Cerebral Palsy

Cerebral palsy (CP) describes a group of disorders of movement/posture causing activity limitation that are attributed to nonprogressive disturbances in the immature brain that can change over time. The immature human brain undergoes organizational changes during intrauterine and postnatal life creating potential temporal periods of selective vulnerability to damage. Understanding the compensatory plasticity process after the brain injury may provide new insights into the pathogenesis of CP.

TGFβ1: Friend or Foe During Recovery in Encephalopathy

The Neuroscientist ◽

10.1177/1073858418793131 ◽

2018 ◽

Vol 25 (3) ◽

pp. 192-198 ◽

Cited By ~ 2

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.

Genome aging: somatic mutation in the brain links age-related decline with disease and nominates pathogenic mechanisms

Human Molecular Genetics ◽

10.1093/hmg/ddz191 ◽

2019 ◽

Vol 28 (R2) ◽

pp. R197-R206 ◽

Cited By ~ 10

Author(s):

Michael A Lodato ◽

Christopher A Walsh

Keyword(s):

Human Brain ◽

Somatic Mutation ◽

Somatic Mutations ◽

Late Onset ◽

Whole Genome ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Age Related ◽

The Brain ◽

AbstractAging is a mysterious process, not only controlled genetically but also subject to random damage that can accumulate over time. While DNA damage and subsequent mutation in somatic cells were first proposed as drivers of aging more than 60 years ago, whether and to what degree these processes shape the neuronal genome in the human brain could not be tested until recent technological breakthroughs related to single-cell whole-genome sequencing. Indeed, somatic single-nucleotide variants (SNVs) increase with age in the human brain, in a somewhat stochastic process that may nonetheless be controlled by underlying genetic programs. Evidence from the literature suggests that in addition to demonstrated increases in somatic SNVs during aging in normal brains, somatic mutation may also play a role in late-onset, sporadic neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. In this review, we will discuss somatic mutation in the human brain, mechanisms by which somatic mutations occur and can be controlled, and how this process can impact human health.

Residual Pituitary Function after Brain Injury-Induced Hypopituitarism: A Prospective 12-Month Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-0504 ◽

2005 ◽

Vol 90 (11) ◽

pp. 6085-6092 ◽

Cited By ~ 224

Author(s):

Gianluca Aimaretti ◽

Maria Rosaria Ambrosio ◽

Carolina Di Somma ◽

Maurizio Gasperi ◽

Salvatore Cannavò ◽

...

Keyword(s):

Brain Injury ◽

High Risk ◽

Gh Deficiency ◽

Pituitary Function ◽

Brain Injured ◽

Injured Patients ◽

The Brain ◽

Abstract Context: Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are conditions at high risk for the development of hypopituitarism. Objective: The objective of the study was to clarify whether pituitary deficiencies and normal pituitary function recorded at 3 months would improve or worsen at 12 months after the brain injury. Design and Patients: Pituitary function was tested at 3 and 12 months in patients who had TBI (n = 70) or SAH (n = 32). Results: In TBI, the 3-month evaluation had shown hypopituitarism (H) in 32.8%. Panhypopituitarism (PH), multiple (MH), and isolated (IH) hypopituitarism had been demonstrated in 5.7, 5.7, and 21.4%, respectively. The retesting demonstrated some degree of H in 22.7%. PH, MH, and IH were present in 5.7, 4.2, and 12.8%, respectively. PH was always confirmed at 12 months, whereas MH and IH were confirmed in 25% only. In 5.5% of TBI with no deficit at 3 months, IH was recorded at retesting. In 13.3% of TBI with IH at 3 months, MH was demonstrated at 12-month retesting. In SAH, the 3-month evaluation had shown H in 46.8%. MH and IH had been demonstrated in 6.2 and 40.6%, respectively. The retesting demonstrated H in 37.5%. MH and IH were present in 6.2 and 31.3%, respectively. Although no MH was confirmed at 12 months, two patients with IH at 3 months showed MH at retesting; 30.7% of SAH with IH at 3 months displayed normal pituitary function at retesting. In SAH, normal pituitary function was always confirmed. In TBI and SAH, the most common deficit was always severe GH deficiency. Conclusion: There is high risk for H in TBI and SAH patients. Early diagnosis of PH is always confirmed in the long term. Pituitary function in brain-injured patients may improve over time but, although rarely, may also worsen. Thus, brain-injured patients must undergo neuroendocrine follow-up over time.

Longitudinal transcriptomics define the stages of myeloid activation in the living human brain after intracerebral hemorrhage

Science Immunology ◽

10.1126/sciimmunol.abd6279 ◽

2021 ◽

Vol 6 (56) ◽

pp. eabd6279

Author(s):

Michael H. Askenase ◽

Brittany A. Goods ◽

Hannah E. Beatty ◽

Arthur F. Steinschneider ◽

Sofia E. Velazquez ◽

...

