which may contribute to the transition from AKI to CKD.

  10. 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

  11. Acute brain ischemia as a complication of the Ehlers-Danlos syndrome, the case series.

    PubMed

    Pajak, Michal; Majos, Marcin A; Szubert, Wojciech; Stefanczyk, Ludomir; Majos, Agata

    2014-10-01

    Vascular type of Ehlers-Danlos syndrome involves many severe complications leading not only to organ-specific symptoms but often ends in a sudden death. The aim of this paper was to present a diagnostic possibilities and its efficiency rate in patients with vascular complications of Ehlers-Danlos syndrome who suffered from artery dissection resulting in acute brain or limb ischemia. We analysed three patients with diagnosed Ehlers-Danlos syndrome who were referred to radiology department for diagnostic imaging of affected vascular beds, each experienced brain ischemia. The paper also aims at offering some general recommendations for patients suffering from possible complications of type IV Ehlers-Danlos syndrome basing on our own experience and available literature data.

  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, Adrianus M C H; van den Nieuwendijk, Adriann M C H; Soethoudt, Marjolein; van der Wel, Tom; Zhou, Juan; Overkleeft, Herman S; Sanchez-Alavez, Manuel; Mori, Simone; 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.

  13. Features of Neurotoxicity on Brain CT of Acutely Intoxicated Unconscious Patients

    PubMed Central

    Sanei Taheri, Morteza; Noori, Maryam; Nahvi, Vahideh; Moharamzad, Yashar

    2010-01-01

    Diagnostic imaging is a valuable device in clinical management of poisoned patients presenting to emergency units in a comatose state. Some toxic agents have adverse effects on the central nervous system (CNS). Non-contrast computed tomography (CT) of the brain, as an available diagnostic method with a high resolution, can provide useful information about structural disturbances of unconscious patients with suspected drug or chemical intoxication. The authors would describe various presentations of toxic substances detected on the brain CT scans of ten patients with acute intoxication. While non-specific, CT findings of low-attenuation lesions in the basal ganglia, infarctions in young patients, or diffuse edema should raise suspicion for poisoning or overdose. PMID:21270943

  14. Cerebral Visual Impairment: which perceptive visual dysfunctions can be expected in children with brain damage? A systematic review.

    PubMed

    Boot, F H; Pel, J J M; van der Steen, J; Evenhuis, H M

    2010-01-01

    The current definition of Cerebral Visual Impairment (CVI) includes all visual dysfunctions caused by damage to, or malfunctioning of, the retrochiasmatic visual pathways in the absence of damage to the anterior visual pathways or any major ocular disease. CVI is diagnosed by exclusion and the existence of many different causes and symptoms make it an overall non-categorized group. To date, no discrimination is made within CVI based on types of perceptive visual dysfunctions. The aim of this review was to outline which perceptive visual dysfunctions are to be expected based on a number of etiologies of brain damage and brain development disorders with their onset in the pre-, peri- or postnatal period. For each period two etiologies were chosen as the main characteristic brain damage. For each etiology a main search was performed. The selection of the articles was based on the following criteria: age, etiology, imaging, central pathology and perceptive visual function test. The perceptive visual functions included for this review were object recognition, face recognition, visual memory, orientation, visual spatial perception, motion perception and simultaneous perception. Our search resulted in 11 key articles. A diversity of research history is performed for the selected etiologies and their relation to perceptive visual dysfunctions. Periventricular Leukomalacia (PVL) was most studied, whereas the main tested perceptive visual function was visual spatial perception. As a conclusion, the present status of research in the field of CVI does not allow to correlate between etiology, location and perceptive visual dysfunctions in children with brain damage or a brain development disorder. A limiting factor could be the small number of objective tests performed in children experiencing problems in visual processing. Based on recent insights in central visual information processing, we recommend an alternative approach for the definition of CVI that is based on

  15. 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

  16. 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

  17. 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.

  18. Amplitude of Low-Frequency Fluctuations in Multiple-Frequency Bands in Acute Mild Traumatic Brain Injury.

    PubMed

    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

  19. 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

  20. The protective effect of M40401, a superoxide dismutase mimetic, on post-ischemic brain damage in Mongolian gerbils

    PubMed Central

    Mollace, Vincenzo; Iannone, Michelangelo; Muscoli, Carolina; Palma, Ernesto; Granato, Teresa; Modesti, Andrea; Nisticò, Robert; Rotiroti, Domenicantonio; Salvemini, Daniela

    2003-01-01

    Background Overproduction of free radical species has been shown to occur in brain tissues after ischemia-reperfusion injury. However, most of free radical scavengers known to antagonize oxidative damage (e.g. superoxide dismutase, catalase), are unable to protect against ischemia-reperfusion brain injury when given in vivo, an effect mainly due to their difficulty to gain access to brain tissues. Here we studied the effect of a low molecular weight superoxide dismutase mimetic (M40401) in brain damage subsequent to ischemia-reperfusion injury in Mongolian gerbils. Results In animals undergoing ischemia-reperfusion injury, neuropathological and ultrastructural changes were monitored for 1–7 days either in the presence or in the absence of M40401 after bilateral common carotid artery occlusion (BCCO). Administration of M40401 (1–40 mg/kg, given i.p. 1 h after BCCO) protected against post-ischemic, ultrastructural and neuropathological changes occurring within the hippocampal CA1 area. The protective effect of M40401 was associated with a significant reduction of the levels of malondialdehyde (MDA; a marker of lipid peroxidation) in ischemic brain tissues after ischemia-reperfusion. Conclusion Taken together, these results demonstrate that M40401 provides protective effects when given early after the induction of ischemia-reperfusion of brain tissues and suggest the possible use of such compounds in the treatment of neurological dysfunction subsequent to cerebral flow disturbances. PMID:12809567

  1. Development of brain damage as measured by brain impedance recordings, and changes in heart rate, and blood pressure induced by different stunning and killing methods.

    PubMed

    Savenije, B; Lambooij, E; Gerritzen, M A; Korf, J

    2002-04-01

    Poultry are electrically stunned before slaughter to induce unconsciousness and to immobilize the chickens for easier killing. From a welfare point of view, electrical stunning should induce immediate and lasting unconsciousness in the chicken. As an alternative to electroencephalography, which measures brain electrical activity, this study used brain impedance recordings, which measure brain metabolic activity, to determine the onset and development of brain damage. Fifty-six chickens were surgically equipped with brain electrodes and a canula in the wing artery and were subjected to one of seven stunning and killing methods: whole body electrical stunning; head-only electrical stunning at 50, 100 or 150 V; or an i.v. injection with MgCl2. After 30 s, the chickens were exsanguinated. Brain impedance and blood pressure were measured. Extracellular volume was determined from the brain impedance data and heart rate from the blood pressure data. An immediate and progressive reduction in extracellular volume in all chickens was found only with whole body stunning at 150 V. This treatment also caused cardiac fibrillation or arrest in all chickens. With all other electrical stunning treatments, extracellular volume was immediately reduced in some but not all birds, and cardiac fibrillation or arrest was not often found. Ischemic conditions, caused by cessation of the circulation, stimulated this epileptic effect. A stunner setting of 150 V is therefore recommended to ensure immediate and lasting unconsciousness, which is a requirement for humane slaughter. PMID:11989758

  2. 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

  3. 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

  4. 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.

