Biomedical subjects

M Windisch

Publications and source records attributed to M Windisch.

At least 19 recordsLinked to original sources

PubMed2000

[New method for the intraoperative biochemical monitoring of cerebrospinal fluid in surgery of thoracoabdominal aortic aneurysms].

Paraplegia remains to be one of the most dangerous complications following thoracoabdominal aortic surgery with an incidence of 0.5 to 40%. Therefore, intraoperative monitoring of spinal cord function is very important when choosing the appropriate surgical technique. Early detection of spinal cord injury continues to be a crucial problem, moreover, the currently applied electrophysiological methods appear to be inaccurate. The aim of the study was to detect prospective spinal cord injury intraoperatively by monitoring the biochemical parameters of the cerebrospinal fluid (CSF). The authors studied the reversible aerobic/anaerobic metabolic changes by monitoring CSF lactate levels, moreover S-100 protein and neuron-specific enolase (NSE) concentrations--specific for neuroglia and neuronal injury, respectively. One of the important methods to prevent paraplegia is the intraoperative CSF drainage, which may improve spinal cord perfusion. Between 1996-1998 51 patients underwent reconstructive thoracic or thoracoabdominal aortic aneurysm operation. The continuously drained CSF was collected in 10 ml fractions during the preparation, whereas during aortic cross-clamping and de-clamping 10 minute fractions were used. All CSF samples were immediately analysed intraoperatively for pH, pCO2, HCO3, potassium and lactate levels, S-100 protein and NSE were analysed by immunoluminescence. CSF lactate levels increased slightly during aortic clamping and a moderate, but non-significant increase was found in the hyperemic phase (reperfusion) in patients without spinal cord ischemia. Spinal cord injury was detected in 7 cases. These patients exhibited a significant CSF-lactate increase (control vs aortic cross-clamping: 1.9 vs 5.3 mmol/l), moreover CSF-lactate remained elevated throughout the whole operation. Paraplegia did not occur, Tarlov 2 paraparesis developed in four cases and three patients displayed cerebral damage. Intraoperative CSF--especially CSF-lactate--monitoring may help the operating team to detect early anaerobic changes of the metabolism the spinal cord.

Acid-Base Equilibrium↗

PubMed2000

A brain derived peptide preparation reduces the translation dependent loss of a cytoskeletal protein in primary cultured chicken neurons.

Neuronal cytoskeletal proteins like the microtubule associated protein 2 (MAP2) are objected to pathological proteolysis in case of Alzheimer's disease and brain ischemia. The neurotrophic peptidergic drug Cerebrolysin (EBEWE Arzneimittel, Austria, Europe) is produced by a standardized enzymatic break-down of lipid free porcine brain proteins. Cerebolysin protected MAP2 in primary neuronal cultures after a brief histotoxic hypoxia and in a rat model of acute brain ischemia. Furthermore the drug was shown to inhibit the proteases mu- and m-calpain dose dependently in several cell free protease activity assays. The question if the higher MAP2 levels are due to an alleviation of proteolysis, to a higher synthesis rate or both is addressed in the current investigation: Monitoring the MAP2 content of primary neuronal cell cultures over a period of eight days revealed MAP2 to reach a peak level on day six in vitro followed by a degradation phase. In other experiments the protein synthesis of Cerebrolysin treated and untreated cells was blocked with cycloheximide at that moment when all cells exhibited the same MAP2 content. After the following MAP2 degradation phase--i.e. after eight days in vitro--the MAP2 contents were determined by western blotting. Cerebrolysin treated cells contained more MAP2 than untreated controls proving that the drug protects MAP2 independently from de novo synthesis, although further work is in progress to investigate if the drug supplementary boosts this effect by increasing MAP2 synthesis.

Amino Acids↗

PubMed2000

Cerebrolysin reduces microglial activation in vivo and in vitro: a potential mechanism of neuroprotection.

Neurotrophins, such as NGF, BDNF and NT-3 play a regulatory role on the function of microglial cells in vivo and in vitro, and the identification of new compounds with neurotrophic properties is becoming a new strategy for the prevention and/or treatment of neurodegenerative disorders. In this study we describe the use of two different models to demonstrate the ability of Cerebrolysin to reduce microglial activation. The results of these in vitro and in vivo studies indicate that Cerebrolysin might exert a neuroimmunotrophic activity reducing the extent of inflammation and accelerated neuronal death under pathological conditions such as those observed in neurodegenerative diseases.

