Cerebrolysin

What it is

Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from porcine brain (PMIDs: 37818733, 36662068, 15). Its biological effects are described as similar to those of endogenous neurotrophic factors. Proposed mechanisms include: induction of neurogenesis, neuroplasticity, neuroprotection, and neurotrophicity; modulation of endogenous neurotrophic factor expression including BDNF, GDNF, NGF, CNTF, VEGF, and IGF-1 (PMIDs: 37052231, 22229324); stabilization of the blood-brain barrier (BBB) by reducing proinflammatory proteins (ICAM-1, HMGB1, TNF-α, NF-κB-p65) and restoring tight junction proteins (ZO-1, occludin, claudin) in vitro; and multi-target neuroprotective effects including anti-inflammatory, antioxidant, and antiapoptotic activity (PMIDs: 37052231, 39832667). Preclinical reviews also describe attenuation of amyloid-beta and phosphorylated tau deposition, and modulation of alpha-synuclein in Parkinson's disease models (PMIDs: 30961867, 30961868). Cerebrolysin has been characterized as a "multimodal" drug acting on multiple pathways simultaneously (PMIDs: 37052231, 43).

Class: Neuropeptide preparation / neurotrophic agent (mixture of low-molecular-weight peptides and amino acids derived from porcine brain)

What it's studied for

• Acute ischemic stroke (AIS) — neuroprotection and functional recovery Mixed
  • Meta-analysis of 7 RCTs (1773 participants). Moderate-certainty evidence: Cerebrolysin probably results in little to no difference in all-cause death (RR 0.96, 95% CI 0.65–1.41). Moderate-certainty evidence suggests no significant reduction in total SAEs, and a potential increase in non-fatal SAEs (RR 2.39, 95% CI 1.10 PMID 37818733 Ziganshina et al., Cochrane Database Syst Rev (2023)
  • Meta-analysis of 9 RCTs (N=1879). Cerebrolysin superior to placebo on NIHSS at Day 30 (MW 0.60, P<0.0001). NNT for clinically relevant NIHSS change: 7.7 (95% CI 5.2–15.0). mRS at Day 90 in moderate-to-severe patients: MW 0.61 (95% CI 0.52–0.69, P=0.0118). Safety comparable to placebo. PMID 29248999 Bornstein et al., Neurol Sci (2018)
  • Rapid HTA of 14 studies (8 SRs/meta-analyses, 6 pharmacoeconomic studies). Cerebrolysin demonstrated advantages in total efficacy rate, neurological function, upper limb motor function, and activities of daily living vs. control, especially in moderate-to-severe AIS. Adverse reactions mild or comparable to control. Cos PMID 38552072 Wan et al., Medicine (2024)
  • Post-hoc analysis of CEREHETIS trial (n=238). Heterogeneity of Cerebrolysin effects on hemorrhagic transformation (HT) and functional outcome by HT risk: positive impact in moderate (HTI=1) and high-risk (HTI≥2) patients; neutral in low-risk (HTI=0). In high-risk patients, symptomatic HT rate decreased by 14.3% (p<0.00 PMID 38512096 Kalinin & Khasanova, Zh Nevrol Psikhiatr (2024)
  • CEREHETIS trial: Cerebrolysin 30 mL/day for 14 days added to alteplase (n=126) vs. alteplase alone (n=215). Significant decrease in symptomatic HT (OR 0.248, 95% CI 0.072–0.851, p=0.019). Reduction in NIHSS at Day 14 (p=0.045). No difference in mRS at Day 90. No serious adverse events attributed to Cerebrolysin. PMID 36973684 Khasanova & Kalinin, BMC Neurol (2023)
  • Non-interventional open-label multicenter study, 398 AIS patients. Cerebrolysin (n=190, 20 IV infusions of 10 mL) and Cerebrolysin plus nootropics (n=122) showed significant improvements vs. comparator in mRS, NIHSS, and MoCA at Day 90 (p<0.001). Well-recovered (mRS 0–2): Cerebrolysin 81.6%, combination 93.4%, comparat PMID 34414874 Tran et al., CNS Neurol Disord Drug Targets (2022)