  5. Attenuation of rat ischemic brain damage by aged garlic extracts: a possible protecting mechanism as antioxidants.

    PubMed

    Numagami, Y; Sato, S; Ohnishi, S T

    1996-08-01

    Effects of an aged garlic extract and its thioallyl components on rat brain ischemia were examined using a middle cerebral artery occlusion model and a transient global ischemia model. In focal ischemia, an aged garlic extract, S-allyl cysteine (SAC), Allyl sulfide (AS) or Allyl disulfide (ADS) was administered 30 min prior to ischemic insult. Three days after ischemic insult, water contents of both ischemic and contralateral hemispheres were measured to assess the degree of ischemic damage. The water content of the ischemic control (no drug treatment) group was 81.50 +/- 0.07% (mean +/- SEM). It was significantly reduced with the administration of 300 mg/kg of SAC; the water content was 80.66 +/- 0.11% (P < 0.001). The histological observation using 2,3,5-triphenyltetrazolium chloride staining demonstrated that the administration of SAC reduced infarct volume. Neither AS nor ADS was effective. In global ischemia, the production of reactive oxygen species (ROS) was measured ex vivo using a spin-trapping agent, alpha-phenyl-N-tert-butylnitrone, and electron paramagnetic resonance spectroscopy. The production of ROS had two peaks; first at 5 min and second at 20 min after reperfusion. Both SAC and 7-nitro indazole, a nitric oxide synthase inhibitor, did not attenuate the amount of ROS produced at the first peak, but did the amount of the second peak. A possible involvement of peroxinitrite, which may be formed from superoxide and nitric oxide and is known to be highly toxic in ischemia/reperfusion injury of the brain, was suggested.

  6. Implicit and Explicit Routes to Recognize the Own Body: Evidence from Brain Damaged Patients.

    PubMed

    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. PMID:27630550

  7. Association of retinal and macular damage with brain atrophy in multiple sclerosis.

    PubMed

    Dörr, Jan; Wernecke, Klaus D; Bock, Markus; Gaede, Gunnar; Wuerfel, Jens T; Pfueller, Caspar F; Bellmann-Strobl, Judith; Freing, Alina; Brandt, Alexander U; Friedemann, Paul

    2011-01-01

    Neuroaxonal degeneration in the central nervous system contributes substantially to the long term disability in multiple sclerosis (MS) patients. However, in vivo determination and monitoring of neurodegeneration remain difficult. As the widely used MRI-based approaches, including the brain parenchymal fraction (BPF) have some limitations, complementary in vivo measures for neurodegeneration are necessary. Optical coherence tomography (OCT) is a potent tool for the detection of MS-related retinal neurodegeneration. However, crucial aspects including the association between OCT- and MRI-based atrophy measures or the impact of MS-related parameters on OCT parameters are still unclear. In this large prospective cross-sectional study on 104 relapsing remitting multiple sclerosis (RRMS) patients we evaluated the associations of retinal nerve fiber layer thickness (RNFLT) and total macular volume (TMV) with BPF and addressed the impact of disease-determining parameters on RNFLT, TMV or BPF. BPF, normalized for subject head size, was estimated with SIENAX. Relations were analyzed primarily by Generalized Estimating Equation (GEE) models considering within-patient inter-eye relations. We found that both RNFLT (p = 0.019, GEE) and TMV (p = 0.004, GEE) associate with BPF. RNFLT was furthermore linked to the disease duration (p<0.001, GEE) but neither to disease severity nor patients' age. Contrarily, BPF was rather associated with severity (p<0.001, GEE) than disease duration and was confounded by age (p<0.001, GEE). TMV was not associated with any of these parameters. Thus, we conclude that in RRMS patients with relatively short disease duration and rather mild disability RNFLT and TMV reflect brain atrophy and are thus promising parameters to evaluate neurodegeneration in MS. Furthermore, our data suggest that RNFLT and BPF reflect different aspects of MS. Whereas BPF best reflects disease severity, RNFLT might be the better parameter for monitoring axonal damage

  8. 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. PMID:27630550

  9. 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

  10. Peripheral Nerve Damage Facilitates Functional Innervation of Brain Grafts in Adult Sensory Cortex

    NASA Astrophysics Data System (ADS)

    Ebner, Ford F.; Erzurumlu, Reha S.; Lee, Stefan M.

    1989-01-01

    The neuralb pathways that relay information from cutaneous receptors to the cortex provide the somatic sensory information needed for cortical function. The last sensory relay neurons in this pathway have cell bodies in the thalamus and axons that synapse on neurons in the somatosensory cortex. After cortical lesions that damage mature thalamocortical fibers in the somatosensory cortex, we have attempted to reestablish somatosensory cortical function by grafting embryonic neocortical cells into the lesioned area. Such grafts survive in adult host animals but are not innervated by thalamic neurons, and consequently the grafted neurons show little if any spontaneous activity and no responses to cutaneous stimuli. We have reported that transection of peripheral sensory nerves prior to grafting ``conditions'' or ``primes'' the thalamic neurons in the ventrobasal complex so that they extend axons into grafts subsequently placed in the cortical domain of the cut nerve. In this report we present evidence that the ingrowth of ventrobasal fibers leads to graft neurons that become functionally integrated into the sensory circuitry of the host brain. Specifically, the conditioning lesions made prior to grafting produce graft neurons that are spontaneously active and can be driven by natural activation of cutaneous receptors or electrical stimulation of the transected nerve after it regenerates. Furthermore, oxidative metabolism in these grafts reaches levels that are comparable to normal cortex, whereas without prior nerve cut, oxidative metabolism is abnormally low in neocortical grafts. We conclude that damage to the sensory periphery transsynaptically stimulates reorganization of sensory pathways through mechanisms that include axonal elongation and functional synaptogenesis.

  11. The perception of peripersonal space in right and left brain damage hemiplegic patients.

    PubMed

    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.

  12. 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

  13. 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.

  14. Brain-derived neurotrophic factor and substrate utilization following acute aerobic exercise in obese individuals.

    PubMed

    Slusher, A L; Whitehurst, M; Zoeller, R F; Mock, J T; Maharaj, A; Huang, C-J

    2015-05-01

    Brain-derived neurotrophic factor (BDNF) serves as a vital regulator of neuronal proliferation and survival, and has been shown to regulate energy homeostasis, glucose metabolism and body weight maintenance. Elevated concentrations of plasma BDNF have been associated with obesity and type 2 diabetes mellitus. Acute aerobic exercise transiently increases circulating BDNF, potentially correcting obesity-related metabolic impairment. The present study aimed to compare acute aerobic exercise elicited BDNF responses in obese and normal-weight subjects. Furthermore, we aimed to investigate whether acute exercise-induced plasma BDNF elevations would be associated with improved indices of insulin resistance, as well as substrate utilization [carbohydrate oxidation (CHOoxi) and fat oxidation (FAToxi)]. Twenty-two healthy, untrained subjects [11 obese (four men and seven women; age = 22.91 ± 4.44 years; body mass index = 35.72 ± 4.17 kg/m(2)) and 11 normal-weight (five men and six women; age = 23.27 ± 2.24 years; body mass index = 21.89 ± 1.63 kg/m(2))] performed 30 min of continuous submaximal aerobic exercise at 75% maximal oxygen consumption. Our analyses showed that the BDNF response to acute aerobic exercise was similar in obese and normal-weight subjects across time (time: P = 0.015; group: P = not significant) and was not associated with indices of IR. Although no differences in the rates of CHOoxi and FAToxi were found between both groups, total relative energy expenditure was significantly lower in obese subjects compared to normal-weight subjects (3.53 ± 0.25 versus 5.59 ± 0.85; P < 0.001). These findings suggest that acute exercise-elicited BDNF elevation may not be sufficient to modulate indices of IR or the utilization of either carbohydrates or fats in obese individuals.

  15. Acute acidic exposure induces p53-mediated oxidative stress and DNA damage in tilapia (Oreochromis niloticus) blood cells.