Keyword(s):

Gene Expression ◽

Brain Injury ◽

Immune Responses ◽

Intracerebral Hemorrhage ◽

Human Brain ◽

Inflammatory Factors ◽

Lipid Mediator ◽

Prostaglandin E ◽

Anti Inflammatory ◽

Opportunities to interrogate the immune responses in the injured tissue of living patients suffering from acute sterile injuries such as stroke and heart attack are limited. We leveraged a clinical trial of minimally invasive neurosurgery for patients with intracerebral hemorrhage (ICH), a severely disabling subtype of stroke, to investigate the dynamics of inflammation at the site of brain injury over time. Longitudinal transcriptional profiling of CD14+ monocytes/macrophages and neutrophils from hematomas of patients with ICH revealed that the myeloid response to ICH within the hematoma is distinct from that in the blood and occurs in stages conserved across the patient cohort. Initially, hematoma myeloid cells expressed a robust anabolic proinflammatory profile characterized by activation of hypoxia-inducible factors (HIFs) and expression of genes encoding immune factors and glycolysis. Subsequently, inflammatory gene expression decreased over time, whereas anti-inflammatory circuits were maintained and phagocytic and antioxidative pathways up-regulated. During this transition to immune resolution, glycolysis gene expression and levels of the potent proresolution lipid mediator prostaglandin E2 remained elevated in the hematoma, and unexpectedly, these elevations correlated with positive patient outcomes. Ex vivo activation of human macrophages by ICH-associated stimuli highlighted an important role for HIFs in production of both inflammatory and anti-inflammatory factors, including PGE2, which, in turn, augmented VEGF production. Our findings define the time course of myeloid activation in the human brain after ICH, revealing a conserved progression of immune responses from proinflammatory to proresolution states in humans after brain injury and identifying transcriptional programs associated with neurological recovery.

Effects of Melatonin on Neurobehavior and Cognition in a Cerebral Palsy Model of plppr5−/− Mice

Frontiers in Endocrinology ◽

10.3389/fendo.2021.598788 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yuxiao Sun ◽

Liya Ma ◽

Meifang Jin ◽

Yuqin Zheng ◽

Dandan Wang ◽

...

Keyword(s):

Spinal Cord ◽

Cerebral Palsy ◽

Object Recognition ◽

Brain Injury ◽

Learning And Memory ◽

Brain Damage ◽

Novel Object Recognition ◽

Wild Type ◽

Novel Object ◽

Cerebral palsy (CP), a group of clinical syndromes caused by non-progressive brain damage in the developing fetus or infant, is one of the most common causes of lifelong physical disability in children in most countries. At present, many researchers believe that perinatal cerebral hypoxic ischemic injury or inflammatory injury are the main causes of cerebral palsy. Previous studies including our works confirmed that melatonin has a protective effect against convulsive brain damage during development and that it affects the expression of various molecules involved in processes such as metabolism, plasticity and signaling in the brain. Integral membrane protein plppr5 is a new member of the plasticity-related protein family, which is specifically expressed in brain and spinal cord, and induces filopodia formation as well as neurite growth. It is highly expressed in the brain, especially in areas of high plasticity, such as the hippocampus. The signals are slightly lower in the cortex, the cerebellum, and in striatum. Noteworthy, during development plppr5 mRNA is expressed in the spinal cord, i.e., in neuron rich regions such as in medial motor nuclei, suggesting that plppr5 plays an important role in the regulation of neurons. However, the existing literature only states that plppr5 is involved in the occurrence and stability of dendritic spines, and research on its possible involvement in neonatal ischemic hypoxic encephalopathy has not been previously reported. We used plppr5 knockout (plppr5−/−) mice and their wild-type littermates to establish a model of hypoxicischemic brain injury (HI) to further explore the effects of melatonin on brain injury and the role of plppr5 in this treatment in an HI model, which mainly focuses on cognition, exercise, learning, and memory. All the tests were performed at 3–4 weeks after HI. As for melatonin treatment, which was performed 5 min after HI injury and followed by every 24h. In these experiments, we found that there was a significant interaction between genotype and treatment in novel object recognition tests, surface righting reflex tests and forelimb suspension reflex tests, which represent learning and memory, motor function and coordination, and the forelimb grip of the mice, respectively. However, a significant main effect of genotype and treatment on performance in all behavioral tests were observed. Specifically, wild-type mice with HI injury performed better than plppr5−/− mice, regardless of treatment with melatonin or vehicle. Moreover, treatment with melatonin could improve behavior in the tests for wild-type mice with HI injury, but not for plppr5−/− mice. This study showed that plppr5 knockout aggravated HI damage and partially weakened the neuroprotection of melatonin in some aspects (such as novel object recognition test and partial nerve reflexes), which deserves further study.

Magnesium induces preconditioning of the neonatal brain via profound mitochondrial protection

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x17746132 ◽

2017 ◽

Vol 39 (6) ◽

pp. 1038-1055 ◽

Cited By ~ 15

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 ◽

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.

