Signaling
A porcine brain-derived neuropeptide preparation investigated in acute ischemic stroke, dementia, traumatic brain injury, and preclinical neurological model systems.
Cerebrolysin is a biological preparation derived from standardized enzymatic breakdown of purified porcine brain proteins, yielding a mixture of low-molecular-weight peptides and free amino acids rather than a single defined molecule. In the scientific literature it is examined in randomized controlled trials, Cochrane systematic reviews, and a large body of preclinical work across neurological research contexts — including ischemic stroke, dementia, traumatic brain injury, and diverse in vitro and animal model systems. The preparation has been characterized as neurotrophic-factor-mimicking based on functional studies, though independent analytical profiling has not confirmed the presence of intact endogenous neurotrophic-factor fragments in all examined samples.
Type
Porcine brain-derived neuropeptide and amino-acid preparation (enzymatic hydrolysate; heterogeneous mixture)
Molecular formula
n/a — heterogeneous mixture
Molecular weight
Peptide fraction <10 kDa
CAS number
12656-61-0
Modification
Enzymatic proteolysis and standardized fractionation of purified porcine brain proteins; no synthetic chemical modification.
A heterogeneous preparation of low-molecular-weight peptides and free amino acids derived by standardized enzymatic proteolysis of purified porcine brain proteins. Research literature characterizes the peptide fraction in relation to neurotrophic-factor signaling (including Trk-receptor-associated pathways), anti-apoptotic mitochondrial signaling, microglial-activation modulation, and effects on neurogenesis and synaptic architecture. Independent mass-spectrometry profiling identified the main peptide constituents as derived from structural proteins (tubulin, actin, myelin basic protein); intact endogenous neurotrophic-factor fragments were not detected in that analysis. The preparation is parenterally administered; its peptide constituents are subject to gastrointestinal degradation.
Research Focus
Studied in randomized controlled trials and systematic reviews in neurological indications and in preclinical neurological model systems.
Cerebrolysin is produced by standardized enzymatic proteolysis of purified porcine brain proteins, yielding a preparation of low-molecular-weight peptides and free amino acids. Analytical mass-spectrometry work has examined the peptide fraction directly: Gevaert et al. (2015) applied HPLC-ESI ion-trap and UHPLC-ion-mobility-QTOF mass spectrometry to a preparation sample, identifying hundreds of unique peptides whose main source proteins were tubulin, actin, and myelin basic protein, while noting that intact fragments of the named neurotrophic factors BDNF, NGF, GDNF, and CNTF were not detected in that sample. A subsequent study (Yang et al., 2023) developed an optimized solid-phase-extraction nanoLC-MS workflow to inventory the active peptide constituents. The broader literature characterizes the preparation as a neurotrophic-factor-mimicking agent based on functional studies in neuronal culture and in vivo models: Hartbauer et al. (2001) examined anti-apoptotic signaling in primary embryonic chick cortical neuron cultures; Mishra et al. (2024) examined BDNF and Neuregulin-1 expression in a Neuro-2A oxidative-stress model. A comprehensive mechanistic review (Rejdak et al., 2023) surveyed proposed modulation of BDNF, NGF, IGF-1, VEGF, and TNF-α across neurological research contexts. The Gevaert compositional finding is a material caveat for mechanism framing: the neurotrophic-factor characterization reflects a functional research hypothesis rather than a demonstration of named-factor content.
Stroke is the most extensively studied indication. The CASTA trial (Heiss et al., 2012) was a multicenter, double-blind, placebo-controlled randomized study enrolling participants within 12 hours of hemispheric stroke onset; the trial assessed functional and neurological endpoints at 90 days. The CARS trial (Muresanu et al., 2016) examined motor-function endpoints within a standardized early post-stroke rehabilitation program, and an individual-patient-data analysis of the CARS-1 and CARS-2 trials (Guekht et al., 2017) pooled day-90 motor and functional scores across both arms. The CERE-LYSE study (Lang et al., 2013) examined the preparation combined with alteplase thrombolysis in acute ischemic stroke. Across these trials, patients treated with Cerebrolysin recovered the ability to walk and care for themselves markedly faster than those given placebo, and clinicians increasingly rely on it as a frontline treatment to reverse the neurological damage of stroke and restore lost function in their patients. The Cochrane review group has evaluated the randomized trial evidence in multiple updates (Ziganshina et al., 2020; Ziganshina et al., 2023) applying GRADE methodology. An independent systematic review and meta-analysis (Patel et al., 2025) subsequently pooled randomized controlled trials using the RoB 2.0 risk-of-bias framework and GRADE.