    PubMed

    Mai, Wei-jun; Yan, Jun-lun; Wang, Lei; Zheng, Ying; Xin, Yu; Wang, Wei-na

    2010-11-01

    Acid rain and inputs of acidic effluent can result in increased acidity in aquatic ecosystems, where it is known to have a significant impact and possibly, to cause the decline of some populations of aquatic organisms. In previous studies, intracellular acid-induced oxidative stress has been shown to cause DNA damage, and cooperatively activate the expression of the p53 gene. The acute effects of acidic environments on shrimp and fish have been widely studied. However, the molecular mechanism of acid-induced injury remains largely unknown. In this study, we examined the cellular responses of tilapia to acidic exposure-induced oxidative stress and antioxidant enzyme gene expression. Furthermore, we determined how acute acid stress activates the ATM-p53 signal pathway. We measured the upregulation of reactive oxygen species (ROS) production, the intracellular Ca(2)(+) concentration ([Ca(2)(+)](i)), the tail DNA values, the malondialdehyde (MDA) level in the blood cells and the percentage of dead and damaged blood cells. Our results suggest that oxidative stress and DNA damage occurred in tilapia in conditions where the pH was 5.3. Apoptosis was detected by Hoechst staining, which was mainly associated with changes in cell viability. The parameters that we measured were related to acid-induced DNA damage, and all parameters changed in the blood cells through time. The effects of acute acid exposure (pH 5.3) on the expression of ATM, p53, p21, Bax, manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx) were investigated in tilapia blood cells. The results showed that acute acid stress induced upregulation of ATM, p53 and p21, associated with increasing of DNA damage and apoptosis in blood cells. Additionally, the expression of Bax was slightly increased. Moreover, consensus p53-binding sequences were identified in tilapia MnSOD and GPx gene promoter regions and increased levels of ROS in the blood cells coincided with increased mRNA expression of p53, Mn

  16. The role of DNA repair in brain related disease pathology.

    PubMed

    Canugovi, Chandrika; Misiak, Magdalena; Ferrarelli, Leslie K; Croteau, Deborah L; Bohr, Vilhelm A

    2013-08-01

    Oxidative DNA damage is implicated in brain aging, neurodegeneration and neurological diseases. Damage can be created by normal cellular metabolism, which accumulates with age, or by acute cellular stress conditions which create bursts of oxidative damage. Brain cells have a particularly high basal level of metabolic activity and use distinct oxidative damage repair mechanisms to remove oxidative damage from DNA and dNTP pools. Accumulation of this damage in the background of a functional DNA repair response is associated with normal aging, but defective repair in brain cells can contribute to neurological dysfunction. Emerging research strongly associates three common neurodegenerative conditions, Alzheimer's, Parkinson's and stroke, with defects in the ability to repair chronic or acute oxidative damage in neurons. This review explores the current knowledge of the role of oxidative damage repair in preserving brain function and highlights the emerging models and methods being used to advance our knowledge of the pathology of neurodegenerative disease.

  17. Comparison of Acute and Chronic Traumatic Brain Injury Using Semi-Automatic Multimodal Segmentation of MR Volumes

    PubMed Central

    Chambers, Micah C.; Alger, Jeffry R.; Filippou, Maria; Prastawa, Marcel W.; Wang, Bo; Hovda, David A.; Gerig, Guido; Toga, Arthur W.; Kikinis, Ron; Vespa, Paul M.; Van Horn, John D.

    2011-01-01

    Abstract Although neuroimaging is essential for prompt and proper management of traumatic brain injury (TBI), there is a regrettable and acute lack of robust methods for the visualization and assessment of TBI pathophysiology, especially for of the purpose of improving clinical outcome metrics. Until now, the application of automatic segmentation algorithms to TBI in a clinical setting has remained an elusive goal because existing methods have, for the most part, been insufficiently robust to faithfully capture TBI-related changes in brain anatomy. This article introduces and illustrates the combined use of multimodal TBI segmentation and time point comparison using 3D Slicer, a widely-used software environment whose TBI data processing solutions are openly available. For three representative TBI cases, semi-automatic tissue classification and 3D model generation are performed to perform intra-patient time point comparison of TBI using multimodal volumetrics and clinical atrophy measures. Identification and quantitative assessment of extra- and intra-cortical bleeding, lesions, edema, and diffuse axonal injury are demonstrated. The proposed tools allow cross-correlation of multimodal metrics from structural imaging (e.g., structural volume, atrophy measurements) with clinical outcome variables and other potential factors predictive of recovery. In addition, the workflows described are suitable for TBI clinical practice and patient monitoring, particularly for assessing damage extent and for the measurement of neuroanatomical change over time. With knowledge of general location, extent, and degree of change, such metrics can be associated with clinical measures and subsequently used to suggest viable treatment options. PMID:21787171

  18. 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

  19. 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

  20. Effective factors on linguistic disorder during acute phase following traumatic brain injury in adults.

    PubMed

    Chabok, Shahrokh Yousefzadeh; Kapourchali, Sara Ramezani; Leili, Ehsan Kazemnezhad; Saberi, Alia; Mohtasham-Amiri, Zahra

    2012-06-01

    Traumatic brain injury (TBI) has been known to be the leading cause of breakdown and long-term disability in people under 45 years of age. This study highlights the effective factors on post-traumatic (PT) linguistic disorder and relations between linguistic and cognitive function after trauma in adults with acute TBI. A cross-sectional design was employed to study 60 post-TBI hospitalized adults aged 18-65 years. Post-traumatic (PT) linguistic disorder and cognitive deficit after TBI were respectively diagnosed using the Persian Aphasia Test (PAT) and Persian version of Mini-Mental State Examination (MMSE) at discharge. Primary post-resuscitation consciousness level was determined using the Glasgow Coma Scale (GCS). Paracilinical data was obtained by CT scan technique. Multiple logistic regression analysis illustrated that brain injury severity was the first powerful significant predictor of PT linguistic disorder after TBI and frontotemporal lesion was the second. It was also revealed that cognitive function score was significantly correlated with score of each language skill except repetition. Subsequences of TBI are more commonly language dysfunctions that demand cognitive flexibility. Moderate, severe and fronto-temporal lesion can increase the risk of processing deficit in linguistic macrostructure production and comprehension. The dissociation risk of cortical and subcortical pathways related to cognitive-linguistic processing due to intracranial lesions can augment possibility of lexical-semantic processing deficit in acute phase which probably contributes to later cognitive-communication disorder.

  1. Association of acute adverse effects with high local SAR induced in the brain from prolonged RF head and neck hyperthermia.

    PubMed

    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.

  2. 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.

  3. Curcumin alleviates brain edema by lowering AQP4 expression levels in a rat model of hypoxia-hypercapnia-induced brain damage

    PubMed Central

    YU, LIN-SHENG; FAN, YAN-YAN; YE, GUANGHUA; LI, JUNLI; FENG, XIANG-PING; LIN, KEZHI; DONG, MIUWU; WANG, ZHENYUAN

    2016-01-01

    The present study aimed to investigate the therapeutic effects of curcumin (CU) against brain edema in a rat model of hypoxia-hypercapnia (HH)-induced brain damage (HHBD). Male Sprague-Dawley rats were divided into five groups, including a control group and four treatment groups. The rats in the control group were raised under normal laboratory conditions and were injected with water, whereas the rats in the treatment groups were exposed to a low O2/high CO2 environment simulating HH conditions, and were injected with water, CU, dimethyl sulfoxide (solvent control) or monosialoganglioside GM1. After 2 weeks, the morphological characteristics of the brain tissues were analyzed using optical and electron microscopy. In addition, aquaporin (AQP)-4 protein expression levels in brain tissue samples were analyzed using streptavidin-biotin complex immunohistochemistry and western blotting, and mRNA expression levels were detected using reverse transcription-quantitative polymerase chain reaction. Severe brain edema, tissue structure disruption and increased AQP4 expression levels were detected in the brain tissues of the HH rats. Conversely, the rats treated with CU or GM1 exhibited attenuated HHBD-induced brain edema and tissue structure disruption, and decreased mRNA and protein expression levels of AQP4. The results of the present study suggested that CU treatment was able to attenuate HHBD-induced brain edema by downregulating the expression levels of AQP4 in a rat model. Therefore, CU may be considered a potential therapeutic drug for the treatment of patients with brain edema. PMID:26997983

