Abstract TMP20: The Therapeutic Gas Carbon Monoxide (CO) Attenuates Vasospasm and Improve Neurobehavioral Function After SAH

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Pradip K Kamat ◽  
Abdullah Ahmad ◽  
Sylvain Dore
Keyword(s):  
Carbon Monoxide ◽  
Brain Injury ◽  
Cerebral Artery ◽  
Neurological Deficit ◽  
Therapeutic Strategy ◽  
Medical Condition ◽  
Delayed Cerebral Ischemia ◽  
Control Group ◽  
Neurological Deficit Score ◽  
Neurobehavioral Function

Introduction: Subarachnoid hemorrhage (SAH) is one of the most devastating forms of hemorrhagic stroke and it is a serious medical condition caused by bleeding of a ruptured aneurysm. The etiopathology of the disease includes early brain injury, vasospasm, and delayed cerebral ischemia. Blood byproducts cause the walls of arteries to constrict and spasm. At physiological concentrations, we and others have reported that carbon monoxide (CO) has functional roles in neuroprotection through anti-inflammation, anti-oxidative stress, and improving blood flow. Hence, this study focuses on the safe noninvasive therapeutic strategy to treat SAH by using CO as therapeutic medical gas. Hypothesis: We propose that CO may prevent SAH by mitigating vasospasm, limiting brain injury and improving functional outcomes. Methods: SAH was induced in adult mice using the endovascular perforation method. Mice were treated either with 250ppm CO or medical Air (at the same flow rate) after 2h of SAH for 1h daily for 7d. Such CO administration protocol keeps carboxyhemoglobin within normal range. Neurobehavioral outcomes such as focal neurological deficit score, open field activity, and motor functions were monitored at day 1 and day 7. Data acquisition and statistical analysis were performed by an investigator blinded to the intervention. Results: At 7d after SAH, CO decreased neurological deficit score (47.4±10.5%, p<0.05), and increased activity (30.0±9.1%, p<0.05) and stereotypic counts (261.5±62.1%, p<0.01) as compared to the air control group. No significant changes in motor function were observed in CO treated mice as compared to SAH at either day 1 or day 7). Of interest, there was a significant increase in CO treated group’s lumen area/wall thickness ratio in the middle cerebral artery (173.5±19.3%, p<0.01) and trended to increase in the anterior cerebral artery (25.5±4.3%, p=0.58) at 7d. Conclusion: This is a first report to demonstrate that CO prevents delayed SAH-induced neurobehavioral deficits, which suggest that post-treatment with CO should be considered a therapeutic strategy against SAH.

scholarly journals THE IMPORTANCE OF CENTRAL CHOLINERGIC SYSTEMS ACTIVATION IN TRAUMATIC BRAIN INJURY

2020 ◽  
Vol 16 (3) ◽  
pp. 3-8
Author(s):  
S.V. Ziablitsev ◽  
S.O. Khudoley
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurological Deficit ◽  
Physiological Saline ◽  
Neurological Deficits ◽  
Control Group ◽  
Post Traumatic Stress ◽  
Acute Period ◽  
Cholinergic Systems ◽  
Release Of Acetylcholine

Relevance. It is known that in traumatic brain injury (TBI), the activity of the central cholinergic systems (CChS) is inhibited, the release of acetylcholine and the expression of cholinergic receptors decrease. The restoration of cholinoreactivity is an urgent area of research and a possible therapeutic direction. Objective – to determine the effect of CChS activation on mortality, neurological disorders, and the activity of the pituitary-corticoadrenal system (PCAS) in the acute period of TBI. Material and methods. TBI was simulated with a free load’s fall on a fixed animal head. To activate the CChS, rats were injected with choline alfoscerate (gliatilin, 6 mg/kg) before the injury, physiological saline was injected in the control group. Neurological deficits were assessed using the 100-point Todd scale. In blood plasma, 3, 24, 48, and 72 hours after injury, the content of adrenocorticotropic hormone and corticosterone was determined by the enzyme immunoassay method (DSL; USA). The results were statistically processed using the SPSS 11.0, MedStat, MedCalc software. Results. Mortality in the control group was 25.0%, in the group with activation of the CChS there were no lethal cases (p<0.05). The neurological deficit in the group with CChS activation was significantly less pronounced compared to the control at all periods of observation. The hormone content had a similar dynamics: it reached a maximum after 24 hours and recovered after 72 hours, however, upon activation of the CChS, the increase was 1.4-1.5 times less (p<0.05). Thus, the use of choline alfoscerate for modeling the CChS activity led to a decrease in mortality and neurological deficit in the acute period of TBI, which was accompanied by a stabilizing PCAS function. Conclusion. The important role of CChS in the implementation of post-traumatic stress reaction of PCAS, as well as the possibility of its pharmacological correction with choline alfoscerate, was established.

