scholarly journals Mitochondria-Targeted Antioxidants as Potential Therapy for the Treatment of Traumatic Brain Injury

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 124 ◽  
Author(s):  
Elena V. Stelmashook ◽  
Nickolay K. Isaev ◽  
Elisaveta E. Genrikhs ◽  
Svetlana V. Novikova
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cortical Lesion ◽  
Lesion Volume ◽  
Negative Effects ◽  
Behavioral Deficits ◽  
Secondary Damage ◽  
Long Time ◽  
The Brain ◽  
Brain Water

The aim of this article is to review the publications describing the use of mitochondria-targeted antioxidant therapy after traumatic brain injury (TBI). Recent works demonstrated that mitochondria-targeted antioxidants are very effective in reducing the negative effects associated with the development of secondary damage caused by TBI. Using various animal models of TBI, mitochondria-targeted antioxidants were shown to prevent cardiolipin oxidation in the brain and neuronal death, as well as to markedly reduce behavioral deficits and cortical lesion volume, brain water content, and DNA damage. In the future, not only a more detailed study of the mechanisms of action of various types of such antioxidants needs to be conducted, but also their therapeutic values and toxicological properties are to be determined. Moreover, the optimal therapeutic effect needs to be achieved in the shortest time possible from the onset of damage to the nervous tissue, since secondary brain damage in humans can develop for a long time, days and even months, depending on the severity of the damage.

scholarly journals Ulinastatin alleviates traumatic brain injury by reducing endothelin-1

2020 ◽  
Vol 12 (1) ◽  
pp. 001-008
Author(s):  
Ting Liu ◽  
Xing-Zhi Liao ◽  
Mai-Tao Zhou
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Water Content ◽  
Brain Edema ◽  
Rat Model ◽  
Neurosurgical Procedures ◽  
Brain Water Content ◽  
The Brain ◽  
Brain Water

Abstract Background Brain edema is one of the major causes of fatality and disability associated with injury and neurosurgical procedures. The goal of this study was to evaluate the effect of ulinastatin (UTI), a protease inhibitor, on astrocytes in a rat model of traumatic brain injury (TBI). Methodology A rat model of TBI was established. Animals were randomly divided into 2 groups – one group was treated with normal saline and the second group was treated with UTI (50,000 U/kg). The brain water content and permeability of the blood–brain barrier were assessed in the two groups along with a sham group (no TBI). Expression of the glial fibrillary acidic protein, endthelin-1 (ET-1), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry and western blot. Effect of UTI on ERK and PI3K/AKT signaling pathways was measured by western blot. Results UTI significantly decreased the brain water content and extravasation of the Evans blue dye. This attenuation was associated with decreased activation of the astrocytes and ET-1. UTI treatment decreased ERK and Akt activation and inhibited the expression of pro-inflammatory VEGF and MMP-9. Conclusion UTI can alleviate brain edema resulting from TBI by inhibiting astrocyte activation and ET-1 production.

The role of estrogen and progesterone, administered alone and in combination, in modulating cytokine concentration following traumatic brain injury

2011 ◽  
Vol 89 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Mohammad Khaksari ◽  
Zahra Soltani ◽  
Nader Shahrokhi ◽  
Gholamreza Moshtaghi ◽  
Gholamreza Asadikaram
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Water Content ◽  
Treated Group ◽  
Inhibitory Effect ◽  
Ovariectomized Rats ◽  
Brain Level ◽  
The Brain ◽  
Brain Water

Cytokines play an important role in the pathophysiology of traumatic brain injury (TBI). This study was designed to determine the effects of administering progesterone (P) and estrogen (E), alone and in combination, on brain water content, blood–brain barrier (BBB) disturbance, and brain level of cytokines following diffuse TBI. Ovariectomized rats were divided into 9 groups, treated with vehicle, E1, E2, P1, P2, E1+P1, E1+P2, E2+P1, and E2+P2. Levels of BBB disruption (5 h), cytokines, and water content (24 h) were evaluated after TBI induced by the Marmarou method. Physiological (E1 and P1) and pharmacological (E2 and P2) doses of estrogen and progesterone were administered 30 min after TBI. Water content in the E1+P2-treated group was higher than in the E1-treated group. The inhibitory effect of E2 on water content was reduced by adding progesterone. The inhibitory effect of E1 and E2 on Evans blue content was reduced by treatment with E1+P1 and E2+P2, respectively. The brain level of IL-1β was reduced in E1 and E2, after TBI. In the E2+P2-treated group, this level was higher than in the E2-treated group. The brain level of TGF-β was also elevated by the administration of progesterone and estrogen alone, and reduced when the hormones were administered in combination. In conclusion, a combined administration of progesterone and estrogen inhibited the decreasing effects of administration of progesterone and estrogen alone on water content and BBB disruption that mediated to change the proinflammatory cytokines.