Amino Acids↗

PubMed2000

Approach towards an integrative drug treatment of Alzheimer's disease.

At present pharmacotherapy of Alzheimer's disease (AD) is limited to acetylcholinesterase inhibitors. These drugs produce small, but consistent improvements of memory and global function, some are also positively influencing activities of daily living. This therapeutic approach neglects the complexity of AD and the fact that most of the degenerating neurons are not cholinergic. Acetylcholinesterase inhibitors are symptomatic drugs, with no influence on disease progression. There is a need for disease modifying compounds, or preventive drugs. Data are indicating that vitamin E has some ability to influence the disease progression. The potency of non-steroidal anti-inflammatory drugs (NSAIDs) or estrogen as preventive agents has to be explored further in prospective clinical studies. The initial hope in the use of naturally occurring neurotrophic factors, like nerve growth factor, to rescue cholinergic neurons from degeneration and to restore cognitive function has been disappointed in first, small clinical studies. The peptidergic drug Cerebrolysin exhibiting neurotrophic stimulation, neuroimmunotrophic regulation and induction of BBB glucose transporter expression, might be able to address the pathological changes of AD at different levels simultaneously. In addition to an impressive preclinical database, results from 3 placebo-controlled, double-blind studies demonstrate significant improvements of cognitive performance, global function and activities of daily living in AD patients. In all studies persisting improvements, up to 6 months after drug withdrawal, indicate a powerful disease modifying activity.

Alzheimer Disease↗

PubMed2000

Oral Cerebrolysin enhances brain alpha activity and improves cognitive performance in elderly control subjects.

Cerebrolysin is a porcine brain derived peptide preparation with potential neurotrophic activity. The effects of a single oral dose of the Cerebrolysin solution (30 ml) on brain bioelectrical activity and on cognitive performance were investigated in healthy elderly people. A single oral dose of Cerebrolysin induced a progressive increase in relative alpha activity power from 1 to 6 hours after treatment in almost all the brain electrodes in elderly control subjects. As compared with baseline alpha power (45.8+/-9.5%), the increase in relative alpha activity in the left occipital electrode (O1) reached significant values at 1 hour (57.2+/-8.5%; p < 0.05), 3 hours (59.4+/-7.6%; p < 0.05) and 6 hours (63.4+/-9.8%; p < 0.05) after Cerebrolysin administration. Enhancement in relative alpha power was accompanied by a generalized decrease in slow delta activity that was maximum at 6 hours after Cerebrolysin intake. A significant improvement in memory performance, evaluated with items of the ADAS cog, was also found in elderly people taken a single dose of oral Cerebrolysin (6.9+/-1.0 errors at baseline versus 4.9+/-1.0 errors after treatment; p < 0.01). This memory improvement was more evident in recognition (2.8+/-0.6 errors vs. 1.5+/-0.7 errors; p < 0.05) than in recall tasks (4.1+/-0.5 errors versus 3.4+/-0.5 errors; ns). These data indicate that Cerebrolysin potentiates brain alpha activity, reduces slow EEG delta frequencies and improves memory performance in healthy elderly humans, suggesting that this compound activates cerebral mechanisms related to attention and memory processes. According to the present results, it seems that oral Cerebrolysin might be useful for the treatment of memory impairment and brain damage in eldely subjects with or without neurodegenerative disorders.

Administration, Oral↗

PubMed2000

Effects of NaCN and ionomycin on neuronal viability and on the abundance of microtubule-associated proteins MAP1, MAP2, and tau in isolated chick cortical neurons.

