Microparticles Impair Hypotensive Cerebrovasodilation and Cause Hippocampal Neuronal Cell Injury after Traumatic Brain Injury

Background & Objective: Traumatic Brain Injury (TBI) is one of the major causes of mortality and morbidity worldwide. It represents mild, moderate and severe effects of physical assault to brain which may cause sequential, primary or secondary ramifications. Primary injury can be due to the first physical hit, blow or jolt to one of the brain compartments. The primary injury is then followed by secondary injury which leads to biochemical, cellular, and physiological changes like blood brain barrier disruption, inflammation, excitotoxicity, necrosis, apoptosis, mitochondrial dysfunction and generation of oxidative stress. Apart from this, there is also an immediate increase in glutamate at the synapses following severe TBI. Excessive glutamate at synapses in turn activates corresponding NMDA and AMPA receptors that facilitate excessive calcium influx into the neuronal cells. This leads to the generation of oxidative stress which further leads to mitochondrial dysfunction, lipid peroxidation and oxidation of proteins and DNA. As a consequence, neuronal cell death takes place and ultimately people start facing some serious disabilies. Conclusion: In the present review we provide extensive overview of the role of reactive oxygen species (ROS)-induced oxidative stress and its fatal effects on brain after TBI.

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Evaluation of the Neuroprotective Effect of Pycnogenol in a Hypoxic-Ischemic Brain Injury Model in Newborn Rats

American Journal of Perinatology ◽

10.1055/s-0041-1730349 ◽

2021 ◽

Author(s):

Ruya Çolak ◽

Aslı Celik ◽

Gulden Diniz ◽

Senem Alkan Özdemir ◽

Osman Yilmaz ◽

...

Keyword(s):

Brain Injury ◽

Cell Injury ◽

Neuroprotective Effect ◽

Neuronal Cell ◽

Terminal Deoxynucleotidyl Transferase ◽

Albino Rats ◽

Protective Agent ◽

Injury Model ◽

Group B ◽

Factor Α

Objective This study aimed to evaluate the efficacy of Pycnogenol (PYC) and its antioxidant and antiapoptotic effect in an experimental hypoxic-ischemic (HI) rat model. Study Design A total of 24 Wistar albino rats who were on the seventh postnatal day were divided into three groups with developed HI brain injury model under the sevoflurane anesthesia: 40 mg/kg PYC was given to Group A, saline was given to Group B, and the sham group was Group C. Neuronal apoptosis was investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling and immunohistochemically stained manually with primer antibodies of tumor necrosis factor-α and interleukin-1β. Results The neuronal cell injury was statistically lower in the PYC treatment group. Conclusion This is the first study that investigates the role of PYC in the HI brain injury model. PYC reduces apoptosis and neuronal injury in the cerebral tissue of the rats. PYC may be a protective agent against hypoxic-ischemic encephalopathy. Key Points

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Proneurotrophins Induce Apoptotic Neuronal Death After Controlled Cortical Impact Injury in Adult Mice

ASN NEURO ◽

10.1177/1759091420930865 ◽

2020 ◽

Vol 12 ◽

pp. 175909142093086

Author(s):

