scholarly journals Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity

2016 ◽  
Vol 311 (5) ◽  
pp. H1202-H1213 ◽  
Author(s):  
Mimily Harsono ◽  
Massroor Pourcyrous ◽  
Elliott J. Jolly ◽  
Amy de Jongh Curry ◽  
Alexander L. Fedinec ◽  
...  
Keyword(s):  
Spectral Power ◽  
Epileptiform Activity ◽  
Circulating Endothelial Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Positive Staining ◽  
Cerebrovascular Injury ◽  
Head Cooling ◽  
Normothermic Group ◽  
Cerebral Vasodilator ◽  
Cerebral Vascular

Epileptic seizures in neonates cause cerebrovascular injury and impairment of cerebral blood flow (CBF) regulation. In the bicuculline model of seizures in newborn pigs, we tested the hypothesis that selective head cooling prevents deleterious effects of seizures on cerebral vascular functions. Preventive or therapeutic ictal head cooling was achieved by placing two head ice packs during the preictal and/or ictal states, respectively, for the ∼2-h period of seizures. Head cooling lowered the brain and core temperatures to 25.6 ± 0.3 and 33.5 ± 0.1°C, respectively. Head cooling had no anticonvulsant effects, as it did not affect the bicuculline-evoked electroencephalogram parameters, including amplitude, duration, spectral power, and spike frequency distribution. Acute and long-term cerebral vascular effects of seizures in the normothermic and head-cooled groups were tested during the immediate (2–4 h) and delayed (48 h) postictal periods. Seizure-induced cerebral vascular injury during the immediate postictal period was detected as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive staining of cerebral arterioles and a surge of brain-derived circulating endothelial cells in peripheral blood in the normothermic group, but not in the head-cooled groups. During the delayed postictal period, endothelium-dependent cerebral vasodilator responses were greatly reduced in the normothermic group, indicating impaired CBF regulation. Preventive or therapeutic ictal head cooling mitigated the endothelial injury and greatly reduced loss of postictal cerebral vasodilator functions. Overall, head cooling during seizures is a clinically relevant approach to protecting the neonatal brain by preventing cerebrovascular injury and the loss of the endothelium-dependent control of CBF without reducing epileptiform activity.

scholarly journals Respiratory-related brain pulsations are increased in epilepsy—a two-centre functional MRI study

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Janne Kananen ◽  
Heta Helakari ◽  
Vesa Korhonen ◽  
Niko Huotari ◽  
Matti Järvelä ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Functional Mri ◽  
Coefficient Of Variation ◽  
Spectral Power ◽  
Neurological Diseases ◽  
Epileptiform Activity ◽  
High Specificity ◽  
Full Band ◽  
Drug Naïve ◽  
Patients With Epilepsy

Abstract Resting-state functional MRI has shown potential for detecting changes in cerebral blood oxygen level-dependent signal in patients with epilepsy, even in the absence of epileptiform activity. Furthermore, it has been suggested that coefficient of variation mapping of fast functional MRI signal may provide a powerful tool for the identification of intrinsic brain pulsations in neurological diseases such as dementia, stroke and epilepsy. In this study, we used fast functional MRI sequence (magnetic resonance encephalography) to acquire ten whole-brain images per second. We used the functional MRI data to compare physiological brain pulsations between healthy controls (n = 102) and patients with epilepsy (n = 33) and furthermore to drug-naive seizure patients (n = 9). Analyses were performed by calculating coefficient of variation and spectral power in full band and filtered sub-bands. Brain pulsations in the respiratory-related frequency sub-band (0.11–0.51 Hz) were significantly (P < 0.05) increased in patients with epilepsy, with an increase in both signal variance and power. At the individual level, over 80% of medicated and drug-naive seizure patients exhibited areas of abnormal brain signal power that correlated well with the known clinical diagnosis, while none of the controls showed signs of abnormality with the same threshold. The differences were most apparent in the basal brain structures, respiratory centres of brain stem, midbrain and temporal lobes. Notably, full-band, very low frequency (0.01–0.1 Hz) and cardiovascular (0.8–1.76 Hz) brain pulses showed no differences between groups. This study extends and confirms our previous results of abnormal fast functional MRI signal variance in epilepsy patients. Only respiratory-related brain pulsations were clearly increased with no changes in either physiological cardiorespiratory rates or head motion between the subjects. The regional alterations in brain pulsations suggest that mechanisms driving the cerebrospinal fluid homeostasis may be altered in epilepsy. Magnetic resonance encephalography has both increased sensitivity and high specificity for detecting the increased brain pulsations, particularly in times when other tools for locating epileptogenic areas remain inconclusive.

