scholarly journals Protective effects of Derinat, a nucleotide-based drug, on experimental traumatic brain injury, and its cellular mechanisms

2021 ◽  
Vol 23 (6) ◽  
pp. 1367-1382
Author(s):  
E. A. Korneva ◽  
E. V. Dmitrienko ◽  
S. Miyamura ◽  
M. Noda ◽  
N. Akimoto
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sodium Salt ◽  
Morphological Changes ◽  
Ischemia Reperfusion ◽  
Brain Area ◽  
Primary Cultures ◽  
Brain Trauma ◽  
Trauma Treatment ◽  
Anti Inflammatory

Traumatic brain injury is the most common cause of death and disability in young people including sport athletes and soldiers, people under 45 years of age in the industrialized countries, representing a growing health problem in developing countries, as well as in aging communities. Treatment of the latter is a serious challenge for modern medicine. This type of injury leads to many kinds of disorders and, quite often, to disability. These issue require development of new methods for brain trauma treatment. The new approach to brain trauma treatment was studied in murine experiments. In particular, sodium salt of deoxyribonucleic acid (DNA) was used. This preparation is a drug known as a mixture of peptides with immunomodulatory effect which is widely used for different kinds of therapy. Derinat, a sodium salt of DNA, isolated from the caviar of Russian sturgeon, is a proven immunomodulator for treatment of diseases associatd with reactive oxygen species (ROS), including brain ischemia-reperfusion (IR) injury. Here we show that treatment with Derinat exert neuroprotective, anti-oxidative, and anti-inflammatory effects in experimental model of traumatic brain injury (TBI) in rats. Intraperitoneal injection of Derinat several times over 3 days after TBI showed less pronounced damage of the injured brain area. Immunohistochemical study showed that the Derinat-induced morphological changes of microglia in cerebral cortex and hippocampus 7 days after TBI. TBI-induced accumulation of 8-oxoguanine (8-oxoG), the marker of oxidative damage, was significantly attenuated by Derinat administration, both on 7th and 14th day after TBI. To investigate cellular mechanism of anti-inflammatory effects, the primary cultures of murine microglia supplied with ATP (50 M and 1 mM), as a substance released at injured site, were used to mimic the in vitro inflammatory response. Derinate treatment caused an increase of glial levels of mRNAs encoding neurotrophic factor (GDNF) and nerve growth factor (NGF) in the presence of ATP, whereas tissue plasminogen activator (tPA) mRNA was inhibited by ATP with or without Derinat. Interleukin-6 (IL-6) mRNA expression was not affected by ATP but was increased by Derinat. Both mRNA and protein levels of ATP-induced TNFα production were significantly inhibited by Derinat. These results partially contribute to understanding mechanisms of immunomodulatory effects of DNA preparations in traumatic brain injury.

scholarly journals Enriching neural stem cell and anti‐inflammatory glial phenotypes with electrical stimulation after traumatic brain injury in male rats

2021 ◽  
Author(s):  
Eunyoung Park ◽  
Johnathan G. Lyon ◽  
Melissa Alvarado‐Velez ◽  
Martha I. Betancur ◽  
Nassir Mokarram ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cell ◽  
Electrical Stimulation ◽  
Brain Injury ◽  
Neural Stem Cell ◽  
Male Rats ◽  
Anti Inflammatory

scholarly journals Pathologically Entangled: Brain trauma-evoked ROS imbalance disrupts Kir channel function in distant peripheral vessels

Function ◽  
2021 ◽  
Author(s):  
Nick Weir ◽  
Thomas A Longden
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Potassium Channels ◽  
Vascular Function ◽  
Inward Rectifier ◽  
Brain Trauma ◽  
Channel Function ◽  
Inward Rectifier Potassium Channels ◽  
Kir Channel

Abstract A Perspective on "Traumatic Brain Injury Impairs Systemic Vascular Function Through Disruption of Inward-Rectifier Potassium Channels"

scholarly journals Resuscitation from hemorrhagic shock after traumatic brain injury with polymerized hemoglobin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cynthia R. Muller ◽  
Vasiliki Courelli ◽  
Alfredo Lucas ◽  
Alexander T. Williams ◽  
Joyce B. Li ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Hemorrhagic Shock ◽  
Ischemia Reperfusion Injury ◽  
Diastolic Pressure ◽  
Ischemia Reperfusion ◽  
Treatment Strategies ◽  
Secondary Bleeding ◽  
Additional Testing ◽  
Systolic Blood Pressure Variability

AbstractTraumatic brain injury (TBI) is often accompanied by hemorrhage, and treatment of hemorrhagic shock (HS) after TBI is particularly challenging because the two therapeutic treatment strategies for TBI and HS often conflict. Ischemia/reperfusion injury from HS resuscitation can be exaggerated by TBI-induced loss of autoregulation. In HS resuscitation, the goal is to restore lost blood volume, while in the treatment of TBI the priority is focused on maintenance of adequate cerebral perfusion pressure and avoidance of secondary bleeding. In this study, we investigate the responses to resuscitation from severe HS after TBI in rats, using fresh blood, polymerized human hemoglobin (PolyhHb), and lactated Ringer’s (LR). Rats were subjected to TBI by pneumatic controlled cortical impact. Shortly after TBI, HS was induced by blood withdrawal to reduce mean arterial pressure (MAP) to 35–40 mmHg for 90 min before resuscitation. Resuscitation fluids were delivered to restore MAP to ~ 65 mmHg and animals were monitored for 120 min. Increased systolic blood pressure variability (SBPV) confirmed TBI-induced loss of autoregulation. MAP after resuscitation was significantly higher in the blood and PolyhHb groups compared to the LR group. Furthermore, blood and PolyhHb restored diastolic pressure, while this remained depressed for the LR group, indicating a loss of vascular tone. Lactate increased in all groups during HS, and only returned to baseline level in the blood reperfused group. The PolyhHb group possessed lower SBPV compared to LR and blood groups. Finally, sympathetic nervous system (SNS) modulation was higher for the LR group and lower for the PolyhHb group compared to the blood group after reperfusion. In conclusion, our results suggest that PolyhHb could be an alternative to blood for resuscitation from HS after TBI when blood is not available, assuming additional testing demonstrate similar favorable results. PolyhHb restored hemodynamics and oxygen delivery, without the logistical constraints of refrigerated blood.