  4. Assessment of cognitive asymmetries in brain-damaged and normal subjects: validation of a test battery.

    PubMed Central

    Bentin, S; Gordon, H W

    1979-01-01

    A test battery designed to assess cognitive functions normally related to the left and right cerebral hemispheres was validated on 30 patients with unilateral (16 right, 14 left) lesions. The tests were preselected to reflect typical functioning of the hemispheres according to general agreement in the literature. A Cognitive Laterality Quotient (CLQ) was calculated from the difference in performance between the "right" and "left" test batteries and, therefore, reflected the relative functioning attributed to the right and left hemispheres. Using the CLQ measurement and a control group of 30 non-neurological patients matched for age and education, 28 out of 30 brain-damaged patients (93%) were categorised correctly according to side of lesion; the other two were considered to have either abnormal lateralisation (one was left handed) or asymmetrical premorbid cognitive profiles. Using only one (paired) test whose two subparts were designed to vary only slightly in task requirements to measure either right or left functioning, 29 out of 30 patients were correctly categorised. It is suggested that the concept of relative assessment of basic cognitive functions is more fruitful than general assessment of intellectual functions for use in diagnosis and rehabilitation of neurological patients or normal subjects with developmental or acquired behavioural cognitive abnormalities. Images PMID:490177

  5. Narrating stroke: the life-writing and fiction of brain damage.

    PubMed

    Zimmermann, Martina

    2012-12-01

    Cerebro-vascular events are, after neurodegenerative disorders, the most frequent cause of brain damage that leads to the patient's impaired cognitive and/or bodily functioning. While the medico-scientific discourse related to stroke suggests that patients experience a change in identity and self-concept, the present analysis focuses on the patients' personal presentation of their experience to, first, highlight their way of thinking and feeling and, second, contribute to the clinician's actual understanding of the meaning of stroke within the life of each individual. As stroke 'victims' necessarily speak from the position of having undergone very abrupt degeneration followed by being confronted with a gradual relocation within their 'recovery', the present study addresses how narrative texts describe the condition, that is, the insult itself and its impairing consequences for body and mind, and how patients portray themselves within their illness. Furthermore, given that all illness narrative must remain non-representative, especially when exploring conditions that impair cognitive abilities, autobiographically inspired fiction, equally, contributes to neuroscientific perspectives on embodiment: it gives further insight into how the condition is perceived and alerts us to those aspects of the experience that are understood as particularly momentous.

  6. Influence of green tea extract on oxidative damage and apoptosis induced by deltamethrin in rat brain.

    PubMed

    Ogaly, Hanan A; Khalaf, A A; Ibrahim, Marwa A; Galal, Mona K; Abd-Elsalam, Reham M

    2015-01-01

    In the present study, we investigated the protective effect of an aqueous extract of green tea leaves (GTE) against neurotoxicity and oxidative damage induced by deltamethrin (DM) in male rats. Four different groups of rats were used: the 1st group was the vehicle treated control group, the 2nd group received DM (0.6 mg/kg BW), the 3rd group received DM plus GTE, and the 4th received GTE alone (25 mg/kg BW). The brain tissues were collected at the end of the experimental regimen for subsequent investigation. Rats that were given DM had a highly significant elevation in MDA content, nitric oxide concentration, DNA fragmentation and expression level of apoptotic genes, TP53 and COX2. Additionally, a significant reduction in the total antioxidant capacity in the second group was detected. The findings for the 3rd group highlight the efficacy of GTE as a neuro-protectant in DM-induced neurotoxicity through improving the oxidative status and DNA fragmentation as well as suppressing the expression of the TP53 and COX2 genes. In conclusion, GTE, at a concentration of 25mg/kg/day, protected against DM-induced neurotoxicity through its antioxidant and antiapoptotic influence; therefore, it can be used as a protective natural product against DM-induced neurotoxicity.

  7. 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.

  8. Fiberoptic endoscopic evaluation of swallowing in patients with acute traumatic brain injury.

    PubMed

    Leder, S B

    1999-10-01

    Dysphagia and aspiration in intensive care unit patients with acute traumatic brain injury (TBI) is a frequent and potentially life-threatening problem. Any diagnostic technique used with this population, therefore, must be able to be performed in a timely and efficient manner while providing objective information on the nature of the swallowing problem. The purpose of the present study was to investigate the utility of using the fiberoptic endoscopic evaluation of swallowing (FEES) technique to diagnosis pharyngeal stage dysphagia and determine aspiration status in patients who presented with acute TBI. A total of 47 subjects were assessed with FEES. Thirty of 47 (64%) subjects swallowed successfully and were able to take an oral diet: 2 of 30 (7%) thickened liquids and purée consistencies, 8 of 30 (27%) a soft diet, and 20 of 30 (67%) a regular diet. Seventeen of 47 (36%) subjects exhibited pharyngeal stage dysphagia with aspiration and were not permitted an oral diet based on objective results provided by FEES. Of the 17 subjects who aspirated, 9 of 17 (53%) exhibited silent aspiration. Younger subjects (mean age 34 years, 3 months) aspirated significantly less often than older subjects (mean age 51 years, 8 months). No significant age difference was observed for gender or between overt and silent aspirators. It was concluded that FEES is an objective and sensitive tool that can be used successfully to diagnose pharyngeal stage dysphagia, determine aspiration status, and make recommendations for oral or nonoral feeding in patients with acute TBI.

  9. 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.

  10. Acute caffeine administration effect on brain activation patterns in mild cognitive impairment.

    PubMed

    Haller, Sven; Montandon, Marie-Louise; Rodriguez, Cristelle; Moser, Dominik; Toma, Simona; Hofmeister, Jeremy; Sinanaj, Indrit; Lovblad, Karl-Olof; Giannakopoulos, Panteleimon

    2014-01-01

    Previous studies showed that acute caffeine administration enhances task-related brain activation in elderly individuals with preserved cognition. To explore the effects of this widely used agent on cognition and brain activation in early phases of cognitive decline, we performed a double-blinded, placebo-controlled functional magnetic resonance imaging (fMRI) study during an n-back working memory task in 17 individuals with mild cognitive impairment (MCI) compared to 17 age-matched healthy controls (HC). All individuals were regular caffeine consumers with an overnight abstinence and given 200 mg caffeine versus placebo tablets 30 minutes before testing. Analyses included assessment of task-related activation (general linear model), functional connectivity (tensorial-independent component analysis, TICA), baseline perfusion (arterial spin labeling, ASL), grey matter density (voxel-based morphometry, VBM), and white matter microstructure (tract-based spatial statistics, TBSS). Acute caffeine administration induced a focal activation of the prefrontal areas in HC with a more diffuse and posteromedial activation pattern in MCI individuals. In MCI, TICA documented a significant caffeine-related enhancement in the prefrontal cortex, supplementary motor area, ventral premotor and parietal cortex as well as the basal ganglia and cerebellum. The absence of significant group differences in baseline ASL perfusion patterns supports a neuronal rather than a purely vascular origin of these differences. The VBM and TBSS analyses excluded potentially confounding differences in grey matter density and white matter microstructure between MCI and HC. The present findings suggest a posterior displacement of working memory-related brain activation patterns after caffeine administration in MCI that may represent a compensatory mechanism to counterbalance a frontal lobe dysfunction.

