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

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Brain Protection in Schizophrenia, Mood and Cognitive Disorders

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.

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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

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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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  1. Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine University Hospital, Uppsala University, Uppsala, Sweden

    Hari Shanker Sharma

  2. Anesthesiology & Intensive Care Medicine, Dept. of Surgical Sciences, University Hospital, Uppsala University, SE-75185, Uppsala, Sweden

    Aruna Sharma BAMS (Kan) (Secretary)

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Correspondence to Hari Shanker Sharma .

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  1. Sha'ar Menashe Mental Health Center, Hadera, 38814, Israel

    Michael S. Ritsner

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Sharma, H.S., Sharma, A. (2010). Breakdown of the Blood-Brain Barrier in Stress Alters Cognitive Dysfunction and Induces Brain Pathology: New Perspectives for Neuroprotective Strategies. In: Ritsner, M. (eds) Brain Protection in Schizophrenia, Mood and Cognitive Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8553-5_9

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