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Background: Traumatic brain injury (TBI) is a common neurosurgical disease in emergency rooms with poor prognosis, imposing severe burdens on patients and their families. Evidence indicates that piracetam and compound porcine cerebroside and ganglioside injection (CPCGI) can improve cognitive levels in TBI patients to enhance functional prognosis, but there is still a research gap regarding the efficacy of CPCGI. This study aims to determine the effectiveness and safety of CPCGI in improving cognitive and functional outcomes in TBI patients. Methods: This study is a multicenter, randomized, parallel-group, double-blind trial aiming to recruit 900 adult patients with mild to moderate TBI. After providing informed consent, 600 patients will be randomly assigned to the CPCGI group (20 ml/d, for 14 days), and 300 patients will be randomized to the piracetam group as a control (20 ml/d, for 14 days), followed up for 3 months after treatment. The primary outcome is the change in the Montreal Cognitive Assessment (MoCA) score from baseline after 3 months. The main secondary outcome measures include Mini-Mental State Examination (MMSE) scores, Glasgow Outcome Scale-Extended (GOS-E), and the Barthel Index at 1 and 3 months. Discussion: This multi-center clinical trial aims to provide high-quality evidence on the efficacy and safety of CPCGI in improving cognitive and functional outcomes in mild to moderate TBI patients. Trial registration: ChiCTR2000040466, date of registration: November 28, 2020.

Objective: To evaluate the clinical safety of compound porcine cerebroside and ganglioside injection in 4239 patients with hemorrhagic stroke after the market, so as to provide reference for clinical rational drug use. Methods: From March 2020 to March2021, a multi-center, prospective and non-controlled clinical study design method was used to analyze the basic situation, medication information, adverse drug reactions and disease outcome of 4239 patients with hemorrhagic stroke who used compound porcine cerebroside and ganglioside injection in 46 medical institutions in China. Results: The average medication time of 4239 hemorrhagic stroke patients was（13.62±2.22） days. Only 13 cases were judged to be adverse drug reactions during medication, and the incidence of adverse reactions was 0.307%. The adverse drug reactions were mainly concentrated in gastrointestinal diseases and systemic diseases. Among the 4239 patients with hemorrhagic stroke, 190 were cured, 3109 improved, 912 had no significant change, and 27 exacerbation, and 1patient died. Among the 13 patients with adverse drug reactions, 10 patients improved after treatment, and 3 patients showed no significant change after treatment. Among the 4239 patients with hemorrhagic stroke with different medication conditions, 49.99% of the patients used a dose of ≤6 m L, and 50.0% of the patients used a dose of ≥8 m L, and there was no significant difference in the incidence of adverse drug reactions between patients with different drug doses（P＞0.05). 0.9% saline was the main vehicle type, followed by 5% glucose, and there was no statistical difference in the incidence of adverse drug reactions between different vehicle types（P＞0.05). 81.17% of the patients did not flush the tube, 17.65% of the patients flushed the tube, and 1.18% of the patients changed the infusion set, and there was no significant difference in the incidence of adverse drug reactions between different measures（P＞0.05). 92.19% of the patients had no irrational drug use, there were irrational drug use in the 7.81% patients, and there was a statistically significant difference in the incidence of adverse drug reactions between the two（P＜0.05). Conclusion: The incidence of adverse reactions of compound porcine cerebroside and ganglioside injection in 4239 patients with hemorrhagic stroke after the market was low and the risk was controllable. At the same time, the adverse reaction symptoms were known or common adverse reactions. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is a common neurosurgical disease in emergency rooms with poor prognosis, imposing severe burdens on patients and their families. Evidence indicates that piracetam and compound porcine cerebroside and ganglioside injection (CPCGI) can improve cognitive levels in TBI patients to enhance functional prognosis, but there is still a research gap regarding the efficacy of CPCGI. This study aims to determine the effectiveness and safety of CPCGI in improving cognitive and functional outcomes in TBI patients., Methods: This study is a multicenter, randomized, parallel-group, double-blind trial aiming to recruit 900 adult patients with mild to moderate TBI. After providing informed consent, 600 patients will be randomly assigned to the CPCGI group (20 ml/d, for 14 days), and 300 patients