Apoptosis after traumatic human spinal cord injury

1998 ◽  
Vol 5 (4) ◽  
pp. E1 ◽  
Author(s):  
Evelyne Emery ◽  
Philipp Aldana ◽  
Mary Bartlett Bunge ◽  
William Puckett ◽  
Anu Srinivasan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Positive Staining ◽  
Apoptotic Cells ◽  
Nuclear Staining ◽  
Human Spinal Cord ◽  
Cord Injury

Object Apoptosis is a form of programmed cell death seen in a variety of developmental and disease states, including traumatic injuries. The main objective of this study was to determine whether apoptosis is observed after human spinal cord injury (SCI). The spatial and temporal expression of apoptotic cells as well as the nature of the cells involved in programmed cell death were also investigated. Methods The authors examined the spinal cords of 15 patients who died between 3 hours and 2 months after a traumatic SCI. Apoptotic cells were found at the edges of the lesion epicenter and in the adjacent white matter, particularly in the ascending tracts, by using histological (cresyl violet, hematoxylin and eosin) and nuclear staining (Hoechst 33342). The suspected presence of apoptotic cells was supported by staining with the terminal deoxynucleotidyl transferase-mediated biotinylated-deoxyuridinetriphosphate nick-end labeling technique and confirmed by immunostaining for the processed form of caspase-3 (CPP-32), a member of the interleukin-1-beta-converting enzyme/Caenorhabditis elegans D 3 family of proteases that plays an essential role in programmed cell death. Apoptosis in this series of human SCIs was a prominent pathological finding in 14 of the 15 spinal cords examined when compared with five uninjured control spinal cords. To determine the type of cells undergoing apoptosis, the authors immunostained specimens with a variety of antibodies, including glial fibrillary acidic protein, 2,′3′-cyclic nucleotide 3′-phosphohydrolase (CNPase), and CD45/68. Oligodendrocytes stained with CNPase and a number of apoptotic nuclei colocalized with positive staining for this antibody. Conclusions These results support the hypothesis that apoptosis occurs in human SCIs and is accompanied by the activation of CPP-32 of the cysteine protease family. This mechanism of cell death contributes to the secondary injury processes seen after human SCI and may have important clinical implications for the further development of protease inhibitors to prevent programmed cell death.

Quantitative EEG Analysis in Angelman Syndrome: Candidate Method for Assessing Therapeutics

2020 ◽  
pp. 155005942097309
Author(s):  
Luis A. Martinez ◽  
Heather A. Born ◽  
Sarah Harris ◽  
Angelique Regnier-Golanov ◽  
Joseph C. Grieco ◽  
...  
Keyword(s):  
Angelman Syndrome ◽  
Spectral Power ◽  
Epileptiform Activity ◽  
Quantitative Eeg ◽  
Total Power ◽  
Quantitative Evidence ◽  
Delta Power ◽  
Eeg Spectral Power ◽  
Minocycline Treatment ◽  
Potential Biomarker

The goal of these studies was to use quantitative (q)EEG techniques on data from children with Angelman syndrome (AS) using spectral power analysis, and to evaluate this as a potential biomarker and quantitative method to evaluate therapeutics. Although characteristic patterns are evident in visual inspection, using qEEG techniques has the potential to provide quantitative evidence of treatment efficacy. We first assessed spectral power from baseline EEG recordings collected from children with AS compared to age-matched neurotypical controls, which corroborated the previously reported finding of increased total power driven by elevated delta power in children with AS. We then retrospectively analyzed data collected during a clinical trial evaluating the safety and tolerability of minocycline (3 mg/kg/d) to compare pretreatment recordings from children with AS (4-12 years of age) to EEG activity at the end of treatment and following washout for EEG spectral power and epileptiform events. At baseline and during minocycline treatment, the AS subjects demonstrated increased delta power; however, following washout from minocycline treatment the AS subjects had significantly reduced EEG spectral power and epileptiform activity. Our findings support the use of qEEG analysis in evaluating AS and suggest that this technique may be useful to evaluate therapeutic efficacy in AS. Normalizing EEG power in AS therefore may become an important metric in screening therapeutics to gauge overall efficacy. As therapeutics transition from preclinical to clinical studies, it is vital to establish outcome measures that can quantitatively evaluate putative treatments for AS and neurological disorders with distinctive EEG patterns.