scholarly journals Paradoxical Increase in Neuronal DNA Fragmentation after Neuroprotective Free Radical Scavenger Treatment in Experimental Traumatic Brain Injury

2001 ◽  
Vol 21 (4) ◽  
pp. 344-350 ◽  
Author(s):  
Anders Lewén ◽  
Ylva Skoglösa ◽  
Fredrik Clausen ◽  
Niklas Marklund ◽  
Pak H. Chan ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Free Radical ◽  
Brain Injury ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Active Form ◽  
Cortical Lesion ◽  
Radical Scavenger ◽  
Lesion Volume ◽  
Screening Process

The mechanisms and role of nerve cell death after traumatic brain injury (TBI) are not fully understood. The authors investigated the effect of pretreatment with the oxygen free radical spin trap α-phenyl- N- tert-butyl-nitrone (PBN) on the number of neurons undergoing apoptosis after TBI in rats. Apoptotic cells were identified by the TUNEL method combined with the nuclear stain, Hoechst 33258, and immunohistochemistry for the active form of caspase-3. Numerous neurons became positive for activated caspase 3 and TUNEL in the cortex at 24 hours after injury, suggesting ongoing biochemical apoptosis. In PBN-treated rats, a significantly greater number of cells were found to be TUNEL positive at 24 hours compared with controls. However, PBN treatment resulted in a reduced cortical lesion volume and improved behavioral outcome two weeks after injury. The authors conclude that a treatment producing an increase in DNA fragmentation in the early phase may be compatible with an overall beneficial effect on outcome after TBI. This should be considered in the screening process for future neuroprotective remedies.

scholarly journals Traumatic brain injury in dogs and cats: a systematic review

2018 ◽  
Vol 63 (No. 8) ◽  
pp. 345-357 ◽  
Author(s):  
LO Dos Santos ◽  
GG Caldas ◽  
CRO Santos ◽  
DB Junior
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Motor Vehicle ◽  
Brain Parenchyma ◽  
Irreversible Damage ◽  
Vehicle Accidents ◽  
Secondary Damage ◽  
Therapeutic Measures ◽  
Crush Injuries ◽  
The Brain

Traumatic brain injury occurs frequently in dogs and cats due to motor vehicle accidents, falls and crush injuries. The primary lesion occurs at the time of injury and causes direct, irreversible damage to the brain parenchyma and vasculature. Secondary lesions occur in the minutes following the trauma due to a combination of physical and biochemical changes that lead to intracranial hypertension. Therefore, knowing the pathophysiology of the cranioencephalic trauma is essential for treatment directed at minimising secondary damage. The approach to the patient affected by traumatic brain injury is based on the ABCD of trauma, guided by the neurological examination with the aid of imaging exams and adequate therapeutic measures. The treatment of patients with cranioencephalic trauma is still in many ways controversial. For that reason, this literature review aims to address the main points regarding the pathophysiology of this disease and to describe the clinical and surgical therapeutic options currently available.

scholarly journals The CNS lymphatic system modulates the adaptive neuro-immune response in the perilesional cortex in a mouse model of traumatic brain injury

2019 ◽  
Author(s):  
Wojciechowski Sara ◽  
Vihma Maria ◽  
Galbardi Barbara ◽  
Virenque Anaïs ◽  
Meike H. Keuters ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Immune Response ◽  
T Cells ◽  
Brain Injury ◽  
Lymphatic Vessels ◽  
Lesion Size ◽  
Lesion Volume ◽  
Post Injury ◽  
Circulating T Cells ◽  
The Brain