will be randomized to the piracetam group as a control (20 ml/d, for 14 days), followed up for 3 months after treatment. The primary outcome is the change in the Montreal Cognitive Assessment (MoCA) score from baseline after 3 months. The main secondary outcome measures include Mini-Mental State Examination (MMSE) scores, Glasgow Outcome Scale-Extended (GOS-E), and the Barthel Index at 1 and 3 months., Discussion: This multi-center clinical trial aims to provide high-quality evidence on the efficacy and safety of CPCGI in improving cognitive and functional outcomes in mild to moderate TBI patients., Trial Registration: ChiCTR2000040466, date of registration: November 28, 2020., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Fei Niu,1,* Ke Qian,2,* Hongyan Qi,3 Yumei Zhao,4 Yingying Jiang,4 Ming Sun4 1Department of Neurotrauma, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, People’s Republic of China; 2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, People’s Republic of China; 3Department of Acupuncture, Lianyungang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Lianyungang City 222000, Jiangsu Province, People’s Republic of China; 4Department of Neuropharmacology, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming SunDepartment of Neuropharmacology, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, 119 South Fourth Ring West Road, Fengtai District, Beijing 100070, People’s Republic of ChinaTel/Fax + 86-10-59975497Email sunming999@yahoo.comBackground: Compound porcine cerebroside and ganglioside injection (CPCGI) has been used for the treatment of certain brain disorders. Apoptosis and inflammation were reported to be involved in the pathogenesis of traumatic brain injury (TBI). Therefore, this study primarily investigated the effects of CPCGI on mitochondrial apoptotic signaling and PARP/NF-κB inflammatory signaling in a rat model of controlled cortical impact (CCI).Materials and Methods: CPCGI (0.6 mL/kg) was administered intraperitoneally 30 min after the induction of CCI. Mitochondrial apoptotic signaling and PARP/NF-κB inflammatory signaling were evaluated 24 h after CCI, and apoptotic cell death, neutrophil infiltration, and astrocyte and microglial activation were determined by TUNEL and immunofluorescent staining 3 days after CCI.Results: 1) CPCGI markedly enhanced cytosolic and mitochondrial Bcl-xL levels, the mitochondrial Bcl-xL/Bax ratio, and mitochondrial cytochrome (cyt) c levels and reduced cytosolic cyt c levels, caspase-3 activity, and nuclear AIF levels in brain tissues after traumatic injury; however, CPCGI had no significant effects on cytosolic or mitochondrial Bax levels, the cytosolic Bcl-xL/Bax ratio, or mitochondrial AIF levels. Moreover, CPCGI markedly reduced the TUNEL staining score in the contusion region. 2) CPCGI markedly reduced cytosolic and nuclear PARP levels and nuclear NF-κB p65 levels in brain tissues after traumatic injury but had no significant effect on cytosolic NF-κB p65 levels. In addition, CPCGI markedly reduced caspase-1 activity and the levels of caspase-1, ICAM-1, TNF-α, and IL-1β in brain tissues after traumatic injury and decreased the immunoreactivities of neutrophils, GFAP and Iba-1 in the region of CCI-induced contusion.Conclusion: These data suggest that CPCGI can reduce brain injury due to trauma by suppressing both mitochondrial apoptotic signaling and PARP/NF-κB inflammatory signaling.Keywords: compound porcine cerebroside and ganglioside injection, traumatic brain injury, mitochondrial apoptotic signaling, PARP/NF-κB inflammatory signaling

Fei Niu,1,* Ke Qian,2,* Hongyan Qi,3 Yumei Zhao,4 Yingying Jiang,4 Wang Jia,2 Ming Sun4 1Department of Neurotrauma, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, People’s Republic of China; 2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, People’s Republic of China; 3Department of Acupuncture, Lianyungang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Lianyungang City 222000, Jiangsu Province, People’s Republic of China; 4Department of Neuropharmacology, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming SunDepartment of Neuropharmacology, Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, 119 South Fourth Ring West Road, Fengtai District, Beijing 100070, People’s Republic of ChinaTel/ Fax +86-10-59975497Email sunming999@yahoo.comBackground: Compound porcine cerebroside and ganglioside injection (CPCGI), which involves injection of a neurotrophic drug, has been widely used to treat certain brain disorders in the clinic; however, the detailed mechanism is unknown. This study investigated whether CPCGI protects the brain from trauma by stimulating antioxidative nuclear factor erythroid-2-related factor 2 (Nrf2) signaling and suppressing calpain overactivation in a rat model of controlled cortical impact (CCI).Materials and Methods: The rat model of