Cerebrolysin treatment attenuates heat shock protein overexpression in the brain following heat stress: an experimental study using immunohistochemistry at light and electron microscopy in the rat.
The possibility that overexpression of heat shock proteins (HSPs) in the CNS represents a neurodestructive signal following hyperthermia was examined in a rat model using a potent neuroprotective drug, Cerebrolysin (Ebewe Pharma, Austria). Rats subjected to four hours of heat stress in a biological oxygen demand incubator at 38 degrees C developed profound hyperthermia (41.23 +/- 0.14 degrees C) and overexpressed HSP 72 kD in several brain regions: cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus, brain stem, and spinal cord compared to controls. This HSP overexpression closely correlated with the leakage of blood-brain barrier permeability and vasogenic edema formation in these brain areas. HSP positive cells are largely confined in the edematous brain regions showing Evans blue leakage. Pretreatment with Cerebrolysin (5 mL/kg, i.v.) 30 minutes before heat stress markedly attenuated hyperthermia (39.48 +/- 0.23 degrees C, P < 0.01) and the induction of HSP to all the brain regions examined. Leakage of Evans blue albumin and increase in brain water content in these brain areas are also markedly reduced with Cerebrolysin pretreatment. These results are the first to show that Cerebrolysin, if administered before heat stress, attenuates hyperthermia induced stress reaction and HSP 72 kD induction. Taken together, these novel observations suggest that upregulation of HSP 72 kD in brain represents neurodestructive signals and a reduction in cellular stress mechanisms leading to decline in HSP expression is neuroprotective in nature.
Sharma
Hari Shanker
HS
Department of Surgical Sciences, Anaesthesiology & Intensive Care Medicine, University Hospital, Uppsala University, Sweden. Sharma@surgsci.uu.se
Muresanu
Dafin
D
Sharma
Aruna
A
Zimmermann-Meinzingen
Sibilla
S
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018882:Heat Stress Disorders / Q000378:metabolism* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D051381:Rats
D000596:Amino Acids; D006360:Heat-Shock Proteins; C006952:cerebrolysin