Abstract W P94: Recovery From Plasticity Impairments in Pediatric But Not Adult Mice Following Cardiac Arrest and Cardiopulmonary Resuscitation

Objectives: The goal of this study was to assess neuronal injury and synaptic plasticity impairments in Purkinje cells in pediatric and adult mice following cardiac arrest and cardiopulmonary resuscitation. We hypothesized that synaptic impairments in pediatrics would be less severe than in adult mice. Methods: Pediatric ( 21-25 day old) and adult (8-12 week) male mice were subjected to 8 minutes cardiac arrest followed by cardiopulmonary resuscitation or sham surgery. Purkinje cells were labeled using anti-calbindin antibody and cell density was analyzed to examine neuronal injury. To examine synaptic function, whole-cell voltage clamp recording on acute cerebellar slices was performed at 1 and 7 days after CA/CPR or sham surgery. Excitatory postsynaptic currents (EPSCs) resulting from parallel (PF) or climbing fiber (CF) stimulation were recorded. Long-term depression (LTD) was induced by simultaneous parallel and climbing fiber stimulation (1 Hz, 5 min). Results: Purkinje cell loss was observed in pediatric (24% cell loss) and adult (32% cell loss) mice following CA/CPR. Long-term depression, a reduction of synaptic strength of PF EPSCs was observed in adult and pediatric sham controls following PF+CF stimulation (46.6 ± 10% of baseline n= 5 and 55.4 ± 6.1% n= 3, respectively). LTD was absent in pediatric and adult mice at 24 hours after CA/CPR (96.1 ± 5.2% n =6 and 89.4 ± 4.5% n=2, respectively). At 7 and 30 days after CA/CPR LTD was absent in adult mice (81.6 ± 10.8% n=6 and 86.5 ± 8.9% n=4) but had returned in pediatric mice at 7 days after CA/CPR (70 ± 5.4% n=3). Conclusions: The results of this study suggest that CA/CPR results in significant Purkinje cell loss in pediatric and adult mice. LTD was absent at 24 hours at both ages and was observed at 7 days after CA/CPR in pediatric but not adult mice. These results suggest enhanced recovery of synaptic plasticity at this developmental stage.

Download Full-text

Does long-term physical exercise counteract age-related Purkinje cell loss? A stereological study of rat cerebellum

The Journal of Comparative Neurology ◽

10.1002/1096-9861(20001211)428:2<213::aid-cne2>3.0.co;2-q ◽

2000 ◽

Vol 428 (2) ◽

pp. 213-222 ◽

Cited By ~ 50

Author(s):

Jytte Overgaard Larsen ◽

Monika Skalicky ◽

Andrus Viidik

Keyword(s):

Physical Exercise ◽

Purkinje Cell ◽

Cell Loss ◽

Rat Cerebellum ◽

Age Related ◽

Purkinje Cell Loss

Download Full-text

Long-term depression in Purkinje neurons is persistently impaired following cardiac arrest and cardiopulmonary resuscitation in mice

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16683691 ◽

2016 ◽

Vol 37 (8) ◽

pp. 3053-3064 ◽

Cited By ~ 6

Author(s):

Nidia Quillinan ◽

Guiying Deng ◽

Kaori Shimizu ◽

Ivelisse Cruz-Torres ◽

Christian Schroeder ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Motor Coordination ◽

Purkinje Neurons ◽

Long Term Depression ◽

Initial Injury ◽

Cerebellar Purkinje Neurons ◽

Whole Cell Recordings ◽

Time Point

Cardiac arrest and cardiopulmonary resuscitation (CA/CPR) produce brain ischemia that results in cognitive and motor coordination impairments subsequent to injury of vulnerable populations of neurons, including cerebellar Purkinje neurons. To determine the effects of CA/CPR on plasticity in the cerebellum, we used whole cell recordings from Purkinje neurons to examine long-term depression (LTD) at parallel fiber (PF) synapses. Acute slices were prepared from adult male mice subjected to 8 min cardiac arrest at 1, 7, and 30 days after resuscitation. Concurrent stimulation of PF and climbing fibers (CFs) resulted in robust LTD of PF-evoked excitatory postsynaptic currents (EPSCs) in controls. LTD was absent in recordings obtained from mice subjected to CA/CPR, with no change in EPSC amplitude from baseline at any time point tested. AMPA and mGluR-mediated responses at the PF were not altered by CA/CPR. In contrast, CF-evoked NMDA currents were reduced following CA/CPR, which could account for the loss of LTD observed. A loss of GluN1 protein was observed following CA/CPR that was surprisingly not associated with changes in mRNA expression. These data demonstrate sustained impairments in synaptic plasticity in Purkinje neurons that survive the initial injury and which likely contribute to motor coordination impairments observed after CA/CPR.

