GM1 ganglioside prevents axonal regeneration inhibition and cognitive deficits in a mouse model of traumatic brain injury

Benady, Amit; Freidin, Dor; Pick, Chaim G.; Rubovitch, Vardit

doi:10.1038/s41598-018-31623-y

Cited by 29 publications

(25 citation statements)

References 45 publications

(50 reference statements)

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“…The weight and the height from which it is imposed determines the severity of the injury, and it can range from a mild level of injury to severe brain injury. This model was chosen because of its ability to simulate traumatic head injuries comparable to those observed in road accidents or falls (4). Based on our results, both groups of smoked mice demonstrated a loss of body weight when compared to control, confirming the common metabolic stimulatory effect of TS.…”

Section: Discussionsupporting

confidence: 53%

“…We used a weight-drop model of TBI (2,4,26). In brief, mice were anesthetized by inhaling Isoflurane vapor for several minutes and then placed on a spongy platform positioned under the weight-drop device.…”

Section: Induction Of Head Injury In Micementioning

confidence: 99%

“…According to the Centers for Disease Control and Prevention (CDC), about 2.5 million people in the U.S. seek emergency care for TBI secondary to motor vehicle accidents, falls, assaults, sports-related events, and other mechanisms every year while more than 5.3 million Americans are currently living with a lifelong disability due to TBI (3). The effects of TBI can cause emotional, physiological, cognitive, motor and behavioral damage ranging from mild to severe deficits and death (4)(5)(6)(7). Mild traumatic brain injury (mTBI) accounts for over 80% of head injuries (3,8).…”

Section: Introductionmentioning

confidence: 99%

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Cerebrovascular and neurological impact of chronic smoking on post traumatic brain injury outcome and recovery: an in vivo study

Sivandzade

Alqahtani

Sifat

et al. 2019

Preprint

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Background: Traumatic Brain Injury (TBI) is among the most prevalent causes of cerebrovascular and neurological damage worldwide. To this end, tobacco smoking (TS) has been shown to promote vascular inflammation, neurovascular impairments and risk of cerebrovascular and neurological disorders through oxidative stress (OS) stimuli targeting the blood-brain barrier (BBB) endothelium among others. It has been recently suggested that premorbid conditions such as TS may exacerbate post-TBI brain damage and impact recovery. The present study aims to investigate and dissect out the pathophysiological mechanisms underlying the exacerbation of TBI in a weight-drop model following chronic TS exposure. Methods: C57BL/6J male mice, age range 6–8 weeks were chronically exposed to TS for three weeks. Test animals were then subjected to TBI by guided vertical head weight drop using a 30 g metal weight free felling from an 80 cm distance before reaching the target. Physical activity and body weight of the mice were analyzed before TBI and 1 h, 24 h and 3 days post-injury. Finally, mice were sacrificed to collect blood and brain samples for subsequent biochemical and molecular analysis. Western blotting was applied to assess the expression of Nrf2 (a key antioxidant transcription factor) as well as tight junction proteins associated with BBB integrity including, ZO-1, Occludin, Claudin-5 from brain tissues homogenates. Levels of NF-kB (a pro-inflammatory transcript factor which antagonizes Nrf2 activity) along with pro-inflammatory cytokines IL-6, IL-10 and TNF-α were measured by ELISA on blood samples. Results: TS promoted significantly increased inflammation and loss of BBB integrity in TBI when compared to TS-Free test mice. Additionally, mice chronically exposed to TS prior to TBI experienced a more significant weight loss, behavioral, and motor activity deficiency and slower post-TBI recovery when compared to TS-free TBI mice. Conclusion: TS promotes a significant exacerbation of post-TBI neurovascular and neurological impairments. Whereas BBB impairment and pro-inflammatory vascular responses induced by chronic TS exposure are likely responsible for the retardation of post-traumatic recovery observed in these animals.

