Chronic Hypertension Aggravates Heat Stress-Induced Brain Damage: Possible Neuroprotection by Cerebrolysin
Whole body hyperthermia (WBH) aggravates brain edema formation and cell damage in chronic hypertensive rats compared with normotensive animals. In this investigation, we examined the influence of cerebrolysin on WBH-induced edema formation and brain patho
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Abstract Whole body hyperthermia (WBH) aggravates brain edema formation and cell damage in chronic hypertensive rats compared with normotensive animals. In this investigation, we examined the influence of cerebrolysin on WBH-induced edema formation and brain pathology in hypertensive and normotensive rats. Rats subjected to 4 h WBH at 38°C in a biological oxygen demand (BOD) incubator showed breakdown of the blood–brain barrier (BBB), reduced cerebral blood flow (CBF), edema formation and cell injuries in several parts of the brain. These effects were further aggravated in chronic hypertensive rats (two-kidney one clip model (2K1C), for 4 weeks) subjected to WBH. Pretreatment with cerebrolysin (5 mL/kg, 24 h and 30 min before heat stress) markedly attenuated the BBB dysfunction and brain pathology in normal animals. However, in hypertensive animals, a high dose of cerebrolysin (10 mL/kg, 24 h and 30 min before heat stress) was needed to attenuate WBH-induced BBB dysfunction and brain pathology. These observations indicate that heat stress could affect differently in normal and hypertensive conditions. Furthermore, our results suggest that patients suffering from various chronic cardiovascular diseases may respond differently to hyperthermia and to neuroprotective drugs, e.g., cerebrolysin not reported earlier.
H.S. Sharma (*) Laboratory of Cerebrovascular Research, Department of Surgical Science, Anaesthesiology and Intensive Care Medicine, University Hospital, Frödingsgatan 12:28, Uppsala, SE-75421, Sweden e-mail: [email protected] D.F. Muresanu Department of Neurology, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj-Napoca, Romania S. Zimmermann-Meinzingen EBEWE Neuro-Pharma, Mondseestrasse 11, Unterach A-4866, Austria
Keywords Cerebrolysin • whole body hyperthermia • hypertensive rats • brain edema • brain pathology • cerebral blood flow
Introduction Heat stress is a serious clinical disorder that induces profound brain dysfunction and death in human populations (6–9). After sudden heat exposure, death can occur without any prior symptoms (11,14). Thus, further studies are required to understand the basic pathophysiology of heatinduced brain damage. In recent years, several thousand people have died in Europe during summer months; although these deaths were linked to heat exposure, the exact mechanism underlying them remains unexplored (16–18). Heat stress has been suggested as the third largest cause of human mortality after cardiovascular and traumatic injuries of the CNS (see (8–11)). However, it is still uncertain whether heat exposure causes greater damage in persons suffering from cardiovascular or metabolic abnormalities (9). Therefore, we investigated the possible effects of heat stress in populations suffering from chronic hypertension (2) or diabetes mellitus (3), the common diseases affecting many people worldwide. We have also shown that chronic hypertensive rats subjected to WBH exhibited exacerbation of BBB dysfunction, brain edema and brain pathology (2) and diabetic rats also s
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