The effects of two toxins, sodium cyanide (NaCN) and ionomycin (IM), on neuronal viability and on the expression of the microtubule-associated proteins MAP1, MAP2, and tau were studied in isolated chick cortical neurons. Cytotoxic hypoxia due to NaCN treatment was performed to mimic acute neuronal damage, whereas long-term IM treatment was used as a model for chronic neuronal impairment. After 5 days in vitro, a cytotoxic lesion was induced either by addition of NaCN (0.01-10 mM) or IM (0.01-10 microM). The NaCN solution was aspirated after 30 min and cells were allowed to regenerate for 6 h, 24 h, 48 h, or 72 h; whereas the permanent IM lesions were left undisturbed during the same periods of time. Neuronal viability was assessed by MTT assay. The abundance of MAP1, MAP2, and tau was evaluated by immunoblotting and, for MAP2, by immunohistochemistry also. Results showed that NaCN and IM lesions dose-dependently decreased viability. Irreversible cell damage occurred after impairment with 10 mM NaCN and 1 microm or 10 microm IM, while neurons lesioned with lower concentrations regenerated partially or adapted to the toxic environment. However, the same level of viability as of untreated cells was never reached. Furthermore abundance of MAPs was changed after both lesions. But while after extended recovery from NaCN lesion protein expression was normalizing (MAP2) or at least still detectable (MAP1A, tau), the consequences of a permanent IM lesion were more severe, since neurons were not able to maintain or even restore their MAP expression. Immunohistochemical experiments for MAP2 revealed that, compared with controls, NaCN and, to a much higher extent, IM treatment resulted in a loss of immunoreactivity in neurites due to progressing cell death.

Animals↗

PubMed2000

Inhibitory effect of a brain derived peptide preparation on the Ca++-dependent protease, calpain.

Overactivated calpain might be a key factor in destruction of cytoskeletal proteins involved in the pathophysiology of ischemia and disorders like Alzheimer's disease. Therapeutic effects imply the possible interference of Cerebrolysin (Ebewe Arzneimittel, Austria) with these molecular events. In this work several in vitro methods have been applied to investigate the interaction between Cerebrolysin and calpain [Enzyme Commission (EC) number: 3.4.22.17]. A conventional caseinolytic assay beside two flourimetric assays using a synthetic peptide substrate and a fluorescence labelled cytoskeletal protein [microtubule-associated protein 2 labelled with 5-([4,6-dichlorotriazin-2-yl]amino) fluorescein (MAP2-DTAF)] respectively for a highly sensitive fluorimetric calpain activity assay were applied for kinetic analysis. The caseinolytic assay showed that the drug inhibits both mu- and m-calpain and to a significantly lower extent also trypsin [Enzyme Commission (EC) number: 3.4.21.1] and papain [Enzyme commission (EC) number: 3.4.22.6]. Dialysis experiments revealed Cerebrolysin mediated calpain inhibition to be reversible. Kinetic analysis exhibited a non-competitive, or tight-binding competitive, mode of inhibition. This latter mode, substantiated by serial dilution experiments, and the likely existence of calpastatin in a brain derivative suggests the occurrence of calpastatin fragments or calpastatin-like fragments in Cerebrolysin. The clearly competitive inhibition of trypsin by the drug indicates distinct mechanisms and active components against different proteases.

Amino Acids↗

PubMed2000

Sustained improvements in patients with dementia of Alzheimer's type (DAT) 6 months after termination of Cerebrolysin therapy.

The present study is an extension of the work of Rüther et al. (1994). 101 patients suffering from DAT were evaluated 6 months after completion of a 4 week (5 days per week) therapy with either 30 ml Cerebrolysin or placebo. The significant and clinically relevant improvements in the global rating (CGI), clinical symptomatology (SCAG), cognitive performance (ZVT-G) as primary efficacy variables, as well as the improvements in the secondary efficacy variables activities of daily living (NAI) and wellbeing (Bf-S), achieved in the Cerebrolysin group after only 4 weeks of active therapy, were maintained to a large extent during the follow-up period. Although there was a moderate tendency in the drug group towards loss of improvement, the differences between baseline and follow-up examination, as well as the differences between the verum and the placebo group, clearly document a sustained improvement in patients treated with Cerebrolysin in the first 4 weeks of the study period. It can be speculated that relatively short treatment courses with Cerebrolysin in patients suffering from neurodegenerative dementia can lead to long term influence on disease progression, which is in accordance with the proposed neurotrophic - nerve growth factor like - mode of action.

Activities of Daily Living↗

PubMed2000

The drug cerebrolysin and its peptide fraction E021 increase the abundance of the blood-brain barrier GLUT1 glucose transporter in brains of young and old rats.