Levetiracetam Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy

2016 ◽  
Vol 33 (6) ◽  
pp. 581-594 ◽  
Author(s):  
Megan Browning ◽  
Deborah A. Shear ◽  
Helen M. Bramlett ◽  
C. Edward Dixon ◽  
Stefania Mondello ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Trauma ◽  
Trauma Therapy

Serum-Based Phospho-Neurofilament-Heavy Protein as Theranostic Biomarker in Three Models of Traumatic Brain Injury: An Operation Brain Trauma Therapy Study

2019 ◽  
Vol 36 (2) ◽  
pp. 348-359 ◽  
Author(s):  
Zhihui Yang ◽  
Tian Zhu ◽  
Stefania Mondello ◽  
Miis Akel ◽  
Aaron T. Wong ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Trauma ◽  
Trauma Therapy

Berberine Protects Secondary Injury in Mice with Traumatic Brain Injury Through Anti-oxidative and Anti-inflammatory Modulation

2018 ◽  
Vol 43 (9) ◽  
pp. 1814-1825 ◽  
Author(s):  
Shu-Xuan Huang ◽  
Guozhen Qiu ◽  
Fu-Rong Cheng ◽  
Zhong Pei ◽  
Zhi Yang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Secondary Injury ◽  
Anti Inflammatory ◽  
Inflammatory Modulation

The Role of Inflammation in Traumatic Brain Injury

Neurotrauma ◽  
2018 ◽  
pp. 211-232
Author(s):  
Sarah C. Hellewell ◽  
Bridgette D. Semple ◽  
Jenna M. Ziebell ◽  
Nicole Bye ◽  
Cristina Morganti-Kossmann
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Glial Cells ◽  
Immune Cell ◽  
Brain Trauma ◽  
Multiple Roles ◽  
Cell Functions ◽  
Macrophage Populations

Inflammation occurring following brain trauma represents a significant constituent of complex secondary responses that dictate patients’ outcome. Although a few decades have passed since its discovery, new aspects of this intriguing phenomenon are still being uncovered, ranging from the multiple roles of mediators regulating the inception, progression, and resolution of neuroinflammation, to the development of antiinflammatory therapies. This review provides a summary of the vast research on traumatic brain injury inflammation. The authors describe the fundamental aspects of cytokine and immune cell functions, the orchestrated collaboration of chemokines and leukocytes, the phenotypic distinction of macrophage populations, and the contribution of glial cells. Among the beneficial properties of neuroinflammation, they briefly discuss cytokines’ impact on neurogenesis; the chapter concludes by touching on the implications of antiinflammatory therapies.

scholarly journals Xenon treatment after severe traumatic brain injury improves locomotor outcome, reduces acute neuronal loss and enhances early beneficial neuroinflammation: a randomized, blinded, controlled animal study

Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Rita Campos-Pires ◽  
Haldis Onggradito ◽  
Eszter Ujvari ◽  
Shughoofa Karimi ◽  
Flavia Valeo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Functional Outcome ◽  
Neuroprotective Effect ◽  
Neuronal Loss ◽  
Brain Trauma ◽  
Lesion Volume ◽  
Oxygen Balance ◽  
Sprague Dawley ◽  
Locomotor Deficits

Abstract Background Traumatic brain injury (TBI) is a major cause of morbidity and mortality, but there are no clinically proven treatments that specifically target neuronal loss and secondary injury development following TBI. In this study, we evaluate the effect of xenon treatment on functional outcome, lesion volume, neuronal loss and neuroinflammation after severe TBI in rats. Methods Young adult male Sprague Dawley rats were subjected to controlled cortical impact (CCI) brain trauma or sham surgery followed by treatment with either 50% xenon:25% oxygen balance nitrogen, or control gas 75% nitrogen:25% oxygen. Locomotor function was assessed using Catwalk-XT automated gait analysis at baseline and 24 h after injury. Histological outcomes were assessed following perfusion fixation at 15 min or 24 h after injury or sham procedure. Results Xenon treatment reduced lesion volume, reduced early locomotor deficits, and attenuated neuronal loss in clinically relevant cortical and subcortical areas. Xenon treatment resulted in significant increases in Iba1-positive microglia and GFAP-positive reactive astrocytes that was associated with neuronal preservation. Conclusions Our findings demonstrate that xenon improves functional outcome and reduces neuronal loss after brain trauma in rats. Neuronal preservation was associated with a xenon-induced enhancement of microglial cell numbers and astrocyte activation, consistent with a role for early beneficial neuroinflammation in xenon’s neuroprotective effect. These findings suggest that xenon may be a first-line clinical treatment for brain trauma.

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