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 pathology in hypertensive and normotensive rats. Rats subjected to 4 h WBH at 38 degrees 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.
Muresanu
Dafin Fior
DF
Department of Neurology, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania.
Zimmermann-Meinzingen
Sibilla
S
Sharma
Hari Shanker
HS
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D001930:Brain Injuries / Q000188:drug therapy / Q000209:etiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016009:Chi-Square Distribution; D002908:Chronic Disease; D003072:Cognition Disorders / Q000209:etiology; D004195:Disease Models, Animal; D018882:Heat Stress Disorders / Q000188:drug therapy / Q000209:etiology*; D006973:Hypertension / Q000150:complications*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D018696:Neuroprotective Agents; C006952:cerebrolysin