CCI was used. Neurological deficits, contusion, and white matter damage were evaluated 3 days after CCI. Calpain activation, Nrf2 signaling and oxidative stress were determined 24 h after CCI.Results: CPCGI dose-dependently reduced neurological deficits, attenuated axonal and myelin sheath injury, and decreased contusion volume 3 days post-CCI. Moreover, CPCGI reduced calpain activity, and enhanced the cytosolic levels of calpastatin, αII-spectrin, microtubule-associated protein 2 (MAP2), neurofilament heavy chain (NF-H) and myelin basic protein (MBP) in traumatic tissues 24 h post-CCI. Furthermore, CPCGI reduced the levels of nuclear Kelch-like ECH-associated protein 1 (Keap1) and thioredoxin interacting protein (TXNIP); increased the levels of cytosolic Nrf2 and thioredoxin 1 (Trx 1) and nuclear Nrf2; increased the cytosolic and nuclear Nrf2/Keap1 and Trx 1/TXNIP ratios; enhanced the levels of heme oxygenase 1 (HO-1), glutathione (GSH), superoxide dismutase activity, and total antioxidative capacity; and reduced the levels of malondialdehyde in TBI tissues.Conclusion: These data confirm the neuroprotective effect of CPCGI against gray and white matter damage due to CCI and suggest that activating Nrf2 signaling and alleviating oxidative stress-mediated calpain activation could be one mechanism by which CPCGI protects against brain trauma.Keywords: compound porcine cerebroside and ganglioside injection, traumatic brain injury, Nrf2 signaling, oxidative stress, calpain

BACKGROUND: The most current application of compound porcine cerebroside and ganglioside injection (CPCGI) focuses on the clinical therapeutic efficacy in some craniocerebral injuries and neonatal hypoxic ischemic encephalopathy, but the molecular mechanism of CPCGI involved in the recovery of nerve function is rarely reported. OBJECTIVE: To study the protective effect and mechanism of CPCGI in a neonatal mouse model of intrauterine hypoxia-induced brain injury. METHODS: Fifteen Kunming mice were randomly divided into control group, hypoxia group and treatment group. At the 14thday after pregnancy, mice in hypoxia group and treatment group were put into a 10% oxygen incubator to make the model of intrauterine hypoxia. After delivery, neonatal mice were intraperitoneally injected with CPCGI and PBS respectively, and mouse development in each group was observed after treatment. Mice in the control group were not hypoxic and treated. The expression of glial fibrillary acidic protein, Neurocan, SynDIGI and collagen IV were observed by immunofluorescence staining and western blot assay. A step-down test was used to test animal memory function. The study protocol was approved by the Animal Ethic Committee of Luohe Medical College in China. RESULTS AND CONCLUSION: Compared with the control group, the expressions of glial fibrillary acidic protein and Neurocan in the hypoxia group were significantly increased, while the expressions of SynDIG1 and collagen IV were significantly decreased. The expression of SynDIG1 and collagen IV in the treatment group was significantly increased than that in the hypoxia group, while the expression of glial fibrillary acidic protein and Neuroncan was significantly decreased than that in the hypoxia group. The learning and memory ability of mice in the hypoxia group was significantly decreased compared with the control group, but was significantly improved after CPCGI treatment. These results suggest that CPCGI can alleviate brain injury and improve learning and memory ability after hypoxic ischemic encephalopathy. The detailed mechanism might be related to inhibiting activation of astrocytes, down-regulating Neuroncan expression, up-regulating collagen IV expression, promoting synaptic reconstruction and reducing cerebrovascular injury. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder causing progressive memory loss and cognitive impairment. The aberrant accumulation of amyloid-β (Aβ) and neuroinflammation are two major events in AD. Aβ-induced neurotoxicity and oxidative stress are also involved in the pathogenesis of AD. The purpose of the current study was to investigate the effect of compound porcine cerebroside and ganglioside injection (CPCGI) on the progression of AD, and to explore the molecular mechanism. In vivo and in vitro models of AD were established and treated with CPCGI. Aβ40 and Aβ42 protein levels were detected using western blotting. Production of pro-inflammatory factors [tumor necrosis factor (TNF)-α and interleukin (IL)-1β] and oxidative stress markers [malondialdehyde (MDA), superoxide dismutase (SOD)] and reactive oxygen species (ROS) production were determined. Cell viability and apoptosis were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5- diphenyl-2-H-tetrazolium bromide assay and flow cytometry analysis respectively. Results demonstrated that CPCGI administration reduced