Effect of extracranial-intracranial bypass and pentobarbital on acute stroke in dogs

1982 ◽  
Vol 56 (1) ◽  
pp. 92-96 ◽  
Author(s):  
Pablo M. Lawner ◽  
John P. Laurent ◽  
Frederick A. Simeone ◽  
Eugene A. Fink
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Neurological Deficit ◽  
Previous Treatment ◽  
Control Group ◽  
Untreated Control Group ◽  
Content Type ◽  
Treatment Groups ◽  
Bypass Group ◽  
Previous Group

✓ Ninety-three mongrel dogs underwent intracranial carotid and middle cerebral artery occlusions. They were then randomized into four groups: 1) the untreated control group (no surgical or medical therapy) showed significant neurological deficit, 16% mortality, and 17% mean hemisphere infarction; 2) in the bypass group (superficial temporal to middle cerebral artery (STA-MCA) anastomosis completed within 3 hours of occlusion), neurological deficit was diminished, mortality was 7%, and mean infarction 5.66%; 3) in the pentobarbital group (single dose of pentobarbital, 35 mg/kg administered intravenously 30 minutes after occlusion), neurological deficit was essentially the same as in the previous group, there was no mortality, and mean infarction was 5.52%; and 4) in the pentobarbital/bypass group (pentobarbital dose plus STA-MCA bypass), neurological deficit was slightly lower than in previous treatment groups, there was no mortality, and mean hemisphere infarction was 1.78%. Extracranial-intracranial bypass produced an immediate 31.6% increase in regional cortical blood flow. The combination of pentobarbital postocclusive therapy and early extracranial-intracranial bypass showed beneficial synergism.

scholarly journals EFFECTS OF MODULATORS OF REDOX-SENSITIVE TRANSCRIPTION FACTORS ON NEUROLOGIC DEFICIT IN RATS AFTER TRAUMATIC BRAIN INJURY

2020 ◽  
Vol 20 (2) ◽  
pp. 198-202
Author(s):  
I.V. Yavtushenko ◽  
V.O. Kostenko
Keyword(s):  
Traumatic Brain Injury ◽  
Transcription Factors ◽  
Survival Rate ◽  
Brain Injury ◽  
Neurological Deficit ◽  
Water Soluble ◽  
Male Rats ◽  
Soluble Form ◽  
Control Group ◽  
Pyrrolidine Dithiocarbamate

This study was aimed as investigating the effects of modulators of transcription factors NF-κB, AP-1 and Nrf2 on the survival rate of white rats and the development of neurological deficits following the simulation of traumatic brain injury (TBI). The study included 110 white Wistar male rats weighing 180-220 g, divided into 6 groups. Control group involved animals after the TBI injury simulation (n=30). The animals of other groups (16 rats in each) were intraperitoneally injected with modulators of transcription factors after the simulation of the trauma for 7 days: ammonium pyrrolidine dithiocarbamate, an inhibitor of nuclear translocation NF-κB, was injected in a dose of 76 mg/kg; AP-1 SR 11302 inhibitor – in a dose of 1 mg/kg; Nrf2-ARE system inductors as dimethyl fumarate in a dose of 15 mg/kg in a 10% dimethyl sulfoxide solution and epigallocatechin-3-gallate in a dose of 1 mg/kg. The test animals were also injected with a water-soluble form of quercetin (corvitin), which acts as an NF-κB inhibitor and Nrf2 inducer, in a dose of 100 mg/kg (10 mg/kg in terms of quercetin). The animals in the control group were injected intraperitoneally with 1 ml of isotonic sodium chloride solution instead of the tested compounds mentioned above. It has been found out that on the 7th day after the simulation of moderate TBI most animals showed signs of neurological deficit including impaired muscle tone (83.3%), impaired coordination (83.3%) and pain reaction (66.7%). Integral indicator of neurological deficit by Todd et al. 100-score grading scale was 51.33±2.95. The use of inhibitors of transcription factors NF-κB (ammonium pyrrolidinedithiocarbamate) and AP-1 (SR 11302), the Nrf2-ARE system inducers (dimethylfumarate and epigallocatechin-3-gallate) and the water-soluble form of quercetin (corvitin) increases rats’ survival rate, significantly limits their signs of neurological deficit and its integral index.

