Whether erythropoietin can be a neuroprotective agent against premature brain injury: cellular mechanisms and clinical efficacy

2021 ◽  
Vol 19 ◽  
Author(s):  
Xueling Ma ◽  
Yuan Shi
Keyword(s):  
Brain Injury ◽  
Animal Models ◽  
Standard Treatment ◽  
Neuroprotective Effect ◽  
Cellular Mechanisms ◽  
Neuroprotective Strategy ◽  
Anti Oxidant ◽  
Premature Brain ◽  
Scientific Rationale

: Preterm infants are at high risk of brain injury. With more understanding of the preterm brain injury's pathogenesis, neuroscientists are looking for more effective methods to prevent and treat it, among which erythropoietin (Epo) is considered as a prime candidate. This review tries to clarify the possible mechanisms of Epo in preterm neuroprotection and summarize updated evidence considering Epo as a pharmacological neuroprotective strategy in animal models and clinical trials. To date, various animal models have validated that Epo is an anti-apoptotic, anti-inflammatory, anti-oxidant, anti-excitotoxic, neurogenetic, erythropoietic, angiogenetic, and neurotrophic agent, thus preventing preterm brain injury. However, although the scientific rationale and preclinical data for Epo's neuroprotective effect are promising, when translated to bedside, the results vary in different studies, especially in its long-term efficacy. Based on existing evidence, it is still too early to recommend Epo as the standard treatment for preterm brain injury.

Propylparaben Reduces the Long-Term Consequences in Hippocampus Induced by Traumatic Brain Injury in Rats: Its Implications as Therapeutic Strategy to Prevent Neurodegenerative Diseases

2020 ◽  
pp. 1-12
Author(s):  
Cindy Santiago-Castañeda ◽  
Marysol Segovia-Oropeza ◽  
Luis Concha ◽  
Sandra Adela Orozco-Suárez ◽  
Luisa Rocha
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurodegenerative Diseases ◽  
Control Group ◽  
Hippocampal Damage ◽  
Neuroprotective Strategy ◽  
Long Term Consequences

Background: Severe traumatic brain injury (TBI), an important risk factor for Alzheimer’s disease, induces long-term hippocampal damage and hyperexcitability. On the other hand, studies support that propylparaben (PPB) induces hippocampal neuroprotection in neurodegenerative diseases. Objective: Experiments were designed to evaluate the effects of subchronic treatment with PPB on TBI-induced changes in the hippocampus of rats. Methods: Severe TBI was induced using the lateral fluid percussion model. Subsequently, rats received subchronic administration with PPB (178 mg/kg, TBI+PPB) or vehicle (TBI+PEG) daily for 5 days. The following changes were examined during the experimental procedure: sensorimotor dysfunction, changes in hippocampal excitability, as well as neuronal damage and volume. Results: TBI+PEG group showed sensorimotor dysfunction (p <  0.001), hyperexcitability (64.2%, p <  0.001), and low neuronal preservation ipsi- and contralateral to the trauma. Magnetic resonance imaging (MRI) analysis revealed lower volume (17.2%; p <  0.01) and great damage to the ipsilateral hippocampus. TBI+PPB group showed sensorimotor dysfunction that was partially reversed 30 days after trauma. This group showed hippocampal excitability and neuronal preservation similar to the control group. However, MRI analysis revealed lower hippocampal volume (p <  0.05) when compared with the control group. Conclusion: The present study confirms that post-TBI subchronic administration with PPB reduces the long-term consequences of trauma in the hippocampus. Implications of PPB as a neuroprotective strategy to prevent the development of Alzheimer’s disease as consequence of TBI are discussed.

scholarly journals Surgically-induced brain injury: where are we now?

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Zachary D. Travis ◽  
Prativa Sherchan ◽  
William K. Hayes ◽  
John H. Zhang
Keyword(s):  
Brain Injury ◽  
Brain Injuries ◽  
Neurosurgical Procedures ◽  
Cellular Mechanisms ◽  
The Past ◽  
Surgical Brain Injury ◽  
Neurosurgical Operation ◽  
Surgical Manipulations ◽  
Surgically Induced

AbstractNeurosurgical procedures cause inevitable brain damage from the multitude of surgical manipulations utilized. Incisions, retraction, thermal damage from electrocautery, and intraoperative hemorrhage cause immediate and long-term brain injuries that are directly linked to neurosurgical operations, and these types of injuries, collectively, have been termed surgical brain injury (SBI). For the past decade, a model developed to study the underlying brain pathologies resulting from SBI has provided insight on cellular mechanisms and potential therapeutic targets. This model, as seen in a rat, mouse, and rabbit, mimics a neurosurgical operation and causes commonly encountered post-operative complications such as brain edema, neuroinflammation, and hemorrhage. In this review, we elaborate on SBI and its clinical impact, the SBI animal models and their clinical relevance, the importance of applying therapeutics before neurosurgical procedures (i.e., preconditioning), and the new direction of applying venom-derived proteins to attenuate SBI.

