Cerebrolysin alleviates early brain injury after traumatic brain injury by inhibiting neuroinflammation and apoptosis via TLR signaling pathway

Abstract

Purpose: Traumatic brain injury (TBI) is a major cause of death and disability. Cerebrolysin (CBL) has been reported to be anti-inflammatory by reducing reactive oxygen species (ROS) production. However, the neuroprotection of CBL in TBI and the potential mechanism are unclear. We aimed to investigate the neuroprotection and mechanisms of CBL in TBI. Methods: The TBI model was established in strict accordance with the Feeney weight-drop model of focal injury. The neurological score, brain water content, neuroinflammatory cytokine levels, and neuronal damage were evaluated. The involvement of the early brain injury modulatory pathway was also investigated. Results: Following TBI, the results showed that CBL administration increased neurological scores and decreased brain edema by alleviating blood‑brain barrier (BBB) permeability, upregulating tight junction protein (ZO‑1) levels, and decreasing the levels of the inflammatory cytokines tumor necrosis factor‑α (TNF‑α), interleukin‑1β (IL‑1β), IL‑6, and NF‑κB. The TUNEL assay showed that CBL decreased hippocampal neuronal apoptosis after TBI and decreased the protein expression levels of caspase‑3 and Bax, increasing the levels of Bcl‑2. The levels of Toll‑like receptor 2 (TLR2) and TLR4 were significantly decreased after CBL treatment. In TBI patients, CBL can also decrease TNF‑α, IL‑1β, IL‑6, and NF‑κB levels. This result indicates that CBL‑mediated inhibition of neuroinflammation and apoptosis ameliorated neuronal death after TBI. The neuroprotective capacity of CBL is partly dependent on the TLR signaling pathway. Conclusions: Taken together, the results of this study indicate that CBL can improve neurological outcomes and reduce neuronal death against neuroinflammation and apoptosis via the TLR signaling pathway in mice.

Comparative neuroprotective effects of Cerebrolysin, dexamethasone, and ascorbic acid on sciatic nerve injury model: Behavioral and histopathological study

“…After chronic sciatic nerve constriction in rats, a functional imbalance between proapoptotic BAX and antiapoptotic BCL2 has been identified (Maione et al, 2002). The decrease in the BAX/BCL2 ratio emphasizes the antiapoptotic effect of Cerebrolysin (Lu et al, 2022), the antiapoptotic effect of local dexamethasone in agreement with previous studies (Hoang et al, 2009;Lee et al, 2015), and the antiapoptotic effect of vitamin C to adapt or overcome Sciatic nerve injury (Sourour et al, 2012;Gong et al, 2022). Similarly, 10.3389/fnana.2023.1090738 the antiapoptotic effect of vitamin C was superior to Cerebrolysin and dexamethasone, which may be referred to as its ability in neutralizing free radicals and ameliorating oxidative stress-mediated cellular apoptosis and cell death.…”

Post-COVID-19 Anosmia and Therapies: Stay Tuned for New Drugs to Sniff Out

“…Several studies are currently evaluating Cerebrolysin efficacy for other conditions, including cerebral palsy, vascular dementia, aneurysmal subarachnoid haemorrhage, and anosmia [ 66 ]. The main pharmacological effect of Cerebrolysin is the restoration of the surrounding and damaged nerve structures, which is deleterious to neurons, causing their degeneration, dysfunction, and death [ 67 ]. Few articles have demonstrated the safety and efficacy of this drug, but noteworthy is a meta-analysis that demonstrated that this blend of peptides can be used as a safe therapy for recovery from severe traumatic brain injury.…”

Notoginsenoside R1 attenuates brain injury in rats with traumatic brain injury: Possible mediation of apoptosis via ERK1/2 signaling pathway

“…To further confirm whether this increase in neuronal survival was associated with anti-apoptotic effects, we performed FJB and TUNEL staining on frozen sections of rat tissue. Both domestic and foreign scholars have used the TUNEL technique to detect DNA fragments formed by apoptosis and found that only a large number of TUNEL-positive cells could be seen in the peripheral area of the injury foci, while no TUNEL-positive cells were expressed in the core necrotic area and the peripheral normal area [ 36 ]. The same was observed in our experiments, wherein, in the Sham group, only few, if any, FJB- and TUNEL-positive apoptotic cells could be seen; in the TBI and TBI+vehicle groups, the number of apoptotic cells was significantly increased; while in the NGR1 treatment groups, the number of apoptotic cells in rat neurons was significantly reduced.…”