scholarly journals New Antioxidant Drugs for Neonatal Brain Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Maria Luisa Tataranno ◽  
Serafina Perrone ◽  
Mariangela Longini ◽  
Giuseppe Buonocore
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Postnatal Period ◽  
Limited Capacity ◽  
Neonatal Brain ◽  
Immature Brain ◽  
Beneficial Effects ◽  
Neurodevelopmental Impairment ◽  
The Brain

The brain injury concept covers a lot of heterogeneity in terms of aetiology involving multiple factors, genetic, hemodynamic, metabolic, nutritional, endocrinological, toxic, and infectious mechanisms, acting in antenatal or postnatal period. Increased vulnerability of the immature brain to oxidative stress is documented because of the limited capacity of antioxidant enzymes and the high free radicals (FRs) generation in rapidly growing tissue. FRs impair transmembrane enzyme Na+/K+-ATPase activity resulting in persistent membrane depolarization and excessive release of FR and excitatory aminoacid glutamate. Besides being neurotoxic, glutamate is also toxic to oligodendroglia, via FR effects. Neuronal cells die of oxidative stress. Excess of free iron and deficient iron/binding metabolising capacity are additional features favouring oxidative stress in newborn. Each step in the oxidative injury cascade has become a potential target for neuroprotective intervention. The administration of antioxidants for suspected or proven brain injury is still not accepted for clinical use due to uncertain beneficial effects when treatments are started after resuscitation of an asphyxiated newborn. The challenge for the future is the early identification of high-risk babies to target a safe and not toxic antioxidant therapy in combination with standard therapies to prevent brain injury and long-term neurodevelopmental impairment.

TGFβ1: Friend or Foe During Recovery in Encephalopathy

2018 ◽  
Vol 25 (3) ◽  
pp. 192-198 ◽  
Author(s):  
Brian H. Kim ◽  
Steven W. Levison
Keyword(s):  
Brain Injury ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Neuronal Survival ◽  
Acute Stage ◽  
Tgfβ Signaling ◽  
Immature Brain ◽  
The Brain ◽  
Survival Mechanisms

The cytokine transforming growth factor (TGF)-β1 is highly induced after encephalopathic brain injury, with data showing that it can both contribute to the pathophysiology and aid in disease resolution. In the immature brain, sustained TGFβ-signaling after injury may prolong inflammation to both exacerbate acute stage damage and perturb the normal course of development. Yet in adult encephalopathy, elevated TGFβ1 may promote a reparative state. In this review, we highlight the context-dependent actions of TGFβ-signaling in the brain during resolution of encephalopathy and focus on neuronal survival mechanisms that are affected by TGFβ1. We discuss the mechanisms that contribute to the disparate actions of TGFβ1 toward elucidating the long-term neurological and neuropsychiatric consequences that follow encephalopathic injury.

scholarly journals Magnesium induces preconditioning of the neonatal brain via profound mitochondrial protection

2017 ◽  
Vol 39 (6) ◽  
pp. 1038-1055 ◽  
Author(s):  
Gabriella Koning ◽  
Anna-Lena Leverin ◽  
Syam Nair ◽  
Leslie Schwendimann ◽  
Joakim Ek ◽  
...  
Keyword(s):  
Brain Injury ◽  
Preterm Labor ◽  
Serum Magnesium ◽  
High Energy ◽  
High Energy Phosphates ◽  
Clinical Implementation ◽  
Neonatal Brain ◽  
Immature Brain ◽  
Old Rats ◽  
The Brain

