scholarly journals Expression of GFAP and Tau Following Blast Exposure in the Cerebral Cortex of Ferrets

2021 ◽  
Vol 80 (2) ◽  
pp. 112-128
Author(s):  
Susan C Schwerin ◽  
Mitali Chatterjee ◽  
Elizabeth B Hutchinson ◽  
Francis T Djankpa ◽  
Regina C Armstrong ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Western Blot ◽  
Blood Vessels ◽  
Blast Injury ◽  
Preclinical Models ◽  
Blast Exposure ◽  
Blast Traumatic Brain Injury ◽  
Human Pathology ◽  
Military Conflicts ◽  
Therapeutic Protocols

Abstract Blast exposures are a hallmark of contemporary military conflicts. We need improved preclinical models of blast traumatic brain injury for translation of pharmaceutical and therapeutic protocols. Compared with rodents, the ferret brain is larger, has substantial sulci, gyri, a higher white to gray matter ratio, and the hippocampus in a ventral position; these attributes facilitate comparison with the human brain. In this study, ferrets received compressed air shock waves and subsequent evaluation of glia and forms of tau following survival of up to 12 weeks. Immunohistochemistry and Western blot demonstrated altered distributions of astrogliosis and tau expression after blast exposure. Many aspects of the astrogliosis corresponded to human pathology: increased subpial reactivity, gliosis at gray-white matter interfaces, and extensive outlining of blood vessels. MRI analysis showed numerous hypointensities occurring in the 12-week survival animals, appearing to correspond to luminal expansions of blood vessels. Changes in forms of tau, including phosphorylated tau, and the isoforms 3R and 4R were noted using immunohistochemistry and Western blot in specific regions of the cerebral cortex. Of particular interest were the 3R and 4R isoforms, which modified their ratio after blast. Our data strongly support the ferret as an animal model with highly translational features to study blast injury.

scholarly journals Allocation of funding into blast injury-related research and blast traumatic brain injury between 2000 and 2019: analysis of global investments from public and philanthropic funders

2020 ◽  
pp. bmjmilitary-2020-001655
Author(s):  
J W Denny ◽  
R J Brown ◽  
M G Head ◽  
J Batchelor ◽  
A S Dickinson
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Open Data ◽  
Blast Injury ◽  
Included Study ◽  
Related Research ◽  
Blast Traumatic Brain Injury ◽  
Research Investment ◽  
Ear Injury ◽  
Injury Research

IntroductionThere is little systematic tracking or detailed analysis of investments in research and development for blast injury to support decision-making around research future funding.MethodsThis study examined global investments into blast injury-related research from public and philanthropic funders across 2000–2019. Research databases were searched using keywords, and open data were extracted from funder websites. Data collected included study title, abstract, award amount, funder and year. Individual awards were categorised to compare amounts invested into different blast injuries, the scientific approaches taken and analysis of research investment into blast traumatic brain injury (TBI).ResultsA total of 806 awards were identified into blast injury-related research globally, equating to US$902.1 million (m, £565.9m GBP). There was a general increase in year-on-year investment between 2003 and 2009 followed by a consistent decline in annual funding since 2010. Pre-clinical research received $671.3 m (74.4%) of investment. Brain-related injury research received $427.7 m (47.4%), orthopaedic injury $138.6 m (15.4%), eye injury $63.7 m (7.0%) and ear injury $60.5m (6.7%). Blast TBI research received a total investment of $384.3 m, representing 42.6% of all blast injury-related research. The U.S. Department of Defense funded $719.3 m (80%).ConclusionsInvestment data suggest that blast TBI research has received greater funding than other blast injury health areas. The funding pattern observed can be seen as reactive, driven by the response to the War on Terror, the rising profile of blast TBI and congressionally mandated research.