Obstetric antecedents of cerebral palsy

Fetal and Maternal Medicine Review ◽

10.1017/s0965539596000022 ◽

1996 ◽

Vol 8 (4) ◽

pp. 199-215 ◽

Cited By ~ 2

Author(s):

Eve Blair

Keyword(s):

Early Childhood ◽

Cerebral Palsy ◽

Movement Disorder ◽

Perinatal Morbidity ◽

Motor Impairments ◽

Immature Brain ◽

Motor Delay ◽

Clinical Description ◽

Definition Of ◽

Cerebral palsy has been defined as a group of non-progressive disorders of movement or posture due to a defect or lesion of the immature brain.1 Cerebral palsy is defined by clinical description only; there is no definitive test. It is not informative about aetiolgy, pathology or prognosis. The definition of cerebral palsy also lacks precision in that neither the age at which the brain is mature nor the severity of the disorder required are specified. Brain development is most rapid in utero and early childhood but continues at a diminished rate throughout life. There is therefore no biological rationale for choosing any particular age to define brain maturity. The defining age below whcih cerebral palsy may be recognised therefore varies between centres for pragmatic reasons usually associated with assertainment. For example, in Western Australia the criterion is set at 5 years,2 since by this age any central motor impairments of congenital or neonatal origin will be apparent and can usually be differentiated from progressive disorders or isolated motor delay. Thus the definition includes a group of children with post-neonatally acquired brain damage resulting in movement disorder. Post-neonatally acquired cerebral palsy differs from presumed congenital or perinatal cerebral palsy in that there is usually no doubt that it was caused by a specific post-neonatal event such as meningitis or head trauma. Although there is an excess of perinatal morbidity amoung children acquiring cerebral palsy post-neonatally,3 suggesting a prior vulnerability in some cases, post neonatally acquired cerebral palsy will not be considred further in this review.

Features of the Clinical Course and Prognosis of Severe Traumatic Brain Injury Outcomes

Russian Sklifosovsky Journal Emergency Medical Care ◽

10.23934/2223-9022-2019-8-4-423-429 ◽

2020 ◽

Vol 8 (4) ◽

pp. 423-429

Author(s):

Y. B. Vasilyeva ◽

A. E. Talypov ◽

M. V. Sinkin ◽

S. S. Petrikov

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Brain Damage ◽

Clinical Course ◽

Neurological Status ◽

Diagnostic Methods ◽

The World ◽

Different Types ◽

The Brain ◽

BACKGROUND. Traumatic brain injury (TBI) is one of the most important contemporary health issues. According to the World Health Organization, TBI is one of three leading causes of death in the world. Despite the development and widespread use of neuroimaging tools and instrumental research methods, clinical diagnosis of TBI is preferred. It is especially relevant at the prehospital stage when it is impossible to use instrumental diagnostic methods.THE AIM OF THE STUDY. To determine the clinical course features and prognosis of treatment outcomes in patients with various types of traumatic brain damage.MATERIAL AND METHODS. We studied the results of examination and treatment of 100 victims with a severe head injury hospitalized during the first days after receiving an injury and undergoing treatment at the N.V. Sklifosovsky Research Institute in 2008–2017. Depending on the type of brain injury patients were divided into 3 groups: Group 1 — isolated hematoma (n=20), Group 2 — hematomas and injuries of the brain (n=40), Group 3 — injuries of the brain (n=40). All patients underwent neurological examination, CT scan of the brain upon admission and over time within 12 days after trauma. In 30 victims, intracranial pressure (ICP) was monitored.RESULTS. We revealed features of the dynamics of individual neurological symptoms in patients with different types of brain damage. In patients with isolated hematomas, neurological status was represented mainly with clinic dislocation syndrome and contralateral hematoma hemiparesis, and clinical pattern significantly depended on intracranial hemorrhage. In patients with combination of hematomas and contusions, the neurological status and its dynamics were less dependent on the volume of the hematoma and were mainly determined by contusions of the midline structures of the brain. In patients with brain injuries, neurological status reliably correlated with injuries of midline structures.CONCLUSION. We revealed significant differences in neurological status, its changes over time and correlation with CT findings in patients with different types of traumatic brain injury.Authors declare lack of the conflicts of interests.

Ultra-high-order ICA: fine overlapping functional parcellations and spatiotemporal reconfiguration

10.1101/2020.03.11.986299 ◽

2020 ◽

Author(s):

Armin Iraji ◽

Zening Fu ◽

Thomas DeRamus ◽

Shile Qi ◽

Srinivas Rachakonda ◽

...

Keyword(s):

Human Brain ◽

Brain Mapping ◽

Spatial Variations ◽

High Order ◽

Human Brain Mapping ◽

Functional Analyses ◽

The Brain ◽

AbstractOur recent findings show that functional organizations evolve spatially over time, highlighting the importance of considering within-subject spatial variations and dynamic functional parcellations in brain functional analyses. Meanwhile, a considerable level of multi-functionality suggests the need for overlapping brain parcellations. In this work, we used ultra-high-order ICA to identify fine overlapping functional dynamic parcellations of the brain. The preliminary result of this work was presented at the organization for human brain mapping workshop (OHBM 2019)1.

New Antioxidant Drugs for Neonatal Brain Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/108251 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 19

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 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.