Cerebrolysin, a mixture of neurotrophic factors induces marked neuroprotection in spinal cord injury following intoxication of engineered nanoparticles from metals.
Spinal cord injury (SCI) is the world's most disastrous disease for which there is no effective treatment till today. Several studies suggest that nanoparticles could adversely influence the pathology of SCI and thereby alter the efficacy of many neuroprotective agents. Thus, there is an urgent need to find suitable therapeutic agents that could minimize cord pathology following trauma upon nanoparticle intoxication. Our laboratory has been engaged for the last 7 years in finding suitable therapeutic strategies that could equally reduce cord pathology in normal and in nanoparticle-treated animal models of SCI. We observed that engineered nanoparticles from metals e.g., aluminum (Al), silver (Ag) and copper (Cu) (50-60 nm) when administered in rats daily for 7 days (50 mg/kg, i.p.) resulted in exacerbation of cord pathology after trauma that correlated well with breakdown of the blood-spinal cord barrier (BSCB) to serum proteins. The entry of plasma proteins into the cord leads to edema formation and neuronal damage. Thus, future drugs should be designed in such a way to be effective even when the SCI is influenced by nanoparticles. Previous research suggests that a suitable combination of neurotrophic factors could induce marked neuroprotection in SCI in normal animals. Thus, we examined the effects of a new drug; cerebrolysin that is a mixture of different neurotrophic factors e.g., brain-derived neurotrophic factor (BDNF), glial cell line derived neurotrophic factor (GDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF) and other peptide fragments to treat normal or nanoparticle-treated rats after SCI. Our observations showed that cerebrolysin (2.5 ml/kg, i.v.) before SCI resulted in good neuroprotection in normal animals, whereas nanoparticle-treated rats required a higher dose of the drug (5.0 ml/kg, i.v.) to induce comparable neuroprotection in the cord after SCI. Cerebrolysin also reduced spinal cord water content, leakage of plasma proteins and the number of injured neurons. This indicates that cerebrolysin in higher doses could be a good candidate for treating SCI cases following nanoparticle intoxication. The possible mechanisms and functional significance of these findings are discussed in this review.
Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, SE-75185 Uppsala, Sweden.
Preeti Kumaran
PK
Menon
Dafin Fior
DF
Muresanu
Aruna
A
Sharma
Herbert
H
Mössler
Hari Shanker
HS
Sharma
D000596:Amino Acids / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology; D006801:Humans; D053768:Metal Nanoparticles / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D013118:Spinal Cord Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D000596:Amino Acids; D018696:Neuroprotective Agents; C006952:cerebrolysin