Chronic hypertension aggravates heat stress induced cognitive dysfunction and brain pathology: an experimental study in the rat, using growth hormone therapy for possible neuroprotection
2007 (English)In: Neuroprotective agents: Eighth international neuroprotection society meeting / [ed] Slikker W; Andrew RJ; Trembly B, 2007, Vol. 1122, no 1, 1-22 p.Conference paper (Refereed)
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.
Place, publisher, year, edition, pages
2007. Vol. 1122, no 1, 1-22 p.
, Annals of the New York academy of sciences, ISSN 0077-8923 ; 1122
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; Animal, Growth Hormone/*therapeutic use, Heat/adverse effects, Hypertension; Renovascular/complications/etiology, Male, Neuroprotective Agents/*therapeutic use, Rats, Rats; Wistar, Rotarod Performance Test/methods, Stress/complications/etiology
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-17160DOI: 10.1196/annals.1403.001ISI: 000252267100001PubMedID: 18077561OAI: oai:DiVA.org:uu-17160DiVA: diva2:44931
8th International Conference on Neuroprotective Agents Mackinac Isl, MI, SEP 18-20, 2006