  • Prospective comparative effectiveness study, 16 countries, 1769 patients with moderate IS (NIHSS 8–15). Median Cerebrolysin dose 30 mL, median duration 10 days. Cerebrolysin superior to standard therapy on 90-day mRS (primary endpoint, MW 0.6157, 95% CI 0.5910–0.6404, P<0.0001) and all secondary endpoints including NIH PMID 40851188 Vosko et al., Int J Stroke (2025) — C-REGS2
  • Meta-analysis, 7 RCTs, 1779 AIS patients. Summary results failed to demonstrate significant superiority of Cerebrolysin on mRS or Barthel Index at Day 90. Neutral effects on mortality and SAEs. Authors concluded routine use cannot be supported by available RCT evidence. PMID 28656143 Zhang et al., Biomed Res Int (2017)
  • Meta-analysis, 6 RCTs, 1649 AIS patients. No significant effect on functional recovery at Day 90 (mRS, NIHSS, Barthel Index). No increased risk of adverse events, SAEs, or mortality. PMID 28458521 Wang et al., Drug Des Devel Ther (2017)
• Acute ischemic stroke adjunct to mechanical thrombectomy (MT) / endovascular thrombectomy (EVT) Human observational
  • Systematic review and meta-analysis of 3 observational studies (294 patients). Cerebrolysin+MT vs. MT alone: Good functional outcome (mRS 0–3) RR 1.56 (95% CI 1.25–1.93, p<0.0001); sICH RR 0.12 (95% CI 0.03–0.48, p=0.03); mortality 64% lower (RR 0.36, 95% CI 0.18–0.68, p=0.02). Authors note limited by small sample size PMID 41880098 Afridi et al., Brain Behav (2026)
  • Propensity score-matched cohort (hypothesis-generating target-trial emulation). Cerebrolysin 30 mL/day for 21 days starting post-EVT, second course at 69–90 days. Cerebrolysin associated with higher 12-month functional independence (aOR 6.10, 95% CI 1.64–22.66, p<0.01), favorable mRS shift (common OR 3.57, 95% CI 1.42– PMID 41739286 Staszewski et al., Transl Stroke Res (2026)
  • Prospective open-label single-center study, 50 patients + 50 propensity-matched historical controls. Cerebrolysin 30 mL IV within 8 h of onset, continued to Day 21, second cycle at 69–90 days. mRS 0–2 at 90 days: 68% vs. 44% (p=0.016, OR 2.7); reduced secondary ICH (14% vs. 40%, p=0.02); lower NIHSS at Day 7 (median 3 PMID 40325343 Staszewski et al., Transl Stroke Res (2025)
• Post-stroke motor and functional rehabilitation (early neurorecovery) Mixed
  • Meta-analysis of CARS-1 and CARS-2 (30 mL/day for 21 days, initiated 24–72 h post-stroke, with standardized rehabilitation). ARAT score at Day 90: MW 0.62 (P<0.0001). NIHSS at Days 14 and 21: MW 0.59 (P<0.002), NNT 7.1 (95% CI 4–22). Safety comparable to placebo. PMID 28707130 Guekht et al., Neurol Sci (2017) — CARS meta-analysis
  • Phase II multicenter RCT, Cerebrolysin 30 mL/day for 21 days starting 24–72 h post-stroke combined with standardized rehabilitation. ARAT at Day 90: MW 0.71 (95% CI 0.63–0.79, P<0.0001). Global status across 12 scales: MW 0.62 (95% CI 0.58–0.65, P<0.0001). Discontinuation rate <5%; safety comparable to placebo. PMID 26564102 Muresanu et al., Stroke (2016) — CARS trial
  • Systematic review with meta-analysis elements (10 studies). Cerebrolysin (10–30 mL) combined with early comprehensive multidisciplinary rehabilitation significantly improved daily activities, upper limb functionality, speech (via speech therapy), and reduced depression. Best results at 30 mL dosage with early initiatio PMID 41782528 Shmonin et al., Zh Nevrol Psikhiatr (2026)
• Post-stroke aphasia recovery Human RCT
  • Prospective, randomized, double-blind, multicenter RCT (n=123 ITT). Cerebrolysin combined with speech-language therapy in 10-day cycles vs. placebo + speech therapy over 90 days. Cerebrolysin group: WAB mean increase 35.58±16.32 vs. 20.77±12.49 in placebo (difference in means 14.81, 95% CI 9.52–20.09, p<0.001). NIHSS a PMID 39957612 Homberg et al., Stroke (2025) — ESCAS trial