Distribution of Oxygen Partial Pressure and Cerebral Blood Vessels in Rat Cerebral Cortex

2002 ◽  
Vol 2002.14 (0) ◽  
pp. 131-132
Author(s):  
Kazuto MASAMOTO ◽  
Tomoko NEGISHI ◽  
Takayoshi KURACHI ◽  
Naosada TAKIZAWA ◽  
Hirosuke KOBAYASHI ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Oxygen Partial Pressure ◽  
Partial Pressure ◽  
Blood Vessels ◽  
Rat Cerebral Cortex ◽  
Cerebral Blood Vessels

scholarly journals A FIRST AUTOCHTNOUS HUMAN CASE OF THE LONGSTANDINDG MICROFILARAEMIA DUE TO DIROFILARIA REPENS IN RUSSIA AND A FIRST EXPERIENCE OF COMBINED THERAPY OF DIROFILARIASIS REPENS

2013 ◽  
Vol 18 (3) ◽  
pp. 47-52
Author(s):  
A. M Bronshteyn ◽  
N. A Malyshev ◽  
S. N Jarov ◽  
L. V Fedianina ◽  
A. A Frolova ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Combined Therapy ◽  
Human Case ◽  
Dirofilaria Repens ◽  
Connective Tissues ◽  
Internal Organs ◽  
First Report ◽  
Human Pathology ◽  
Russian Patient

A case of the longstandindg microfilaraemia due to Dirofilaria repens is presented as a 57-years-old female . This is the first report of the longstandindg microfilaraemia in a Russian patient due to infection of D. repens. The microfilariae of D. repens were detected due to multiple investigations of fresh drops of blood. The longstandindg microfilaraemia due to D. repens is discussed regarding their role in human pathology. As the larvae mature into adult wormes they migrate through blood vessels and the subdermal connective tissues causing pruritis, oedematous lesions on the skin, itching and pain as they pass beneath the conjunctivae and penetrate internal organs. The patient was successfully treated with doxycycline, albendazole and diethylcarbamazine.

scholarly journals Maladaptive neuropathological syndrome of blood vessel aging

2019 ◽  
pp. 33-40
Author(s):  
A. A. Artemenkov
Keyword(s):  
Cerebral Cortex ◽  
Blood Vessel ◽  
Blood Vessels ◽  
Cortical Neurons ◽  
Circulatory System ◽  
Vascular Wall ◽  
Modern Human ◽  
Wall Thickening ◽  
Additional Risk Factor ◽  
The Relationship

This article discusses the relationship between maladaptation and blood vessel aging. The work shows that upright posture created an additional load on the circulatory system, and the lifestyle of a modern human is an additional risk factor of cardiovascular diseases. It has been suggested that a disorder of the nervous regulation of vascular tone is the main etiopathogenetic mechanism of morphofunctional changes in blood vessels and their aging. We discussed the statute that vascular reactions in humans is based on the formation of a maladaptive circuit in the cerebral cortex, consisting of a matrix of motor, sensory and associative cortical neurons involved in the maladaptive process. This hypothesis is based on the fact that any irritations entering the cerebral cortex from the periphery (thermal, pain, and others) cause cortical-vascular reflex reactions that change their tonic activity. Based on this principle, a model of vascular aging is further constructed, which is based on the maladaptive damage to all layers of the vascular wall (intima, media and adventitia). The opinion is expressed about the need for early diagnosis and prevention of vascular disorders to maintain human health. In conclusion, it is concluded that if the age of a person is really determined by the age of his blood vessels, then in order to achieve active longevity it is necessary to normalize the relationship in the adaptation-maladaptation-environment. Detailed study of hypertrophy and calcification of blood vessels is needed, since aging always reveals vascular wall thickening and stiffness increase.

Antitumor activity of pazopanib (P) and trametinib (T) in preclinical models of osteosarcoma (OS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e22509-e22509
Author(s):  
Giulia Chiabotto ◽  
Maria Laura Centomo ◽  
Alessandra Merlini ◽  
Lorenzo D'Ambrosio ◽  
Dario Sangiolo ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Antitumor Activity ◽  
Western Blot ◽  
Cell Lines ◽  
Fold Change ◽  
Janus Kinase ◽  
Preclinical Models ◽  
Log2 Fold Change ◽  
In Vivo Antitumor Activity

