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

Xa, Alvarez; Vr, Lombardi; Fernández‐Novoa, L.; Garcı́a, Magdalena; Sampedro, Carolina; Cagiao, A.M. Martínez; Cacabelos, Ramón; Windisch, Manfred

doi:10.1007/978-3-7091-6781-6_30

Cited by 35 publications

(41 citation statements)

References 20 publications

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“…Cerebrolysin has been demonstrated to reduce inflammation, stabilize calcium homeostasis, and prevent neuronal death in different in vitro and in vivo models of brain ischemia. 3,24,53 Furthermore, delayed Cerebrolysin treatment initiated 24 hours after stroke onset did not affect infarct volume but significantly improved functional outcome in rats. 69 This benefit may result from Cerebrolysin-induced promotion of neural stem cell proliferation and neurogenesis.…”

Section: Discussionmentioning

confidence: 85%

Improvement in functional recovery with administration of Cerebrolysin after experimental closed head injury

Zhang¹,

Chopp

Meng³

et al. 2013

JNS

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Object Cerebrolysin is a unique peptide preparation that mimics the action of neurotrophic factors. This study was designed to investigate the effects of acute treatment of experimental closed head injury (CHI) in rats with Cerebrolysin on neurological function. Methods Adult male Wistar rats (n = 60) were subjected to impact acceleration–induced CHI. Closed head injured rats received intraperitoneal injection of saline (n = 30) or Cerebrolysin (2.5 ml/kg, n = 30) starting 1 hour postinjury and administered once daily until they were killed (2 or 14 days after CHI). To evaluate functional outcome, the modified neurological severity score (mNSS), foot fault, adhesive removal, and Morris water maze (MWM) tests were performed. Animals were killed on Day 14 (n = 20) after injury, and their brains were removed and processed for measurement of neuronal cells, axonal damage, apoptosis, and neuroblasts. The remaining rats (n = 40) were killed 2 days postinjury to evaluate cerebral microvascular patency by fluorescein isothiocyanate (FITC)–dextran perfusion (n = 16) and to measure the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase–9 (MMP-9) by using real-time reverse transcriptase-polymerase chain reaction (RT-PCR, n = 8) and by immunohistochemical analysis (n = 16). Results At 14 days post-CHI, the Cerebrolysin treatment group exhibited significant improvements in functional outcomes (the adhesive removal, mNSS, foot-fault, and MWM tests), and significantly more neurons and neuroblasts were present in the dentate gyrus (DG) (p < 0.05) compared with the saline-treated group (p < 0.05). At 2 days post-CHI, the Cerebrolysin group exhibited a significantly higher percentage of phosphorylated neurofilament H (pNF-H)–positive staining area in the striatum (p < 0.05), a significant increase in the percentage of FITC-dextran perfused vessels in the brain cortex (p < 0.05), a significant increase in the number of VEGF-positive cells (p < 0.05), and a significant reduction in the MMP-9 staining area (p < 0.05) compared with the saline-treated group. There was no significant difference in mRNA levels of MMP-9 and VEGF in the hippocampus and cortex 48 hours postinjury between Cerebrolysin- and saline-treated rats that sustained CHI. Conclusions Acute Cerebrolysin treatment improves functional recovery in rats after CHI. Cerebrolysin is neuroprotective for CHI (increased neurons in the dentate gyrus and the CA3 regions of the hippocampus and increased neuroblasts in the dentate gyrus) and may preserve axonal integrity in the striatum (significantly increased percentage of pNF-H–positive tissue in the striatum). Reduction of MMP-9 and elevation of VEGF likely contribute to enhancement of vascular patency and integrity as well as neuronal survival induced by Cerebrolysin. These promising results suggest that Cerebrolysin may be a useful treatment in improving the recovery of patients with CHI.

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Section: Discussionmentioning

confidence: 85%

Improvement in functional recovery with administration of Cerebrolysin after experimental closed head injury

Zhang¹,

Chopp

Meng³

et al. 2013

JNS

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“…Akay et al [13] demonstrated the rescue of medial septal cholinergic neurons in a model of fimbria fornix transection after peripheral injection of Cere indicating that the small molecules are able to penetrate blood-brain barrier in pharmacodynamically significant amounts. Experimental data are also indicating that Cere protects against neurodegeneration induced by hypoxia, ischemia, glutamate and Aβ toxicity [14][15][16]; exerts pro-cognitive effects in rats with beta-amyloid (Abeta) implants into the hippocampus [14], in ApoE knock-out mice [17] and in aged rats [18,19]; reduces Abeta1-42 levels and synaptic pathology in hAPP transgenic mice [20]; increases neurogenesis in the rat hippocampus [21]; reduces microglial activation and the overexpression of IL-1β induced by stimulation with lipopolysaccharide in vitro and in vivo [14,22,23]; and decreases the production of Abeta by regulating amyloid precursor protein maturation in a transgenic model of AD [24]. All these results suggest a potential positive action of Cere on molecular, morphological and behavioural alterations shared by AD and VaD.…”

Section: Introductionmentioning

confidence: 99%

A pilot study to evaluate the effects of Cerebrolysin on cognition and qEEG in vascular dementia: Cognitive improvement correlates with qEEG acceleration

Mureșanu

Alvarez

Moessler³

et al. 2008

Journal of the Neurological Sciences

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“…18–20 Clinical and experimental studies suggested its effectiveness in aging-associated conditions: memory impairment 21 and diabetes. 22 However, to the best our knowledge, cerebrolysin effect on longevity has not been evaluated.…”

Section: Discussionmentioning

confidence: 99%

Cerebrolysin Accelerates Metamorphosis and Attenuates Aging-Accelerating Effect of High Temperature in Drosophila Melanogaster

Navrotskaya¹,

Oxenkrug²,

Vorobyova³

et al. 2014

Am J Neuroprotect Neuroregen

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Cerebrolysin® (CBL) is a neuroprotective drug used for the treatment of neurodegenerative diseases. CBL’s mechanisms of action remain unclear. Involvement of tryptophan (TRP)–kynurenine (KYN) pathway in neuroprotective effect of CBL might be suggested considering that modulation of KYN pathway of TRP metabolism by CBL, and protection against eclosion defect and prolongation of life span of Drosophila melanogaster with pharmacologically or genetically-induced down-regulation of TRP conversion into KYN. To investigate possible involvement of TRP–KYN pathway in mechanisms of neuroprotective effect of CBL, we evaluated CBL effects on metamorphosis and life span of Drosophila melanogaster maintained at 23 °C and 28 °C ambient temperature. CBL accelerated metamorphosis, exerted strong tendency (p = 0.04) to prolong life span in female but not in male flies, and attenuated aging-accelerating effect of high (28 °C) ambient temperature in both female and male flies. Further research of CBL effects on metamorphosis and resistance to aging-accelerating effect of high temperature might offer new insights in mechanisms of its neuroprotective action and expand its clinical applications.

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

Cited by 35 publications

References 20 publications

Improvement in functional recovery with administration of Cerebrolysin after experimental closed head injury

Improvement in functional recovery with administration of Cerebrolysin after experimental closed head injury

A pilot study to evaluate the effects of Cerebrolysin on cognition and qEEG in vascular dementia: Cognitive improvement correlates with qEEG acceleration

Cerebrolysin Accelerates Metamorphosis and Attenuates Aging-Accelerating Effect of High Temperature in Drosophila Melanogaster

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