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Breakdown of the Blood-Brain Barrier in Stress Alters Cognitive Dysfunction and Induces Brain Pathology: New Perspectives for Neuroprotective Strategies

Chapter

Abstract

Emotional, psychological or environmental stress (e.g., heat or nanoparticles) influences brain function. However, the detailed mechanisms of stress induced brain dysfunction are not well known. Research carried out in our laboratory since last 20 years show that various kinds of stressors depending on their magnitude and durations alter the blood-brain barrier (BBB) permeability to proteins leading to brain pathology. These stressed animals also show marked behavioral and cognitive deficits at the time of the BBB leakage. Entry of several restricted elements from the blood to the brain compartment after breakdown of the BBB results in immunological, biochemical and pathological reaction causing brain edema formation and cell injury. Blockade of several neurochemical receptors, e.g., serotonin, prostaglandin or opioids as well as neutralization of key neurodestructive elements, i.e., neuronal nitric oxide synthase (nNOS), Tumor necrosis factor-alpha (TNF-α), dynorphin A or hemeoxygenase-2 (HO-2) using specific drugs or antibodies against these factors reduces BBB disturbances, cognitive and behavioral dysfunction, and brain pathology. Based on these new evidences, it appears that the BBB is the gateway to neuropsychiatric diseases. Thus, efforts should be made to maintain a healthy BBB in various brain diseases to achieve neuroprotection. The possible mechanisns of BBB breakdown and brain pathology in stress in relation to altered cognitive and sensory-motor functions is discussed in this review.

Keywords

Blood-brain barrier Stress Brain pathology Serotonin Prostaglandin Cytokines Cognitive dysfunction Sensory motor abnormalities Brain edema Neuropsychiatry diseases 

Abbreviations

BBB

Blood-brain barrier

bbb

brain-blood-barrier

nNOS

neuronal nitric oxide synthase

TNF-α

Tumor necrosis factor alpha

HO-2

Hemeoxygenase-2

IPS

Information processing system

GAS

General adaptation syndrome

CRF

Corticotrophin releasing factor

ACTH

Adrenocorticotrophic hormone

HPA

Hypothalamus pituitary adrenal axis

TRH

Thyrotrophin releasing hormone

PVN

Para ventricular nucleaus

DHEAS

dehydroepiandrosterone sulfate

WN-25

West Nile virus

SFV-A7

Semliki Forest virus

EBA

Evans blue albumin

PS

Paradoxical sleep

SWS

Slow wave sleep

ROS

Reactive oxygen species

WBH

whole body hyperthermia

BSCB

Blood-spinal cord barrier

Dyn

Dynorphin A

5-HT

5-hydroxytryptamine

CNS

Central nervous system

p-CPA

para-Cholorophenylalanine

H1

Histamine H1 receptor

H2

Histamine H2 receptor

5,7-DHT

5,7-dihydroxytryptamine

6-OHDA

6-hydroxydopamine

Notes

Acknowledgments

Author’s research described here is supported by Grants from Swedish Medical Research Council (2710), Stockholm Sweden, Göran Gustafsson Foundation, Stockholm, Sweden; Alexander von Humboldt Foundation, Bonn, Germany, European Office of Aerospace Research and Development (EOARD), London Office, UK. Technical assistant of Mari-Anne Carlsson, Kerstin Flink, Ingmarie Olsson and Kerstin Rystedt are highly appreciated.

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Laboratory of Cerebrovascular Research, Department of Surgical SciencesAnesthesiology & Intensive Care Medicine University Hospital, Uppsala UniversityUppsalaSweden
  2. 2.Anesthesiology & Intensive Care Medicine, Dept. of Surgical SciencesUniversity Hospital, Uppsala UniversityUppsalaSweden

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