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Section: Discussionsupporting

confidence: 53%

Section: Induction Of Head Injury In Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cerebrovascular and neurological impact of chronic smoking on post traumatic brain injury outcome and recovery: an in vivo study

Sivandzade

Alqahtani

Sifat

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, every year, more than 5.3 million Americans live with a lifelong disability caused by TBI [8][9][10]. In those that survive, the effects of TBI can cause emotional, physiological, cognitive, motor, and behavioral impairments ranging from mild to severe [5,[11][12][13][14]. Mild traumatic brain injury (mTBI) accounts for over 80% of head injuries [1].…”

Section: Introductionmentioning

confidence: 99%

Traumatic Brain Injury and Blood–Brain Barrier (BBB): Underlying Pathophysiological Mechanisms and the Influence of Cigarette Smoking as a Premorbid Condition

Sivandzade

Alqahtani

Cucullo

2020

IJMS

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Traumatic brain injury (TBI) is among the most pressing global health issues and prevalent causes of cerebrovascular and neurological disorders all over the world. In addition to the brain injury, TBI may also alter the systemic immune response. Thus, TBI patients become vulnerable to infections, have worse neurological outcomes, and exhibit a higher rate of mortality and morbidity. It is well established that brain injury leads to impairments of the blood–brain barrier (BBB) integrity and function, contributing to the loss of neural tissue and affecting the response to neuroprotective drugs. Thus, stabilization/protection of the BBB after TBI could be a promising strategy to limit neuronal inflammation, secondary brain damage, and acute neurodegeneration. Herein, we present a review highlighting the significant post-traumatic effects of TBI on the cerebrovascular system. These include the loss of BBB integrity and selective permeability, impact on BBB transport mechanisms, post-traumatic cerebral edema formation, and significant pathophysiological factors that may further exacerbate post-traumatic BBB dysfunctions. Furthermore, we discuss the post-traumatic impacts of chronic smoking, which has been recently shown to act as a premorbid condition that impairs post-TBI recovery. Indeed, understanding the underlying molecular mechanisms associated with TBI damage is essential to better understand the pathogenesis and progression of post-traumatic secondary brain injury and the development of targeted treatments to improve outcomes and speed up the recovery process. Therapies aimed at restoring/protecting the BBB may reduce the post-traumatic burden of TBI by minimizing the impairment of brain homeostasis and help to restore an optimal microenvironment to support neuronal repair.

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“…In transgenic mice lacking all major gangliosides (sialyltransferase(ST)-I knockout mice), developmental deficits were observed in the peripheral nervous system (PNS) [54]. Furthermore, administration of monosialotetrahexosylganglioside (GM1) ganglioside can ameliorate nervous system damage and mitigate the effects of a variety of neurodegenerative processes [56].…”

Section: Introductionmentioning

confidence: 99%

Glycan Mimetics from Natural Products: New Therapeutic Opportunities for Neurodegenerative Disease

et al. 2019

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Neurodegenerative diseases (NDs) affect millions of people worldwide. Characterized by the functional loss and death of neurons, NDs lead to symptoms (dementia and seizures) that affect the daily lives of patients. In spite of extensive research into NDs, the number of approved drugs for their treatment remains limited. There is therefore an urgent need to develop new approaches for the prevention and treatment of NDs. Glycans (carbohydrate chains) are ubiquitous, abundant, and structural complex natural biopolymers. Glycans often covalently attach to proteins and lipids to regulate cellular recognition, adhesion, and signaling. The importance of glycans in both the developing and mature nervous system is well characterized. Moreover, glycan dysregulation has been observed in NDs such as Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Therefore, glycans are promising but underexploited therapeutic targets. In this review, we summarize the current understanding of glycans in NDs. We also discuss a number of natural products that functionally mimic glycans to protect neurons, which therefore represent promising new therapeutic approaches for patients with NDs.

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GM1 ganglioside prevents axonal regeneration inhibition and cognitive deficits in a mouse model of traumatic brain injury

Cited by 29 publications

References 45 publications

Cerebrovascular and neurological impact of chronic smoking on post traumatic brain injury outcome and recovery: an in vivo study

Cerebrovascular and neurological impact of chronic smoking on post traumatic brain injury outcome and recovery: an in vivo study

Traumatic Brain Injury and Blood–Brain Barrier (BBB): Underlying Pathophysiological Mechanisms and the Influence of Cigarette Smoking as a Premorbid Condition

Glycan Mimetics from Natural Products: New Therapeutic Opportunities for Neurodegenerative Disease

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