Laura E. Montroull ◽

Deborah E. Rothbard ◽

Hur D. Kanal ◽

Veera D’Mello ◽

Vincent Dodson ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Cell Death ◽

Brain Injury ◽

Neuronal Death ◽

Apoptotic Cell ◽

Neuronal Cell ◽

Adult Brain ◽

Neurotrophin Receptor ◽

Cortical Impact ◽

Impact Injury

The p75 neurotrophin receptor (p75NTR) can regulate multiple cellular functions including proliferation, survival, and apoptotic cell death. The p75NTR is widely expressed in the developing brain and is downregulated as the nervous system matures, with only a few neuronal subpopulations retaining expression into adulthood. However, p75NTR expression is induced following damage to the adult brain, including after traumatic brain injury, which is a leading cause of mortality and disability worldwide. A major consequence of traumatic brain injury is the progressive neuronal loss that continues secondary to the initial trauma, which ultimately contributes to cognitive decline. Understanding mechanisms governing this progressive neuronal death is key to developing targeted therapeutic strategies to provide neuroprotection and salvage cognitive function. In this study, we demonstrate that a cortical impact injury to the sensorimotor cortex elicits p75NTR expression in apoptotic neurons in the injury penumbra, confirming previous studies. To establish whether preventing p75NTR induction or blocking the ligands would reduce the extent of secondary neuronal cell death, we used a noninvasive intranasal strategy to deliver either siRNA to block the induction of p75NTR, or function-blocking antibodies to the ligands pro-nerve growth factor and pro-brain-derived neurotrophic factor. We demonstrate that either preventing the induction of p75NTR or blocking the proneurotrophin ligands provides neuroprotection and preserves sensorimotor function.

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Effects of Transient Receptor Potential Cation 5 (TRPC5) Inhibitor, NU6027, on Hippocampal Neuronal Death after Traumatic Brain Injury

International Journal of Molecular Sciences ◽

10.3390/ijms21218256 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8256 ◽

Cited By ~ 1

Author(s):

Min Kyu Park ◽

Bo Young Choi ◽

A Ra Kho ◽

Song Hee Lee ◽

Dae Ki Hong ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neuronal Death ◽

Transient Receptor Potential ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Treated Group ◽

Therapeutic Window ◽

Permanent Disability ◽

Fluoro Jade B

Traumatic brain injury (TBI) can cause physical, cognitive, social, and behavioral changes that can lead to permanent disability or death. After primary brain injury, translocated free zinc can accumulate in neurons and lead to secondary events such as oxidative stress, inflammation, edema, swelling, and cognitive impairment. Under pathological conditions, such as ischemia and TBI, excessive zinc release, and accumulation occurs in neurons. Based on previous research, it hypothesized that calcium as well as zinc would be influx into the TRPC5 channel. Therefore, we hypothesized that the suppression of TRPC5 would prevent neuronal cell death by reducing the influx of zinc and calcium. To test our hypothesis, we used a TBI animal model. After the TBI, we immediately injected NU6027 (1 mg/kg, intraperitoneal), TRPC5 inhibitor, and then sacrificed animals 24 h later. We conducted Fluoro-Jade B (FJB) staining to confirm the presence of degenerating neurons in the hippocampal cornus ammonis 3 (CA3). After the TBI, the degenerating neuronal cell count was decreased in the NU6027-treated group compared with the vehicle-treated group. Our findings suggest that the suppression of TRPC5 can open a new therapeutic window for a reduction of the neuronal death that may occur after TBI.

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Safety and Efficacy of Erythropoietin in Traumatic Brain Injury Patients: A Pilot Randomized Trial

Critical Care Research and Practice ◽

10.1155/2010/209848 ◽

2010 ◽

Vol 2010 ◽

pp. 1-5 ◽

Cited By ~ 20

Author(s):

R. Nirula ◽

R. Diaz-Arrastia ◽

K. Brasel ◽

J. A. Weigelt ◽

K. Waxman

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Randomized Trial ◽

Treatment Effect ◽

Neuronal Cell Death ◽

Neuron Specific Enolase ◽

Neuronal Cell ◽

Trauma Patients ◽

Stroke Patients ◽

Rule Out

Background. Erythropoietin (EPO) is a neuroprotective agent utilized in stroke patients. This pilot study represents the first randomized trial of EPO in traumatic brain injury (TBI) patients.Methods. Adult, blunt trauma patients with evidence of TBI were randomized to EPO or placebo within 6 hours of injury. Baseline and daily serum S-100B and Neuron Specific Enolase (NSE) levels were measured.Results. TBI was worse in the EPO (n=11) group compared to placebo patients (n=5). The use of EPO did not impact NSE (P=.89) or S100 B (P=.53) levels compared to placebo.Conclusions. At the dose used, EPO did not reduce neuronal cell death compared to placebo; however, TBI severity was worse in the EPO group while levels of NSE and S100-B were similar to the less injured placebo group making it difficult to rule out a treatment effect. A larger, balanced study is necessary to confirm a potential treatment effect.

