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An Experimental Study in the Rat, Using Growth Hormone Therapy for Possible Neuroprotection
a Neurology Department, University of Cluj-Napoca, Cluj-Napoca, Romania b Laboratory of Cerebrovascular Research, Institute of Surgical Sciences, Department of Anaesthesiology and Intensive Care, University Hospital, Uppsala University, Uppsala, Sweden
Key Words: heat stress hyperthermia hypertension blood–brain barrier growth hormone edema cerebral blood flow neuroprotection brain damage
Address for correspondence: Hari Shanker Sharma, Ph.D., Dr.Med.Sci., Professor of Neurobiology (MRC), Frödingsgatan 12:28, SE-75421 Uppsala, Sweden. sharma{at}surgsci.uu.se
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.
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