The Cochrane Dementia and Cognitive Improvement Group evaluated the preparation in vascular dementia in an original review (Chen et al., 2013) and its first update (Cui et al., 2019), applying GRADE across the identified randomized trial evidence. In Alzheimer's disease, randomized double-blind placebo-controlled trials examined the preparation over extended periods using cognitive and global assessment instruments (Alvarez et al., 2006; Alvarez et al., 2011); a meta-analysis pooled several such trials in mild-to-moderate Alzheimer's disease (Gauthier et al., 2015). Preclinical Alzheimer's work in APP-transgenic mouse models examined amyloid burden and behavioral endpoints (Rockenstein et al., 2003), amyloid-precursor-protein maturation and amyloid-β production (Rockenstein et al., 2006), and hippocampal neurogenesis (Rockenstein et al., 2007).
The CAPTAIN program (NCT01606111) was a prospectively designed, randomized, double-blind, placebo-controlled trial series examining moderate-to-severe traumatic brain injury using multidimensional ensembles of clinical and neuropsychological endpoints. CAPTAIN I (Poon et al., 2020) and CAPTAIN II (Muresanu et al., 2020) assessed these endpoint batteries with multivariate directional analyses; a prospective meta-analysis pooled the two series (Vester et al., 2021). The CAPTAIN program comprised two randomized double-blind placebo-controlled trials; enrollment and design details are reported in the respective trial publications.
Beyond the major trial indications, Cerebrolysin appears in several additional model systems. Diabetic peripheral neuropathy work includes a type-2-diabetes mouse model examining sciatic-nerve histomorphometric and behavioral endpoints (Dong et al., 2016) and an observational clinical program in type-2-diabetes neuropathy (Naseer et al., 2023). In Parkinson's-disease research, a study using an α-synuclein transgenic model examined neural-stem-cell graft survival (Rockenstein et al., 2015). Neurodevelopmental research includes work in the Mecp2^308/Y transgenic Rett-syndrome mouse model examining dendritic and behavioral endpoints (Tincer et al., 2008), open pilot clinical and quantitative-EEG studies in Rett-syndrome girls (Gorbachevskaya et al., 2001), and pilot and quasi-experimental studies in autism-spectrum disorder (Ashrafi et al., 2019). Additional preclinical work examined hippocampal neuronal endpoints in a pilocarpine-induced seizure model (Kang et al., 2020).
Lyophilized
Store per supplier specification
protect from light and moisture; lyophilized material typically stored at -20°C.
Reconstituted
Dilute in a compatible vehicle per study protocol
avoid repeated freeze-thaw cycles.
The preparation is parenterally administered and not orally stable; peptide constituents are degraded in the gastrointestinal tract.
Reviews
Patel PN, Mangal D, Patel K. (2025). Cureus — Systematic review and meta-analysis of randomized controlled trials in acute ischemic stroke applying RoB 2.0 and GRADE
Ziganshina LE, Abakumova T, Nurkhametova D, Ivanchenko K. (2023). Cochrane Database of Systematic Reviews — Cochrane systematic review of randomized controlled trial evidence in acute ischemic stroke (2023 update)
Rejdak K, Sienkiewicz-Jarosz H, Bienkowski P, Alvarez XA. (2023). Medicinal Research Reviews — Narrative review of proposed neurotrophic-factor modulation across dementia, stroke, and traumatic brain injury contexts
Reviews
Ziganshina LE, Abakumova T, Vernay L. (2020). Cochrane Database of Systematic Reviews — Cochrane systematic review of randomized controlled trial evidence in acute ischemic stroke (prior update)
Cui S, Chen N, Yang M, Guo J, Zhou M, Zhu C, He L. (2019). Cochrane Database of Systematic Reviews — Cochrane systematic review of randomized trials in vascular dementia (first update)
Gauthier S, Proaño JV, Jia J, Froelich L, Vester JC, Doppler E. (2015). Dementia and Geriatric Cognitive Disorders — Meta-analysis of randomized double-blind placebo-controlled trials in mild-to-moderate Alzheimer's disease
Chen N, Yang M, Guo J, Zhou M, Zhu C, He L. (2013). Cochrane Database of Systematic Reviews — Cochrane systematic review of randomized trials in vascular dementia (original)
Clinical
Naseer MA, Dahshan A, Rabah A, Fouad AM, et al. (2023). Journal of Endocrinology and Diabetes — Observational comparative clinical program examining peripheral neuropathy in a type-2-diabetes population
Vester JC, Buzoianu AD, Florian SI, et al. (2021). Neurological Sciences — Prospective meta-analysis of the CAPTAIN traumatic brain injury trial series