scholarly journals Brain-derived circulating endothelial cells in peripheral blood of newborn infants with seizures: a potential biomarker for cerebrovascular injury

2015 ◽  
Vol 3 (3) ◽  
pp. e12345 ◽  
Author(s):  
Massroor Pourcyrous ◽  
Shyamali Basuroy ◽  
Dilyara Tcheranova ◽  
Kristopher L. Arheart ◽  
Mohamad T. Elabiad ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peripheral Blood ◽  
Newborn Infants ◽  
Circulating Endothelial Cells ◽  
Cerebrovascular Injury ◽  
Potential Biomarker

The cold receptor TRPM8 activation leads to attenuation of endothelium-dependent cerebral vascular functions during head cooling

2021 ◽  
pp. 0271678X2110180
Author(s):  
Alex L Fedinec ◽  
Jianxiong Liu ◽  
Rong Zhang ◽  
Mimily Harsono ◽  
Massroor Pourcyrous ◽  
...  
Keyword(s):  
Mild Hypothermia ◽  
Brain Parenchyma ◽  
Trpm8 Channel ◽  
Cranial Window ◽  
Head Cooling ◽  
Window Technique ◽  
Pial Arterioles ◽  
Cold Sensitive ◽  
The Brain ◽  
Cerebral Vascular

Using the cranial window technique, we investigated acute effects of head cooling on cerebral vascular functions in newborn pigs. Head cooling lowered the rectal and extradural brain temperatures to 34.3 ± 0.6°C and 26.1 ± 0.6°C, respectively. During the 3-h hypothermia period, responses of pial arterioles to endothelium-dependent dilators bradykinin and glutamate were reduced, whereas the responses to hypercapnia and an endothelium-independent dilator sodium nitroprusside (SNP) remained intact. All vasodilator responses were restored after rewarming, suggesting that head cooling did not produce endothelial injury. We tested the hypothesis that the cold-sensitive TRPM8 channel is involved in attenuation of cerebrovascular functions. TRPM8 is immunodetected in cerebral vessels and in the brain parenchyma. During normothermia, the TRPM8 agonist icilin produced constriction of pial arterioles that was antagonized by the channel blocker AMTB. Icilin reduced dilation of pial arterioles to bradykinin and glutamate but not to hypercapnia and SNP, thus mimicking the effects of head cooling on vascular functions. AMTB counteracted the impairment of endothelium-dependent vasodilation caused by hypothermia or icilin. Overall, mild hypothermia produced by head cooling leads to acute reversible reduction of selected endothelium-dependent cerebral vasodilator functions via TRPM8 activation, whereas cerebral arteriolar smooth muscle functions are largely preserved.

scholarly journals Epileptic seizures increase circulating endothelial cells in peripheral blood as early indicators of cerebral vascular damage

2010 ◽  
Vol 298 (6) ◽  
pp. H1687-H1698 ◽  
Author(s):  
Helena Parfenova ◽  
Charles W. Leffler ◽  
Dilyara Tcheranova ◽  
Shyamali Basuroy ◽  
Aliz Zimmermann
Keyword(s):  
Endothelial Cells ◽  
Peripheral Blood ◽  
Glucose Transporter ◽  
Mononuclear Cells ◽  
Epileptic Seizures ◽  
Vascular Damage ◽  
Cerebral Vessels ◽  
Circulating Endothelial Cells ◽  
Cerebral Vascular ◽  
Early Indicators