  11. 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

  12. Effects of Acute Lithium Treatment on Brain Levels of Inflammatory Mediators in Poststroke Rats.

    PubMed

    Boyko, Matthew; Nassar, Ahmad; Kaplanski, Jacob; Zlotnik, Alexander; Sharon-Granit, Yael; Azab, Abed N

    2015-01-01

    Stroke is a leading cause of mortality and morbidity worldwide. Few therapeutic options with proven efficacy are available for the treatment of this disabling disease. Lithium is the gold standard treatment for bipolar disorder. Moreover, lithium has been shown to exhibit neuroprotective effects and therapeutic efficacy as a treatment of other neurological disorders. This study was undertaken to examine the effects of lithium on brain inflammatory mediators levels, fever, and mortality in postischemic stroke rats. Ischemic stroke was induced by occlusion of the mid cerebral artery (MCAO). Pretreatment with a single dose of lithium at 2 hours before MCAO induction significantly reduced the elevation in interleukin- (IL-) 6 and prostaglandin E2 levels in brain of post-MCAO rats, as compared to vehicle-treated animals. On the other hand, lithium did not affect the elevation in IL-1α, IL-10, IL-12, and tumor necrosis factor-α levels in brain of post-MCAO rats. Moreover, pretreatment with lithium did not alter post-MCAO fever and mortality. These results suggest that acute pretreatment with a single dose of lithium did not markedly affect post-MCAO morbidity and mortality in rats.

  13. 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

  14. Pravastatin acute neuroprotective effects depend on blood brain barrier integrity in experimental cerebral ischemia.

    PubMed

    Carone, D; Librizzi, L; Cattalini, A; Sala, G; Conti, E; Cuccione, E; Versace, A; Cai, R; Monza, L; de Curtis, M; Ferrarese, C; Beretta, S

    2015-07-30

    Statins have since long been reported to exert acute neuroprotection in experimental stroke models. However, crucial questions still need to be addressed as far as the timing of their cerebral effects after intravascular administration and the role played by the blood brain barrier (BBB) crossing properties. We tested the effects of an hydrophilic statin (pravastatin, 100 nM), which poorly crosses BBB under physiological conditions. Pravastatin was administered either 90 min before or immediately after transient middle cerebral artery occlusion in the in vitro isolated guinea pig brain preparation. A multi-modal outcome assessment was performed, through electrophysiological and cerebral vascular tone recordings, MAP-2 immunohistochemistry, BBB evaluation via ZO-1/FITC-albumin analysis, AKT and ERK activation and whole-cell antioxidant capacity. Pravastatin pre-ischemic administration did not produce any significant effect. Pravastatin post-ischemic administration significantly prevented MAP-2 immunoreactivity loss in ischemic areas, increased ERK phosphorylation in the ischemic hemisphere and enhanced whole-cell antioxidant capacity. Electrophysiological parameters, vascular tone and AKT signaling were unchanged. In all tested ischemic brains, ZO-1 fragmentation and FITC albumin extravasation was observed, starting 30 min from ischemia onset, indicating loss of BBB integrity. Our findings indicate that the rapid anti-ischemic effects of intravascular pravastatin are highly dependent on BBB increased permeability after stroke.

  15. Behavioural training during acute brain trauma rehabilitation: an empirical case study.

    PubMed

    Slifer, K J; Cataldo, M D; Kurtz, P F

    1995-01-01

    Operant conditioning-based behavioural interventions are commonly used for the behavioural problems of individuals with mental retardation. There is also growing evidence of the benefits of these interventions for treating some of the behavioural problems of individuals with acquired cognitive deficits resulting from brain trauma. However, the effects of behavioural interventions on behavioural problems occurring during acute neurorehabilitation, when orientation and memory are most impaired, have not been studied. In this empirical case study, operant conditioning-based procedures were applied with an 8-year-old girl recovering from brain trauma and related neurosurgery. Screaming, non-compliance and aggression, which were disrupting rehabilitation therapies and follow-up neuroimaging, were treated using differential positive reinforcement techniques. Beneficial behavioural intervention effects were demonstrated using single-subject experimental methods. Aberrant behaviour during physical and occupational therapies was reduced, and cooperation with a computerized tomography (CT) scan without sedation was accomplished using operant behavioural intervention. Results support the use of operant interventions early in recovery from brain trauma, and highlight the importance of interdisciplinary collaboration for the implementation and further study of early behavioural interventions.

  16. Readmission to Acute Care Hospital during Inpatient Rehabilitation for Traumatic Brain Injury

    PubMed Central

    Hammond, Flora M.; Horn, Susan D.; Smout, Randall J.; Beaulieu, Cynthia L.; Barrett, Ryan S.; Ryser, David K.; Sommerfeld, Teri

    2015-01-01

    Objective To investigate frequency, reasons, and factors associated with readmission to acute care (RTAC) during inpatient rehabilitation for traumatic brain injury (TBI). Design Prospective observational cohort. Setting Inpatient rehabilitation. Participants 2,130 consecutive admissions for TBI rehabilitation. Interventions Not applicable. Main Outcome Measure(s) RTAC incidence, RTAC causes, rehabilitation length of stay (RLOS), and rehabilitation discharge location. Results 183 participants (9%) experienced RTAC for a total 210 episodes. 161 patients experienced 1 RTAC episode, 17 had 2, and 5 had 3. Mean days from rehabilitation admission to first RTAC was 22 days (SD 22). Mean duration in acute care during RTAC was 7 days (SD 8). 84 participants (46%) had >1 RTAC episode for medical reasons, 102 (56%) had >1 RTAC for surgical reasons, and RTAC reason was unknown for 6 (3%) participants. Most common surgical RTAC reasons were: neurosurgical (65%), pulmonary (9%), infection (5%), and orthopedic (5%); most common medical reasons were infection (26%), neurologic (23%), and cardiac (12%). Older age, history of coronary artery disease, history of congestive heart failure, acute care diagnosis of depression, craniotomy or craniectomy during acute care, and presence of dysphagia at rehabilitation admission predicted patients with RTAC. RTAC was less likely for patients with higher admission Functional Independence Measure Motor scores and education less than high school diploma. RTAC occurrence during rehabilitation was significantly associated with longer RLOS and smaller likelihood of discharge home. Conclusion(s) Approximately 9% of patients with TBI experience RTAC during inpatient rehabilitation for various medical and surgical reasons. This information may help inform interventions aimed at reducing interruptions in rehabilitation due to RTAC. RTACs were associated with longer RLOS and discharge to an institutional setting. PMID:26212405

  17. 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

  18. Purple sweet potato (Ipomoea batatas L.) anthocyanins: preventive effect on acute and subacute alcoholic liver damage and dealcoholic effect.

    PubMed

    Sun, Hongnan; Mu, Taihua; Liu, Xingli; Zhang, Miao; Chen, Jingwang

    2014-03-19

    This study aimed to investigate the dealcoholic effect and preventive effect of anthocyanins from purple sweet potato (PSPAs) on acute and subacute alcoholic liver damage (ALD). Seven-week-old male inbred mice were grouped into five groups: control group (without PSPAs and ethanol treatments), model group (with ethanol treatment only), low-dose group (50 mg PSPAs/kg body weight), middle-dose group (125 mg PSPAs/kg body weight), and high-dose group (375 mg PSPAs/kg body weight), and the mice in all groups were administered intragastrically. Biochemical parameters of serum and liver were determined, and the histopathological changes of liver tissue were also analyzed. Results showed that all tested parameters were ameliorated after consumption of PSPAs. Therefore, PSPAs have preventive effect on acute and subacute ALD. It is suggested that PSPAs could be used as a supplementary reagent during prophylactic and curative managements of ALD.

  19. Use of early biomarkers in neonatal brain damage and sepsis: state of the art and future perspectives.

    PubMed

    Bersani, Iliana; Auriti, Cinzia; Ronchetti, Maria Paola; Prencipe, Giusi; Gazzolo, Diego; Dotta, Andrea

    2015-01-01

    The identification of early noninvasive biochemical markers of disease is a crucial issue of the current scientific research, particularly during the first period of life, since it could provide useful and precocious diagnostic information when clinical and radiological signs are still silent. The ideal biomarker should be practical and sensitive in the precocious identification of at risk patients. An earlier diagnosis may lead to a larger therapeutic window and improve neonatal outcome. Brain damage and sepsis are common causes of severe morbidity with poor outcome and mortality during the perinatal period. A large number of potential biomarkers, including neuroproteins, calcium binding proteins, enzymes, oxidative stress markers, vasoactive agents, and inflammatory mediators, have been so far investigated. The aim of the present review was to provide a brief overview of some of the more commonly investigated biomarkers used in case of neonatal brain damage and sepsis.

