國立虎尾科技大學 |

Intergenerational Perioperative Neurocognitive Disorder in Young Adult Male Rats with Traumatic Brain Injury.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Intergenerational Perioperative Neurocognitive Disorder in Young Adult Male Rats with Traumatic Brain Injury./
Author:	Ju, Lingsha.
Description:	1 online resource (134 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 85-04, Section: B.
Contained By:	Dissertations Abstracts International85-04B.
Subject:	Health sciences. -
Online resource:	click for full text (PQDT)
ISBN:	9798380606370

Intergenerational Perioperative Neurocognitive Disorder in Young Adult Male Rats with Traumatic Brain Injury.
Ju, Lingsha.

Intergenerational Perioperative Neurocognitive Disorder in Young Adult Male Rats with Traumatic Brain Injury. - 1 online resource (134 pages)

Source: Dissertations Abstracts International, Volume: 85-04, Section: B.

Thesis (Ph.D.)--University of Florida, 2023.

Includes bibliographical references

Hundreds of millions of patients of all ages undergo general anesthesia (GA) for surgery or periods of sedation each year, making adverse effects of GA/surgery a public health concern of paramount importance. Accelerated neurocognitive decline after GA/surgery, also known as perioperative neurocognitive disorder (PND), is a widely recognized public health problem. Advanced age, which tracks with an increasing prevalence of elevated stress, inflammation, and neurodegenerative diseases, is the most consistent contributing factor in the development of PND. This preclinical study in rats was designed to test the hypothesis that young adults with pathophysiological conditions characterized by excessive stress and inflammation are also predisposed to PND. Traumatic brain injury (TBI), a dominant cause of disability in young adults, involves lasting dysregulation of stress response systems, neuroinflammation, and cognitive decline. Patients with TBI frequently require GA/surgery or sedation. Based on findings of our background studies of stress-like intergenerational effects of the general anesthetic sevoflurane in rats and data in the literature on heritable effects of stress in humans, we further hypothesized that stress- and inflammation-like effects of TBI, surgery and sevoflurane, interact to induce neurobehavioral abnormalities in future offspring of the exposed young adult rats (intergenerational PND). We found that young adult male rats (F0 generation), subjected to surgery (as part of a procedure to inflict TBI), a midline fluid percussion-induced moderate TBI, and subsequent exposure to sevoflurane, exhibited greater acute and persistent dysregulation of hypothalamic-pituitary-adrenal (HPA) axis, increased inflammation markers, and behavioral deficits. These deficits were also more profound in their future offspring (F1 generation), almost exclusively in F1 males. Matched hypermethylated CpG sites in the glucocorticoid receptor gene, Gr, (Nr3c1) in the spermatozoa of sires and in the hippocampus of male offspring, reduced Gr expression in the F1 male hippocampus, and exacerbated GR-dependent HPA axis responses to stress in F1 males support the involvement of epigenetic mechanisms in the intergenerational transmission of adverse effects of paternal surgery/TBI/sevoflurane. This preclinical study in rats provides first experimental evidence of intergenerational PND, e.g., paternal TBI/surgery/sevoflurane-induced neuroendocrine and neurobehavioral abnormalities in the exposed sires and their future unexposed male, but not female, offspring.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798380606370Subjects--Topical Terms:

1179212
Health sciences.
Subjects--Index Terms:

IntergenerationIndex Terms--Genre/Form:

554714
Electronic books.

Intergenerational Perioperative Neurocognitive Disorder in Young Adult Male Rats with Traumatic Brain Injury.
LDR:04040ntm a2200409K 4500 001 1141598
005 20240318062649.5
006 m o d
007 cr mn ---uuuuu
008 250605s2023 xx obm 000 0 eng d
020 $a 9798380606370
035 $a (MiAaPQ)AAI30568202
035 $a AAI30568202
040 $a MiAaPQ $b eng $c MiAaPQ $d NTU
100 1 $a Ju, Lingsha. $3 1465486
245 1 0 $a Intergenerational Perioperative Neurocognitive Disorder in Young Adult Male Rats with Traumatic Brain Injury.
264 0 $c 2023
300 $a 1 online resource (134 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertations Abstracts International, Volume: 85-04, Section: B.
500 $a Advisor: Martynyuk, Anatoly E.;Cooke, Paul S.
502 $a Thesis (Ph.D.)--University of Florida, 2023.
504 $a Includes bibliographical references
520 $a Hundreds of millions of patients of all ages undergo general anesthesia (GA) for surgery or periods of sedation each year, making adverse effects of GA/surgery a public health concern of paramount importance. Accelerated neurocognitive decline after GA/surgery, also known as perioperative neurocognitive disorder (PND), is a widely recognized public health problem. Advanced age, which tracks with an increasing prevalence of elevated stress, inflammation, and neurodegenerative diseases, is the most consistent contributing factor in the development of PND. This preclinical study in rats was designed to test the hypothesis that young adults with pathophysiological conditions characterized by excessive stress and inflammation are also predisposed to PND. Traumatic brain injury (TBI), a dominant cause of disability in young adults, involves lasting dysregulation of stress response systems, neuroinflammation, and cognitive decline. Patients with TBI frequently require GA/surgery or sedation. Based on findings of our background studies of stress-like intergenerational effects of the general anesthetic sevoflurane in rats and data in the literature on heritable effects of stress in humans, we further hypothesized that stress- and inflammation-like effects of TBI, surgery and sevoflurane, interact to induce neurobehavioral abnormalities in future offspring of the exposed young adult rats (intergenerational PND). We found that young adult male rats (F0 generation), subjected to surgery (as part of a procedure to inflict TBI), a midline fluid percussion-induced moderate TBI, and subsequent exposure to sevoflurane, exhibited greater acute and persistent dysregulation of hypothalamic-pituitary-adrenal (HPA) axis, increased inflammation markers, and behavioral deficits. These deficits were also more profound in their future offspring (F1 generation), almost exclusively in F1 males. Matched hypermethylated CpG sites in the glucocorticoid receptor gene, Gr, (Nr3c1) in the spermatozoa of sires and in the hippocampus of male offspring, reduced Gr expression in the F1 male hippocampus, and exacerbated GR-dependent HPA axis responses to stress in F1 males support the involvement of epigenetic mechanisms in the intergenerational transmission of adverse effects of paternal surgery/TBI/sevoflurane. This preclinical study in rats provides first experimental evidence of intergenerational PND, e.g., paternal TBI/surgery/sevoflurane-induced neuroendocrine and neurobehavioral abnormalities in the exposed sires and their future unexposed male, but not female, offspring.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2024
538 $a Mode of access: World Wide Web
650 4 $a Health sciences. $3 1179212
650 4 $a Neurosciences. $3 593561
650 4 $a Surgery. $3 644132
653 $a Intergeneration
653 $a Sevoflurane
653 $a Neurocognitive disorder
653 $a Elevated stress
653 $a Traumatic brain injury
655 7 $a Electronic books. $2 local $3 554714
690 $a 0566
690 $a 0576
690 $a 0317
690 $a 0778
710 2 $a ProQuest Information and Learning Co. $3 1178819
710 2 $a University of Florida. $b Medicine. $3 1465487
773 0 $t Dissertations Abstracts International $g 85-04B.
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30568202 $z click for full text (PQDT)