The brain-derived peptidergic drug Cerebrolysin has been found to support the survival of neurons in vitro and in vivo. In the present study, we investigated the effects of Cerebrolysin and its peptide preparation E021 on spatial learning and memory, as well as on the abundance of the blood-brain barrier GLUT1 glucose transporter (GLUT1) in 2-month-old and 24-month-old rats. Young rats were treated with the drugs or saline (2.5 ml/kg/day) daily on postnatal days 1-7, and old rats for 19 consecutive days. For behavioural testing the Morris water maze was used. The abundance of GLUT1 was determined in brain slices by immunocytochemistry. Quantification of the density of the GLUT1 immunostaining was performed using light microscopy and a computerised image analysing system. All drug-treated rats, young and old, exhibit shorter escape latencies in the water maze, on all testing days (p < 0.01), indicating improved cognitive performance. Immunohistochemical data show an age-related decrease of the density of GLUTI (p < 0.05). In young animals, the administration of the drugs led to an increase of the abundance of GLUT1 in all experimental groups (p < 0.01). In old rats, the treatment with Cerebrolysin, but not with E021, resulted in an increase in the immunoreactive GLUT1 (p < 0.01). The elevated abundance of GLUT1 after the administration of both peptidergic substances might be supportive for the cognitive effects of this drug, by causing an improved nutritional supply of glucose to the neurons.

Aging↗

PubMed2000

Two peptidergic drugs increase the synaptophysin immunoreactivity in brains of 6-week-old rats.

An increase of synaptic density has been found in the hippocampus, the dendate gyrus and in the entorhinal cortex of 6-week-old rats after 7 days of treatment with the peptidergic drug Cerebrolysin, its peptide preparation E021 and the diluted peptide preparation E021dil. Rats received drugs on postnatal days 1-7 (2.5 ml/kg, each day). Controls received saline. The animals were sacrificed on days 42-48 of their life, after they had undergone behavioural testing in a Morris water maze. Slices of brain were stained immunohistochemically with anti-synaptophysin, a specific marker of presynaptic terminals. The synaptophysin-immunoreactivity of presynaptic terminals was quantified using light microscopy and a computerised image analysis system. Our results showed that rats benefit from the treatment with both drugs. A significant increase in the number of synaptophysin-immunoreactive presynaptic terminals was found in the entorhinal cortex and the hippocampal subfields CA1, CA2, CA3 stratum radiatum and CA3 stratum lucidum. The increased immunoreactive presynaptic terminals found in the present study are in accordance with the positive effects of the drugs on spatial learning and memory in young rats (Gschanes & Windisch 1999).

Amino Acids↗

PubMed1999

Early postnatal treatment with peptide preparations influences spatial navigation of young and adult rats.

The brain derived peptidergic drug Cerebrolysin has been found to support the survival of neurons in vitro and in vivo. Positive effects on learning and memory have been demonstrated in various animal models and also in clinical trials. In the present study the effects of early postnatal administration of Cerebrolysin (Cere, 10 mg/ml peptides) or an enriched peptide fraction of Cere (E021, 80.6 mg/ml peptides) were investigated in young, young adult, and old adult rats. Rat pups received the drugs or saline for control on postnatal days 1-7. The animals were tested in the Morris water maze (MWM) either in the 5th week, in the 3rd or the 16th month of life for 6 consecutive days (test days 1-6), eight trials per day. In order to prevent the chance finding of the hidden platform, the rigid underwater platform was replaced by a collapsible island, resting at the bottom of the pool. The platform was raised when the animal stayed in the target area for 2 s. In the young and young adult rats both Cere and E021 treated rats showed shorter escape latencies than saline treated controls on all 6 test days. No significant differences in the swimming speed were evaluated for the young rats, although in 3-month-old drug-tested animals a moderate increase of the swimming speed was investigated. For 16-month-old animals no significant differences in either escape latencies or swimming speed was found. Summarizing, early postnatal application of Cere or E021 improved the spatial learning and memory of young rats and led to long-lasting behavioural effects at least up to 3 months after treatment.

Aging↗

PubMed1999

In vivo upregulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived peptides.

Glucose is the critical metabolic fluid for the brain, and the transport of this nutrient from blood to brain is limited by the blood-brain barrier (BBB) GLUT1 glucose transporter. The expression of the BBB-GLUT1 gene is augmented in brain endothelial cultured cells incubated with brain-derived trophic factors and the brain-derived peptide preparation Cerebrolysin (C1, EBEWE, Austria). The aim of the present investigation was to determine if C1 induces similar changes in the expression of the BBB-GLUT1 gene following its administration to rats in vivo. The BBB glucose transporter activity was investigated with the intracarotid artery perfusion technique using [3H]diazepam as cerebral blood flow marker. The acute or chronic administration of C1 markedly increased the brain permeability surface area of D-[14C]glucose compared to controls (D-[14C]glucose/[3H]diazepam ratio, 1.6- to 1.9-fold increase in frontal cortex, P < 0.05). Increased activity of the BBB glucose transporter was correlated with a significant rise in the abundance of the BBB-GLUT1 protein measured by both Western blot analysis and immunocytochemistry, and with a decrease in the transcript levels of this transporter. Data presented here demonstrate that the in vivo administration of Cl increases the transport of glucose from blood to brain via BBB-GLUT1 gene expression.