Favorable Effects of Astaxanthin on Brain Damage due to Ischemia- Reperfusion Injury

2020 ◽  
Vol 23 (3) ◽  
pp. 214-224 ◽  
Author(s):  
Esra Cakir ◽  
Ufuk Cakir ◽  
Cuneyt Tayman ◽  
Tugba Taskin Turkmenoglu ◽  
Ataman Gonel ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Brain Damage ◽  
Neurological Deficit ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Degradation Products ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Cortex Cell

Background: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. Objective: The aim of this study was to investigate the role of ASX on brain IRI. Methods: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. Results: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05). Conclusion: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.

scholarly journals Remotely delivered environmental enrichment intervention for traumatic brain injury: Study protocol for a randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e039767
Author(s):  
Zorry Belchev ◽  
Mary Ellene Boulos ◽  
Julia Rybkina ◽  
Kadeen Johns ◽  
Eliyas Jeffay ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Active Control ◽  
Environmental Enrichment ◽  
Spatial Navigation ◽  
Controlled Trial ◽  
Control Group ◽  
Hippocampal Atrophy ◽  
Active Control Group ◽  
Navigation Group

IntroductionIndividuals with moderate-severe traumatic brain injury (m-sTBI) experience progressive brain and behavioural declines in the chronic stages of injury. Longitudinal studies found that a majority of patients with m-sTBI exhibit significant hippocampal atrophy from 5 to 12 months post-injury, associated with decreased cognitive environmental enrichment (EE). Encouragingly, engaging in EE has been shown to lead to neural improvements, suggesting it is a promising avenue for offsetting hippocampal neurodegeneration in m-sTBI. Allocentric spatial navigation (ie, flexible, bird’s eye view approach), is a good candidate for EE in m-sTBI because it is associated with hippocampal activation and reduced ageing-related volume loss. Efficacy of EE requires intensive daily training, prohibitive within most current health delivery systems. The present protocol is a novel, remotely delivered and self-administered intervention designed to harness principles from EE and allocentric spatial navigation to offset hippocampal atrophy and potentially improve hippocampal functions such as navigation and memory for patients with m-sTBI.Methods and analysisEighty-four participants with chronic m-sTBI are being recruited from an urban rehabilitation hospital and randomised into a 16-week intervention (5 hours/week; total: 80 hours) of either targeted spatial navigation or an active control group. The spatial navigation group engages in structured exploration of different cities using Google Street View that includes daily navigation challenges. The active control group watches and answers subjective questions about educational videos. Following a brief orientation, participants remotely self-administer the intervention on their home computer. In addition to feasibility and compliance measures, clinical and experimental cognitive measures as well as MRI scan data are collected pre-intervention and post-intervention to determine behavioural and neural efficacy.Ethics and disseminationEthics approval has been obtained from ethics boards at the University Health Network and University of Toronto. Findings will be presented at academic conferences and submitted to peer-reviewed journals.Trial registration numberVersion 3, ClinicalTrials.gov Registry (NCT04331392).

FGF10 Attenuates Experimental Traumatic Brain Injury through TLR4/MyD88/NF-κB Pathway

2021 ◽  
pp. 1-9
Author(s):  
Qinhan Hou ◽  
Hongmou Chen ◽  
Quan Liu ◽  
Xianlei Yan
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Expression ◽  
Water Content ◽  
Neurological Deficit ◽  
Neuronal Apoptosis ◽  
Neuronal Damage ◽  
Intraventricular Injection ◽  
Brain Water Content ◽  
Brain Water

