scholarly journals Investigation of the direct and indirect mechanisms of primary blast insult to the brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jose E. Rubio ◽  
Ginu Unnikrishnan ◽  
Venkata Siva Sai Sujith Sajja ◽  
Stephen Van Albert ◽  
Franco Rossetti ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Silver Staining ◽  
Blast Waves ◽  
Whole Body ◽  
Direct Mechanism ◽  
Blast Exposure ◽  
Tissue Changes ◽  
Induced Changes ◽  
The Brain

AbstractThe interaction of explosion-induced blast waves with the head (i.e., a direct mechanism) or with the torso (i.e., an indirect mechanism) presumably causes traumatic brain injury. However, the understanding of the potential role of each mechanism in causing this injury is still limited. To address this knowledge gap, we characterized the changes in the brain tissue of rats resulting from the direct and indirect mechanisms at 24 h following blast exposure. To this end, we conducted separate blast-wave exposures on rats in a shock tube at an incident overpressure of 130 kPa, while using whole-body, head-only, and torso-only configurations to delineate each mechanism. Then, we performed histopathological (silver staining) and immunohistochemical (GFAP, Iba-1, and NeuN staining) analyses to evaluate brain-tissue changes resulting from each mechanism. Compared to controls, our results showed no significant changes in torso-only-exposed rats. In contrast, we observed significant changes in whole-body-exposed (GFAP and silver staining) and head-only-exposed rats (silver staining). In addition, our analyses showed that a head-only exposure causes changes similar to those observed for a whole-body exposure, provided the exposure conditions are similar. In conclusion, our results suggest that the direct mechanism is the major contributor to blast-induced changes in brain tissues.

scholarly journals Glymphatic System in the Central Nervous System, a Novel Therapeutic Direction Against Brain Edema After Stroke

2021 ◽  
Vol 13 ◽  
Author(s):  
Xiangyue Zhou ◽  
Youwei Li ◽  
Cameron Lenahan ◽  
Yibo Ou ◽  
Minghuan Wang ◽  
...  
Keyword(s):  
Brain Edema ◽  
Brain Tissue ◽  
Molecular Mechanisms ◽  
Glymphatic System ◽  
System A ◽  
Function Recovery ◽  
The Central Nervous System ◽  
The Stability ◽  
The Brain

Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke.

scholarly journals P11.62 Brain distribution models to select polymer-delivered drugs for the intra-cavity treatment of malignant glioma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii58-iii58
Author(s):  
J Rowlinson ◽  
P McCrorie ◽  
S Smith ◽  
D Barrett ◽  
D Kim ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Brain Homogenate ◽  
Systemic Toxicity ◽  
The Body ◽  
Whole Body ◽  
Label Free ◽  
In Vivo Models ◽  
Franz Cell ◽  
Diffusion Rates ◽  
The Brain

Abstract BACKGROUND Conventional oral or intravenous chemotherapy distributes drugs to the whole body whereby systemic toxicity to healthy parts of the body (e.g. bone marrow failure) limits the maximum dose that can be achieved in the brain. This presents a particular concern for CNS tumours where the blood-brain-barrier (BBB) restricts drug influx from the circulation. The ability to deliver chemotherapy locally at the tumour site offers the opportunity to target residual cancer cells post-surgery whilst minimising systemic toxicity. We have developed a poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) polymer matrix that forms a porous paste at room temperature when mixed with chemotherapy-containing saline, solidifying only at body temperature, with close apposition to the irregular surgical cavity. It is important that we can observe whether the drugs released from PLGA/PEG can penetrate brain parenchyma beyond the surgical resection margin at therapeutic doses. Currently the only way to measure the distribution of drugs in the body is to inject radioactive drugs into an animal. We aim to establish drug distribution parameters using label-free mass spectrometry imaging methods, prior to selection of drug formulations for clinically-relevant in vivo models. Drugs that penetrate the brain the furthest will be identified as good candidates for localised brain cancer drug delivery using PLGA/PEG paste. MATERIAL AND METHODS Diffusion rates were measured by examining the proportion of olaparib, dasatnib, carboplatin, etoposide, paclitaxel and gemcitabine at 2mg/ml concentration, which passes through 1mm slices of rat brain tissue within Franz cell chambers over a 6 hour period. The spatio-temporal distribution of label-free olaparib and dasatinib within mouse brain homogenate was quantitatively measured using innovative 3D OrbiSIMS, a hybrid time-of-flight / OrbitrapTM secondary ion mass spectrometer. RESULTS Within the Franz cell model, carboplatin and gemcitabine showed the highest diffusion rate diffusion at 16.4 and 6.53 µg/cm2/h respectively whereas olaparib, etoposide and paclitaxel were relatively poorly diffused at 1.87, 3.82 and 2.27 µg/cm2/h respectively. The minimum threshold of OrbiSIMS detection for label-free olaparib and dasatinib ions was 0.025 mg/ml and 0.2 mg/ml respectively throughout brain homogenate. CONCLUSION This study demonstrates different diffusion rates through brain tissue, between label-free chemotherapy drugs of distinct chemistries, with highest diffusion rates observed for carboplatin and gemcitabine. We also demonstrate label-free detection of olaparib and dasatinib using the innovative 3D OrbiSIMS method. These models will facilitate the rapid identification of agents most amenable for localised biomaterial-based chemotherapy delivery with high brain penetrance.