Circulating endothelial cells (CECs) are nonhematopoetic mononuclear cells in peripheral blood that are dislodged from injured vessels during cardiovascular disease, systemic vascular disease, and inflammation. Their occurrence during cerebrovascular insults has not been previously described. Epileptic seizures cause the long-term loss of cerebrovascular endothelial dilator function. We hypothesized that seizures cause endothelial sloughing from cerebral vessels and the appearance of brain-derived CECs (BCECs), possible early indicators of cerebral vascular damage. Epileptic seizures were induced by bicuculline in newborn pigs; venous blood was then sampled during a 4-h period. CECs were identified in the fraction of peripheral blood mononuclear cells by the expression of endothelial antigens (CD146, CD31, and endothelial nitric oxide synthase) and by Ulex europeaus lectin binding. In control animals, few CECs were detected. Seizures caused a time-dependent increase in CECs 2–4 h after seizure onset. Seizure-induced CECs coexpress glucose transporter-1, a blood-brain barrier-specific glucose transporter, indicating that these cells originate in the brain vasculature and are thus BCECs. Seizure-induced BCECs cultured in EC media exhibited low proliferative potential and abnormal cell contacts. BCEC appearance during seizures was blocked by a CO-releasing molecule (CORM-A1) or cobalt protoporphyrin (heme oxygenase-1 inducer), which prevented apoptosis in cerebral arterioles and the loss of cerebral vascular endothelial function during the late postictal period. These findings suggest that seizure-induced BCECs are injured ECs dislodged from cerebral microvessels during seizures. The correlation between the appearance of BCECs in peripheral blood, apoptosis in cerebral vessels, and the loss of postictal cerebral vascular function suggests that BCECs are early indicators of late cerebral vascular damage.

Trophoblast Apoptosis in Human Placenta at Term as Detected by Expression of a Cytokeratin 18 Degradation Product of Caspase

2002 ◽  
Vol 126 (12) ◽  
pp. 1480-1486
Author(s):  
Rigmor Austgulen ◽  
Lisa Chedwick ◽  
Christina Vogt Isaksen ◽  
Lars Vatten ◽  
Catherine Craven
Keyword(s):  
Monoclonal Antibody ◽  
Human Placenta ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Positive Staining ◽  
Cytokeratin 18 ◽  
Caspase Cleavage ◽  
Nonspecific Staining ◽  
Normal Placenta ◽  
Extravillous Trophoblasts ◽  
Apoptotic Cascade

Abstract Context.—Apoptosis occurs in the normal placenta. The monoclonal antibody M30 is directed against a novel epitope of cytokeratin 18 (CK18) that is formed by caspase cleavage early in the apoptotic cascade, and this antibody may therefore be useful for evaluating trophoblast apoptosis. Objective.—We undertook the present study to evaluate the use of monoclonal antibody M30 to assess trophoblast apoptosis in placenta at term. Methods.—We stained paraffin-embedded placental tissues from 15 deliveries at term with M30. We compared positive M30 staining and CK18 staining (as detected by a monoclonal antibody directed against CK18) of trophoblasts in serial slides. We also compared apoptotic rates as detected by M30 and TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling) in 7 of the placentas. Results.—In fields of villous tissue, most M30-positive cells were CK18-positive syncytiotrophoblasts. Approximately half of M30-positive cells occurred as focal positive staining in the syncytial layer, and half occurred as abundant staining of syncytiotrophoblasts in areas with increased intervillous or perivillous fibrinoid. We found very few M30-positive cells in villous stroma. In decidual/basal plate tissues, most (two thirds) of the M30-positive cells were CK18-positive extravillous trophoblasts, whereas one third were syncytiotrophoblasts of anchoring villi. Since TUNEL detects apoptosis in both epithelial and nonepithelial cells, more cells were positively stained with TUNEL than with M30 in some tissue fields. However, our observations suggest that M30 was more sensitive than TUNEL in recognizing apoptotic trophoblasts and had less nonspecific staining than TUNEL. Conclusion.—We recommend the use of monoclonal antibody M30 for apoptosis studies in placental tissues. This antibody is easy to handle, the staining obtained seems specific, and the nonspecific staining seems negligible.

