The Role of Functionalized Magnetic Iron Oxide Nanoparticles in the Central Nervous System Injury and Repair: New Potentials for Neuroprotection with Cerebrolysin Therapy

Abstract

Functionalized Magnetic Iron Oxide Nanoparticles (FMIONPs) are being explored for the development of various biomedical applications, e.g., cancer chemotherapy and/or several other radiological or diagnostic purposes. However, the effects of these NPs per se on the central nervous system (CNS) injury or repair are not well known. This review deals with different aspects of FMIONPs in relation to brain function based on the current literature as well as our own investigation in animal models of CNS injuries. It appears that FMIONPs are innocuous when administered intravenously within the CNS under normal conditions. However, abnormal reactions to FMIONPs in the brain or spinal cord could be seen if they are combined with CNS injuries e.g., hyperthermia or traumatic insults to the brain or spinal cord. Thus, administration of FMIONPs in vivo following whole body hyperthermia (WBH) or a focal spinal cord injury (SCI) exacerbates cellular damage. Since FMIONPs could help in diagnostic purposes or enhance the biological effects of radiotherapy/chemotherapy it is likely that these NPs may have some adverse reaction as well under disease condition. Thus, under such situation, adjuvant therapy e.g., Cerebrolysin (Ever NeuroPharma, Austria), a suitable combination of several neurotrophic factors and active peptide fragments are the need of the hour to contain such cellular damages caused by the FMIONPs in vivo. Our observations show that co-administration of Cerebrolysin prevents the FMIONPs induced pathologies associated with CNS injuries. These observations support the idea that FMIONPs are safe for the CNS in disease conditions when co-administered with cerebrolysin. This indicates that cerebrolysin could be used as an adjunct therapy to prevent cellular damages in disease conditions where the use of FMIONPs is required for better efficacy e.g., cancer treatment.

Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: Effects on neurological and behavioral outcomes in acute ischemic stroke

“…Cerebrolysin, a neuronal metabolic activator including various free amino acids and low molecular weight peptides, has been used to treat cerebrovascular diseases for many years. Previous studies have shown that it can improve neurological outcome by preventing cell death, free radical formation and inflammation, and by counteracting excitotoxicity and accelerating the recovery of neurological function (6)(7)(8)(9). Clinical trials have shown that the usage of Cerebrolysin is reliable and effective with regard to the recovery of consciousness, language and hemiplegia in patients with AIS (11)(12)(13).…”

“…Cerebrolysin is a peptide-containing preparation that also exerts beneficial effects on ischemic stroke; preclinical studies have shown that Cerebrolysin substantially improves neurological outcome and promotes neurological functional recovery following ischemia by preventing cell death, the formation of free radicals, inflammation and by counteracting excitotoxicity (6)(7)(8)(9). Clinical trials have been performed to test the efficacy and safety of NBP and Cerebrolysin in the treatment of patients with acute ischemic stroke (AIS), and encouraging results have been reported (10)(11)(12)(13).…”

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

“…For this purpose, a broad range of nanoparticles with different sizes, architectures, and surface properties have been engineered for brain drug delivery. 27,28 These include liposomes, 29,30 polymeric nanoparticles, 31,32 carbon nanotubes, 33,34 nanofibers, 35,36 dendrimers, 37,38 micelles, 39 inorganic nanoparticles made of iron oxide, 40 and gold nanoparticles. 41 Unfortunately, it is beyond the scope of this article to review potential advantages -or disadvantages -of each of these nanocarriers in the imaging and/or therapy of the brain.…”

PLGA Nanoparticles Loaded Cerebrolysin: Studies on Their Preparation and Investigation of the Effect of Storage and Serum Stability with Reference to Traumatic Brain Injury

“…How is cerebrolysin able to reduce brain edema formation and/or BBB breakdown in TBI? This is not well known from our investigation [23][24][25][26]. However, available evidences suggests that cerebrolysin could induce neuroprotection or neurorepair because of exogenous supply of selective neurotrophic factors, e.g., brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and insulin-like growth factor 1 (IGF-1) along with many active peptide fragments needed for nutrition of neurons and glial cells [23][24][25][26].…”

“…30 min, 1 h, and 2 h after TBI. The animals were allowed to survive 8 h after injury [23][24][25][26].…”