Magnesium sulphate (MgSO4) given to women in preterm labor reduces cerebral palsy in their offspring but the mechanism behind this protection is unclear, limiting its effective, safe clinical implementation. Previous studies suggest that MgSO4 is not neuroprotective if administered during or after the insult, so we hypothesised that MgSO4 induces preconditioning in the immature brain. Therefore, we administered MgSO4 at various time-points before/after unilateral hypoxia-ischemia (HI) in seven-day-old rats. We found that MgSO4 treatment administered as a bolus between 6 days and 12 h prior to HI markedly reduced the brain injury, with maximal protection achieved by 1.1 mg/g MgSO4 administered 24 h before HI. As serum magnesium levels returned to baseline before the induction of HI, we ascribed this reduction in brain injury to preconditioning. Cerebral blood flow was unaffected, but mRNAs/miRNAs involved in mitochondrial function and metabolism were modulated by MgSO4. Metabolomic analysis (H+-NMR) disclosed that MgSO4 attenuated HI-induced increases in succinate and prevented depletion of high-energy phosphates. MgSO4 pretreatment preserved mitochondrial respiration, reducing ROS production and inflammation after HI. Therefore, we propose that MgSO4 evokes preconditioning via induction of mitochondrial resistance and attenuation of inflammation.

scholarly journals GPR110 ligands reduce chronic optic tract gliosis and visual deficit following repetitive mild traumatic brain injury in mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Huazhen Chen ◽  
Karl Kevala ◽  
Elma Aflaki ◽  
Juan Marugan ◽  
Hee-Yong Kim
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Visual Evoked Potential ◽  
Evoked Potential ◽  
Optic Tract ◽  
Primary Microglia ◽  
Visual Dysfunction ◽  
The Brain

Abstract Background Repetitive mild traumatic brain injury (mTBI) can result in chronic visual dysfunction. G-protein receptor 110 (GPR110, ADGRF1) is the target receptor of N-docosahexaenoylethanolamine (synaptamide) mediating the anti-neuroinflammatory function of synaptamide. In this study, we evaluated the effect of an endogenous and a synthetic ligand of GPR110, synaptamide and (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-hydroxy-2-methylpropyl) docosa-4,7,10,13,16,19-hexaenamide (dimethylsynaptamide, A8), on the mTBI-induced long-term optic tract histopathology and visual dysfunction using Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), a clinically relevant model of mTBI. Methods The brain injury in wild-type (WT) and GPR110 knockout (KO) mice was induced by CHIMERA applied daily for 3 days, and GPR110 ligands were intraperitoneally injected immediately following each impact. The expression of GPR110 and proinflammatory mediator tumor necrosis factor (TNF) in the brain was measured by using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in an acute phase. Chronic inflammatory responses in the optic tract and visual dysfunction were assessed by immunostaining for Iba-1 and GFAP and visual evoked potential (VEP), respectively. The effect of GPR110 ligands in vitro was evaluated by the cyclic adenosine monophosphate (cAMP) production in primary microglia isolated from adult WT or KO mouse brains. Results CHIMERA injury acutely upregulated the GPR110 and TNF gene level in mouse brain. Repetitive CHIMERA (rCHIMERA) increased the GFAP and Iba-1 immunostaining of glia cells and silver staining of degenerating axons in the optic tract with significant reduction of N1 amplitude of visual evoked potential at up to 3.5 months after injury. Both GPR110 ligands dose- and GPR110-dependently increased cAMP in cultured primary microglia with A8, a ligand with improved stability, being more effective than synaptamide. Intraperitoneal injection of A8 at 1 mg/kg or synaptamide at 5 mg/kg significantly reduced the acute expression of TNF mRNA in the brain and ameliorated chronic optic tract microgliosis, astrogliosis, and axonal degeneration as well as visual deficit caused by injury in WT but not in GPR110 KO mice. Conclusion Our data demonstrate that ligand-induced activation of the GPR110/cAMP system upregulated after injury ameliorates the long-term optic tract histopathology and visual impairment caused by rCHIMERA. Based on the anti-inflammatory nature of GPR110 activation, we suggest that GPR110 ligands may have therapeutic potential for chronic visual dysfunction associated with mTBI.