scholarly journals Perinatal hypoxic-ischemic brain injury in large animal models: Relevance to human neonatal encephalopathy

2018 ◽  
Vol 38 (12) ◽  
pp. 2092-2111 ◽  
Author(s):  
Raymond C Koehler ◽  
Zeng-Jin Yang ◽  
Jennifer K Lee ◽  
Lee J Martin
Keyword(s):  
Brain Injury ◽  
Animal Models ◽  
Cerebral Hypoperfusion ◽  
Large Animal ◽  
Perinatal Hypoxia ◽  
Cellular Mechanisms ◽  
Fetal Sheep ◽  
Newborn Piglets ◽  
Large Animal Models ◽  
Hypoxia Ischemia

Perinatal hypoxia-ischemia resulting in death or lifelong disabilities remains a major clinical disorder. Neonatal models of hypoxia-ischemia in rodents have enhanced our understanding of cellular mechanisms of neural injury in developing brain, but have limitations in simulating the range, accuracy, and physiology of clinical hypoxia-ischemia and the relevant systems neuropathology that contribute to the human brain injury pattern. Large animal models of perinatal hypoxia-ischemia, such as partial or complete asphyxia at the time of delivery of fetal monkeys, umbilical cord occlusion and cerebral hypoperfusion at different stages of gestation in fetal sheep, and severe hypoxia and hypoperfusion in newborn piglets, have largely overcome these limitations. In monkey, complete asphyxia produces preferential injury to cerebellum and primary sensory nuclei in brainstem and thalamus, whereas partial asphyxia produces preferential injury to somatosensory and motor cortex, basal ganglia, and thalamus. Mid-gestational fetal sheep provide a valuable model for studying vulnerability of progenitor oligodendrocytes. Hypoxia followed by asphyxia in newborn piglets replicates the systems injury seen in term newborns. Efficacy of post-insult hypothermia in animal models led to the success of clinical trials in term human neonates. Large animal models are now being used to explore adjunct therapy to augment hypothermic neuroprotection.

Neuroprotective effect of apigenin against hypoxic-ischemic brain injury in neonatal rats via activation of the PI3K/Akt/Nrf2 signaling pathway

2021 ◽  
Author(s):  
Changchang Fu ◽  
Yihui Zheng ◽  
Kun Lin ◽  
Hongzeng Wang ◽  
Tingting Chen ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Neuroprotective Effect ◽  
Ischemic Brain Injury ◽  
Neonatal Rats ◽  
Ischemic Brain ◽  
Nrf2 Signaling Pathway ◽  
Hypoxic Ischemic Brain Injury

Neonatal hypoxic-ischemic (HI) brain injury can lead to mortality and severe long-term disabilities including cerebral palsy and brain injury.

scholarly journals Seizure-associated spreading depression is a major feature of ictal events in two animal models of chronic epilepsy

2018 ◽  
Author(s):  
Fatemeh Bahari ◽  
Paddy Ssentongo ◽  
Jiayang Liu ◽  
John Kimbugwe ◽  
Carlos Curay ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Animal Models ◽  
Spreading Depression ◽  
Chronic Epilepsy ◽  
Spreading Depolarization ◽  
Spontaneous Seizures ◽  
Animal Models Of Epilepsy ◽  
Models Of Epilepsy

AbstractSpreading depression is characterized by slow, propagating wave of cellular depolarization (SD) and is wildly associated with migraine, stroke, and traumatic brain injury. Seizures and spreading depression (or spreading depolarization, SD) have long been reported to coincide in acute seizure induction experiments. However, SD has not been observed associated with spotaneous seizures in animal or clinical recordings. Recently, advances in acquisition systems for neurointensive care units have made routine observations of SD possible. In clinical epilepsy, SD has been suggested as a candidate mechanism for migraine/headache like events following seizures as well as for post-ictal generalized suppression. In animal models of epilepsy, seizure-induced brainstem SD has also been demonstrated as a mechanism of sudden unexplained death in epilepsy (SUDEP). The interplay between seizures and SD has also been suggested in computational models, where the two are components of the repetoir of neuronal activity.However, the spatiotemporal dynamics of SD with respect to spontaneous seizures in chronically epileptic brain remains ambigous. We analyzed continuous long-term DC sensitive EEG measurements from two fundamentally different animal models of chronic epilepsy. We found that SD was associated with approximately one-third of all spontaneous seizures in each model. Additionally, SDs participated in the organization of seizure clusters. These findings demonstrate that the underlying dynamic of epileptic events is broader than seizures alone.Significance StatementSpreading depression is characterized by slow, propagating wave of cellular spreading depolarization (SD) and is wildly associated with migraine, stroke, and traumatic brain injury. Although recently the linkage between SD and induced seizures has been recognized, the mechanistic relationship between SD and spontaneous seizures remains poorly understood. Here, we utilized long-term, stable, near-DC measurements of the brain activity in two fundamentally different animal models of epilepsy to investigate the SD-seizure interplay. We found that SD is a frequent phenomenon in the epileptic brain, in these models is associated with more than a third of all seizures, and appears to connect seizures in seizure clusters. Although in one model SD stereotypically propagates out from a single focus in the hippocampus, depression of the field-potentials is observed synchronously across much of the hippocampus. These observations highlight the value of stable DC measurements for accurate understanding of SD and its propagation. We found that spontaneous ictal events that include both seizures and SD are frequent in animal models of epilepsy. These findings suggest that SD could be a valuable target for treatment and control of epilepsy.