Traumatic brain injury (TBI) can induce neuronal apoptosis and neuroinflammation, resulting in substantial neuronal damage and behavioral disorders. Fibroblast growth factors (FGFs) have been shown to be critical mediators in tissue repair. However, the role of FGF10 in experimental TBI remains unknown. In this study, mice with TBI were established via weight-loss model and validated by increase of modified neurological severity scores (mNSS) and brain water content. Secondly, FGF10 levels were elevated in mice after TBI, whereas intraventricular injection of Ad-FGF10 decreased mNSS score and brain water content, indicating the remittance of neurological deficit and cerebral edema in TBI mice. In addition, neuronal damage could also be ameliorated by stereotactic injection of Ad-FGF10. Overexpression of FGF10 increased protein expression of Bcl-2, while it decreased Bax and cleaved caspase-3/PARP, and improved neuronal apoptosis in TBI mice. In addition, Ad-FGF10 relieved neuroinflammation induced by TBI and significantly reduced the level of interleukin 1β/6, tumor necrosis factor α, and monocyte chemoattractant protein-1. Moreover, Ad-FGF10 injection decreased the protein expression level of Toll-like receptor 4 (TLR4), MyD88, and phosphorylation of NF-κB (p-NF-κB), suggesting the inactivation of the TLR4/MyD88/NF-κB pathway. In conclusion, overexpression of FGF10 could ameliorate neurological deficit, neuronal apoptosis, and neuroinflammation through inhibition of the TLR4/MyD88/NF-κB pathway, providing a potential therapeutic strategy for brain injury in the future.

scholarly journals Physical Activity and Sport for Acquired Brain Injury (PASABI): A Non-Randomized Controlled Trial

Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 122
Author(s):  
Marta Pérez-Rodríguez ◽  
Saleky García-Gómez ◽  
Javier Coterón ◽  
Juan José García-Hernández ◽  
Javier Pérez-Tejero
Keyword(s):  
Quality Of Life ◽  
Physical Activity ◽  
Brain Injury ◽  
Functional Capacity ◽  
Intervention Group ◽  
Chronic Phase ◽  
Acquired Brain Injury ◽  
Control Group ◽  
Wide Range

Background and objectives: Acquired brain injury (ABI) is the first cause of disability and physical activity (PA) is a key element in functional recovery and health-related quality of life (HRQoL) during the subacute and chronic phases. However, it is necessary to develop PA programs that respond to the heterogeneity and needs of this population. The aim of this study was to assess the effectiveness of a PA program on the HRQoL in this population. Materials and Methods: With regard to recruitment, after baseline evaluations, participants were assigned to either the intervention group (IG, n = 38) or the control group (CG, n = 35). Functional capacity, mood, quality of life and depression were measured pre- and post-intervention. The IG underwent the “Physical Activity and Sport for Acquired Brain Injury” (PASABI) program, which was designed to improve HRQoL (1-h sessions, two to four sessions/week for 18 weeks). The CG underwent a standard rehabilitation program without PA. Results: Results for the IG indicated significant differences and large effect sizes for the physical and mental dimensions of quality of life, as well as mood and functional capacity, indicating an increase in HRQoL. No significant differences were found for the CG across any variables. Conclusions: The PASABI program was feasible and beneficial for improving physiological and functionality variables in the IG. The wide range of the activities of the PASABI program allow its application to a large number of people with ABI, promoting health through PA, especially in the chronic phase.

scholarly journals Effects of post-interventional antiplatelet therapy on angiographic vasospasm, delayed cerebral ischemia, and clinical outcome after aneurysmal subarachnoid hemorrhage: a single-center experience

2021 ◽  
Author(s):  
Claudia Ditz ◽  
Björn Machner ◽  
Hannes Schacht ◽  
Alexander Neumann ◽  
Peter Schramm ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Functional Outcome ◽  
Antiplatelet Therapy ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Control Group ◽  
Lesion Volume ◽  
Single Center ◽  
Single Center Experience

AbstractPlatelet activation has been postulated to be involved in the pathogenesis of delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to investigate potentially beneficial effects of antiplatelet therapy (APT) on angiographic CVS, DCI-related infarction and functional outcome in endovascularly treated aSAH patients. Retrospective single-center analysis of aSAH patients treated by endovascular aneurysm obliteration. Based on the post-interventional medical regime, patients were assigned to either an APT group or a control group not receiving APT. A subgroup analysis separately investigated those APT patients with aspirin monotherapy (MAPT) and those receiving dual treatment (aspirin plus clopidogrel, DAPT). Clinical and radiological characteristics were compared between groups. Possible predictors for angiographic CVS, DCI-related infarction, and an unfavorable functional outcome (modified Rankin scale ≥ 3) were analyzed. Of 160 patients, 85 (53%) had received APT (n = 29 MAPT, n = 56 DAPT). APT was independently associated with a lower incidence of an unfavorable functional outcome (OR 0.40 [0.19–0.87], P = 0.021) after 3 months. APT did not reduce the incidence of angiographic CVS or DCI-related infarction. The pattern of angiographic CVS or DCI-related infarction as well as the rate of intracranial hemorrhage did not differ between groups. However, the lesion volume of DCI-related infarctions was significantly reduced in the DAPT subgroup (P = 0.011). Post-interventional APT in endovascularly treated aSAH patients is associated with better functional outcome at 3 months. The beneficial effect of APT might be mediated by reduction of the size of DCI-related infarctions.