• Alzheimer's disease (AD) — cognitive and global function Mixed
  • Meta-analysis of 6 RCTs (30 mL/day) in mild-to-moderate AD. Cognitive function at 4 weeks: SMD −0.40 (95% CI −0.66 to −0.13, p=0.0031). Global clinical change at 4 weeks: OR 3.32 (95% CI 1.20–9.21) and at 6 months: OR 4.98 (95% CI 1.37–18.13). Global benefit at 4 weeks and 6 months: MW 0.57 (p<0.001 for both). Safety c PMID 25832905 Gauthier et al., Dement Geriatr Cogn Disord (2015)
  • 30-year review of Cerebrolysin in AD. Clinical trials demonstrated safety and efficacy; may enhance and prolong cholinergic drug efficacy. Results suggest disease-modifying potential. Doses of 10 and 30 mL most effective; up to 60 mL most effective for neuropsychiatric symptoms in later-stage AD (PMID: 22514793). PMID 32808294 Gavrilova & Alvarez, Med Res Rev (2021)
  • 3-year open comparative RCT (n=100 aMCI patients). Annual Cerebrolysin courses (20 IV infusions of 20 mL over 4 weeks) vs. no therapy. Lower cognitive deficit progression and significantly lower conversion to dementia in treated group. Authors suggest disease-modifying effect. PMID 39435777 Ponomareva et al., Zh Nevrol Psikhiatr (2024)
  • Prospective comparative study (n=88 first-degree AD relatives with aMCI). 46 received 3 annual Cerebrolysin courses (20 IV infusions of 20 mL in 100 mL isotonic saline). Zero aMCI-to-dementia conversions in treated group over 2.5 years vs. 9.5% annual conversion in comparators. Significant improvement on all cognitive PMID 37655416 Selezneva & Gavrilova, Zh Nevrol Psikhiatr (2023)
• Vascular dementia Mixed
  • Cochrane review of 6 RCTs (597 participants), mild-to-moderate vascular dementia. Cerebrolysin improved cognitive function (SMD 0.36, 95% CI 0.13–0.58) and global function (RR 2.69, 95% CI 1.82–3.98); both very low-quality evidence. No deaths reported in one trial; no significant difference in adverse events in 2 trial PMID 31710397 Cui et al., Cochrane Database Syst Rev (2019)
  • Review: Cerebrolysin may be effective against VD by targeting neuroinflammation, BBB injury, and chronic cerebral hypoperfusion. Can cross the BBB. Underlying neuroprotective mechanisms not fully elucidated. PMID 39832667 Al-Kuraishy et al., Neuroscience (2025)
• Traumatic brain injury (TBI) — moderate to severe Mixed
  • Prospective meta-analysis of 2 phase IIIb/IV RCTs (n=185, moderate-severe TBI, GCS 6–12). Cerebrolysin 50 mL/day for 10 days + two additional cycles of 10 mL/day for 10 days. Primary multidimensional endpoint: small-to-medium effect at Day 30 (MW 0.60, 95% CI 0.52–0.66, p=0.0156) and Day 90 (MW 0.60, 95% CI 0.52–0.68, PMID 33620612 Vester et al., Neurol Sci (2021) — CAPTAIN trials meta-analysis
  • Retrospective multicenter cohort, 87 severe TBI patients. Cerebrolysin 30 mL/day for 14 days, then 10 mL/day for 14 days (n=42) vs. standard care (n=45). Favorable outcome at Day 21: 87% vs. 50% (p<0.00001). GOS ≥4: 39% vs. 18% (p=0.043). Mean hospital stay ~7 days shorter (p<0.00001). No significant difference in 28-d PMID 35344761 Lucena & Briones, Clin Neurol Neurosurg (2022)
  • Retrospective study, 44 TBI patients (11 Cerebrolysin, 33 control). Cerebrolysin 30 mL IV infusions added to standard rehabilitation. Significant improvement in functional and cognitive scales at 4 and 7 months vs. control, with moderate residual disability and reduced care needs in Cerebrolysin group. PMID 37900065 Soto et al., J Med Life (2023)
• Amyotrophic lateral sclerosis (ALS) Human RCT