e22509 Background: Receptor tyrosine kinases (RTKs) and their signal transducers are suitable targets for the treatment of advanced OS. We evaluated the antitumor activity of the RTK inhibitor P and the MEK inhibitor T and deeply investigated molecular mechanisms behind their activity and potential escape. Methods: Flow cytometry and western blot analyses were carried out in 7 OS cell lines to study the expression of RTK P targets and the activation of their pathways, respectively. Cell viability and colony growth were evaluated after 72h and 7-day treatment respectively, with scalar doses of both single agents and their constant combination. Cell cycle distribution and apoptosis were evaluated by flow cytometry after 72h. In vivo antitumor activity was studied in NOD/SCID mice bearing MNNG-HOS xenografts after 3 weeks of treatment. Cell migration was studied by scratch assays. The involvement of MAPK-PI3K pathway key transducers was explored by Vantage 3D RNA Panel and Nanostring technology, validated by western blot and confirmed by silencing experiments. Results: P targets are expressed on OS cell lines and their pathways are activated. P+T have synergistic antitumor activity (combination index < 1) in OS cell lines by inducing apoptosis (6/7) and inhibiting both ERK1/2(7/7) and AKT (7/7). Furthermore, in vivo antitumor activity was shown in OS bearing mice (tumor volume: P+T/untreated = 0.036, p = 0.002). P+T significantly down-modulated RTK EphaA2 (mean log2 fold change RNA P+T/untreated = -2.02±0.50) and induced Janus kinase MEK6 (mean log2 fold change RNA P+T/untreated = 2.9±0.51). EphA2 silencing reduced cellular proliferation and migration of OS cells. Impeding MEK6-up-regulation in P+T treated cells significantly increased the antitumor effect (51.5±14.3%) of the studied drugs. Conclusions: P+T exert antitumor activity in OS preclinical models through ERK and AKT inhibition and EphA2 downmodulation. MEK6-upregulation after P+T is likely implied in escape mechanism.

scholarly journals A Low-Protein Isocaloric Diet During Gestation Affects Brain Development and Alters Permanently Cerebral Cortex Blood Vessels in Rat Offspring

1999 ◽  
Vol 129 (8) ◽  
pp. 1613-1619 ◽  
Author(s):  
Nadia Bennis-Taleb ◽  
Claude Remacle ◽  
Joseph J. Hoet ◽  
Brigitte Reusens
Keyword(s):  
Cerebral Cortex ◽  
Brain Development ◽  
Blood Vessels ◽  
Isocaloric Diet ◽  
Rat Offspring ◽  
Low Protein

scholarly journals Blast Exposure and Risk of Recurrent Occupational Overpressure Exposure Predict Deployment TBIs

2019 ◽  
Vol 185 (5-6) ◽  
pp. e538-e544 ◽  
Author(s):  
Jennifer N Belding ◽  
Shannon Fitzmaurice ◽  
Robyn Martin Englert ◽  
Isabell Lee ◽  
Brad Kowitz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Health Assessment ◽  
Active Duty ◽  
Low Risk ◽  
Institutional Review Board ◽  
Ongoing Research ◽  
Blast Exposure ◽  
Institutional Review ◽  
Military Conflicts ◽  
High Level

Abstract Introduction Traumatic brain injury (TBI) has been the leading cause of morbidity and mortality in recent military conflicts and deployment-related TBIs are most commonly caused by blast. However, knowledge of risk factors that increase susceptibility to TBI following an acute, high-level blast is limited. We hypothesized that recurrent occupational overpressure exposure (ROPE) may be one factor that increases susceptibility to mild TBI (mTBI) following blast. Materials and Methods Using military occupational specialty as a proxy, we examined the effects of high versus low ROPE on mTBI following blast exposure. Initial analyses included 111,641 active-duty-enlisted U.S. Marines who completed the 2003 or 2008 version of the Post-Deployment Health Assessment. Final analyses examined probable mTBI screens among Marines with at least one qualifying exposure as a function of whether the exposure was a blast and level of ROPE (N = 12,929). This study was approved by the Institutional Review Board at the Naval Health Research Center. Results Blast and ROPE were both independently and jointly associated with a probable mTBI. Marines who experienced a blast (vs other qualifying exposure) and those in high (vs low) risk occupations were 1.07 and 1.23 times more likely to sustain a probable mTBI, respectively. Furthermore, among those who experienced a blast during deployment, those in high-risk occupations were 1.45 times more likely than those in low-risk occupations to sustain a probable mTBI. Conclusions Blast exposure and ROPE were independently associated with mTBIs, and Marines with both blast exposure during deployment and ROPE were especially likely to sustain an mTBI. This suggests that ROPE heightens the risk of mTBI following blast. Ongoing research is examining the severity, symptomology, and sequelae of TBIs as a function of ROPE.

Sign in / Sign up

Export Citation Format

Share Document