<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>

Abstract

Background: 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, αIIspectrin, 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.

<p>Antiapoptotic and Anti-Inflammatory Effects of CPCGI in Rats with Traumatic Brain Injury</p>

“…11,12 A previous study revealed that CPCGI exerts protective effects against TBI by upregulating the Nrf2 signaling pathway, lessening oxidative stress and suppressing the overactivation of calpain. 13 This study primarily investigated whether CPCGI protects the brain against TBI through repressing both mitochondrial apoptotic and PARP/NF-κB inflammatory signaling after TBI.…”

Compound porcine cerebroside and ganglioside injections improved anxiety and cognitive dysfunction through the NF-κB pathway in cerebral ischemia-reperfusion injury

“…found that GM1, the active ingredient of CPCGI, inhibited in ammation and activation of NF-κB signaling pathway, respectively. Meanwhile, a recent study proved that CPCGI could reduce cortical neuronal apoptosis by inhibiting NF-κB signaling pathway in traumatic brain injury [35]. Conversely, we concluded that CPCGI attenuates hippocampal in ammation and thus reduces neuronal apoptosis by inhibiting the phosphorylation expression level of NF-κB signaling pathway.…”