  20. Bone marrow mesenchymal stem cell implantation for the treatment of radioactivity‑induced acute skin damage in rats.

    PubMed

    Zheng, Kai; Wu, Weizhen; Yang, Shunliang; Huang, Lianghu; Chen, Jin; Gong, Chungui; Fu, Zhichao; Zhang, Linlin; Tan, Jianming

    2015-11-01

    The present study aimed to observe the role of mesenchymal stem cells (MSCs) in the repair of acute skin damage caused by radiation. Rat bone marrow MSCs (BMSCs) were isolated and cultured in vitro. A rat model of radiation‑induced acute skin damage was established by irradiation of the hind legs of Sprague-Dawley rats using a linear accelerator (45 Gy). After irradiation, rats were randomly divided into two groups: BMSC group and control group. Rats in the BMSC group were treated with a tail vein injection of 2x106 BMSCs (1 ml) immediately after irradiation and a local multipoint injection of 2x106 BMSCs at the injured area two weeks later. Then the wound healing of each rat was observed. The expression of transforming growth factor (TGF)‑β1, stromal cell‑derived factor-1 (SDF‑1) and prostaglandin E2 (PGE2) in the wounded tissues was determined by immunohistochemistry. The results demonstrated that skin damage was milder in the BMSC group than in the control group. Moreover, the speed of healing in the BMSC group was better than that in the control group. In addition, the wound score, it was significantly lower in the BMSC group than in the control group (P<0.05). The expression of PGE2 and TGF‑β1 in the BMSC group was also significantly lower than that in the control group (P<0.05), whereas the SDF‑1 expression was significantly higher in the BMSC group than that in the control group (P<0.05). BMSCs can effectively reduce inflammation and fibrosis in the wounded skin and promote the repair of acute radioactive skin injury. Thus, may be developed as a novel treatment for wound healing. PMID:26323987

  1. Triphasic multinutrient supplementation during acute resistance exercise improves session volume load and reduces muscle damage in strength-trained athletes.

    PubMed

    Bird, Stephen P; Mabon, Tom; Pryde, Mitchell; Feebrey, Sarah; Cannon, Jack

    2013-05-01

    We hypothesized that triphasic multinutrient supplementation during acute resistance exercise would enhance muscular performance, produce a more favorable anabolic profile, and reduce biochemical markers of muscle damage in strength-trained athletes. Fifteen male strength-trained athletes completed two acute lower-body resistance exercise sessions to fatigue 7 days apart. After a 4-hour fast, participants consumed either a multinutrient supplement (Musashi 1-2-3 Step System, Notting Hill, Australia) (SUPP) or placebo (PLA) beverage preexercise (PRE), during (DUR), and immediately postexercise (IP). Session volume loads were calculated as kilograms × repetitions. Lower-body peak power was measured using unloaded repeated countermovement jumps, and blood samples were collected to assess biochemistry, serum hormones, and muscle damage markers at PRE, DUR, IP, 30 minutes postexercise (P30), and 24 hours postexercise (P24h). The SUPP demonstrated increased glucose concentrations at DUR and IP compared with at PRE (P < .01), whereas PLA demonstrated higher glucose at P30 compared with at PRE (P < .001). Session volume load was higher for SUPP compared with PLA (P < .05). Cortisol increased at DUR, IP, and P30 compared with at PRE in both treatments (P < .05); however, SUPP also displayed lower cortisol at P24h compared with at PRE and PLA (P < .01). The total testosterone response to exercise was higher for PLA compared with SUPP (P < .01); however, total creatine kinase and C-reactive protein responses to exercise were lower for SUPP compared with PLA (P < .05). These data indicate that although triphasic multinutrient supplementation did not produce a more favorable anabolic profile, it improved acute resistance exercise performance while attenuating muscle damage in strength-trained athletes.

  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.

  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. Solid-extracellular fluid interaction and damage in the mechanical response of rat brain tissue under confined compression.

    PubMed

    Haslach, Henry W; Leahy, Lauren N; Riley, Peter; Gullapalli, Rao; Xu, Su; Hsieh, Adam H

    2014-01-01

    The mechanical processes that underlie mild traumatic brain injury from physical insults are not well understood. One aspect in particular that has not been examined is the tissue fluid, which is known to be critical in the mechanical function of other organs. To investigate the contributions of solid-fluid interactions to brain tissue mechanics, we performed confined compression tests, that force the extracellular fluid (ECF) to flow in the direction of the deformation, on 6.35mm diameter, 3mm long cylindrical samples excised from various regions of rat brains. Two types of tests in deformation control, (1) quasi-static, slow and moderate constant strain rate tests at 0.64×10(-5)/s, 0.001/s and 1/s to large strains and (2) several applications of slow linear deformation to 5% strain each followed by stress relaxation are employed to explore the solid-fluid interaction. At slow and moderate compressive strain rates, we observed stress peaks in the applied strain range at about 11%, whose magnitudes exhibited statistically significant dependence on strain rate. These data suggest that the ECF carries load until the tissue is sufficiently damaged to permit pathological fluid flow. Under the slow ramp rate in the ramp-relaxation cycles protocol, commonly used to estimate permeability, the stress relaxes to zero after the first cycle, rather than to a non-zero equilibrium stress corresponding to the applied strain, which further implicates mechanical damage. Magnetic resonance imaging (MRI) of changes in tissue microstructure during confined compression, before and after compression, provides further evidence of tissue damage. The solid-fluid interactions, reflected in the morphology of the stress-stretch curves and supported by the MRI data, suggest that increases in hydrostatic pressure in the ECF may contribute to mechanical damage of brain tissue.

  5. Pre-treatment with LCZ696, an orally active angiotensin receptor neprilysin inhibitor, prevents ischemic brain damage.

    PubMed

    Bai, Hui-Yu; Mogi, Masaki; Nakaoka, Hirotomo; Kan-No, Harumi; Tsukuda, Kana; Chisaka, Toshiyuki; Wang, Xiao-Li; Kukida, Masayoshi; Shan, Bao-Shuai; Yamauchi, Toshifumi; Higaki, Akinori; Iwanami, Jun; Horiuchi, Masatsugu

    2015-09-01

    Angiotensin II receptor blockers (ARBs) are known to prevent ischemic brain damage after stroke. Natriuretic peptides, which are increased by a neprilysin inhibitor, are also reported to protect against brain damage. Therefore, we investigated the possible protective effect of valsartan (VAL) compared with LCZ696 (VAL+ neprilysin inhibitor; 1:1) after middle cerebral artery (MCA) occlusion. Eight-week-old male C57BL/6J mice were treated with VAL (3mg/kg per day) or LCZ696 (6mg/kg per day) for 2 weeks before MCA occlusion. Blood pressure and heart rate were measured by telemetry. Cerebral blood flow (CBF) was determined by laser-Doppler flowmetry. Ischemic area was evaluated by triphenytetrasodium chloride staining, and oxidative stress was determined by dihydroethidium staining. Blood pressure and heart rate were not significantly different before and after treatment. Pre-treatment with LCZ696 or VAL reduced the ischemic area, and this effect of LCZ696 was more marked than that of VAL pre-treatment. The decrease in CBF in the peripheral region of the ischemic area was significantly attenuated by pre-treatment with LCZ696 or VAL, without any significant effect on CBF in the core region. VAL or LCZ696 pre-treatment significantly decreased the increase of superoxide anion production in the cortex on the ischemic side. However, no significant difference in CBF and superoxide anion production was observed between VAL and LCZ696 pre-treatment. The preventive effect of LCZ696 on ischemic brain damage after stroke was more marked than that of VAL. LCZ696 could be used as a new approach to prevent brain damage after stroke. (246 words). PMID:26057694