Download Full-text

Administration of Memantine During Ethanol Withdrawal in Neonatal Rats: Effects on Long-Term Ethanol-Induced Motor Incoordination and Cerebellar Purkinje Cell Loss

Alcoholism Clinical and Experimental Research ◽

10.1111/j.1530-0277.2010.01351.x ◽

2010 ◽

Vol 35 (2) ◽

pp. 355-364 ◽

Cited By ~ 18

Author(s):

Nirelia M. Idrus ◽

Nancy N. H. McGough ◽

Edward P. Riley ◽

Jennifer D. Thomas

Keyword(s):

Purkinje Cell ◽

Cell Loss ◽

Ethanol Withdrawal ◽

Cerebellar Purkinje Cell ◽

Neonatal Rats ◽

Motor Incoordination ◽

Purkinje Cell Loss

Download Full-text

Acute and Long-Term Purkinje Cell Loss Following a Single Ethanol Binge During the Early Third Trimester Equivalent in the Rat

Alcoholism Clinical and Experimental Research ◽

10.1111/j.1530-0277.2012.01743.x ◽

2012 ◽

Vol 36 (8) ◽

pp. 1365-1373 ◽

Cited By ~ 18

Author(s):

Nirelia M. Idrus ◽

Ruth M. A. Napper

Keyword(s):

Purkinje Cell ◽

Cell Loss ◽

Third Trimester ◽

Purkinje Cell Loss

Download Full-text

Faculty Opinions recommendation of Normal motor learning during pharmacological prevention of Purkinje cell long-term depression.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1012343.358556 ◽

2006 ◽

Author(s):

Ted Abel

Keyword(s):

Motor Learning ◽

Purkinje Cell ◽

Long Term Depression ◽

Pharmacological Prevention

Download Full-text

Autistic-Like Behaviors, Oxidative Stress Status, and Histopathological Changes in Cerebellum of Valproic Acid Rat Model of Autism Are Improved by the Combined Extract of Purple Rice and Silkworm Pupae

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/3206561 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 13

Author(s):

Nartnutda Morakotsriwan ◽

Jintanaporn Wattanathorn ◽

Woranan Kirisattayakul ◽

Kowit Chaisiwamongkol

Keyword(s):

Oxidative Stress ◽

Valproic Acid ◽

Purkinje Cell ◽

Rat Model ◽

Cell Loss ◽

Hot Plate ◽

Hot Plate Test ◽

Silkworm Pupae ◽

Oxidative Stress Status ◽

Purkinje Cell Loss

Due to the crucial role of oxidative stress on the pathophysiology of autism and the concept of synergistic effect, the benefit of the combined extract of purple rice and silkworm pupae (AP1) for autism disorder was the focus. Therefore, we aimed to determine the effect of AP1 on autistic-like behaviors, oxidative stress status, and histopathological change of cerebellum in valproic acid (VPA) rat model of autism. VPA was injected on postnatal day (PND) 14 and the animals were orally given AP1 at doses of 50, 100, and 200 mg·kg−1BW between PND 14 and PND 40. The autism-like behaviors were analyzed via hot-plate, rotarod, elevated plus-maze, learning, memory, and social behavior tests. Oxidative stress and the histological change in the cerebellum were assessed at the end of study. AP1 treated rats improved behaviors in all tests except that in hot-plate test. The improvement of oxidative stress and Purkinje cell loss was also observed in the cerebellum of VPA-treated rats. Our data suggest that AP1 partially reduced autism-like behaviors by improving oxidative stress and Purkinje cell loss. Further research is required to identify the active ingredients in AP1 and gender difference effect.

Download Full-text