  • Phase II double-blind placebo-controlled RCT (n=20; 1:1 ratio). Cerebrolysin 10 mL IV once daily 5×/week (Month 1) then 3×/week (Months 2–3) added to riluzole 50 mg PO BID. ALS-FRS-r at Month 1: +2.3 points vs. −0.9 in placebo (P=0.005). Effect maintained over 3 months. Combination well tolerated. Authors report first PMID 38585517 Firstenfeld et al., J Med Life (2023)
• Neonatal hypoxic-ischemic encephalopathy (HIE) / high-risk preterm infants Mixed
  • RCT in high-risk preterm infants <32 weeks with abnormal neurological assessment. Cerebrolysin 0.1 mL/kg weekly for 3 months added to early intervention program. Failed gross motor at 12 months corrected age: 33% (Cerebrolysin) vs. 70% (control), p=0.009. Significant improvement also in fine motor, language, and person PMID 33935111 Samir et al., J Neonatal Perinat Med (2022)
  • Review: Cerebrolysin 0.1 mL/kg body weight twice per week shown to provide gross motor and speech deficit improvement in HIE/PA. Up to 6-month treatment window post-ischemic insult described. Biomarker establishment recommended. PMID 34494216 Fiani et al., Acta Neurol Belg (2021)
• Post-ischemic depression (anxiety- and depressive-like behaviors) Animal studies only
  • Mouse model of post-ischemic depression (bCCAO + spatial restraint stress). Cerebrolysin 2.5 mL/kg treatment reversed anxiety- and depressive-like behaviors, improved sociability, reduced serum corticosterone, reduced hippocampal NF-κB and Iba-1, and increased BDNF and p-CREB/CREB. Combined with enriched environment al PMID 35500360 Farajdokht et al., J Stroke Cerebrovasc Dis (2022)
• Depression (augmentation of lithium) Animal studies only
  • Rat reserpine model of depression. Cerebrolysin, lithium, or combination alleviated behavioral, oxidative stress, acetylcholinesterase, and monoamine changes and improved BDNF and histopathology vs. reserpine alone. Lithium + Cerebrolysin combination showed clearest beneficial effect, suggesting potential as adjuvant a PMID 38394763 Abdelaty et al., J Psychiatr Res (2024)
• Blood-brain barrier protection / endothelial cell permeability In vitro only
  • In vitro human cerebral endothelial cell permeability assay. Cerebrolysin significantly reversed tPA- and fibrin-impaired endothelial cell permeability; reduced proinflammatory/procoagulation proteins (ICAM-1, HMGB1, TNF-α, phospho-NF-κB-p65); elevated tight junction proteins (ZO-1, occludin, claudin). Cerebroprotein h PMID 33661804 Teng et al., Neuroreport (2021)
• Parkinson's disease (preclinical/nanodelivery models) Animal studies only
  • Review of animal model studies. Nanowired delivery of Cerebrolysin reported to reduce dopaminergic neuron loss, attenuate BBB breakdown, and induce superior neuroprotection vs. standard delivery in PD models. PMID 30961868 Ozkizilcik et al., Prog Brain Res (2019)
• Spinal cord injury (preclinical) Animal studies only
  • Rat SCI model. Cerebrolysin 2.5 mL/kg IV before SCI provided neuroprotection in normal animals; 5.0 mL/kg required for comparable neuroprotection in nanoparticle-intoxicated rats. Reduced spinal cord water content, plasma protein leakage, and injured neurons. PMID 22229324 Menon et al., CNS Neurol Disord Drug Targets (2012)
• Hair repigmentation (unexpected observed effect) Human observational
  • Case series of 5 patients (mean age 70.6 years) receiving Cerebrolysin for neurological conditions. Scalp hair repigmentation observed during treatment; biopsy showed greater melanin and MART-1/Melan-A staining post-treatment. Authors describe this as a previously unreported effect. PMID 36411485 Villarreal-Reyna et al., Eur J Med Res (2022)