Amino Acids↗

PubMed1999

Two peptidergic drugs increase the synaptophysin immunoreactivity in brains of 24-month-old rats.

The brain-derived peptidergic drug Cerebrolysin has been found to support the survival of neurones in vitro and in vivo. Positive effects on learning and memory have been demonstrated in various animal models and also in clinical trails. In the present study, the effects of Cerebrolysin and its peptide preparation E021 on the synapse density in the hippocampus, the dentate gyrus and in the entorhinal cortex of 24-month-old rats were investigated. Rats received the drugs or saline for control for 19 consecutive days (2.5 ml/kg per day). Slices of the brains were immunohistochemically stained with anti-synaptophysin, which is a specific marker of presynaptic terminals. Quantification of the synapse density was done by using light microscopy and a computerised image analysing system. Our results clearly showed that the rats benefit from the administration of both drugs, showing an enhancement in the number of synaptophysin-immunostained presynaptic terminals in the entorhinal cortex, the dentate gyrus, and also in the hippocampal subfields CA1, CA2, CA3 stratum lucidum and CA3 stratum radiatum. It can be assumed that these effects are the reason for improved cognitive performances of rats treated with Cerebrolysin and E021.

Amino Acids↗

PubMed1999

Effects of Cerebrolysin on in vitro primary microglial and astrocyte rat cell cultures.

In recent years the potential use of neurotrophic factors in the prevention and/or treatment of neurodegenerative diseases has received much attention. To determine whether Cerebrolysin, a porcine brain-derived peptide preparation, was able to modulate in vitro lipopolysaccharide (LPS)-induced microglial activation and to test the direct effect of Cerebrolysin on astrocyte morphology, survival and proliferation, rat glial and astrocyte cell culture experiments were carried out. The morphology of microglia, ameboid/activated and flat/resting, was examined under contrast microscopy and cell counts obtained. In addition, the release of interleukin (IL)-1 beta and brain-derived neurotrophic factor (BDNF) was measured from cell culture supernatant using an enzyme-linked-immunoassay (ELISA). The results obtained in this study clearly suggest a protective effect of Cerebrolysin as revealed by downregulation of microglial activation after LPS treatment as well as by the control of IL-1 beta expression. No significant differences were observed on astrocyte morphology, survival or the production and/or release of BDNF. In conclusion, these in vitro studies indicate that Cerebrolysin might exert a neuroimmunotrophic function which can in turn reduce the extent of inflammation and accelerate neuronal death under pathological conditions such as human neurodegenerative disorders.

Amino Acids↗

PubMed1998

Neurotrophic activities and therapeutic experience with a brain derived peptide preparation.

In spite that the use of naturally occurring neurotrophic factors like NGF, BDNF, CNTF, GDNF and others for treatment of neurodegenerative disorders seems promising because of their pharmacological properties, until now no large scale clinical trials have been published. One of the reasons is that these molecules are unable to penetrate through the blood brain barrier, making invasive application strategies like intracerebroventricular infusion necessary. Another one is the fact that in first clinical studies, several undesirable side-effects like hyperalgesia or weight loss have been reported. Major efforts are now put into development of improved application procedures and in treatment protocols for avoiding the known side-effects. Already 7 years ago it has been demonstrated that Cerebrolysin, a peptidergic drug, produced from purified brain proteins by standardized enzymatic breakdown, containing biologically active peptides, is exerting nerve growth factor like activity on neurons from dorsal root ganglia. Still ongoing investigations are showing growth promoting efficacy of this drug in different neuronal populations from peripheral and central nervous system. The current findings are in accordance with several older publications, enabling now a more clear interpretation of these findings. In addition to the direct neurotrophic effect, the drug also shows clear neuroprotective properties after different types of lesion in vitro and in vivo, resembling the pharmacological activities of naturally occurring nerve growth factors. Neurotrophic and neuroprotective efficacy has been shown with a broad variety of methods in different models and it is remarkable that all biochemical and morphological drug dependent alterations are resulting in improvements of learning and memory. Because of these experimental results, clinical trials using cerebrolysin in Alzheimer's patients have been performed, demonstrating a quick improvement in the overall state of the patients, particularly enhancing the cognitive performance. It is remarkable that these effects are long lasting after cessation of the active treatment procedure. Even 6 months after stop of drug application improvements in AD-patients are detectable. Therefore it is concluded that cerebrolysin is able to induce repair phenomena, resulting in long term stabilization. In contrast to the naturally occurring growth factors, tolerability of this drug is extremely high, without any reports about serious side-effects in these clinical studies.