Differential Effects of Hypothermia on Early and Late Epileptiform Events After Severe Hypoxia in Preterm Fetal Sheep

2007 ◽  
Vol 97 (1) ◽  
pp. 572-578 ◽  
Author(s):  
L. Bennet ◽  
J. M. Dean ◽  
G. Wassink ◽  
A. J. Gunn
Keyword(s):  
Marked Reduction ◽  
Epileptiform Activity ◽  
Neuronal Loss ◽  
Close Correlation ◽  
Recovery Phase ◽  
Early Recovery ◽  
Fetal Sheep ◽  
Specific Suppression ◽  
Head Cooling ◽  
Early Recovery Phase

Moderate cerebral hypothermia is consistently neuroprotective after experimental hypoxia-ischemia; however, its mechanisms remain poorly defined. Using a model of complete umbilical cord occlusion for 25 min in 0.7 gestation fetal sheep, we examined the effects of cerebral hypothermia (fetal extradural temperature reduced from 39.5 ± 0.2°C to <34°C; mean ± SD), from 90 min to 70 h after the end of the insult, on postocclusion epileptiform activity. In the first 6 h after the end of occlusion, fetal electroencephalographic (EEG) activity was abnormal with a mixture of fast and slow epileptiform transients superimposed on a suppressed background; seizures started a mean of 8 h after occlusion. There was a close correlation between numbers of these EEG transients and subsequent neuronal loss in the striatum after 3 days recovery ( r2 = 0.65, P = 0.008). Hypothermia was associated with a marked reduction in numbers of epileptiform transients in the first 6 h, reduced amplitude of seizures, and reduced striatal neuronal loss. In conclusion, neuroprotection with delayed, prolonged head cooling after a severe asphyxial insult in the preterm fetus was associated with potent, specific suppression of epileptiform transients in the early recovery phase but not of numbers of delayed seizures.

Importance of Flow Cytometry in the Immunophenotyping Characterization of Mantle Cell Lymphoma in State of Rio Grande Do Norte, Brazil

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-15
Author(s):  
Aldair Sousa Paiva ◽  
Alessandra Suelen Jardim Silva ◽  
Lenilton Silva DA Silva Júnior ◽  
Gustavo Henrique de Medeiros Oliveira ◽  
Hugo Henrique de Freitas Ferreira ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Heavy Chain ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Correct Selection ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Lymphoid Tissues ◽  
Positive Staining ◽  
Ki 67 ◽  
Detailed Assessment

Introduction:Mantle Cell Lymphoma (MCL) is a disease of a neoplastic nature characterized by proliferation in lymphoid tissues, classified as non-Hodgkin's lymphoma of B lymphocytes (NHBL). The nomenclature derives from the specific pathophysiology of this disease, that proliferates in the marginal area of the mantle of the germinal center of the lymph nodes.Objective:Carry out a detailed assessment of the immunophenotypic profile using the flow cytometry (CF) technique in 26 patients, NHBL to confirm mantle lymphoma.Materials and Methods:Biological samples from 26 patients, these being from peripheral blood (SP) or bone marrow (MO), of patients with suspected MCL were marked with monoclonal antibodies conjugated to fluorochromes and subsequently analyzed by FC.Results:all patients with a confirmed diagnosis of LCM were positive for pan-B antigens CD19, CD20 (strong) and CD22 (strong), CD19+/CD5+ and ciclin-D1 in 100% of cases. In addition to these, CD23, CD56, CD38, CD79b, Ki-67, Bcl-2, FMC-7 and HLA-Dr also obtained positive staining, as well as the immunoglobulin heavy chain (IgH) in all cases, and isotypes of immunoglobulins, IgD, IgG and IgM in most cases, with a predominance of the heavy chain of the lambda light chain in 79% of cases. Antigens related to T lymphocytes such as CD1a, CD2, CD3, CD7, TCR alpha/beta, TCR gamma/delta, CD4 and CD8, as well as antigens related to NK cells (CD16-56) and lymphoid progenitor cells (CD10 and Terminal- deoxynucleotidyl-transferase) were negative, as were CD200, antigens related to hairy cell leukemia (CD103, CD11c and CD123) and multiple myeloma (CD138).Discussion:According to the expression of the antigens, the antibodies were positive for: Cyclin D, CD19, CD20, CD22, CD38, Ki-67, Bcl-2, FMC-7 and CD79b, which are relevant to the diagnosis of this disease. Conclusion: Flow cytometry immunophenotyping is the technique currently used to confirm the diagnosis of neoplasms, such as LCM, which, due to its specific phenotype, helps in the correct selection of treatment. Disclosures No relevant conflicts of interest to declare.

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