AbstractRationaleThe recently discovered meningeal lymphatic vessels (mLVs) have been proposed to be the missing link between the immune and the central nervous systems. The role of mLVs in modulating the neuro-immune response following a brain injury, however, has not been analyzed. Parenchymal T lymphocyte infiltration has been previously reported as part of secondary events after traumatic brain injury (TBI), suggestive of an adaptive neuro-immune response. The phenotype of these cells has remained mostly uncharacterized. In this study, we identified the subpopulations of T cells infiltrating the perilesional areas 30 days post-injury (an early-chronic time point). Furthermore, we analyzed how the lack of mLVs affects the magnitude and the type of immune response in the brain after TBI.MethodsTBI was induced in K14-VEGFR3-Ig transgenic (TG) mice or in their littermate controls (WT; wild type), applying a controlled cortical impact (CCI). One month after TBI, T cells were isolated from cortical areas ipsilateral or contralateral to the trauma and from the spleen, then characterized by flow cytometry. Lesion size in each animal was evaluated by MRI.ResultsIn both WT and TG-CCI mice, we found a prominent T cell infiltration in the brain confined to the perilesional cortex and hippocampus. The majority of infiltrating T cells were cytotoxic CD8+ expressing a CD44hiCD69+ phenotype, suggesting that these are effector resident memory T cells. K14-VEGFR3-Ig mice showed a significant reduction of infiltrating CD4+ T lymphocytes, implying that mLVs are important in establishing a proper neuro-immune response. Extension of the lesion (measured as lesion volume from MRI) did not differ between the genotypes. Finally, TBI did not relate with alterations in peripheral circulating T cells, as assessed one month after injury induction.ConclusionsOur data support the hypothesis that mLVs are pivotal for a proper and specific neuro-immune response after TBI, which is principally mediated by the resident memory CD8+ T cells.

scholarly journals Ribonuclease-1 treatment after traumatic brain injury preserve the integrity of the neurovascular unit, decreases inflammatory response and delays secondary brain damage in mice

2021 ◽  
Author(s):  
Tobias J. Krämer ◽  
Per Hübener ◽  
Bruno Pöttker ◽  
Christina Gölz ◽  
Axel Neulen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Vascular Dysfunction ◽  
Neurovascular Unit ◽  
Mechanical Damage ◽  
Inflammatory Cells ◽  
Systemic Circulation ◽  
Lesion Volume ◽  
Secondary Damage ◽  
Functional Benefit

Abstract Traumatic brain injury (TBI) involves primary mechanical damage and delayed secondary damage caused by vascular dysfunction and neuroinflammation. Intracellular components released into the parenchyma and systemic circulation, termed danger-associated molecular patterns (DAMPs), are major drivers of vascular dysfunction and neuroinflammation. These DAMPs include cell-free RNAs (cfRNAs), which damage the blood–brain barrier (BBB), thereby promoting edema, procoagulatory processes, and infiltration of inflammatory cells. We tested the hypothesis that intraperitoneal injection of Ribonuclease-1 (RNase1, two doses of 20, 60, or 180 µg/kg) at 30 min and 12h after controlled-cortical-impact (CCI) can reduce secondary lesion expansion compared to vehicle treatment 24h and 120h post-CCI. The lowest total dose (40 µg/kg) was most effective at reducing lesion volume (−31% RNase 40µg/kg vs. vehicle), brain water accumulation (−5.5%), and loss of BBB integrity (−21.6%) at 24h post-CCI. RNase1 also reduced perilesional leukocyte recruitment (−53.3%) and microglial activation (−18.3%) at 120h post-CCI, but there was no difference in lesion volume at this time and no functional benefit. Treatment with RNase1 in the early phase following TBI stabilizes the BBB and impedes leukocyte immigration, thereby suppressing neuroinflammation. RNase1-treatment may be a novel approach to delay brain injury to extend the window for treatment opportunities after TBI.

Contribution of estrogen receptors alpha and beta in the brain response to traumatic brain injury

2013 ◽  
Vol 119 (2) ◽  
pp. 353-361 ◽  
Author(s):  
Saleh Zahedi Asl ◽  
Mohammad Khaksari ◽  
Ali Siahposht Khachki ◽  
Nader Shahrokhi ◽  
Shahla Nourizade
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Water Content ◽  
Female Rats ◽  
Blue Dye ◽  
Brain Water Content ◽  
Neuroprotective Effects ◽  
Selective Agonist ◽  
The Brain ◽  
Brain Water

Object Although there is evidence that estradiol has neuroprotective effects after traumatic brain injury (TBI) in female rats, it is unclear which estrogen receptor (ER) subtype, ERα or ERβ, mediates this effect. The authors therefore examined the roles of the different ERs in this effect. Here the authors used the ERα selective agonist propyl pyrazole triol (PPT) and the ERβ selective agonist diarylpropionitrile (DPN) alone and in combination in female rats to investigate this question. Methods Before the ovariectomized animals were injured using the Marmarou TBI technique, they were randomly divided into the following 9 groups: control, sham, TBI, vehicle, E1 (physiological dose of 17-β estradiol), E2 (pharmacological dose of 17-β estradiol), PPT, DPN, and PPT+DPN. Levels of blood-brain barrier (BBB) disruption (5 hours) and water content (24 hours) were evaluated after TBI. In groups receiving drugs or vehicle, treatment was administered as a single dose intraperitoneally 30 minutes after induction of TBI. Results Results showed that brain edema or brain water content after TBI was lower (p < 0.001) in the E2, PPT, DPN, and PPT+DPN groups than it was in the vehicle group. After trauma, the Evans blue dye content or BBB permeability was significantly higher in the TBI and vehicle groups (p < 0.001) than in the E2, PPT, DPN, and PPT+DPN groups. The inhibitory effects of PPT+DPN on brain water content, neurological scores, and Evans blue dye content were the highest for all groups. Although both PPT and DPN increased neurological scores after TBI, PPT appears to be more effective in increasing neurological scores. Conclusions Neuroprotective effects of estradiol on brain edema, BBB permeability, and neurological scores are mediated through both ERα and ERβ. This may suggest a therapeutic potential in the brain trauma for ER-specific agonists.

