Superior neuroprotective effects of cerebrolysin in nanoparticle-induced exacerbation of hyperthermia-induced brain pathology.
In recent years, the incidence of heat stroke and associated brain pathology are increasing Worldwide. More than half of the world's population are living in areas associated with high environmental heat especially during the summer seasons. Thus, new research is needed using novel drug targets to achieve neuroprotection in heat-induced brain pathology. Previous research from our laboratory showed that the pathophysiology of brain injuries following heat stroke are exacerbated by chronic intoxication of engineered nanoparticles of small sizes (50-60 nm) following identical heat exposure in rats. Interestingly, in nanoparticle-intoxicated animals the known neuroprotective agents in standard doses failed to induce effective neuroprotection. This suggests that the dose-response of the drugs either requires modification or new therapeutic agents are needed to provide better neuroprotection in nanoparticle-intoxicated animals after heat stroke. This review is focused on the use of cerebrolysin, a mixture of several neurotrophic factors and active peptide fragments, in relation to other neuroprotective agents normally used to treat ischemic stroke in clinics in nanoparticle-induced exacerbation of brain damage in heat stroke. It appears that cerebrolysin exerts the most superior neuroprotective effects in heat stress as compared to other neuroprotective agents on brain pathology in normal rats. Interestingly, to induce effective neuroprotection in nanoparticle-induced exacerbation of brain pathology a double dose of cerebrolysin is needed. On the other hand, double doses of the other drugs were quite ineffective in reducing brain damage. These observations suggest that the drug type and doses are important factors in attenuating nanoparticle-induced exacerbation of brain pathology in heat stroke. The functional significance and possible mechanisms of drug-induced neuroprotection in nanoparticle-treated, heat-stressed rats are discussed.
Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, SE-75185 Uppsala, Sweden.
Aruna
A
Sharma
Dafin Fior
DF
Muresanu
Herbert
H
Mössler
Hari Shanker
HS
Sharma
D000596:Amino Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use; D001929:Brain Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D018883:Heat Stroke / Q000503:physiopathology*; D006801:Humans; D053768:Metal Nanoparticles / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D012720:Severity of Illness Index
D000596:Amino Acids; D000927:Anticonvulsants; D018696:Neuroprotective Agents; C006952:cerebrolysin