scholarly journals Premyelinated Central Axons Express Neurotoxic NMDA Receptors: Relevance to Early Developing White-Matter Injury

2014 ◽  
Vol 35 (4) ◽  
pp. 543-553 ◽  
Author(s):  
Tahani Huria ◽  
Narasimha Murthy Beeraka ◽  
Badrah Al-Ghamdi ◽  
Robert Fern
Keyword(s):  
White Matter ◽  
Cognitive Deficits ◽  
Ischemic Injury ◽  
Cellular Component ◽  
White Matter Injury ◽  
Loss Of Function ◽  
Cellular Mechanisms ◽  
Axon Injury ◽  
Subunit Expression ◽  
Gold Labelling

Ischemic-type injury to developing white matter is associated with the significant clinical condition cerebral palsy and with the cognitive deficits associated with premature birth. Premyelinated axons are the major cellular component of fetal white matter and loss of axon function underlies the disability, but the cellular mechanisms producing ischemic injury to premyelinated axons have not previously been described. Injury was found to require longer periods of modelled ischemia than at latter developmental points. Ischemia produced initial hyperexcitability in axons followed by loss of function after Na+ and Ca2+ influx. N-methyl-D-aspartate- (NMDA) type glutamate receptor (GluR) agonists potentiated axon injury while antagonists were protective. The NMDA GluR obligatory Nr1 subunit colocalized with markers of small premyelinated axons and expression was found at focal regions of axon injury. Ischemic injury of glial cells present in early developing white matter was NMDA GluR independent. Axons in human postconception week 18 to 23 white matter had a uniform prediameter expansion phenotype and postembedded immuno-gold labelling showed Nr1 subunit expression on the membrane of these axons, demonstrating a shared key neuropathologic feature with the rodent model. Premyelinated central axons therefore express high levels of functional NMDA GluRs that confer sensitivity to ischemic injury.

scholarly journals Cellular Mechanisms of Toll-Like Receptor-3 Activation in the Thalamus Are Associated With White Matter Injury in the Developing Brain

2015 ◽  
Vol 74 (3) ◽  
pp. 273-285 ◽  
Author(s):  
Regina Vontell ◽  
Veena Supramaniam ◽  
Josephine Wyatt-Ashmead ◽  
Pierre Gressens ◽  
Mary Rutherford ◽  
...  
Keyword(s):  
White Matter ◽  
Developing Brain ◽  
White Matter Injury ◽  
Toll Like Receptor ◽  
Cellular Mechanisms

The optimal choices of animal models of white matter injury

2019 ◽  
Vol 30 (3) ◽  
pp. 245-259 ◽  
Author(s):  
Yan Zeng ◽  
Huiqing Wang ◽  
Li Zhang ◽  
Jun Tang ◽  
Jing Shi ◽  
...  
Keyword(s):  
White Matter ◽  
Animal Models ◽  
Preterm Infants ◽  
Newborn Infants ◽  
White Matter Injury ◽  
Neurological Injury ◽  
Large Animal ◽  
Cellular Mechanisms ◽  
Human Infants ◽  
Large Animal Models

AbstractWhite matter injury, the most common neurological injury in preterm infants, is a major cause of chronic neurological morbidity, including cerebral palsy. Although there has been great progress in the study of the mechanism of white matter injury in newborn infants, its pathogenesis is not entirely clear, and further treatment approaches are required. Animal models are the basis of study in pathogenesis, treatment, and prognosis of white matter injury in preterm infants. Various species have been used to establish white matter injury models, including rodents, rabbits, sheep, and non-human primates. Small animal models allow cost-effective investigation of molecular and cellular mechanisms, while large animal models are particularly attractive for pathophysiological and clinical-translational studies. This review focuses on the features of commonly used white matter injury animal models, including their modelling methods, advantages, and limitations, and addresses some clinically relevant animal models that allow reproduction of the insults associated with clinical conditions that contribute to white matter injury in human infants.