Ambient temperature modulates hypoxic-induced changes in rat body temperature and activity differentially

2001 ◽  
Vol 280 (4) ◽  
pp. R1190-R1196 ◽  
Author(s):  
B. Bishop ◽  
G. Silva ◽  
J. Krasney ◽  
H. Nakano ◽  
A. Roberts ◽  
...  
Keyword(s):  
Body Temperature ◽  
Ambient Temperature ◽  
Induced Responses ◽  
Brain Pathology ◽  
Level Of Activity ◽  
Time Courses ◽  
Induced Changes ◽  
Subsequent Rise ◽  
The Brain

When rats, acclimated to an ambient temperature (Ta) of 29°C, are exposed to 10% O2 for 63 h, the circadian rhythms of body temperature (Tb) and level of activity (La) are abolished, Tb falls to a hypothermic nadir followed by a climb to a hyperthermic peak, Laremains depressed (Bishop B, Silva G, Krasney J, Salloum A, Roberts A, Nakano H, Shucard D, Rifkin D, and Farkas G. Am J Physiol Regulatory Integrative Comp Physiol 279: R1378–R1389, 2000), and overt brain pathology is detected (Krasney JA, Farkas G, Shucard DW, Salloum AC, Silva G, Roberts A, Rifkin D, Bishop B, and Rubio A. Soc Neurosci Abstr 25: 581, 1999). To determine the role of Ta in these hypoxic-induced responses, Tb and La data were detected by telemetry every 15 min for 48 h on air, followed by 63 h on 10% O2 from rats acclimated to 25 or 21°C. Magnitudes and rates of decline in Tb after onset of hypoxia were inversely proportional to Ta, whereas magnitudes and rates of Tb climb after the hypothermic nadir were directly proportional to Ta. No hyperthermia, so prominent at 29°C, occurred at 25 or 21°C. The hypoxic depression of La was least at 21°C and persisted throughout the hypoxia. In contrast, Ta was a strong determinant of the magnitudes and time courses of the initial fall and subsequent rise in Tb. We propose that the absence of hyperthermia at 21 and 25°C as well as a persisting hypothermia may protect the brain from overt pathology.

scholarly journals TRANSGENIC MOUSE MODELS OF ALZHEIMER’S DISEASE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S835-S835
Author(s):  
Charnae A Henry-Smith ◽  
Xianlin Han
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Myelin Sheath ◽  
Thinking Skills ◽  
Drug Dosage ◽  
Whole Body ◽  
To Receive ◽  
The Brain

Abstract Alzheimer’s disease is a progressive brain disease that slowly destroys memory and thinking skills. Alzheimer’s is characterized by an increase in Aβ plaques , and tau tangles. Neurons in the brain have axons covered in myelin sheath that connect microglia and astrocytes. The myelin sheath is composed of about 70% lipid composition; Sulfatide contributing to 30% overall. Sulfatide changes the morphology of primary microglia to their activated form. To study the role of microglia activation and sulfatide levels, three different mouse models were created: APP KI mice, CST Whole Body Ko mice, and cCST (conditional) KO. In order to create the genotype of the APP KI mice, a breeding mouse line was created. The APP KI gene had to be introduced in Plp1-Cre and cCST KO crossed mice to receive a working mouse model. During the duration of breeding for the APP KI mice, a preliminary experiment was performed on the CST KO mice. These mice were given the PLX3397 diet with the aim to remove the microglia and to see the effect of Aβ plaques. The PLX3397 will reduce the microglia targeting the CSF1R. After consuming the diet, the mice were harvested to collect tissues from the brain and spinal cord. Lipidomics and immunohistology were performed. In conclusion, we will continue the breeding of the CST flox/flox / Plp1-Cre / APP KI mice, and the drug dosage and treatment to be used in our APP KI mice will be based on preliminary data from our CST mice.

scholarly journals New Light on the Brain: The Role of Photosensitizing Agents and Laser Light in the Management of Invasive Intracranial Tumors

2003 ◽  
Vol 2 (4) ◽  
pp. 303-309 ◽  
Author(s):  
M. Sam Eljamel
Keyword(s):  
Brain Tissue ◽  
Malignant Gliomas ◽  
Surgical Excision ◽  
Normal Brain ◽  
Full Potential ◽  
Intracranial Tumors ◽  
Dismal Prognosis ◽  
Photosensitizing Agents ◽  
The Brain

Invasive intracranial tumors, particularly malignant gliomas, are very difficult to eradicate surgically and carry a dismal prognosis. The vast majority relapse locally indicating that their cure is dependent on radical and complete local excision. However, their ability to invade and hide among normal brain tissue, our inability to visualize and detect them, the low tolerance of brain tissue to ionizing radiation and the presence of the blood brain barrier are the main causes of our failure to eradicate them. Photodynamic detection with 100% specificity and more than 80% sensitivity offers an excellent chance of visualizing camouflaged tumor nests. Also, photodynamic therapy offers a very good chance of targeted destruction of the remaining tumor cells safely following surgical excision and may double the survival of patients harboring these awful tumors. More work needs to be done to refine this promising technology to exploit it to its full potential.

scholarly journals Does Blast Exposure to the Torso Cause a Blood Surge to the Brain?