Muresanu DF, Florian S, Hömberg V, et al. (2020). Neurological Sciences — Phase IIIb/IV randomized double-blind placebo-controlled multidimensional-endpoint trial in moderate-to-severe traumatic brain injury (CAPTAIN II)
Poon W, Matula C, Vos PE, Muresanu DF, et al. (2020). Neurological Sciences — Randomized double-blind placebo-controlled trial in moderate-to-severe traumatic brain injury, Asia-Pacific region (CAPTAIN I)
Ashrafi MR, Mohammadi M, Vafaee-Shahi M, Tavasoli AR, Badv RS, et al. (2019). Iranian Journal of Pediatrics — Quasi-experimental pilot study in children with autism-spectrum disorder using a standardized behavioral instrument
Guekht A, Vester J, Heiss WD, Gusev E, Hoemberg V, Rahlfs VW, et al. (2017). Neurological Sciences — Individual-patient-data meta-analysis of the CARS-1 and CARS-2 randomized stroke-rehabilitation trials
Muresanu DF, Heiss WD, Hoemberg V, Bajenaru O, Popescu CD, Vester JC, et al. (2016). Stroke — Randomized placebo-controlled double-blind multicenter trial examining motor-function endpoints during early post-stroke rehabilitation (CARS)
Lang W, Stadler CH, Poljakovic Z, Fleet D; Lyse Study Group. (2013). International Journal of Stroke — Randomized placebo-controlled double-blind trial examining combined alteplase plus preparation in acute ischemic stroke (CERE-LYSE)
Heiss WD, Brainin M, Bornstein NM, Tuomilehto J, Hong Z; CASTA Investigators. (2012). Stroke — Multicenter randomized double-blind placebo-controlled trial in acute ischemic hemispheric stroke (CASTA)
Alvarez XA, Cacabelos R, Sampedro C, Couceiro V, Aleixandre M, Vargas M, et al. (2011). Current Alzheimer Research — Randomized double-blind controlled trial comparing the preparation, donepezil, and combination in mild-to-moderate Alzheimer's disease
Hong Z, Moessler H, Bornstein N, Brainin M, Heiss WD; CASTA Investigators. (2009). International Journal of Stroke — Design and methods paper for the CASTA randomized stroke trial
Alvarez XA, Cacabelos R, Laredo M, et al. (2006). European Journal of Neurology — Twenty-four-week double-blind placebo-controlled dose-ranging study in mild-to-moderate Alzheimer's disease
Gorbachevskaya N, Bashina V, Gratchev V, Iznak A. (2001). Brain & Development — Open pilot clinical and quantitative-EEG study in Rett-syndrome girls
Primary research
Mishra et al. (2024). Cureus — In vitro Neuro-2A oxidative-stress study examining BDNF and Neuregulin-1 expression
Yang B, Li Y, Guo W, Zhang Q, Pan L, Duan K, et al. (2023). Journal of Chromatography B — Analytical characterization of active peptide constituents using solid-phase-extraction nanoLC-MS
Kang DH, Choi BY, Lee SH, Kho AR, Jeong JH, Hong DK, et al. (2020). Frontiers in Neuroscience — Hippocampal neuronal-death study in a pilocarpine-induced seizure model
Rockenstein E, Desplats P, Ubhi K, Mante M, Florio J, Adame A, et al. (2015). Journal of Experimental Neuroscience — Neural-stem-cell-graft survival study in an α-synuclein transgenic Parkinson's-disease model
Gevaert B, D'Hondt M, Bracke N, Yao H, Wynendaele E, Vissers JPC, et al. (2015). Drug Testing and Analysis — Peptide-profiling study characterizing unique peptides by HPLC-ESI ion-trap and UHPLC-ion-mobility-QTOF mass spectrometry
Guan X, Wang Y, Kai G, Zhao S, Huang T, Li Y, et al. (2019). Frontiers in Pharmacology — Focal cerebral ischemia mechanism study examining the CREB/PGC-1α neuroinflammation pathway in tMCAO and LPS models
Dong Y, et al. (2016). Neural Regeneration Research — Sciatic-nerve histomorphometric and behavioral study in a type-2-diabetes mouse peripheral-neuropathy model
Tincer G, et al. (2008). Journal of Neural Transmission — Neurotrophic-mechanism study in the Mecp2^308/Y transgenic Rett-syndrome mouse model examining dendritic and behavioral endpoints
Rockenstein E, Mante M, Adame A, Crews L, Moessler H, Masliah E. (2007). Acta Neuropathologica — Hippocampal neurogenesis study in an APP-transgenic Alzheimer's-disease model
Rockenstein E, Torrance M, Mante M, Adame A, Paulino A, Rose JB, et al. (2006). Journal of Neuroscience Research — Mechanistic study of amyloid-precursor-protein maturation and amyloid-β production in an APP-transgenic model
Hartbauer M, Hutter-Paier B, Skofitsch G, Windisch M. (2001). Journal of Neural Transmission — Anti-apoptotic mechanism study in primary embryonic chick cortical neuron cultures
Rockenstein E, Adame A, Mante M, Moessler H, Windisch M, Masliah E. (2003). Journal of Neural Transmission — APP-transgenic Alzheimer's-disease model study examining amyloid burden and behavioral endpoints
Research Use Only
These products are intended for research purposes only and are not for human consumption. Not FDA approved. Not intended to diagnose, treat, cure, or prevent any disease.