Abstract TP564: Diabetic but Not Control Rats Develop White Matter Injury and Cognitive Deficits in a Microemboli Injection Model of VCID

Stroke ◽  
2019 ◽  
Vol 50 (Suppl_1) ◽  
Author(s):  
Weiguo Li ◽  
Heba Ahmed ◽  
Ping-Chang Lin ◽  
Guangkuo Dong ◽  
Roxan Ara ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Deficits ◽  
White Matter Injury ◽  
Injection Model

scholarly journals Preconditioning with partial caloric restriction confers long-term protection against grey and white matter injury after transient focal ischemia

2018 ◽  
Vol 39 (7) ◽  
pp. 1394-1409 ◽  
Author(s):  
Jia Zhang ◽  
Wenting Zhang ◽  
Xuguang Gao ◽  
Yongfang Zhao ◽  
Di Chen ◽  
...  
Keyword(s):  
White Matter ◽  
Caloric Restriction ◽  
Food Access ◽  
Ischemic Injury ◽  
Focal Ischemia ◽  
White Matter Injury ◽  
Morris Water Maze Test ◽  
Protective Effects ◽  
Ad Libitum ◽  
Transient Focal Ischemia

Caloric restriction (CR) has been extensively examined as a preventative strategy against aging and various diseases, but CR effects on cerebral ischemia are largely unknown. We subjected C57BL6/J mice to ad libitum food access (LF) or a diet restricted to 70% of ad libitum food access (RF) for two to four weeks followed by 60 min of transient focal ischemia (tFCI). RF for four weeks protected against subsequent tFCI-induced infarct. RF improved sensorimotor function after stroke in the foot fault and corner tests, as well as performance in the Morris water maze test. In addition, RF preserved ischemic white matter tract integrity assessed by histology and compound action potential. Sirt1 and Sirt3 were both upregulated in RF ischemic brain, but heterozygous deletion of Sirt1 or knockout of Sirt3 did not alter the protection induced by RF against ischemic injury. RF induced significant release of adiponectin, a hormone related to glucose metabolism. Knockout of adiponectin decreased RF-induced protection after tFCI. These data demonstrate the novel finding that white matter, as well as neurons, benefit from CR prior to cerebral ischemic injury, and that adiponectin may contribute to these protective effects.

scholarly journals Ionic Mechanisms of Aglycemic Axon Injury in Mammalian Central White Matter

2001 ◽  
Vol 21 (4) ◽  
pp. 385-395 ◽  
Author(s):  
Angus M. Brown ◽  
Regina Wender ◽  
Bruce R. Ransom
Keyword(s):  
White Matter ◽  
Time Course ◽  
White Matter Injury ◽  
Similar Time ◽  
Axon Injury ◽  
Adult Rat ◽  
Compound Action Potentials ◽  
Intracellular Compartments ◽  
Ionic Mechanisms ◽  
Qualitative Measure

The authors investigated ionic mechanisms underlying aglycemic axon injury in adult rat optic nerve, a central white matter tract. Axon function was assessed using evoked compound action potentials (CAPs). Glucose withdrawal led to delayed CAP failure, an alkaline extracellular pH shift, and an increase in extracellular [K+]. Sixty minutes of glucose withdrawal led to irreversible axon injury. Aglycemic axon injury required extracellular calcium; the extent of injury progressively declined as bath [Ca2+] was decreased. To evaluate Ca2+ movements during aglycemia, the authors recorded extracellular [Ca2+] ([Ca2+]o) using Ca2+-sensitive microelectrodes. Under control conditions, [Ca2+]o fell with a similar time course to CAP failure, indicating extracellular Ca2+ moved to an intracellular position during aglycemia. The authors quantified the magnitude of [Ca2+]o decrease as the area below baseline [Ca2+]o during aglycemia and used this as a qualitative measure of Ca2+ influx. The authors studied the mechanisms of Ca2+ influx. Blockade of Na+ influx reduced Ca2+ influx and improved CAP recovery, suggesting Na+-Ca2+ exchanger involvement. Consistent with this hypothesis, bepridil reduced axon injury. In addition, diltiazem or nifedipine decreased Ca2+ influx and increased CAP recovery. The authors conclude aglycemic central white matter injury is caused by Ca2+ influx into intracellular compartments through reverse Na+-Ca2+ exchange and L-type Ca2+ channels.

scholarly journals Neuroanatomical, Sensorimotor and Cognitive Deficits in Adult Rats with White Matter Injury Following Prenatal Ischemia

2011 ◽  
Vol 22 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Maxime Delcour ◽  
Paul Olivier ◽  
Caroline Chambon ◽  
Julien Pansiot ◽  
Michaël Russier ◽  
...  
Keyword(s):  
White Matter ◽  
Cognitive Deficits ◽  
White Matter Injury ◽  
Adult Rats
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