scholarly journals Developmental Dysfunction of the Central Nervous System Lymphatics Modulates the Adaptive Neuro-Immune Response in the Perilesional Cortex in a Mouse Model of Traumatic Brain Injury

2021 ◽  
Vol 11 ◽  
Author(s):  
Sara Wojciechowski ◽  
Anaïs Virenque ◽  
Maria Vihma ◽  
Barbara Galbardi ◽  
Erin Jane Rooney ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Central Nervous System ◽  
Immune Response ◽  
T Cells ◽  
Nervous System ◽  
Brain Injury ◽  
T Cell ◽  
Lesion Volume ◽  
The Central Nervous System ◽  
The Brain

RationaleThe recently discovered meningeal lymphatic vessels (mLVs) have been proposed to be the missing link between the immune and the central nervous system. The role of mLVs in modulating the neuro-immune response following a traumatic brain injury (TBI), however, has not been analyzed. Parenchymal T lymphocyte infiltration has been previously reported as part of secondary events after TBI, suggestive of an adaptive neuro-immune response. The phenotype of these cells has remained mostly uncharacterized. In this study, we identified subpopulations of T cells infiltrating the perilesional areas 30 days post-injury (an early-chronic time point). Furthermore, we analyzed how the lack of mLVs affects the magnitude and the type of T cell response in the brain after TBI.MethodsTBI was induced in K14-VEGFR3-Ig transgenic (TG) mice or in their littermate controls (WT; wild type), applying a controlled cortical impact (CCI). One month after TBI, T cells were isolated from cortical areas ipsilateral or contralateral to the trauma and from the spleen, then characterized by flow cytometry. Lesion size in each animal was evaluated by MRI.ResultsIn both WT and TG-CCI mice, we found a prominent T cell infiltration in the brain confined to the perilesional cortex and hippocampus. The majority of infiltrating T cells were cytotoxic CD8+ expressing a CD44hiCD69+ phenotype, suggesting that these are effector resident memory T cells. K14-VEGFR3-Ig mice showed a significant reduction of infiltrating CD4+ T lymphocytes, suggesting that mLVs could be involved in establishing a proper neuro-immune response. Extension of the lesion (measured as lesion volume from MRI) did not differ between the genotypes. Finally, TBI did not relate to alterations in peripheral circulating T cells, as assessed one month after injury.ConclusionsOur results are consistent with the hypothesis that mLVs are involved in the neuro-immune response after TBI. We also defined the resident memory CD8+ T cells as one of the main population activated within the brain after a traumatic injury.

Lessons Learned From Coaching Postsecondary Students With Traumatic Brain Injury

2020 ◽  
Vol 5 (1) ◽  
pp. 88-96
Author(s):  
Mary R. T. Kennedy
Keyword(s):  
College Students ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sense Of Self ◽  
Scientific Evidence ◽  
Sudden Onset ◽  
Lessons Learned ◽  
Speech Language Pathologists ◽  
The Brain ◽  
Exhaustive List

Purpose The purpose of this clinical focus article is to provide speech-language pathologists with a brief update of the evidence that provides possible explanations for our experiences while coaching college students with traumatic brain injury (TBI). Method The narrative text provides readers with lessons we learned as speech-language pathologists functioning as cognitive coaches to college students with TBI. This is not meant to be an exhaustive list, but rather to consider the recent scientific evidence that will help our understanding of how best to coach these college students. Conclusion Four lessons are described. Lesson 1 focuses on the value of self-reported responses to surveys, questionnaires, and interviews. Lesson 2 addresses the use of immediate/proximal goals as leverage for students to update their sense of self and how their abilities and disabilities may alter their more distal goals. Lesson 3 reminds us that teamwork is necessary to address the complex issues facing these students, which include their developmental stage, the sudden onset of trauma to the brain, and having to navigate going to college with a TBI. Lesson 4 focuses on the need for college students with TBI to learn how to self-advocate with instructors, family, and peers.

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