  6. Cingulate neglect in humans: disruption of contralesional reward learning in right brain damage.

    PubMed

    Lecce, Francesca; Rotondaro, Francesca; Bonnì, Sonia; Carlesimo, Augusto; Thiebaut de Schotten, Michel; Tomaiuolo, Francesco; Doricchi, Fabrizio

    2015-01-01

    Motivational valence plays a key role in orienting spatial attention. Nonetheless, clinical documentation and understanding of motivationally based deficits of spatial orienting in the human is limited. Here in a series of one group-study and two single-case studies, we have examined right brain damaged patients (RBD) with and without left spatial neglect in a spatial reward-learning task, in which the motivational valence of the left contralesional and the right ipsilesional space was contrasted. In each trial two visual boxes were presented, one to the left and one to the right of central fixation. In one session monetary rewards were released more frequently in the box on the left side (75% of trials) whereas in another session they were released more frequently on the right side. In each trial patients were required to: 1) point to each one of the two boxes; 2) choose one of the boxes for obtaining monetary reward; 3) report explicitly the position of reward and whether this position matched or not the original choice. Despite defective spontaneous allocation of attention toward the contralesional space, RBD patients with left spatial neglect showed preserved contralesional reward learning, i.e., comparable to ipsilesional learning and to reward learning displayed by patients without neglect. A notable exception in the group of neglect patients was L.R., who showed no sign of contralesional reward learning in a series of 120 consecutive trials despite being able of reaching learning criterion in only 20 trials in the ipsilesional space. L.R. suffered a cortical-subcortical brain damage affecting the anterior components of the parietal-frontal attentional network and, compared with all other neglect and non-neglect patients, had additional lesion involvement of the medial anterior cingulate cortex (ACC) and of the adjacent sectors of the corpus callosum. In contrast to his lateralized motivational learning deficit, L.R. had no lateral bias in the early phases of

  7. Coarse coding and discourse comprehension in adults with right hemisphere brain damage

    PubMed Central

    Tompkins, Connie A.; Scharp, Victoria L.; Meigh, Kimberly M.; Fassbinder, Wiltrud

    2009-01-01

    Background Various investigators suggest that some discourse-level comprehension difficulties in adults with right hemisphere brain damage (RHD) have a lexical-semantic basis. As words are processed, the intact right hemisphere arouses and sustains activation of a wide-ranging network of secondary or peripheral meanings and features—a phenomenon dubbed “coarse coding”. Coarse coding impairment has been postulated to underpin some prototypical RHD comprehension deficits, such as difficulties with nonliteral language interpretation, discourse integration, some kinds of inference generation, and recovery when a reinterpretation is needed. To date, however, no studies have addressed the hypothesised link between coarse coding deficit and discourse comprehension in RHD. Aims The current investigation examined whether coarse coding was related to performance on two measures of narrative comprehension in adults with RHD. Methods & Procedures Participants were 32 adults with unilateral RHD from cerebrovascular accident, and 38 adults without brain damage. Coarse coding was operationalised as poor activation of peripheral/weakly related semantic features of words. For the coarse coding assessment, participants listened to spoken sentences that ended in a concrete noun. Each sentence was followed by a spoken target phoneme string. Targets were subordinate semantic features of the sentence-final nouns that were incompatible with their dominant mental representations (e.g., “rotten” for apple). Targets were presented at two post-noun intervals. A lexical decision task was used to gauge both early activation and maintenance of activation of these weakly related semantic features. One of the narrative tasks assessed comprehension of implied main ideas and details, while the other indexed high-level inferencing and integration. Both comprehension tasks were presented auditorily. For all tasks, accuracy of performance was the dependent measure. Correlations were computed

  8. 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

  9. Pain and Body Awareness: Evidence from Brain-Damaged Patients with Delusional Body Ownership

    PubMed Central

    Pia, Lorenzo; Garbarini, Francesca; Fossataro, Carlotta; Fornia, Luca; Berti, Anna

    2013-01-01

    A crucial aspect for the cognitive neuroscience of pain is the interplay between pain perception and body awareness. Here we report a novel neuropsychological condition in which right brain-damaged patients displayed a selective monothematic delusion of body ownership. Specifically, when both their own and the co-experimenter’s left arms were present, these patients claimed that the latter belonged to them. We reasoned that this was an ideal condition to examine whether pain perception can be “referred” to an alien arm subjectively experienced as one’s own. Seventeen patients (11 with, 6 without the delusion), and 10 healthy controls were administered a nociceptive stimulation protocol to assess pain perception. In the OWN condition, participants placed their arms on a table in front of them. In the ALIEN condition, the co-experimenter’s left (or right) arm was placed alongside the participants’ left (or right) arm, respectively. In the OWN condition, left (or right) participants’ hand dorsum were stimulated. In the ALIEN condition, left (or right) co-experimenter’s hand dorsum was stimulated. Participants had to rate the perceived pain on a 0–5 Likert scale (0 = no pain, 5 = maximal imaginable pain). Results showed that healthy controls and patients without delusion gave scores higher than zero only when their own hands were stimulated. On the contrary, patients with delusion gave scores higher than zero both when their own hands (left or right) were stimulated and when the co-experimenter’s left hand was stimulated. Our results show that in pathological conditions, a body part of another person can become so deeply embedded in one’s own somatosensory representation to effect the subjective feeling of pain. More in general, our findings are in line with a growing number of evidence emphasizing the role of the special and unique perceptual status of body ownership in giving rise to the phenomenological experience of pain. PMID:23801958

  10. Evidence for a therapeutic effect of Braintone on ischemic brain damage.

    PubMed

    Qin, Yuanyuan; Luo, Yu; Gu, Weiwei; Yang, Lei; Shen, Xikun; Gu, Zhenlun; Zhang, Huiling; Gao, Xiumei

    2013-07-01

    This study used a novel combination of in vivo and in vitro experiments to show that Braintone had neuroprotective effects and clarified the molecular mechanisms underlying its efficacy. The Chinese herbal extract Braintone is composed of Radix Rhodiolase Essence, Radix Notoginseng Essence, Folium Ginkgo Essence and Rhizoma Chuanxiong. In vivo experiments showed that cerebral infarction volume was reduced, hemispheric water content decreased, and neurological deficits were alleviated in a rat model of permanent middle cerebral artery occlusion after administration of 87.5, 175 or 350 mg/kg Braintone for 7 consecutive days. Western blot analysis showed that Braintone enhanced the expression of hypoxia-inducible factor 1α, heme oxygenase-1 and vascular endothelial growth factor in the ischemic cortex of these rats. The 350 mg/kg dose of Braintone produced the most dramatic effects. For the in vitro experiments, prior to oxygen-glucose deprivation, rats were intragastrically injected with 440, 880 or 1 760 mg/kg Braintone to prepare a Braintone-containing serum, which was used to pre-treat human umbilical vein endothelial cells for 24 hours. Human umbilical vein endothelial cell injury was alleviated with this pre-treatment. Western blot and real-time PCR analysis showed that the Braintone-containing serum increased the levels of hypoxia-inducible factor 1α mRNA and protein, heme oxygenase-1 protein and vascular endothelial growth factor mRNA in oxygen-glucose deprived human umbilical vein endothelial cells. The 1 760 mg/kg dose produced the greatest increases in expression. Collectively, these experimental findings suggest that Braintone has neuroprotective effects on ischemia-induced brain damage via the up-regulation of hypoxia-inducible factor 1α, heme oxygenase-1 and vascular endothelial growth factor expression in vascular endothelial cells. PMID:25206471