scholarly journals A Hypothesis: Hydrogen Sulfide Might Be Neuroprotective against Subarachnoid Hemorrhage Induced Brain Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yong-Peng Yu ◽  
Xiang-Lin Chi ◽  
Li-Jun Liu
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
The Brain

Gases such as nitric oxide (NO) and carbon monoxide (CO) play important roles both in normal physiology and in disease. Recent studies have shown that hydrogen sulfide (H2S) protects neurons against oxidative stress and ischemia-reperfusion injury and attenuates lipopolysaccharides (LPS) induced neuroinflammation in microglia, exhibiting anti-inflammatory and antiapoptotic activities. The gas H2S is emerging as a novel regulator of important physiologic functions such as arterial diameter, blood flow, and leukocyte adhesion. It has been known that multiple factors, including oxidative stress, free radicals, and neuronal nitric oxide synthesis as well as abnormal inflammatory responses, are involved in the mechanism underlying the brain injury after subarachnoid hemorrhage (SAH). Based on the multiple physiologic functions of H2S, we speculate that it might be a promising, effective, and specific therapy for brain injury after SAH.

Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury

2021 ◽  
Vol 28 ◽  
Author(s):  
Lucas Alexandre Santos Marzano ◽  
Fabyolla Lúcia Macedo de Castro ◽  
Caroline Amaral Machado ◽  
João Luís Vieira Monteiro de Barros ◽  
Thiago Macedo e Cordeiro ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Hippocampal Neurogenesis ◽  
Cognitive Outcomes ◽  
Adult Hippocampal Neurogenesis ◽  
The Brain

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

Sa2015 Traumatic Brain Injury and Intestinal Dysfunction: Investigating a Putative Role of the Brain-Gut Axis in Long-Term Consequences of Injury

2015 ◽  
Vol 148 (4) ◽  
pp. S-384
Author(s):  
Elise L. Ma ◽  
Allen Smith ◽  
Neemesh Desai ◽  
Alan Faden ◽  
Terez Shea-Donohue
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Putative Role ◽  
Long Term Consequences ◽  
The Brain

Visualization of immature brain lesions: MR patterns of long-term outcomes. Case reports

2021 ◽  
Vol 2 (2) ◽  
pp. 94-99
Author(s):  
Anatoly V. Anikin ◽  
Milana A. Basargina ◽  
Eugeniya V. Uvakina
Keyword(s):  
White Matter ◽  
Premature Infants ◽  
Periventricular Leukomalacia ◽  
Brain Magnetic Resonance Imaging ◽  
Brain Lesions ◽  
Gestation Period ◽  
Long Term Outcomes ◽  
Immature Brain ◽  
The Brain

The periventricular and deep white matter of the immature brain of premature infants has an increased vulnerability to various, primarily ischemic injuries. The leading mechanism of selective vulnerability of the white matter of the large hemispheres in children with a low gestation period is the lack of formation of adjacent blood circulation zones between the main arteries of the developing brain. Magnetic resonance imaging has a high sensitivity to detect damage to the brain substance, both in the acute period and in the period of long-term outcomes. Periventricular leukomalacia (PVL) is one of the variants of brain damage in premature infants and the most common term in the conclusions of diagnostic doctors (ultrasound, CT, MRI). Considering the pathomorphological criteria, not always detected changes in the white matter of the large hemispheres are PVL. Diffuse (telencephalic) gliosis and diffuse leukomalacia are ordinary and typical variants of damage to the white matter of the large hemispheres in extremely premature infants, with a gestation period of up to 30-32 weeks. In the first variant, atrophic changes predominate with a pronounced decrease in the volume of white matter and a secondary expansion of the lateral ventricles. Diffuse leukomalacia is most often mistaken for PVL, but the localization of the white matter lesion of the large hemispheres is extensive and extends beyond the peri- and paraventricular region. Clinical examples show various variants of primary non-hemorrhagic brain lesions in prematurely born children in the long-term period. The analysis of the revealed changes is carried out, taking into account current data on developing the brain and pathomorphological criteria.

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