Aβ40 and Aβ42 accumulation, and inhibited inflammatory response and oxidative stress in the in vivo rat model of AD, evidenced by decreased Aβ40 and Aβ42 protein expression, reduced levels of TNF-α and IL-1β, reduced MDA content, enhanced SOD activity, and reduced ROS level. It was found that CPCGI enhanced cell viability and reduced cell apoptosis of Aβ25-35 induced PC12 cells. In addition, the mitogen-activated protein kinase/NF-κB pathway was involved in the protective effect of CPCGI on AD. Taken together, the data demonstrated that CPCGI exerted a protective effect on AD by reducing Aβ accumulation, inhibiting inflammatory response and oxidative stress, In addition to preventing neuronal apoptosis. [ABSTRACT FROM AUTHOR]

Mingyang Wang,* Yi Zhang,* Lu Feng, Ji Zheng, Shujie Fan, Junya Liu, Nan Yang, Yanyong Liu, Pingping Zuo Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China *These authors contributed equally to this work Background: Compound porcine cerebroside and ganglioside injection (CPCGI) is a neurotrophic drug used clinically to treat certain functional disorders of brain. Despite its extensive usage throughout China, the exact mechanistic targets of CPCGI are unknown. This study was carried out to investigate the protective effect of CPCGI against ischemic neuronal damage in rats with middle cerebral artery occlusion (MCAO) reperfusion injury and to investigate the neuroprotective mechanisms of CPCGI. Materials and methods: Adult male Sprague-Dawley rats were subjected to MCAO surgery for 2 hours followed by reperfusion. The rats were administered CPCGI once a day for 14 days after reperfusion, and behavioral tests were performed 1, 3, 7, and 14 days post MCAO. Hematoxylin–eosin staining was used to measure infarct volume, and immunohistochemical analysis was performed to determine the number of NeuN-positive neurons in the ischemic cortex penumbra. Finally, the relative expression levels of proteins associated with apoptosis (Bcl-2, Bax, and GADD45α), synaptic function (Synaptophysin, SNAP25, Syntaxin, and Complexin-1/2), and mitochondrial function (KIFC2 and UCP3) were determined by Western blot. Results: CPCGI treatment reduced infarct size, decreased neurological deficit scores, and accelerated the recovery of somatosensory function 14 days after MCAO. In addition, CPCGI reduced the loss of NeuN-positive cells in the ischemic cortex penumbra. In the ischemic cortex, CPCGI treatment decreased GADD45α expression, increased the Bcl-2/Bax ratio, augmented Synaptophysin, SNAP25, and Complexin-1/2 expression, and increased the expression of KIFC2 and UCP3 compared with sham rats 14 days after MCAO reperfusion injury. Conclusion: CPCGI displays neuroprotective properties in rats subjected to MCAO injury by inhibiting apoptosis and improving synaptic and mitochondrial function. Keywords: compound porcine cerebroside and ganglioside injection, cerebral ischemia reperfusion, multitarget, neuroprotection

Background: Compound porcine cerebroside and ganglioside injection (CPCGI) is a neurotrophic drug used clinically to treat certain functional disorders of brain. Despite its extensive usage throughout China, the exact mechanistic targets of CPCGI are unknown. This study was carried out to investigate the protective effect of CPCGI against ischemic neuronal damage in rats with middle cerebral artery occlusion (MCAO) reperfusion injury and to investigate the neuroprotective mechanisms of CPCGI. Materials and methods: Adult male Sprague-Dawley rats were subjected to MCAO surgery for 2 hours followed by reperfusion. The rats were administered CPCGI once a day for 14 days after reperfusion, and behavioral tests were performed 1, 3, 7, and 14 days post MCAO. Hematoxylin-eosin staining was used to measure infarct volume, and immunohistochemical analysis was performed to determine the number of NeuN-positive neurons in the ischemic cortex penumbra. Finally, the relative expression levels of proteins associated with apoptosis (Bcl-2, Bax, and GADD45α), synaptic function (Synaptophysin, SNAP25, Syntaxin, and Complexin-1/2), and mitochondrial function (KIFC2 and UCP3) were determined by Western blot. Results: CPCGI treatment reduced infarct size, decreased neurological deficit scores, and accelerated the recovery of somatosensory function 14 days after MCAO. In addition, CPCGI reduced the loss of NeuN-positive cells in the ischemic cortex penumbra. In the ischemic cortex, CPCGI treatment decreased GADD45α expression, increased the Bcl-2/Bax ratio, augmented Synaptophysin, SNAP25, and Complexin-1/2 expression, and increased the expression of KIFC2 and UCP3 compared with sham rats 14 days after MCAO reperfusion injury. Conclusion: CPCGI displays neuroprotective properties in rats subjected to MCAO injury by inhibiting apoptosis and improving synaptic and mitochondrial function. [ABSTRACT FROM AUTHOR]