scholarly journals Endothelin ETB Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders

2021 ◽  
Vol 22 (9) ◽  
pp. 4333
Author(s):  
Yutaka Koyama
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurotrophic Factors ◽  
Drug Target ◽  
Therapeutic Strategy ◽  
Reactive Astrocytes ◽  
Brain Disorders ◽  
Etb Receptor ◽  
Target Molecules ◽  
Endothelin B

In brain disorders, reactive astrocytes, which are characterized by hypertrophy of the cell body and proliferative properties, are commonly observed. As reactive astrocytes are involved in the pathogenesis of several brain disorders, the control of astrocytic function has been proposed as a therapeutic strategy, and target molecules to effectively control astrocytic functions have been investigated. The production of brain endothelin-1 (ET-1), which increases in brain disorders, is involved in the pathophysiological response of the nervous system. Endothelin B (ETB) receptors are highly expressed in reactive astrocytes and are upregulated by brain injury. Activation of astrocyte ETB receptors promotes the induction of reactive astrocytes. In addition, the production of various astrocyte-derived factors, including neurotrophic factors and vascular permeability regulators, is regulated by ETB receptors. In animal models of Alzheimer’s disease, brain ischemia, neuropathic pain, and traumatic brain injury, ETB-receptor-mediated regulation of astrocytic activation has been reported to improve brain disorders. Therefore, the astrocytic ETB receptor is expected to be a promising drug target to improve several brain disorders. This article reviews the roles of ETB receptors in astrocytic activation and discusses its possible applications in the treatment of brain disorders.

scholarly journals Mean Platelet Volume and Platelet Distribution Width as Markers in the Diagnosis of Acute Gangrenous Appendicitis

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Zhe Fan ◽  
Jiyong Pan ◽  
Yingyi Zhang ◽  
Ziyi Wang ◽  
Ming Zhu ◽  
...  
Keyword(s):  
Mean Platelet Volume ◽  
Medical Condition ◽  
Roc Curves ◽  
Disease Diagnosis ◽  
Control Group ◽  
Platelet Distribution Width ◽  
Platelet Volume ◽  
Distribution Width ◽  
Gangrenous Appendicitis ◽  
Wbc Count

Introduction.Acute gangrenous appendicitis (AGA) is a common medical condition; however, the grade of appendicitis usually cannot be established preoperatively. We have attempted to identify some indicators, such as the mean platelet volume (MPV) and the platelet distribution width (PDW), to diagnose AGA.Aims.To evaluate whether or not the MPV and PDW are suitable markers to diagnose AGA.Methods.A retrospective study of 160 patients with AGA and 160 healthy patients was undertaken. Disease diagnosis was confirmed based on the pathologic examination of surgical specimens. Patient white blood cell (WBC) count, neutrophil ratio (NR), platelet (PLT) count, MPV, PDW, and hematocrit (HCT) were analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the sensitivity and specificity of these indices in AGA.Results.There were no significant differences between the AGA and control groups in age and gender. Compared to the control group, the WBC count, NR, and PDW were significantly higher (P<0.001, resp.) and the MPV and HCT were significantly lower (P<0.001, resp.) in the AGA group. The diagnostic specificities of the WBC count, NR, PLT count, MPV, PDW, and HCT were 86.3%, 92.5%, 58.1%, 81.7%, 83.9%, and 66.3%, respectively. Therefore, the NR had the highest diagnostic specificity for the diagnosis of AGA.Conclusions.This is the first study to assess the MPV and PDW in patients with AGA. Our present study showed that the MPV is reduced and the PDW is increased in patients with AGA; the sensitivity of PDW was superior to the MPV. A decreased MPV value and an increased PDW could serve as two markers to diagnose AGA. The NR had the highest specificity for the diagnosis of AGA.

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