Aged↗

PubMed1998

The influence of Cerebrolysin and E021 on spatial navigation of 24-month-old rats.

In the present study the behavioural effects of Cerebrolysin (Cere), a peptidergic nootropic drug, and E021, the concentrated peptide fraction of Cere, were investigated in 24-month-old rats. Rats passing a pretest to exclude motor- and eye-deficits were treated with either drugs or saline as control (2.5 ml/kg, intraperitoneally i.p.) for 19 days. Animals were tested in a standard Morris water maze on day 16 after pretest for 4 consecutive days (test days 1-4), eight trials per day. No significant differences of escape latency between males and females were found, therefore, results were pooled. Both Cere and E021 treated rats showed significant lower escape latencies than saline treated controls on all four test days (p < 0.01). More pronounced effects of both drugs were found for female rats. Female rats showed no significant differences in motor activity whereas drug treated males swam quicker on test day 1 (Cere p < 0.01: E021 p < 0.05) and day 2 (Cere p < 0.01). In the present experiments it was demonstrated that i.p. administration of both Cere and E021 improves the spatial learning and memory of 24 month-old male and female rats.

Amino Acids↗

PubMed1998

Cerebrolysin protects isolated cortical neurons from neurodegeneration after brief histotoxic hypoxia.

A brief period of histotoxic hypoxia exhibits certain metabolic features resembling the in vivo situation of ischemia. In this study the neuroprotective effects of the peptidergic nootropic drug Cerebrolysin (Cere) against iodoacetate induced histotoxic hypoxia were investigated. For that purpose isolated cortical neurons from 9 day chicken embryos were precultured with 0 to 6.4 mg.Cere/ml medium. At the 8th day in vitro histotoxic hypoxia was induced by incubation with 0.01 or 0.1 mM iodoacetate. Cells were allowed to recover from toxic stress for 3, 6, 24 or 48 hours. Cere protected neurons dose dependently from delayed neuronal cell death due to 0.01 mM iodoacetate even after a recovery period of 48h. After induction of histotoxic hypoxia by 0.1 mM iodoacetate high concentrations of Cere again led to neuronal protection after the 3 and 6 h recovery period. Moreover the influence of Cere on the cytoskeletal protein MAP2 in neurons submitted to 0.01 mM iodoacetate was investigated. With Western blotting and immunohistochemical techniques it has been demonstrated that the drug clearly increased MAP2 abundance after histotoxic hypoxia. The present study points out that after severe damage of cortical neurons with iodoacetate Cere is able to protect neurons from delayed neuronal cell death maybe by maintaining neuronal plasticity due to avoidance of the cytoskeletal breakdown.

Amino Acids↗

PubMed1998

Further evidence that Cerebrolysin protects cortical neurons from neurodegeneration in vitro.

The effects of Cerebrolysin on isolated chicken cortical neurons in an iron induced oxidative stress model and in a combined iron-glutamate model have been examined. In a first part of experiments it has been shown that under low serum conditions exposure of neurons to different concentrations of ammonium-iron (III)citrate (1, 5 microM AC-Fe3+) for 8 days caused a significant reduction in neuronal survival. Cerebrolysin not only prevented iron induced neurodegeneration, demonstrating that ionic iron was responsible for the cell damage, moreover, it increased the neuronal viability up to tenfold with respect to the controls. In the second part of the study neurons pre-incubated for 8 days with AC-Fe3+ were additionally lesioned with 1 mM L-glutamate and allowed to recover for another 48 h. Under these conditions cerebrolysin again clearly counteracted the in vitro destructive effects of glutamate. Besides consequences on the viability and survival of neurons Cerebrolysin increased abundance of the microtubule-associated protein MAP2, which is known to play a an important role in maintaining normal neuronal function.

Amino Acids↗