Reversible Behavioral Deficits in Rats during a Cycle of Demyelination-Remyelination of the Fimbria

Grinkina, Natalia; Abdel-Baki, Samah G.; Bergold, Peter J.

doi:10.1371/journal.pone.0053775

Cited by 23 publications

(23 citation statements)

References 26 publications

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“…The widespread white matter injury in the CHI-2 group of mice is the likely cause of the substantial deficits on the active place avoidance task (Figs 3 – 5 ). We previously showed that rats with localized demyelination of the fimbria do not acquire the active place avoidance task [ 9 ]. The fimbria of the CHI-1 mice had similar silver and LFB staining as the sham-CHI group ( Fig 5 ).…”

Section: Discussionmentioning

confidence: 99%

“…Behavioral deficits, however, did arise using an active place avoidance task after a single closed head impact. The deficits on the active place avoidance task that arose after a single impact likely result from a need for both hippocampi and their commissural connections to acquire the task [ 9 , 10 ]. TBI models frequently damage the hippocampi and their commissural connections.…”

Section: Introductionmentioning

confidence: 99%

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Righting Reflex Predicts Long-Term Histological and Behavioral Outcomes in a Closed Head Model of Traumatic Brain Injury

Grinkina¹,

Yang²,

Haber³

et al. 2016

PLoS ONE

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Blunt impact produces a heterogeneous brain injury in people and in animal models of traumatic brain injury. We report that a single closed head impact to adult C57/BL6 mice produced two injury syndromes (CHI-1 and CHI-2). CHI-1 mice spontaneously reinitiated breathing after injury while CHI-2 mice had prolonged apnea and regained breathing only after cardiopulmonary resuscitation and supplementation of 100% O2. The CHI-1 group significantly regained righting reflex more rapidly than the CHI-2 group. At 7 days post-injury, CHI-1, but not CHI-2 mice, acquired but had no long-term retention of an active place avoidance task. The behavioral deficits of CHI-1 and CHI-2 mice were retained one-month after the injury. CHI-1 mice had loss of hippocampal neurons and localized white matter injury at one month after injury. CHI-2 had a larger loss of hippocampal neurons and more widespread loss of myelin and axons. High-speed videos made during the injury were followed by assessment of breathing and righting reflex. These videos show that CHI-2 mice experienced a larger vertical g-force than CHI-1 mice. Time to regain righting reflex in CHI-2 mice significantly correlated with vertical g-force. Thus, physiological responses occurring immediately after injury can be valuable surrogate markers of subsequent behavioral and histological deficits.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Righting Reflex Predicts Long-Term Histological and Behavioral Outcomes in a Closed Head Model of Traumatic Brain Injury

Grinkina¹,

Yang²,

Haber³

et al. 2016

PLoS ONE

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“…The extent of the demyelination induced by CPZ in the current study and in some previous studies might not be able to induce the spatial learning and working memory impairment. The spatial learning and memory ability might rely less on the communication between two brain regions (coordination by white matter) and more on other brain structures (Grin'kina et al, ). In a future study, we will investigate demyelination changes in more brain regions.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural abnormalities and loss of myelinated fibers in the corpus callosum of demyelinated mice induced by cuprizone

Yun

Cheng

Peng

et al. 2016

J of Neuroscience Research

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It is now accepted that white matter abnormalities play an important role in demyelinating diseases and a wide range of psychiatric disorders. Experimental demyelination (especially induced by cuprizone) has been investigated extensively. However, details regarding demyelination and ultrastructural changes of myelinated fibers have not been previously reported. Therefore, we determined the extent of demyelination using quantitative stereology. Mice exposed to cuprizone in the current study showed abnormal anxiety-like behavior without impaired spatial learning or memory. The myelinated fibers in whole corpus callosum of mice exposed to cuprizone showed extensive myelin deficiencies and occasional axonal injuries. The total length of the myelinated fibers in whole corpus callosum of mice exposed to cuprizone was significantly decreased by 45% compared with control mice. The loss of myelinated fibers was mainly due to the marked loss of the fibers with a diameter of 0.4 to 0.8 μm. The g-ratio of the myelinated fibers in the corpus callosum of mice exposed to cuprizone (0.69 ± 0.02) was significantly decreased compared with control mice (0.76 ± 0.02). These results might help us to further understand the role of white matter abnormalities in demyelinating diseases or a wide range of psychiatric disorders. © 2016 Wiley Periodicals, Inc.

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“…Improved cognitive function due to gangliosides [ 5 , 27 ] and phospholipids [ 28 ] could also be mediated through promoting myelination. However the supplementation of BSC did not alter the myelin density in all the brain regions examined.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Supplementation with Beta Serum Concentrate (BSC), a Complex of Milk Lipids, during Post-Natal Brain Development Improves Memory in Rats

et al. 2015

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We have previously reported that the supplementation of ganglioside-enriched complex-milk-lipids improves cognitive function and that a phospholipid-enriched complex-milk-lipid prevents age-related cognitive decline in rats. This current study evaluated the effects of post-natal supplementation of ganglioside- and phospholipid-enriched complex-milk-lipids beta serum concentrate (BSC) on cognitive function in young rats. The diet of male rats was supplemented with either gels formulated BSC (n = 16) or blank gels (n = 16) from post-natal day 10 to day 70. Memory and anxiety-like behaviors were evaluated using the Morris water maze, dark–light boxes, and elevated plus maze tests. Neuroplasticity and white matter were measured using immunohistochemical staining. The overall performance in seven-day acquisition trials was similar between the groups. Compared with the control group, BSC supplementation reduced the latency to the platform during day one of the acquisition tests. Supplementation improved memory by showing reduced latency and improved path efficiency to the platform quadrant, and smaller initial heading error from the platform zone. Supplemented rats showed an increase in striatal dopamine terminals and hippocampal glutamate receptors. Thus BSC supplementation during post-natal brain development improved learning and memory, independent from anxiety. The moderately enhanced neuroplasticity in dopamine and glutamate may be biological changes underlying the improved cognitive function.

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Reversible Behavioral Deficits in Rats during a Cycle of Demyelination-Remyelination of the Fimbria

Cited by 23 publications

References 26 publications

Righting Reflex Predicts Long-Term Histological and Behavioral Outcomes in a Closed Head Model of Traumatic Brain Injury

Righting Reflex Predicts Long-Term Histological and Behavioral Outcomes in a Closed Head Model of Traumatic Brain Injury

Ultrastructural abnormalities and loss of myelinated fibers in the corpus callosum of demyelinated mice induced by cuprizone

Long-Term Supplementation with Beta Serum Concentrate (BSC), a Complex of Milk Lipids, during Post-Natal Brain Development Improves Memory in Rats

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