scholarly journals CXCL-12 Attenuates Neuroinflammation via the CXCR4/PI3K/Akt Signaling Pathway in a Rat Model of SAH

2020 ◽  
Author(s):  
Gang Zuo ◽  
Ran Gu ◽  
Lu Wang ◽  
Cameron Lenahan ◽  
Hao Qu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Neuroprotective Effect ◽  
Underlying Mechanism ◽  
Akt Signaling ◽  
Immunofluorescence Staining ◽  
Neurological Deficits ◽  
High Morbidity ◽  
Sprague Dawley ◽  
Short And Long Term

Abstract BackgroundSubarachnoid hemorrhage (SAH) is a cerebrovascular disease associated with high morbidity and mortality. CXCR4 provides a neuroprotective effect, which can alleviate brain injury and inflammation induced by stroke. The purpose of this study was to evaluate the anti-inflammatory effects and mechanisms of CXCR4 after SAH. Methods: SAH was induced via endovascular perforation. 185 male Sprague-Dawley rats were used. Recombinant human cysteine-X-cysteine chemokine ligand 12 (rh-CXCL-12) was administered intranasally at 1 h after SAH induction. To investigate the underlying mechanism, the inhibitors of CXCR4 and P13K, AMD3100 and LY294002, respectively, were administered intraperitoneally at 1 h before SAH. The short- and long-term neurobehavior were assessed, followed by performing western blot and immunofluorescence staining. ResultsWestern blotting suggested that the expressions of endogenous CXCL-12 and CXCR4 were increased, and peaked at 24 h following SAH. Immunofluorescence staining showed that CXCR4 was expressed on microglia. Rh-CXCL-12 treatment reduced the number of M1 macrophages and improved the short- and long-term neurological deficits after SAH. Meanwhile, rh-CXCL-12 treatment increased the levels of CXCL-12, CXCR4, PI3K, and p-Akt, and reduced the levels of IL-1β, IL-6, and TNF-α. Moreover, the administration of AMD3100 and LY294002 abolished the post-SAH neurobehavioral and neuroinflammatory improvements of CXCL-12 and its regulation of PI3K and p-Akt protein levels.ConclusionsThe CXCR4/PI3K/Akt signaling pathway may be involved in CXCL-12-mediated reduction of post-SAH neuroinflammation. Early administration of CXCL-12 may be a preventive and therapeutic strategy against delayed brain injury after SAH.

Traumatic Brain Injury: A Trauma Surgeon's Perspective

2012 ◽  
Vol 22 (3) ◽  
pp. 82-89
Author(s):  
Oscar D. Guillamondegui
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Multidisciplinary Approach ◽  
Trauma Team ◽  
The United States ◽  
Long Term Outcomes ◽  
Term Care ◽  
Injured Brain ◽  
The Moment

Traumatic brain injury (TBI) is a serious epidemic in the United States. It affects patients of all ages, race, and socioeconomic status (SES). The current care of these patients typically manifests after sequelae have been identified after discharge from the hospital, long after the inciting event. The purpose of this article is to introduce the concept of identification and management of the TBI patient from the moment of injury through long-term care as a multidisciplinary approach. By promoting an awareness of the issues that develop around the acutely injured brain and linking them to long-term outcomes, the trauma team can initiate care early to alter the effect on the patient, family, and community. Hopefully, by describing the care afforded at a trauma center and by a multidisciplinary team, we can bring a better understanding to the armamentarium of methods utilized to treat the difficult population of TBI patients.

Prosodic Impairment Associated With Traumatic Brain Injury

2009 ◽  
Vol 19 (3) ◽  
pp. 97-102
Author(s):  
Billy Irwin
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Detailed Analysis ◽  
Acoustic Characteristics ◽  
Individual Variations

Abstract Purpose: This article discusses impaired prosody production subsequent to traumatic brain injury (TBI). Prosody may affect naturalness and intelligibility of speech significantly, often for the long term, and TBI may result in a variety of impairments. Method: Intonation, rate, and stress production are discussed in terms of the perceptual, physiological, and acoustic characteristics associated with TBI. Results and Conclusions: All aspects of prosodic production are susceptible to the effects of damage resulting from TBI. There are commonly associated prosodic impairments; however, individual variations in specific aspects of prosody require detailed analysis.

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