2020 ◽  
Vol 8 ◽  
Author(s):  
Jose E. Rubio ◽  
Maciej Skotak ◽  
Eren Alay ◽  
Aravind Sundaramurthy ◽  
Dhananjay Radhakrishnan Subramaniam ◽  
...  
Keyword(s):  
Brain Injury ◽  
Carotid Artery ◽  
Brain Tissue ◽  
Shear Stresses ◽  
Fe Model ◽  
Cerebral Vasculature ◽  
Blast Exposure ◽  
Indirect Mechanism ◽  
Wall Shear ◽  
The Brain

The interaction of explosion-induced blast waves with the torso is suspected to contribute to brain injury. In this indirect mechanism, the wave-torso interaction is assumed to generate a blood surge, which ultimately reaches and damages the brain. However, this hypothesis has not been comprehensively and systematically investigated, and the potential role, if any, of the indirect mechanism in causing brain injury remains unclear. In this interdisciplinary study, we performed experiments and developed mathematical models to address this knowledge gap. First, we conducted blast-wave exposures of Sprague-Dawley rats in a shock tube at incident overpressures of 70 and 130 kPa, where we measured carotid-artery and brain pressures while limiting exposure to the torso. Then, we developed three-dimensional (3-D) fluid-structure interaction (FSI) models of the neck and cerebral vasculature and, using the measured carotid-artery pressures, performed simulations to predict mass flow rates and wall shear stresses in the cerebral vasculature. Finally, we developed a 3-D finite element (FE) model of the brain and used the FSI-computed vasculature pressures to drive the FE model to quantify the blast-exposure effects in the brain tissue. The measurements from the torso-only exposure experiments revealed marginal increases in the peak carotid-artery overpressures (from 13.1 to 28.9 kPa). Yet, relative to the blast-free, normotensive condition, the FSI simulations for the blast exposures predicted increases in the peak mass flow rate of up to 255% at the base of the brain and increases in the wall shear stress of up to 289% on the cerebral vasculature. In contrast, our simulations suggest that the effect of the indirect mechanism on the brain-tissue-strain response is negligible (<1%). In summary, our analyses show that the indirect mechanism causes a sudden and abundant stream of blood to rapidly propagate from the torso through the neck to the cerebral vasculature. This blood surge causes a considerable increase in the wall shear stresses in the brain vasculature network, which may lead to functional and structural effects on the cerebral veins and arteries, ultimately leading to vascular pathology. In contrast, our findings do not support the notion of strain-induced brain-tissue damage due to the indirect mechanism.

Effect of Two Graded Doses of Whole-Body X-Irradiation and Radioprotection by the Use of S-Phenethyl Formamidino 4 (N-Ethyl Isothioamide) Morpholine Dihydrochloride

1983 ◽  
Vol 22 (05) ◽  
pp. 237-245 ◽  
Author(s):  
P. K. Chaturvedi ◽  
S. N. Pandeya ◽  
S. S. Hasan
Keyword(s):  
Radiation Effects ◽  
Whole Body ◽  
X Irradiation ◽  
Radiation Induced ◽  
Induced Changes ◽  
The Brain

The protection offered by a newly synthesized compound (S-phenethyl-formamidino-4(N-ethyl isothioamide) morpholine dihydrochloride) against radiation effects on DNA, RNA and protein biosynthetic processes in the brain, and on metabolites of 5-HT and nor-adrenalin, i.e., 5-HIAA and VMA, in the urine, including the radiobiological damage to thyroid and testes, was evaluated. The use of the compound prior to irradiation prevented radiation-induced changes in the thyroid and testes. The radiation-induced alterations in the pattern of DNA, RNA, protein in the brain, and in 5-HIAA and VMA in urine could be averted by treatment with this compound prior to each dose of X-irradiation.

Studies on the Role of Fibrinolysis and Fibrinogen Degradation Products (FDP) in Analgesic Action of Morphine

1972 ◽  
Vol 28 (03) ◽  
pp. 359-366 ◽  
Author(s):  
Włodzimierz Buczko ◽  
Konstanty Wiśniewski
Keyword(s):  
Molecular Weight ◽  
Brain Tissue ◽  
Clinical Effect ◽  
Degradation Products ◽  
Analgesic Action ◽  
Fibrinogen Degradation Products ◽  
The Brain

SummaryThe role of fibrinolysis and FDP in the analgesic action of morphine in mice and rats was studied. It was shown that during activation of blood fibrinolysis, both the accumulation of morphine in the brain tissue of rats and the clinical effect of this drug were increased. Similar results were observed after morphine given simultaneously with FDP obtained in vitro. The data from the analysis of FDP carried out on Sephadex G-25 Fine columns suggest that only FDP of molecular weight of about 10,000 potentiate the action of morphine; smaller peptides decreased the action of this drug.

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