학술논문

Chronic hypertension aggravates heat stress induced cognitive dysfunction and brain pathology: an experimental study in the rat, using growth hormone therapy for possible neuroprotection
Document Type
Source
Neuroprotective agents Annals of the New York academy of sciences. :1-22
Subject
Animals
Behavior
Animal
Blood Pressure/drug effects
Blood-Brain Barrier/drug effects/pathology
Body Temperature/drug effects/physiology
Brain/pathology/*physiopathology
Brain Edema/etiology/prevention & control
Cerebrovascular Circulation/drug effects
Chronic Disease
Cognition Disorders/etiology/*pathology/*prevention & control
Disease Models
Growth Hormone/*therapeutic use
Heat/adverse effects
Hypertension
Renovascular/complications/etiology
Male
Neuroprotective Agents/*therapeutic use
Rats
Wistar
Rotarod Performance Test/methods
Stress/complications/etiology
MEDICINE
MEDICIN
Language
English
ISSN
0077-8923
Abstract
Hyperthermia following heat stress results in profound brain edema formation and damage to the central nervous system (CNS). However, whether acute or chronic diseases such as cardiovascular, endocrine, or metabolic ailments further influence the vulnerability of human populations to heat-related deaths is still unclear. In this investigation, we examined the effect of hyperthermia on chronic hypertensive rats. The influence of growth hormone (GH) as a therapy to attenuate brain dysfunction was also evaluated. Subjecting rats to 4 h of heat stress at 38°C in a biological oxygen demand (BOD) incubator resulted in profound impairment of motor and cognitive functions, breakdown of the blood-brain barrier (BBB), reduction in regional cerebral blood flow (CBF), edema formation, and brain damage. These effects were further aggravated when chronic hypertensive rats (two-kidney, one-clip model for 4 weeks) were subjected to similar hyperthermic conditions (38°C for 4 h). Interestingly, the behavioral alterations and impairment of motor and cognitive functions in hypertensive rats were much worse than those in the normotensive animals subjected to heat stress. Pretreatment with GH (50 μg/kg/min i.v. for 60 min, before heat stress) significantly attenuated behavioral and cognitive deficits in normotensive rats and reduced the BBB dysfunction and brain pathology. On the other hand, similar treatment with GH in hypertensive animals only mildly reduced brain damage or cognitive dysfunction after heat stress. These novel observations indicate that patients suffering from various chronic diseases respond differently to various health hazards such as hyperthermia and to other neuroprotective agents.