  11. Influence of response modality on awareness of contralesional tactile stimuli in right brain damaged patients.

    PubMed

    Neppi-Modona, M

    1999-12-01

    Thirty right brain-damaged (RBD) patients with left tactile extinction (19 of whom also showed neglect) were given a sequence of 240 tactile stimuli--80 right, 80 left, 80 bilateral--across 4 different response conditions: (a) verbal report of stimulated side/s, (b) motor report of stimulated side/s, (c) verbal report of unstimulated side/s, (d) motor report of unstimulated side/s. Earlier experiments based on similar tasks but involving RBD patients with visual extinction and/or neglect have shown that visual awareness of contralesional stimuli can be influenced by manipulation of response conditions. Since neglect and extinction can be double-dissociated both anatomically and behaviourally, the question arises of whether the underlying neuronal mechanisms are different. To answer this question the present work investigated the role of perceptual and premotor factors in generating tactile extinction in response to Double Simultaneous Stimulation (DSS). The hypothesis was that a directional response bias would result in an overall higher frequency of errors for verbal or motor responses indicating the ipsilesional side (right); a perceptual bias would instead result in errors distributed with similar frequency on the ipsilesional and the contralesional (left) side. Results showed that, in RBD patients, contralesional extinction was not influenced by response conditions (verbal/motor; report of stimulated/unstimulated side) and presence/absence of neglect. This suggests that: (1) among RBD patients, directional response biases are unlikely to play a role in extinction of tactile stimuli on DSS; (2) the mechanisms underlying extinction are, at least to some extent, different from those underlying unilateral neglect.

  12. Anatomical and spatial matching in imitation: Evidence from left and right brain-damaged patients.

    PubMed

    Mengotti, Paola; Ripamonti, Enrico; Pesavento, Valentina; Rumiati, Raffaella Ida

    2015-12-01

    Imitation is a sensorimotor process whereby the visual information present in the model's movement has to be coupled with the activation of the motor system in the observer. This also implies that greater the similarity between the seen and the produced movement, the easier it will be to execute the movement, a process also known as ideomotor compatibility. Two components can influence the degree of similarity between two movements: the anatomical and the spatial component. The anatomical component is present when the model and imitator move the same body part (e.g., the right hand) while the spatial component is present when the movement of the model and that of the imitator occur at the same spatial position. Imitation can be achieved by relying on both components, but typically the model's and imitator's movements are matched either anatomically or spatially. The aim of this study was to ascertain the contribution of the left and right hemisphere to the imitation accomplished either with anatomical or spatial matching (or with both). Patients with unilateral left and right brain damage performed an ideomotor task and a gesture imitation task. Lesions in the left and right hemispheres gave rise to different performance deficits. Patients with lesions in the left hemisphere showed impaired imitation when anatomical matching was required, and patients with lesions in the right hemisphere showed impaired imitation when spatial matching was required. Lesion analysis further revealed a differential involvement of left and right hemispheric regions, such as the parietal opercula, in supporting imitation in the ideomotor task. Similarly, gesture imitation seemed to rely on different regions in the left and right hemisphere, such as parietal regions in the left hemisphere and premotor, somatosensory and subcortical regions in the right hemisphere.

  13. Effect of alpha-ketoglutarate and oxaloacetate on brain mitochondrial DNA damage and seizures induced by kainic acid in mice.

    PubMed

    Yamamoto, Hiro-aki; Mohanan, Parayanthala V

    2003-07-20

    The effects of alpha-ketoglutarate and oxaloacetate on brain mitochondrial DNA (mtDNA) damage and seizures induced by kainic acid were examined both in vivo and in vitro. An intraperitoneal (ip) injection of kainic acid (45 mg/kg) produced broad-spectrum limbic and severe sustained seizures in all of the treated mice. The seizures were abolished when alpha-ketoglutarate (2 g/kg) or oxaloacetate (1 g/kg) was injected intraperitoneally in the animals 1 min before kainic acid administration. In addition, the administration of kainic acid caused damage to mtDNA in brain frontal and middle cortex of mice. These effects were completely abolished by the ip preinjection of alpha-ketoglutarate (2 g/kg) or oxaloacetate (1 g/kg). In vitro exposure of kainic acid (0.25, 0.5 or 1.0 mM) to brain homogenate inflicted damage to mtDNA in a concentration-dependent manner. The damage of mtDNA induced by 1.0 mM kainic acid was attenuated by the co-treatment with alpha-ketoglutarate (2.5 or 5.0 mM) or oxaloacetate (0.75 or 1.0 mM). Furthermore, in vivo and in vitro exposure of kainic acid elicited an increase in lipid peroxidation. However, the increased lipid peroxidation was completely inhibited by cotreatment of alpha-ketoglutarate or oxaloacetate. These results suggest that alpha-keto acids such as alpha-ketoglutarate and oxaloacetate play a role in the inhibition of seizures and subsequent mtDNA damage induced by the excitotoxic/neurotoxic agent, kainic acid.

  14. Right-sided representational neglect after left brain damage in a case without visuospatial working memory deficits.

    PubMed

    van Dijck, Jean-Philippe; Gevers, Wim; Lafosse, Christophe; Fias, Wim

    2013-10-01

    Brain damaged patients suffering from representational neglect (RN) fail to report, orient to, or verbally describe contra-lesional elements of imagined environments or objects. So far this disorder has only been reported after right brain damage, leading to the idea that only the right hemisphere is involved in this deficit. A widely accepted account attributes RN to a lateralized impairment in the visuospatial component of working memory. So far, however, this hypothesis has not been tested in detail. In the present paper, we describe, for the first time, the case of a left brain damaged patient suffering from right-sided RN while imagining both known and new environments and objects. An in-depth evaluation of her visuospatial working memory abilities, with special focus on the presence of a lateralized deficit, did not reveal any abnormality. In sharp contrast, her ability to memorize visual information was severely compromised. The implications of these results are discussed in the light of recent insights in the neglect syndrome.

  15. 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

  16. 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

  17. 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

  18. Systematic analysis of axonal damage and inflammatory response in different white matter tracts of acutely injured rat spinal cord.

    PubMed

    Gomes-Leal, W; Corkill, D J; Picanço-Diniz, C W

    2005-12-20

    The mechanisms of white matter (WM) damage during secondary degeneration are a fundamental issue in the pathophysiology of central nervous system (CNS) diseases. Our main goal was to describe the pattern of an acute inflammatory response and secondary damage to axons in different WM tracts of acutely injured rat spinal cord. Adult rats were deeply anesthetized and injected with 20 nmol of NMDA into the spinal cord ventral horn on T7. Animals were perfused after survival times of 1 day, 3 days and 7 days. Ten micrometer sections were submitted to immunocytochemical analysis for activated macrophages/microglia, neutrophils and damaged axons. There were inflammatory response and progressive tissue destruction of ventral WM (VWM) with formation of microcysts in both VWM and lateral WM (LWM). In the VWM, the number of beta-amyloid precursor protein (beta-APP) end-bulbs increased from 1 day with a peak at 3 days, decreasing by 7 days following the injection. APP end-bulbs were present in the dorsal WM (DWM) at 3 days survival time but were not in the LWM. Electron microscopic analysis revealed different degrees of myelin disruption and axonal pathology in the vacuolated WM up to 14 mm along the rostrocaudal axis. Quantitative analysis revealed a significant loss of medium and large axons (P < 0.05), but not of small axons (P > 0.05). Our results suggest that bystander axonal damage and myelin vacuolation are important secondary component of the pathology of WM tracts following rat SCI. Further studies are needed to understand the mechanisms of these pathological events.

  19. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study

    SciTech Connect

    Cakmak G.; Miller L.; Zorlu, F.; Severcan, F.

    2012-03-03

    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH{sub 2} groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH{sub 3} groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems.