Compound porcine cerebroside and ganglioside injection attenuates cerebral ischemia–reperfusion injury in rats by targeting multiple cellular processes

Abstract

BackgroundCompound 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 methodsAdult 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.ResultsCPCGI 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.ConclusionCPCGI displays neuroprotective properties in rats subjected to MCAO injury by inhibiting apoptosis and improving synaptic and mitochondrial function.

Compound Porcine Cerebroside and Ganglioside Injection (CPCGI) Attenuates Sevoflurane-Induced Nerve Cell Injury by Regulating the Phosphorylation of p38 MAP Kinase (p38MAPK)/Nuclear Factor kappa B (NF-κB) Pathway

“…CPCGI, which is a potent treatment for many diseases, is involved in reducing cell apoptosis and enhancing synaptic functions. Previous studies have reported that CPCGI promotes neurogenesis by mediating cell apoptosis in hippocampal neurons, and its neuroprotective effects in MCAO-induced injury models have also been documented [6]. However, whether CPCGI participates in the progression of sevoflurane-stimulated injury in hippocampal neuronal cells has been unclear.…”

“…CPCGI (drug approval H22026472, China) has widespread clinical use for Alzheimer's disease, craniocerebral injury, spinal cord injury, and traumatic peripheral nerve injury therapy in China [6][7][8]. In addition, monosialotetrahexosyl ganglioside (GM-1) and hypoxanthine, the main components of CPCG, can promote the metabolism of brain tissue, are involved in neuron growth, differentiation, and regeneration, and accelerate the brain blood circulation [9][10][11][12][13][14].…”

“…In addition, monosialotetrahexosyl ganglioside (GM-1) and hypoxanthine, the main components of CPCG, can promote the metabolism of brain tissue, are involved in neuron growth, differentiation, and regeneration, and accelerate the brain blood circulation [9][10][11][12][13][14]. The effective ingredients of CPCGI (polypeptide, GM-1, and hypoxanthine) have also been reported to possess a significant curative effect for stroke treatment in rats [6]. However, the protective response of CPCGI to neuronal damage stimulated by sevoflurane has not yet been described.…”

<p>CPCGI Reduces Gray and White Matter Injury by Upregulating Nrf2 Signaling and Suppressing Calpain Overactivation in a Rat Model of Controlled Cortical Impact</p>

“…9 In 2010, the China Food and Drug Administration approved compound porcine cerebroside and ganglioside injection (CPCGI), a neurotrophic drug, for use in the treatment of stroke, Alzheimer's disease, and central and peripheral nerve injuries. [10][11][12][13] The main components of CPCGI include polypeptides, various gangliosides, and hypoxanthine, etc. CPCGI has been reported to improve cerebral blood circulation and neurological function, reduce apoptotic cell death, and prompt the recovery of synaptic and mitochondrial function in a rat model of focal cerebral ischemia.…”

“…CPCGI has been reported to improve cerebral blood circulation and neurological function, reduce apoptotic cell death, and prompt the recovery of synaptic and mitochondrial function in a rat model of focal cerebral ischemia. 10 , 13 However, there is no report about the protective effects of CPCGI against TBI. In the present study, we primarily investigated whether CPCGI protected the brain against TBI through upregulating Nrf2 signaling and suppressing calpain overactivation due to oxidative stress in a rat model of controlled cortical impact (CCI).…”