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Peroxisome Proliferator-Activated Receptors: “Key” Regulators of Neuroinflammation after Traumatic Brain Injury

PPAR Research ◽

10.1155/2008/538141 ◽

2008 ◽

Vol 2008 ◽

pp. 1-7 ◽

Cited By ~ 27

Author(s):

Philip F. Stahel ◽

Wade R. Smith ◽

Jay Bruchis ◽

Craig H. Rabb

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neuronal Cell Death ◽

Synthetic Cannabinoids ◽

Experimental Studies ◽

Neuronal Cell ◽

Peroxisome Proliferator ◽

Therapeutic Concept ◽

Anti Inflammatory ◽

Peroxisome Proliferator Activated Receptors

Traumatic brain injury is characterized by neuroinflammatory pathological sequelae which contribute to brain edema and delayed neuronal cell death. Until present, no specific pharmacological compound has been found, which attenuates these pathophysiological events and improves the outcome after head injury. Recent experimental studies suggest that targeting peroxisome proliferator-activated receptors (PPARs) may represent a new anti-inflammatory therapeutic concept for traumatic brain injury. PPARs are “key” transcription factors which inhibit NFκBactivity and downstream transcription products, such as proinflammatory and proapoptotic cytokines. The present review outlines our current understanding of PPAR-mediated neuroprotective mechanisms in the injured brain and discusses potential future anti-inflammatory strategies for head-injured patients, with an emphasis on the putative beneficial combination therapy of synthetic cannabinoids (e.g., dexanabinol) with PPARαagonists (e.g., fenofibrate).

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Disruption of Bax Protein Prevents Neuronal Cell Death but Produces Cognitive Impairment in Mice following Traumatic Brain Injury

Journal of Neurotrauma ◽

10.1089/neu.2007.0441 ◽

2008 ◽

Vol 25 (7) ◽

pp. 755-767 ◽

Cited By ~ 39

Author(s):

Roya Tehranian ◽

Marie E. Rose ◽

Vincent Vagni ◽

Alicia M. Pickrell ◽

Raymond P. Griffith ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Cell Death ◽

Cognitive Impairment ◽

Brain Injury ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Bax Protein

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Modeling the pathobiology of repetitive traumatic brain injury in immortalized neuronal cell lines

Brain Research ◽

10.1016/j.brainres.2011.09.047 ◽

2011 ◽

Vol 1425 ◽

pp. 123-131 ◽

Cited By ~ 9

Author(s):

Michael J. Kane ◽

Haris Hatic ◽

Vedad Delic ◽

John S. Dennis ◽

Carrie L. Butler ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Cell Lines ◽

Neuronal Cell ◽

Neuronal Cell Lines

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Therapeutic Time Window for Edaravone Treatment of Traumatic Brain Injury in Mice

BioMed Research International ◽

10.1155/2013/379206 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 11

Author(s):

Kazuyuki Miyamoto ◽

Hirokazu Ohtaki ◽

Kenji Dohi ◽

Tomomi Tsumuraya ◽

Dandan Song ◽

...

Keyword(s):

Oxidative Stress ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Neuronal Death ◽

Time Window ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Therapeutic Time Window

Traumatic brain injury (TBI) is a major cause of death and disability in young people. No effective therapy is available to ameliorate its damaging effects. Our aim was to investigate the optimal therapeutic time window of edaravone, a free radical scavenger which is currently used in Japan. We also determined the temporal profile of reactive oxygen species (ROS) production, oxidative stress, and neuronal death. Male C57Bl/6 mice were subjected to a controlled cortical impact (CCI). Edaravone (3.0 mg/kg), or vehicle, was administered intravenously at 0, 3, or 6 hours following CCI. The production of superoxide radicals (O2∙-) as a marker of ROS, of nitrotyrosine (NT) as an indicator of oxidative stress, and neuronal death were measured for 24 hours following CCI. Superoxide radical production was clearly evident 3 hours after CCI, with oxidative stress and neuronal cell death becoming apparent after 6 hours. Edaravone administration after CCI resulted in a significant reduction in the injury volume and oxidative stress, particularly at the 3-hour time point. Moreover, the greatest decrease inO2∙-levels was observed when edaravone was administered 3 hours following CCI. These findings suggest that edaravone could prove clinically useful to ameliorate the devastating effects of TBI.

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